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Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.
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Objective The modified rapid one-step extraction (ROSE) method was employed in the Mycoplasma pneumoniae (Mp)genomic DNA extraction,in order to establish an easy DNA extraction method,which is used in Mp Loop Mediated Isothermal Amplification(LAMP) and suitable for high throughput without any expensive instruments.Methods In line with the character of Mp,a one-step Mp acid extraction method was established on the basis of ROSE.The studies had been carried out on comparing the modified ROSE DNA extraction with the classical methods of Boiling,CTAB,Alkali solution and reagent kit in extraction quality,quantity,reagent kinds,operation steps and extraction time.The extracted DNA of the Mp culture solution by these five methods had been used in LAMP to test the extraction efficiency.20 cases of Throat swab specimens from children with mycoplasma pneumonia were selected from January to March of 2016,and the throat swab specimens were extracted by the improved ROSE method then applied to LAMP detection system.Results Purity,comparison of ROSE method and other four methods were P＜0.05,the difference was statistically significant and ROSE was slightly better than the alkaline lysis method and boiling method,but lower than the CTAB method and kit method;Yield,results were compared with ROSE method and other four methods:there was no significant difference in q=0.95 (P＞0.05) compared with ROSE method and boiling method.The ROSE method was significantly different from the other three methods (P＜0.05),so the yield of ROSE method was higher than that of alkaline lysis method,CTAB method and kit method.Instrument and equipment,extracting procedure,extracting time and quantity ROSE,Boiling and Alkali solution were obvious ly better than CTAB and reagent kit.The extracted DNA by these five methods could be used in LAMP reaction,and the results showed no significant difference.Conclusion This study established an original one-step DNA genomic extraction method of Mp,which had been successfully applied in the Mp LAMP withoutany expensive instruments.Offer a groundbreaking method detecting Mp for the hospitals at all levels including the primary medical organizations.
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Objective To investigate whether soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) as the early diagnostic biomarker of acute ST elevation myocardial infarction (STEAMI).Methods Sixty-five patients with STEAMI and 30 patients with stable coranary heart disease or other heart disease(control group) were enrolled as our subjects.Serum sLOX-1 levels were measured.Results The median(P25,P75) of Serum sLOX-1 in the patients with STEMI were 210.0 (130.0,356.0) ng/L,significantly higher than that of control group(65.5 (55.2,85.2) ng/L,Z =6.17,P ＜ 0.001).Logistic regression analysis revealed that sLOX-1 alone was an independent factor associated with STEAMI (B =0.036,P ＜ 0.001).The area under the ROC curve of sLOX-1 for detecting STEMI was 0.895,and 95％ CI was 0.831-0.959 (P＜0.001).Taking sLOX-1 =87.5 ng/L as cut-off value,the sensitivity was 89.6％ and specificity was 82.4％for the diagnosis of STEAMI.Conclusion Serum sLOX-1 was significantly higher in the STEAMI and it might served as the early diagnostic marker for STEAMI.
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Objective To explore the efficiency and safety of fondaparinux and low molecular weight heparin(LMWH) on the elder patients with non-ST-segnent elevation acute coronary syndromes (NSTE-ACS).Methods One hundred and forty patients over 75 years old with NSTE-ACS were randomly divided into treatment group(n =70) and control group (n =70).Patients in treatment group were given the conventional treatment combined with fondaparinux,and in control group were given the basis of conventional treatment combined with LMWH.The therapeutic efficacy,the cardiovascular events at 4 d,7 d and 30 d during the treatment and bleeding incidence rate were observed.Reslts There was no statistically significant difference between the treatment group and control group in the total effective rate (x2 =0.475,P ＞ 0.05.Meanwhile,no significant differences were found between the two groups in cardiovascular events at 4 d,7 d and 30 d (x2 =0.257,0.475 and 0.317,P ＞0.05).The incidence rate of bleeding in treatment group was obviously lower than that in control group and there was statistically significant difference (2.9％ vs.31.4％ ; x2 =20.115,P ＜0.01).Conclusion The effectiveness of fondaparinux used in elderly patients with non-ST-segment elevation acute coronary syndromes is similar with LMWH,but the incidence rate of bleeding is lower than LMWH.
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Objective To compare the short-term prognostic value of glycohemoglobin (HbA1c) and admission plasma glucose in non-diabetic patients with acute ST-elevation myocardial infarction.Methods Eighty-four non-diabetic patients with acute ST-elevation myocardial infarction from January 2010 to June 2011 were included.Both HbA1c and plasma glucose was measured on admission.Cardiovascular event was followed up in 30 days.Results The average of HbA1c and admission plasma glucose was as cut-off point.The patients were divided into HbA1c ＜ 5.5％ group (40 cases) and HbA1c ≥5.5％ group (44 cases) according to HbA1c level.The patients were divided into admission plasma glucose ≤ 8.6 mmol/L group (42 cases) and admission plasma glucose ＞ 8.6 mmol/L group (42 cases) according to admission plasma glucose.The incidence of cardiovascular event in 30 days in admission plasma glucose ＞ 8.6 mmol/L group was higher than that in admission plasma glucose ≤ 8.6 mmol/L group [19.0％ (8/42) vs.2.4％ (1/42)],and there was significant difference(P＜ 0.05).There was no significant difference in the incidence of cardiovascular event in 30 days between HbA1c ≥5.5％ group and HbA1c ＜ 5.5％ group (P ＞ 0.05).Admission plasma glucose showed weak correlation with blood creatine kinase isoenzyme MB peak (r =0.233,P ＜0.05).Conclusion In non-diabetic patients with acute ST-elevation myocardial infarction,elevated admission plasma glucose levels are associated with higher cardiovascular event in 30 days.
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Objective To evaluate the effectiveness of different medicine treatment strategies on the social functions promotion on the patients with treatment-resistant depression (TRD). Methods 375 Patients with TRD were randomly grouped into 8 groups, and each group was received 8 weeks different treatment for paroxetine,venlafaxine, mirtazapine, paroxetine plus risperidone, paroxetine plus sodium valproate, paroxetine plus buspirone, paroxetine plus trazodone,or paroxetine plus thyroxine, respectively. The efficacy and social functions were evaluated with HAMD-17, SDSS and SF-36. Results There were significant difference in SDSS scores between 8th week and the baseline( P＜0.01 ) , and for social functions factor scores of SF-36 there was significant difference between 4th ,8th week and the baseline in each groups( P＜0.01 ). There were significant difference in social functions factor scores of SF-36 and subtracting scores between 4th and 8th week in all groups except group paroxetine and group venlafaxine(P ＜ 0.05 or P ＜ 0.01 ). There were significant difference in SDSS subtracting scores at 8th week among 8 groups( paroxetine plus risperidone group 7.05 ± 6.39, mirtazapine group 6.53 ± 4.75, paroxetine plusthyroxine group 5.14 ± 4.94, paroxetine group 5.13 ± 4.94 ,paroxetine plus trazodone group 5.00 ± 4.94, paroxetine plus sodium valproate group 4.60 ± 4.09, venlafaxine group 4.57 ± 4.18, paroxetine plus buspirone group 4.24 ± 4.95 ) ( Z = 2.076, P ＜ 0.05 ), between group paroxetine plus risperidone and group venlafaxine , group paroxetine plus sodium valproate, group paroxetine plus buspirone,as group mirtazapine and group paroxetine plus buspirone(P＜ 0.05 ), respectively. The influencing factors on improving social functions are the severity, improvement of depressive symptoms and latest onset time. Conclusions These 8 treatment strategies all can promote social functions on the patients with TRD. But the intensity and chronological order of improvement werent the same among 8 groups. The influencing factors on improving social functions are the severity, improvement of depressive symptoms and latest onset time.
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Objective To study the feasibility and safety for using anesthesia gastroscopy in aged-patients over 80 years old.Methods Selecting 84 cases of aged-patients over 80 years old as anesthesia group(group 1),22 cases of aged-patients over 80 years old as normal gastroscopy group(group 2)and 100 cases of young-middle age as anesthesia control group(group 3).Low dose propofol and fentanyl combined atropine were injected into venous in anesthesia gastroscopy.The BP,HR,SpO2,patients reactions during gastroscopy,stomach peristalsis rates,awake time were detected before,during and after gastroscopy.Results Patients in group 1 felt much less discomfortable than those in group 2.Anesthesia group felt much satisfactorily than normal gastroscopy group.The BP,HR,SpO2 in group 1 were decreased transitorily during examination and resumed rapidly after examination.There were no severe complications in anesthesia gastroscopy.However,the BP and HR were increased obviously in normal gastroscopy group.The dosage of propofol in group 1 was much less than that in group 3.Conclusions The use of anesthesia gastroscopy with low dose propofol and fentanyl combined atropine intravenously in aged-patients over 80 years old is safe and comfortable.
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Objective To explore the effect of hypoxia on cultured rat Sertoli cells in vitro.Methods In a Sertoli-germ cells co-culture system,the effect of hypoxia on the morphological characteristics of Sertoli cells were observed,including the number of Sertoli cells,the cytoskeleton changes after Coomassie brilliant blue staining and the detachment of germ cells.Results The loosing and retracting of cytoskeleton in Sertoli cells was found.Both survival rate of Sertoli cells and detachment of germ cells showed time-response relation.Conclusion Hypoxia damages Sertoli cells.