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Objective:To analyze the effect of microRNA-506 (miR-506) on M2 macrophages polarization and immune intervention in pancreatic cancer mice.Methods:Macrophages from peripheral blood of healthy volunteers were cultured in vitro, polarized into M1 or M2 type macrophages, and transfected with miR-506 or control sequence (miR-ctrl), respectively. Polarized macrophages from M1+ miR-ctrl group, M1+ miR-506 group, M2+ miR-ctrl group and M2+ miR-506 group were collected. The relative expression of marker genes of M1 and M2 type macrophages of four groups were analyzed by qRT-PCR. The characteristic functions of M1 and M2 type macrophages of four groups were also detected, such as phagocytosis and nitric oxide (NO) synthesis (characteristic function of M1 type macrophages), arginase 1 activity and the secretion of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), interleukin-10 (IL-10) (characteristic function of M2 type macrophages). Sixty healthy male C57BL/6 mice without specific pathogen, weighing 20-25 g, were randomly divided into miR-ctrl programmed death-1 (PD-1) group, miR-506 PD-1 group, miR-ctrl iso group, and miR-506 iso group. They were injected with miR-506, miR-ctrl, PD-1 antibodies, and isotype control antibodies, with 15 in each group. The tumor volume, tumor weight, Ki-67 and interferon γ expression were analyzed three weeks later. Results:Compared with M2+ miR-ctrl group, the relative expression of M1 type macrophage marker genes increased, and the relative expression of M2 type macrophage marker genes decreased in M2+ miR-506 group, with significant difference (all P<0.05). Compared with M2+ miR-ctrl group, the phagocytic function and NO synthesis of macrophages in M2+ miR-506 group increased, the activity of arginase 1 and the secretion of VEGF, TGF-β and IL-10 decreased, with significant difference (all P<0.05). There was no significant differences in tumor weight, volume, Ki-67, and interferon γ expression between miR-ctrl iso and miR-ctrl PD-1 group (all P>0.05). The tumor weight, tumor volume and Ki-67 in miR-506 PD-1 group were lower than those in miR-ctrl PD-1 group [(0.32±0.13) g vs (0.85±0.24) g; (0.72±0.23) cm 3 vs (2.03±0.21) cm 3; (25.9±10.3)% vs (55.6±12.5)%], while interferon-γ expression was significantly higher than that in miR-ctrl PD-1 group [(122.4±15.3) ng/g vs (82.4±22.2) ng/g] (all P<0.05). Conclusion:miR-506 inhibits the polarization of M2 macrophages and increases the anti PD-1 immunotherapy sensitivity in pancreatic cancer.
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In atherosclerosis, chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species (ROS). In this study, we devised a highly sensitive H2O2-scavenging nano-bionic system loaded with probucol (RPP-PU), to treat atherosclerosis more effectively. The RPP material had high sensitivity to H2O2, and the response sensitivity could be reduced from 40 to 10 μmol/L which was close to the lowest concentration of H2O2 levels of the pathological environment. RPP-PU delayed the release and prolonged the duration of PU in vivo. In Apolipoprotein E deficient (ApoE‒/‒) mice, RPP-PU effectively eliminated pathological ROS, reduced the level of lipids and related metabolic enzymes, and significantly decreased the area of vascular plaques and fibers. Our study demonstrated that the H2O2-scavenging nano-bionic system could scavenge the abundant ROS in the atherosclerosis lesion, thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.
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Objective:To explore the effect of miR-506 on the tumor associated macrophage (TAM) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC).Methods:Panc02 cells were used to establish in situ tumorigenesis mouse model. Tumor bearing C57BL/6 mice were divided into miR-ctrl C57 group and miR-506 C57 group, with 15 mice in each group. miR-ctrl or miR-506 coated with DOPC liposomes (miR-ctrl/DOPC or miR-506/DOPC) were injected intraperitoneally. The tumor weight and volume were measured, the changes of tumor infiltrating immune cells were detected by flow cytometry and the survival time of mice was monitored. To eliminate the influence of immune system, tumor bearing nude mice were divided into miR-ctrl nude group and mir-506 nude group, with 5 mice in each group. miR-ctrl/DOPC or miR-506/DOPC were injected intraperitoneally. To eliminate the influence of macrophages, tumor bearing C57BL/6 mice were randomly divided into control group and macrophage clearance group and injected intraperitoneally with PBS or clodronate liposome (Clo), with 10 mice in each group. Then each group was randomly divided into two groups (miR-ctrl PBS group and miR-506 PBS group, miR-ctrl Clo group and miR-506 Clo group), miR-ctrl PBS group and miR-ctrl Clo group were injected with miR-ctrl/DOPC via intraperitoneal injection, miR-506 PBS group and miR-506 Clo group were injected with miR-506/DOPC. Results:In C57BL/6 mice model, the tumor volume (1.04±0.23)×10 3 mm 3 and tumor weight (0.51±0.10)g of miR-506 C57 group was lower than those in miR-ctrl C57 group (1.92±0.34)×10 3 mm 3 and (0.99±0.19) g, the overall survival of miR-506 C57 group was longer than that of miR-ctrl C57 group. The ratio of M2/M1 in miR-506 C57 group (1.19±0.46) was lower than that in miR-ctrl C57 group (2.85±0.40). In BALB/C nude mice model, the tumor volume and tumor weight showed no significant difference between miR-506 nude group and miR-ctrl nude group. Compared with the miR-ctrl PBS group, the proportion of regulatory T cells decreased [(4.70±1.86)% vs. (12.00±2.24)%], the proportion of cytotoxic T cells increased [(10.54±1.89)% vs. (4.54±1.25)%], the proportion of apoptotic cytotoxic T cells decreased [(14.00±4.00)% vs. (26.80±4.27)%] and the concentration of IFN-γ increased in miR-506 PBS group [(89.60±14.69) vs. (28.00±13.69) ng/g]. However, after clearance of macrophages by Clo, there was no significant difference in the above indexes between mir-506 Clo group and miR-ctrl Clo group. Conclusion:MiR-506 inhibits the progression of PDAC and reverses its immunosuppressive TME in a macrophage dependent manner.
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Transjugular intrahepatic portosystemic shunt (TIPS) is a surgery which was commonly used in portal hypertension therapy.It can control and prevent the complication caused by portal hypertension,such as esophageal gastric-fundus variceal bleeding.However,there is a fundamental flaw in the TIPS due to its lack of maintaining a long-lasting and effective shunt,and most of the stenosis or occlusion are in the draining vein:the hepatic vein.Accompanied by direct intrahepatic portosystemic shunt (DIPS),which has shown its advantage compared with traditional TIPS operation,such as the block of hepatic vein can be avoided,the radiation dose as well as the operation time is lesser,DIPS is safer and so on.Here we reviewed to present a brief introduction of DIPS development history and core concerns of the major medical centers at present.
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Objective To analyze the clinical characteristics of type 1 autoimmune pancreatitis (AIP) in patients.Methods The clinical data of 27 patients with type 1 AIP treated at Fujian Provincial Hospital from January 2012 to October 2018 were retrospectively analyzed.Results There are 25 males (92.6％) and 2 females (7.4％) (ratio 12.5∶1).The age of disease onset was (59.5 ± 14.3) years.The most common presenting symptoms were jaundice and abdominal pain (both 59.3％).The most common complication was IgG4-related sclerosing cholangitis (63.0％).Magnetic Resonance Cholangiopancreatograhpy (MRCP) conducted on 26 patients showed the diffuse type 1 AIP was most common (53.8％),only 2 patients (7.7％) presented with a main pancreatic duct stricture.The pancreatic segment of bile duct narrowing was very common (84.6％),and most patients presented as tapered narrowings (65.4％).Standard glucocorticoid therapy was given to these 27 patients who responded well with clinical and laboratory remissions.Two patients were given maintenance glucocorticoid therapy for a high level of serum IgG4.Conclusions Type 1 AIP can present as a local manifestation of IgG4-related disease.The most common complication is IgG4-related sclerosing cholangitis.Glucocorticoid therapy was effective but some patients required maintenance therapy.
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Objective To investigate the change of the nutritional status of elderly patients in Chinese major hospitals dynamically with nutritional risk screening 2002 (NRS 2002) and subjective global assessment (SGA) during hospitalization.Methods A prospective,multi-center survey was conducted on over 65 years old patients who were admitted in departments of gastroenterology,respiratory medicine,general surgery,geriatrics,thoracic surgery,neurology,orthopedics and medical oncology of 9 large hospitals in China for 7-30 days between June 2014 and September 2014.On admission and within 24 hours after discharge,the clinical data were recorded,physical indices were measured,and laboratory examination were conducted.NRS 2002 and SGA were used to make an evaluation.The nutritional supports and clinical outcomes were also recorded and then the correlation between nutritional status and clinical outcomes were analyzed.Results A total of 2558 patients above 65 years old were included into the study.Compared with their status on admission,their grip strength,upper arm circumference and crural circumference were reduced significantly at discharge (P＜0.05).The total protein,albumin and hemoglobin levels were significantly lower than those on admission (P＜0.05).The incidence of nutritional risk (NRS 2002 score ≥ 3) and malnutrition (SGA B + C) on admission were lower than those at discharge (51.1％ vs 53.0％,32.6％ vs 35.6％).The hospitalization time and medical expenses were higher in patients with malnutrition on admission than in those with normal nutrition intakes.The nutritional status at discharge was negatively correlated with hospitalization time and medical expenses.61.3％ patients having nutritional risk did not take nutritional support during the hospital stay,while utilization rate of parenteral nutrition was higher than that of enteral nutrition in patients receiving nutritional support (19.6％ vs 11.9％).Conclusion Elderly patients have higher possibilities of facing nutritional risk or malnutrition on admission,these are associated with poor clinical outcomes and their nutritional status will not improve significantly at discharge.Therefore,the screening and evaluation of nutritional status in elderly patients during hospitalization should be conducted and their nutritional intervention should be standardized so as to improve the clinical outcomes.
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Objective To investigate the relationship between the serum level of vancomycin and its clinical efficacy as well as adverse reactions in adult patient so as to provide recommendations for clinical management. Methods An open observational research was performed from 1st July 2013 to 31st December 2017 in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, which recruited the adult patients who were infected with Gram positive (G+) bacteria and treated with vancomycin. The initial dose was decided by the patient's creatinine clearance rate, and the treating dose was directed by the serum drug concentration and the patient's clinical response. By recording the associated clinical information (pathogen eradication, blood test results, adverse reactions, etc.), the clinical outcome and adverse reactions for vancomycin to treat G+bacterial infections were analyzed. Results Eighty-nine cases who meet research standards were finally recruited, with 67.42% of male patients, and an average age of (50.5±17.9) years. The most common type of infection was bloodstream infection (61.80%), followed by low respiratory infection (17.98%). Infections caused by Staphylococcus aureus accounted for 39.33%. The bacterial eradication rate was 89.89% (80/89) and the total effective rate was 77.53% (69/89). The effective rate was 80.30% (53/66) with minimum inhibitory concentration (MIC) < 2 mg/L vs. 69.57% (16/23) with MIC ≥ 2 mg/L, the difference was not statistically significant (χ2= 1.129, P = 0.288). The effective rate was 72.92% (35/48) with trough levels <10 mg/L vs. 82.93% (34/41) with trough levels ≥ 10 mg/L, the difference was not statistically significant (χ2= 1.272, P = 0.259). There were 4 cases of vancomycin associated nephrotoxicity, the incidence of nephrotoxicity was 4.49%, and the vancomycin serum trough levels were 17.22-28.53 mg/L. There were 33 cases of liver dysfunction, and elevated γ-glutamine transferase, alkaline phosphatase and aspartate aminotransferase were most common. There were 2 cases of neutropenia and 2 patients appeared rash during vancomycin period. Conclusions Treatment outcomes were similar regardless of vancomycin MIC and serum trough level. The incidence of vancomycin associated nephrotoxicity rises apparently when serum trough level is over 15 mg/L. Clinical Trial Registry Chinese Clinical Trail Registry, ChiCTR-OPC-16007920.
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Objective:To explore the relationship between angiotensin converting enzyme (ACE) gene insertion/dele‐tion (I/D) polymorphism and familial essential hypertension (EH) .Methods :Fluorescent in situ hybridization stai‐ning DNA sequencing test was used to detect ACE gene I/D genotype frequency and allele frequency in 46 familial EH patients (familial EH group) ,64 EH patients without family history (non‐familial EH group) and 43 healthy people (healthy control group) .Results:In healthy control group ,non -familial EH group ,familial EH group ACE gene DD genotype frequency was 11.6% ,32.3% and 37.0% ;distribution frequency of D allele was 33.7% , 52.3% and 57.6% respectively .Compared with healthy control group ,there were significant rise in ACE gene DD genotype and D allele frequency in familial EH group and non -familial EH group (P0.05) .Conclusion:ACE gene DD genotype and D allele may be genetic predisposing genes of patients with essential hypertension ,and there is no significant difference in genetic constituent ratio between familial EH patients and non‐familial EH patients .
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Objective To evaluate the efficacy and safety of therapeutic drug monitoring (TDM ) based vancomycin dose adjustment in patients with gram‐positive infections .Methods A cohort study was designed with 128 inpatients undergoing TDM in Huashan Hospital from January 2005 to September 2014 .The clinical data of these patients were used to analyze the efficacy and safety of vancomycin therapy by Cox model and survival analysis .Results The patients undergoing TDM‐based dose adjustment had a higher daily dose and blood trough concentration ,which may lead to better bacteriological efficacy and overall efficacy .Cox proportional hazards model analysis showed that TDM‐based dose adjustment is a protective factor .No safety‐related risk factor was found .Conclusions TDM‐based vancomycin dose adjustment is important for patients to achieve better outcomes in fighting gram‐positive infections .
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Objective To analyze the relationship between plasma concentration and efficacy , adverse drug reactions by monitoring vancomycin serum concentrations for appropriately treating the infections caused by methicillin‐resistant Staphylococcus aureus or other gram‐positive cocci .Methods Vancomycin concentration was monitored in the patients with indications for vancomycin therapy .Blood sample was taken after vancomycin was administered for at least 4 doses .The blood sample collected within 30 minutes before dosing was used to determine the trough blood concentration .The samples were taken within 30 minutes to 1 hour after infusion of vancomycin were used to estimate the peak concentration by fluorescence polarization immunoassay .The clinical data were collected at the same time to analyze clinical efficacy and safety .Results Vancomycin trough concentration ranged from 3 .22 mg/L to 50 .79 mg/L in 25 patients ,specifically ,＜ 5 mg/L in 3 cases ,5‐＜10 mg/L in 11 cases ,10‐15 mg/L in 3 cases ,and > 15 mg/L in 8 csaes .Peak concentration ranged from 13 .57 mg/L to 60 .47 mg/L ,specifically ,＜ 25 mg/L in 14 cases ,25‐40 mg/L in 7 cases ,and > 40 mg/L in 4 cases .The infection was cured in 80 .0% (20/25) of the patients .The gram‐positive cocci were eradicated in 87 .5% (21/24) of the patients .The dosage of vancomycin was adjusted in 13 patients according to the results of blood concentration monitoring .Majority of these patients (12/13 ,92 .3% ) were cured .Renal impairment was observed in 4 patients .Conclusions Vancomycin is safe and effective in treatment of methicillin‐resistant Staphylococcus aureus and other gram‐positive bacterial infections . Vacomycin concentration varies from person to person . Serum concentration monitoring is required to achieve best outcomes and the goal of individualized treatment of vancomycin.
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Objective To explore the effect of intravenous infusion flow rebuilt on the patients’safety and nursing quality in intravenous infusion center.Methods Risk safety factors about intravenous infusion process in intravenous infusion center were analyzed and the work flow were rebuilt and optimized?The satisfaction rate,the reception time and the disinfection time for tourniquets were compared before and after work flow rebuilt.Results After work flow rebuilt,the satisfaction rate raised from 92?5%to 94?5%?There were significant differences among the reception time and the disinfection time for tourniquets before and after work flow rebuilt (all P<0?05)?After work flow rebuilt,both the reception time and the time for dealing with tourniquets are shorter than before. Conclusions The rebuilt work flow can make nurses work efficiently and enhance the patients’nursing quality?
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OBJECTIVE:To discuss the curative effects,adverse drug reactions(ADRs)and cost—effectiveness of 3 kinds of nitroimidazole drugs for treatment of trichomonal vaginitis.METHODS:111 cases of trichomonal vaginitis were randomly divided into 3 groups,administered with metronidazol(group A),tinidazole (group B),and ornidazol(group C)respectively,the curative effects and ADRs were observed and cost-effectiveness analysis was made in all groups.RESULTS:The costs in 3 groups were 0.74 yuan,33.6 yuan and 41.2 yuan respectively.The cure rates were 59.4%,81.6%and 97.2%,respectively.The cost-effectiveness ratios were 0.01,0.41,and 0.42 respectively.The increment cost -effectiveness ratios in group B and C were 1.48 and 1.07,as compared with group A.The occurrences of ADRs were 62.2%,18.4%,and11.1%respectively.CONCLUSION:Among 3 regimes,regime C is the preferred one.
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Objectives:To determine the content of aminoacids in gastric cancer tissue and study the relationship between alterations of amino acids and cancer stages. Methods:19 free amino acids of cancer tissue and paracancerous normal mucose were determined in 41 cases of gastric cancer. Results:Most free amino acids were significantly increased in gastric cancer tissue as compared with those of paracancerous normal gastric tissue.The contents of proline,valine,methionine,isoleucine,leucine in advanced gastric cancer were significantly higher than those in early cases. Conclusions:Gastric tumor tissue contains high amount of most free amino acids particularly in cases with advanced cancer..
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OBJECTIVE:To prepare a three-pulse drug release system of nimodipine and study its drug release.METHODS:Solid dispersion technique and dry-coating method were respectively applied to prepare immediate-release mini-tablets and Pulsatile mini-tablets with lag-time of 4 h or 8 h.Then those mini-tablets were filled into capsule to obtain a three-pulse drug release system and subjected to in vitro dissolution test.DSC was employed to determine drug status in solid dispersion.RESULTS:Immediate-release mini-tablets were released more than 95% in 30 min.Pulsatile mini-tablets were released less than 10% in 4 h or 8 h of lag-time period.After lag-time period,pulsatile mini-tablets were released completely in 3 h.The whole pulsatile drug release system achieved three times of drug release at 5 min,4 h,8 h,respectively.Nimodipine kept amorphous form and were delivered into carrier evenly.CONCLUSION:A three-pulse drug release system of nimodipine has been prepared successfully.