BACKGROUND:In the process of exploring the mechanism of Alzheimer's disease,the important role of bioinformatics for common target screening has been revealed,enabling the use of its screening results as a basis for exploring the therapeutic effects of drugs on the disease. OBJECTIVE:To predict the targets of liraglutide,a glucagon-like peptide-1 receptor agonist,in the treatment of Alzheimer's disease by bioinformatics and molecular biology. METHODS:DisGeNET database and SEA database were used to obtain the common genes of Alzheimer's disease and liraglutide.GO/KEGG enrichment analysis of common targets was conducted using DAVID online database.Protein-protein interaction networks were constructed using STRING database.The optimal dosage of liraglutide was determined using cell counting kit-8 assay.Expression of key proteins was analyzed using immunofluorescence and immunoblotting techniques.The mouse hippocampal neuron HT22 cell line was used for ex vivo experiments,and the cells were randomly divided into three groups:HT22 group,HT22+Aβ group,and HT22+Aβ+Lir group.No special treatment was done in the HT22 group,while Aβ1-42 was used to intervene in the HT22 cell line for 24 hours to construct an Aβ injury cell model in the HT22+Aβ group.In additional to modeling,liraglutide was added to the HT22+Aβ+Lir group for 12 hours. RESULTS AND CONCLUSION:A total of 3 333 genes associated with Alzheimer's disease were screened from DisGeNET database.Then 147 potential targets of liraglutide were obtained from SEA database.Finally,64 common targets of Alzheimer's disease and Liraglutide were determined using R packets.GO/KEGG analysis of common targets using DAVID online database suggested that common targets were mainly enriched in the following biological processes:neuroactive ligand-receptor interaction,renin-angiotensin system,bladder cancer,endopeptidase activity,peptide receptor activity,G protein-coupled peptide receptor activity,and transport vesicles.The obtained 64 common target proteins were imported into SRTING online database for protein-protein interaction network construction,and the top three genes,matrix metalloproteinases 2,9 and interleukin 1β,were obtained.The activity of cultured cells was detected by the cell counting kit-8 kit.Liraglutide at 100 nmol/L was the optimal concentration for antagonizing Aβ1-42.In the western blot and immunofluorescence assays,the expression of matrix metalloproteinases 2,9 and interleukin 1β was significantly increased in the HT22+Aβ group compared with the HT22 group(P＜0.05)but significantly decreased in the HT22+Aβ+Lir group compared with the HT22+Aβ group(P＜0.05).To conclude,the above bioinformatics data and secondary validation of differential genes in the GEO database suggest that both matrix metalloproteinases 2,9 and interleukin 1β could be potential targets of liraglutide in the treatment of Alzheimer's disease.

Objective:To retrieve the evidence for the prevention and control of lung infection risk factors after hip fracture surgery in geratic patients at home and abroad, so as to summarize the best evidence.Methods:Clinical decision-making, guidelines and evidence summary were systematically retrieved in UpToDate, British Medical Journal (BMJ) Best Practice, Guidelines International Network, National Guideline Clearinghouse, National Institute for Health and Care Excellence, British Orthopaedic Association, Australian and New Zealand Society for Geriatric Medicine, European Society of Trauma and Emergency Surgery, European Respiratory Society and Chinese Medical Association, and the search time limit was from the establishment of the database to September 30, 2020. The thematic evidence summary literature was supplementally searched in PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI) and other databases, and the search time limit was from January 1, 2018 to September 30, 2020.Results:Totals of 2 clinical decisions, 15 evidence-based guidelines, and 1 evidence summary were included. A total of 64 pieces of evidence were summarized from the aspects of perioperative multidisciplinary team construction, personnel training, risk factor screening and evaluation, and risk factor control.Conclusions:Prevention of lung infections after hip fractures in geratic patients requires multidisciplinary collaboration. It is of positive significance to transform the evidence included in this study into a clustered, multidisciplinary clinical implementation plan for the purpose of prevention and control.

Objective:To systematically evaluate and analyze the risk factors for postoperative pulmonary infection in elderly patients with hip fractures.Methods:Two researchers independently searched PubMed, Cochrarne Library, Web of Science, Embase, CINAHL, Chinese Biomedical Literature Database, China National Knowledge Internet (CNKI), VIP, Wanfang database on the cohort or case-control studies on risk factors for postoperative lung infection in elderly patients with hip fracture hip fractures. The search time limit was from the establishment of the databases to June 15, 2020. After literature screening, literature quality evaluation and data extraction, Meta-analysis was performed using RevMan 5.4 software.Results:A total of 17 literatures were included, including 11 Chinese literatures and 6 English literatures. Meta-analysis results showed that male, age of 75 years or older, surgery waiting time greater than 48 hours, surgery time greater than 2 hours, general anesthesia, smoking (history), combination with stroke, anemia, combination with chronic obstructive pulmonary disease (COPD), combination with respiratory disease, hypoproteinemia, American Society of Anesthesiologists gradeⅢ orⅣ, mechanical ventilation, serum vitamin 25 (OH) D deficiency, admission to Intensive Care Unit, combination with diabetes mellitus, the number of preoperative complications greater than 3, cognitive dysfunction and low functional status were risk factors of postoperative lung infection in elderly patients with hip fractures ( P<0.05) . Conclusions:The postoperative pulmonary infection in elderly patients with hip fractures is affected by many factors. It is suggested to establish a multidisciplinary team to timely and accurately identify risk factors of postoperative pulmonary infection and take active measures to prevent the occurrence of postoperative pulmonary infection.

Objective To explore the safety application of organs from infectious donors. Methods Clinical data of 67 donors and recipients undergoing orthotopic liver transplantation were retrospectively analyzed. According to the occurrence of infections and infection sites in donors, all recipients were divided into the bloodstream infection group (n=16, donors with non-drug resistant bacterial infections), non-bloodstream infection group (n=20, donors with other site infections) and non-infection group (n=31). Perioperative clinical parameters including preoperative model for end-stage liver disease (MELD) score, operative time, anhepatic phase, intraoperative blood loss and intraoperative blood transfusion were statistically compared among three groups. The recovery of liver function and coagulation function in the recipients was observed at postoperative 1, 3, 7, 14 and 21 d. The incidence rate of complications and mortality rate in the recipients were recorded within 1 month after liver transplantation. The recovery of postoperative infection-related parameters including white blood cell (WBC), neutrophil pet (NE%) and procalcitonin (PCT) level in the recipients was observed. The application rate and application time of restricted antibiotics were recorded. Results Perioperative clinical parameters in the recipients did not significantly differ among three groups (all P > 0.05). At each time point after liver transplantation, the liver function, coagulation function, incidence rate of complications and mortality rate in the recipients did not significantly differ among three groups (all P > 0.05). The NE% of recipients at postoperative 3 and 7 d in the bloodstream infection group was significantly higher than those in non-bloodstream infection and non-infection groups (all P < 0.05). The PCT levels of recipients at postoperative 3, 7 and 14 d in the bloodstream infection group were significantly higher than those in the non-bloodstream infection and non-infection groups (all P < 0.05). The application rate and application time of restricted antibiotics in the recipients with bloodstream infections were significantly higher or longer than their counterparts in the non-bloodstream infection and non-infection groups (all P < 0.05). Conclusions It is safe to apply liver grafts from donors with bloodstream infection of non-drug resistant bacteria or other site infections when antibiotics are applied as early as possible.

OBJECTIVE:To develop a method for simultaneous determination of irinotecan(CPT-11)and its active metabo-lite 7-ethyl-10-hydroxycamptothecin(SN-38)in human plasma.METHODS:After precipitated by acetonitrile and acidified with hy-drochloric acid,using camptothecin as internal standard,the plasma sample was determined by HPLC-FLD. The determination was performed on Waters Luna C18column with mobile phase consisted of 0.05 mol/L sodium dihydrogen phosphate-acetonitrile(70:30, V/V,adjusted pH to 4.0 by phosphoric acid)at flow rate of 1 mL/min. The excitation wavelength was set at 380 nm;the emis-sion wavelengths of CPT-11 and SN-38 were set at 480 nm and 535 nm,respectively. The column temperature was 25 ℃ and the sample size was 20 μL. RESULTS:The linear ranges were 200-1 000 ng/mL for CPT-11(r=0.999 4,n=5)and 5-45 ng/mL for SN-38(r=0.999 2,n=5). RSDs of inter-day and intra-day were 1.68%-5.57%. The relative recoveries of CPT-11 and SN-38 were 90.12%-106.93%(RSD<8%,n=5)and 92.07%-102.56%(RSD<6%,n=5);the extraction recoveries of CPT-11 and SN-38 were 72.23%-86.56%(RSD<6%,n=5)and 71.98%-83.44%(RSD<7%,n=5),respectively. The plasma concentra-tions of CPT-11 and SN-38 in 5 patients with colon cancer were 431.13-617.19,13.97-31.89 ng/mL(1 h after intravenous drip-ping)and 398.14-584.43,11.61-29.94 ng/mL(2 h after intravenous dripping). CONCLUSIONS:The method is simple,rapid, sensitive,reproducible and suitable for the determination of plasma concentration and pharmacokinetic study of CPT-11 and its metabolite SN-38.

OBJECTIVE To observe the neurotoxicity of 1-bromopropane(BP) and investigate the protective effects of edaravone(Edv) against BP-induced deficits of spatial learning and memory ability in rats by its anti-inflammatory mechanism. METHODS Adult male Wistar rats were ig given BP 800 mg·kg-1 to develop the model, followed by Edv 1, 3 and 5 mg·kg-1 ip treatment respectively 4 h later for consecutive 12 d. From the 7th day (d 7), all rats were subjected to the five-day place navigation in Morris water maze (MWM) to measure the escape latency and the total swimming distance. On d 6 of MWM, spatial probe test was performed and the crossing times of rats were recorded to evaluate the spatial memory ability. At the end of the behavioral experiment, four rats in each group were randomly selected and the frozen section of the whole brain was sliced for thionin staining and immunohisto?chemistry. The other eight sacrifced rat brains from each group were harvested for the determination of the tumor necrosis factor-α (TNF-α) and nitric oxide (NO) by ELISA and nitrate reductase method, respectively. RESULTS The results of MWM test showed that compared with control rats the escape latencies of rats in BP group were increased by 60.8%, 81.9%,124.0% and 323.3%, respectively, during the d 2-d 5 of MWM, and the total swimming distance increased by 47.0%, 66.4%, 106.0% and 277.6%, respectirely. All the differences between BP group and control group were significant (P<0.05, P<0.01). In the spatial probe trial, the crossing times of rats in BP group were significantly decreased, compared with the control rats (P<0.01). Morphologically, thionin staining and immunohistochemistry revealed significant microglia activation and neuron loss in the rat forebrains, accompanied by a 147.6% and 18.7% increase in NO and TNF-α levels in rats treated with BP respectively compared with control values (P<0.05, P<0.01). After co-treatment at different dosages of Edv with BP, the escape latencies of rats in BP+Edv 5 mg·kg-1 group were decreased by 38.4%and 44.3%(P<0.01), and the total swimming distance decreased 34.5%and 43.3%(P<0.05, P<0.01), respectively, compared with the BP treated rats on the d 4 and d 5 of MWM test. The microglia activation and neuron damage in the brain of rats induced by BP treatment were significantly alleviated in BP+Edv groups. In addition, the contents of NO and TNF-α were decreased in BP+Edv 1, 3 and 5 mg · kg-1 groups, with a decrease of 53.8%, 55.4% and 59.8% in NO, and 12.2%, 15.8% and 22.2% in TNF-α(P<0.05, P<0.01), respectively. CONCLUSION Edv could effectively protect against central neurotoxicity induced by BP via anti-neuro?inflammation.

Objective To study the pathological features of two huge spontaneous tumors in Wistar and GK rats. Methods Forty Wistar rats and 40 GK rats were included in this study. Among those rats, two huge spontaneous tumors were observed in a Wistar rat at 14 months of age and in a GK rat at 22 months of age. The growth and survival status of the tumor?bearing rats were recorded. The tumors were surgically removed, and their pathological features were examined using HE and immunohistochemical staining (vimentin, CK19, α?SMA, CD31, CD34, S?100, NF及Ki?67). Results Both the two tumors were completely resected by surgery without much difficulties, and both host rats survived well after the operation. The weight of the two huge tumors was 502 g and 119 g, which corresponding to 64% and 24% of the body weight of their host rats, respectively. The tumors surface had a complete capsule, with a clear boundary separating from the normal surrounding tissues, and no vascular pedicle structure was found. According to the results of immunohistochemical staining, both the two tumors were diagnosed as benign fibroma. Conclusion This type of huge spontaneous tumors is benign fibroma. Besides the impact on the activities of the rats, the tumors have no significant impact on the living conditions in the hosts.

OBJECTIVETo establish subcutaneous xenograft models of gastric cancer in nude mice and to screen the predictive biomarkers of bevacizumab effectiveness.

METHODSSubcutaneous xenograft models were established using BGC823 gastric cancer cell line in 20 male 4-week old BALB/C-nu/nu nude mice and were randomly divided into four groups, bevacizumab group(15 mg/kg), 5-FU group(15 mg/kg), combined group and control group, with 5 mice in each group. Bevacizumab and 5-FU were administered intraperitoneally every other day for three weeks. After treatment, tumor size and inhibition rate were calculated. Expression of CD31 was examined by immunohistochemistry for evaluation of microvascular density(MVD). Levels of human vascular endothelial growth factor(VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PIGF) and interleukin 8(IL-8) were tested by enzyme linked immunosorbent assay(ELISA).

RESULTSCompared to the control group, bevacizumab group and combined group had a significantly lower MVD(5.2±1.0 and 4.3±1.2 vs. 13.8±1.6, P<0.05), a smaller tumor volume [(305.6±184.1) mm(3) and (242.2±71.4) mm(3) vs.(1535.2±625.1) mm(3), P<0.05], and lower levels of VEGF and IL-8 in tumor tissues [VEGF:(351.6±84.1) ng/L and (242.2±71.4) ng/L vs. (1256.7±702.1) ng/L, P<0.05); IL-8:(20 903±1485) ng/L and (27 489±6772) ng/L vs. (57 032±2437) ng/L, P<0.05]. The above parameters were not significantly different between 5-FU group and control group(all P>0.05). Levels of bFGF and IGF were not significantly different among four groups as well(all P>0.05).

CONCLUSIONVEGF and IL-8 may be used to be biomarkers candidates to predict bevacizumab effectiveness on human gastric cancer.

Animals ; Antibodies, Monoclonal, Humanized ; Bevacizumab ; Biomarkers ; Cell Line, Tumor ; Fluorouracil ; Heterografts ; Humans ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Stomach Neoplasms ; Vascular Endothelial Growth Factor A ; Xenograft Model Antitumor Assays

OBJECTIVETo review the clinical features of duodenal gastrointestinal stromal tumors(GISTs), and to compare the clinical efficacy among different surgical treatments for duodenal GISTs.

METHODSClinicalpathological data of 36 cases of duodenal GISTs undergoing operation in The First Affiliated Hospital of Sun Yat-sen University from January 2000 to July 2013 were retrospectively analyzed. All the patients received surgical treatments, including 15 cases with regional resection, 8 cases with segmental resection, 12 cases with pancreaticoduodenectomy (PD), and 1 case with liver biopsy, respectively. Clinical efficacy between pancreaticoduodenectomy (PD) and non-PD (NPD) was compared.

RESULTSNine of 36 cases (25%) developed postoperative complications who were all in the PD group. Eight patients recovered and healed finally after active treatment, and 1 case was complicated with acute pancreatitis, pancreatic fistula and intra-abdominal infection. The median follow-up time was 54 months and the 5-year overall survival (OS) rate and 5-year recurrence-free survival (RFS) rate were 78.1% and 72.1%, respectively. The 5-year OS rate in the PD group and the NPD group was 61.1% and 61.1% respectively. The 5-year RFS rate in the PD group and the NPD group was 85.8% and 78.8% respectively. Statistical analysis showed no significant difference between the both groups (P=0.71 and P=0.89).

CONCLUSIONSFor duodenal GISTs patients, regional resection and segmental resection have similar clinical outcomes to pancreaticoduodenectomy while the former two can obviously decrease the incidence of postoperative complications. Based on the premise of R0 resection guaranteed, regional sectional and segmental resection with less injury should be the surgical treatment of choice.

Duodenal Neoplasms ; Gastrointestinal Stromal Tumors ; Humans ; Intraabdominal Infections ; Pancreatic Fistula ; Pancreaticoduodenectomy ; Postoperative Complications ; Retrospective Studies ; Survival Rate

Objective To establish subcutaneous xenograft models of gastric cancer in nude mice and to screen the predictive biomarkers of bevacizumab effectiveness. Methods Subcutaneous xenograft models were established using BGC823 gastric cancer cell line in 20 male 4-week old BALB/C-nu/nu nude mice and were randomly divided into four groups, bevacizumab group (15 mg/kg), 5-FU group (15 mg/kg), combined group and control group, with 5 mice in each group. Bevacizumab and 5-FU were administered intraperitoneally every other day for three weeks. After treatment , tumor size and inhibition rate were calculated. Expression of CD31 was examined by immunohistochemistry for evaluation of microvascular density (MVD). Levels of human vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PIGF) and interleukin 8 (IL-8) were tested by enzyme linked immunosorbent assay (ELISA). Results Compared to the control group, bevacizumab group and combined group had a significantly lower MVD (5.2±1.0 and 4.3±1.2 vs. 13.8 ±1.6, P<0.05), a smaller tumor volume [(305.6 ±184.1) mm3 and (242.2 ±71.4) mm3 vs. (1535.2 ±625.1) mm3, P<0.05], and lower levels of VEGF and IL-8 in tumor tissues [VEGF:(351.6±84.1) ng/L and (242.2±71.4) ng/L vs. (1256.7±702.1) ng/L, P<0.05); IL-8:(20 903± 1485) ng/L and (27 489±6772) ng/L vs. (57 032±2437) ng/L, P<0.05]. The above parameters were not significantly different between 5-FU group and control group (all P>0.05). Levels of bFGF and IGF were not significantly different among four groups as well (all P>0.05). Conclusion VEGF and IL-8 may be used to be biomarkers candidates to predict bevacizumab effectiveness on human gastric cancer.