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Objective:To prepare 99Tc m-hydrazinonicotinamide(HYNIC)-αCD8/Fab ( 99Tc m-αCD8/Fab), and explore the predictive value of 99Tc m-αCD8/Fab SPECT/CT imaging for the efficacy of anti-programmed death-1 (PD-1) immunotherapy. Methods:The αCD8/Fab was modified with HYNIC- N-hydroxysuccinimide (NHS) and IRDye800-NHS to form HYNIC-αCD8/Fab and IRDye800-αCD8/Fab (Dye-αCD8/Fab), respectively. 99Tc m-αCD8/Fab was prepared in sodium bicarbonate buffer (pH=8.5), with SnCl 2 being used as the reducing agent. The labeling yield and radiochemical purity of 99Tc m-αCD8/Fab and its stability in PBS and fetal bovine serum (FBS) were tested in vitro. The mouse spleen and human peripheral blood lymphocytes were isolated for cell-specific binding and blocking experiments of 99Tc m-αCD8/Fab in vitro. SPECT/CT imaging was used to analyze the specific binding ability of the 99Tc m-αCD8/Fab probe in CT26 colon cancer mouse models (BALB/c). The near infrared fluorescence imaging and SPECT/CT imaging were performed to detect the intra-tumoral CD8 + T cell infiltration after anti-PD-1 therapy in tumor bearing mice, and the results were further verified by HE and immunofluorescence staining. CD8 + T cell depletion study was performed to determine the role of CD8 + T cells in the tumor responses to anti-PD-1 therapy. Two-way analysis of variance was used to compare the data difference. Results:The labeling yield of 99Tc m-αCD8/Fab was 90% with a high radiochemical purity (95%) and good stability in vitro (radiochemical purity still more than 80% after 720 min in PBS and FBS). 99Tc m-αCD8/Fab could specifically bind to mouse CD8 + T cells ((10.30±0.81) percent added radioactive dose (%AD)/10 6 cells), compared with the binding ability in human peripheral blood lymphocytes group and CD8 antibody blocking group ((1.78±0.61) and (1.59±0.25) %AD/10 6 cells; F=10.07, P<0.001). SPECT/CT imaging showed that 99Tc m-αCD8/Fab had markedly higher tumor uptake in the CT26 colon cancer mouse models. Near-infrared fluorescence imaging showed that the tumor uptake of 99Tc m-αCD8/Fab in the responsive group was significantly higher than in the nonresponsive group after anti-PD-1 treatment ((8.9±1.1)% vs (7.1±0.8)%; F=4.69, P=0.024), and SPECT/CT imaging found the similar result. HE and immunofluorescence staining of tumor and lymph nodes showed that the proportion of lymphocyte infiltration was higher in the responsive group. Furthermore, CD8 + T cell depletion significantly reversed the therapeutic effect of anti-PD-1 immunotherapy in tumor-bearing mice. Conclusions:In this study, 99Tc m-αCD8/Fab was successfully obtained. CD8-specific SPECT imaging could sensitively visualize the tumor-infiltrating CD8 + T cells, suggesting the potential application value to predict and evaluate the efficacy of immunotherapy in the clinical settings.
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Objective To study the relieving cough effect ofPuji-Xuanfei-Xiaodu decoction on acute bronchitis.Methods 87 patients with acute bronchitis of exterior cold and interior heat were randomly divided into two groups(44 cases in a therapy group and 43 cases in a control group).Puji-Xuanfei-Xiaodu decoction was given to the patients in the therapy group and acute bronchitis syrup was given to the control group, to observe the influence on symptoms of cough, sputum, fever and headache. The course of treatment was 7 days. Results On the reliving cough aspect, 28 cases (63.6%) showed cure effect and 13 cases (29.5%) effctive, the total effective rate was 93.2% in therapy group with 44 cases; while in control group (43 cases), 15 cases (43.9%) showed cure effect and 23 cases (53.5%) effctive, the total effective rate was 88.4%. The symptoms of cough, phlegm, fever, headache and aversion to wind were significantly decreased in two groups. In therapy group, the numbers of cure effect, remarkable effect and efficacy were 22 (50%) ,11(25%) and 8 (18.2%) cases respectively, the total effective rate was 93.19% while the numbers of cure effect, remarkable effect and efficacy were 14 (32.6%) ,8(18.6%) and 12 (27.9%) cases respectively, the total effective rate was 79.07% in control group. The total effective ratio of two groups had significant difference (P>0.05).ConclusionsPuji-Xuanfei-Xiaodu decoction is effective in relieving cough.
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Objective To investigate the effect of reformative ventilation method (head-high leg-low 30°-declivate prone position ) in the ventilation of acute respiratory distress syndrome ( ARDS ) patients, and compared with normal prone position ventilation. Methods Forty-four patients of ARDS underwent ventilation were divided into prone position group (22 cases) and reformative prone position group (22cases) by random digits talle. Continuous 30° semireclining position was kept in normal time. The patients of the two groups underwent different prone position ventilation 4 hours every day,and indexes of hemodynamics and respiration before,during and after prone position ventilation were recorded and analyzed. Results After prone position ventilation, oxygenation index of two groups improved similarly (P ＞ 0.05 ). In prone position group, lung compliance decreased [2 h, ( 25.6 ± 5.8 ) ml/cm H2O ( 1 cm H2O = 0.098 kPa) vs. ( 37.2 ± 20.5 )ml/cm H2O] ,average airway pressure increased [2 h, ( 18.5 ± 3.9) cm H2O vs. ( 15.6 ± 5.3 )cm H2O] ,heart rate increased [2 h, ( 112.0 ± 16.2 ) beats/min vs. ( 102.0 ± 11.3 ) beats/min], mean arterial blood pressure decreased [2 h, (86.0 ± 6.7) mm Hg ( 1 mm Hg = 0.133 kPa) vs. (93.5 ± 7.5 ) mm Hg] ,central venous pressure increased[2 h, ( 15.5 ± 3.3 ) cm H2O vs. ( 12.6 ± 4.3 ) cm H2O]. These changes persistently existed during prone position ventilation (P ＜ 0.05 ),and they disappeared in 1 hour when recovered to 30 °semireclining position. Conclusion Reformative prone position ventilation not only has same effect on improving oxygenation index, but also obviates adverse effect on lung compliance and hemodynamics.
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Objective To research the clinical significance of acetated Ringer solution and succinylated gelatin in the fluid resuscitation of sepsis patients.Method Fifty-nine sepsis patients were divided into two groups:lactic acid Ringer solution and hetastarch (group A,27 cases)and acetated Ringer solution and suecinylated gelatin (group B,32 cases),compared the fluid resuscitation and other parameter.Results There were no significant difference in the central venous pressure,mean arterial pressure and the dose of noradrenaline (P ＞ 0.05).The activated partial thrombeplastin time in group A was longer than that in group B[(58±10),(74±13)s vs(48±7),(54 ±11) s in 6,24 hours],fibrinogen concentration was lower than that in group B [(3.3 ±0.8),(1.6±0.3)g/L vs (4.2±1.1),(2.1±0.2)g/L in 6,24 hours] (P＜0.05).Serum lactic acid,creatinine,calcium concentration in group A [(6.9±0.8)retool/L,(289 ~ 27)μ mol/L,(2.1 ±0.3)mmol/L]were higher than those in group B [(3.2 ±1.1)mmol/L, (193 ±42)μmol/L, (1.7±0.2)mmol/L](P＜0.05),there was no difference in APACHE Ⅲ scores on the third day between two groups (P＞0.05).Conclusions Acetated Ringer solution and succinylated gelatin in the fluid resuscitation of sepsis patients has the same effect,but fewer impacts on serum coagulation,serum lactic acid and renal function than lactic acid Ringer solution and hetastareh.They may be more suitable for fluid resuscitation of sepsis patients,but hypecalcemia is easy to happen,and there is no significant evidences proving the prognosis.
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Objective:To assess the relationship between the characteristic of drug resistance in Acinetobacter baumannii and the syndrome of traditional Chinese medicine(TCM) in intensive care unit(ICU).Methods:Sixty-six strains of Acinetobacter baumannii were isolated from sputum specimens of patients in our ICU from March 2005 to February 2006.The data of the drug sensitivity test in vitro was analyzed.The relation between the syndrome of TCM and drug resistance in Acinetobacter baumannii was probed.Results:The 66 strains of Acinetobacter baumannii were drug resistant to multiple kinds of anti-bacterial drugs(sensitivity rate