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Objective To examine the effects of Toxoplasma gondii infection on the proportion, quantity, differentiation and function of mouse and human uterine natural killer cells (uNK cells), so as to explore the role of uNK cells in abortion of early pregnancy caused by T. gondii infection. Methods Pregnant mice were injected intraperitoneally with T. gondii tachyzoites on day 6.5 of pregnancy, and the abortion mouse model caused by T. gondii infections was constructed. Mouse uterine lymphocytes were isolated on day 9.5 of pregnancy. Human uterine lymphocytes were isolated from fresh human decidual specimens after abortion in normal early pregnancy and co-cultured with tachyzoites of the T. gondii RH strain for 48 h at T. gondii/uterine lymphocytes ratios of 0.5:1, 1:1 and 2:1. The phenotypes of mouse uNK cells (CD122, NK1.1, DX5) and human uNK cells (CD3, CD56, CD11b, CD27) and the expression of intracellular cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by flow cytometry. Mouse and human uNK cells were sorted by magnetic beads, and the cytotoxicity of uNK cells was tested using the lactate dehydrogenase (LDH) release assay at effector/target cell ratios of 1:1, 5:1, 10:1 and 20:1 with mouse or human uNK cells as effector cells and mouse YAC-1 cells or human K562 cells as target cells. Results On day 9.5 of pregnancy, the mouse abortion rate was significantly higher in the infected group than that in the control group (83.02% vs. 3.51%; χ2 = 71.359, P < 0.001). Significantly lower absolute number of uNK cells [(4 547 ± 1 610) cells/mouse vs. (8 978 ± 3 339) cells/mouse; U = 2.000, P < 0.05], lower NK1.1 expression on uNK cell surface [(74.53 ± 8.37)% vs. (93.00 ± 1.11)%; U = 0.000, P < 0.05], higher proportion of NK1.1-DX5-cells [(20.10 ± 8.03)% vs. (5.04 ± 0.68)%; U = 0.000, P < 0.05], lower proportion of NK1.1+ DX5+ cells [(21.70 ± 12.48)% vs. (45.75 ± 2.26)%; U = 0.000, P < 0.05] and higher IFN-γ expression [(16.74 ± 1.36)% vs. (8.13 ± 1.90)%; U = 0.000, P < 0.05] were detected in the infected group than in the control group, while no significant difference was seen in TNF-α expression between the two groups [(67.98 ± 9.20)% vs. (52.93 ± 10.42)%; U = 2.000, P > 0.05]. The mouse uNK cells showed a strong cytotoxicity in the infected group, and the cytotoxicity gradually increased with the effector/target cell ratio. The cytotoxicity of uNK cells against YAC-1 cells was 2.30%, 4.32%, 8.12% and 12.65% in the infected group and 1.21%, 1.63%, 2.51% and 3.22% in the control group at effector/target cell ratios of 1:1, 5:1, 10:1 and 20:1, respectively. Following co-culture of human uterine lymphocytes and tachyzoites of the T. gondii RH strain for 48 h, the proportion [TOX 2:1 group vs. control group: (6.61 ± 1.75)% vs. (17.48 ± 4.81)%; F = 7.307, P < 0.01], and absolute number of human uNK cells in uterine lymphocytes of human uNK cells in uterine lymphocytes [TOX 2:1 group vs. control group: (12 104 ± 5 726) cells/well vs. (65 285 ± 21 810) cells/well; H = 11.540, P < 0.01] were significantly lower in the infected group than in the control group. A lower proportion of CD56brightCD16- NK cells [TOX 2:1 group vs. control group: (25.25 ± 5.90)% vs. (36.03 ± 4.51)%; F = 3.213, P > 0.05] and higher proportion of CD56dimCD16+ NK cells [TOX 2:1 group vs. control group: (11.15 ± 2.15)% vs. (7.09 ± 2.24)%; F = 2.992, P > 0.05] were detected in uNK cells in the infected group than in the control group, and the ratio of CD56brightCD16- cells/CD56dimCD16+ cells was significantly lower in the infected group than in the control group [TOX2:1 group vs. control group: (2.37 ± 0.92) vs. (5.58 ± 2.39); H = 8.228, P < 0.05]. In addition, the proportion of CD11b+CD27- cells in human uNK cells was significantly higher in the infected group than in the control group [TOX 2:1 group vs. control group: (30.28 ± 6.91)% vs. (17.48 ± 4.67)%; H = 6.556, P < 0.05], while no significant differences were found between the two groups in terms of IFN-γ [TOX 2:1 group vs. control group: (14.13 ± 1.28)% vs. (15.19 ± 1.64)%; F = 1.639, P > 0.05] or TNF-α expression [TOX 2:1 group vs. control group: (54.76 ± 10.02)% vs. (50.33 ± 3.67)%; F = 0.415, P > 0.05]. Human uNK cells presented a strong cytotoxicity in the infected group, and the cytotoxicity gradually increased with the effector/target cell ratio. The cytotoxicity of human uNK cells against K562 cells was 11.90%, 28.11%, 49.91% and 73.35% in the infected group and 12.21%, 21.63%, 33.51% and 48.22% in the control group at effector/target cell ratios of 1:1, 5:1, 10:1 and 20:1, respectively. Conclusions T. gondii infection presents diverse effects on the differentiation and secretion ability of mouse and human uNK cells. However, T. gondii infection causes a reduction in the absolute number and enhances the cytotoxicity of both mouse and human uNK cells.
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Objective To investigate the safety and efficacy of 177Lu-prostate specific membrane antigen (PSMA)-617 in the treatment of metastatic castration-resistant prostate cancer (mCRPC).Methods From August 2017 to September 2018,11 patients(average age 70.6 years) with mCRPC who underwent 177Lu-PSMA-617 therapy in Nanjing First Hospital were studied.All patients underwent 68Ga-PSMA-11 PET/CT before therapy to assess the tumor radioactive uptake.Blood routine examination and renal function test results were documented before and after therapy to assess the safety.The efficacy was reflected by the changes of prostate specific antigen (PSA) levels and maximum standardized uptake value (SUVmax) on 68Ga-PSMA-11 PET/CT imaging.Paired t test and Wilcoxon's sign rank test were used to analyze the data.Results No acute side effects were observed after therapy of 177Lu-PSMA-617.There were no statistically significant differences after therapy in WBC counts,RBC counts,and PLT,as well as Hb levels (t values:-0.28-1.11,all P＞ 0.05).No kidney toxicity was found.The PSA level after 177Lu-PSMA-617 therapy was significantly lower than that before therapy (80.70 (14.29,1 538.00) μg/L vs 604.60 (88.41,3 980.00) μg/L;u =59,P =0.023).Of the 11 patients,only 2 had elevated PSA levels and disease progression,while the other 9 patients had varying decreases,of which 2/11 decreased by ＞30％ and 7/11 decreased by ＞50％.After therapy,SUVmax of metastatic lesions and metastatic lymph nodes were decreased in 9 and 2 patients respectively.Conclusions 177Lu-PSMA-617 has a good therapeutic value for mCRPC.It is safe and has no obvious side effects.
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Objective@#To synthesis 177Lu-prostate specific membrane antigen (PSMA)-I&T with automated module, evaluate the biodistribution and pharmacokinetics in mice and study the targeting property in human prostate cancer cell line LNCaP Clone FGC.@*Methods@#The iQS-TS automated module was applied in labeling 177Lu-PSMA-I&T. Radiochemical purity and stability were determined with high performance liquid chromatography (HPLC). The biodistribution was observed in normal ICR mice and U-SPECT/CT imaging was performed in LNCaP Clone FGC tumor-bearing mice. Independent-sample t test was used to analyze the data.@*Results@#177Lu-PSMA-I&T was stable in vitro and in vivo, with the radiolabeled yield of (91.5±4.9)% and radiochemical purity >99%. The half maximal inhibitory concentration (IC50) of 177Lu-PSMA-I&T binding to LNCaP Clone FGC cells was (26.74±3.53) nmol/L. The uptake of 177Lu-PSMA-I&T by LNCaP Clone FGC cells increased with time and significantly decreased after the inhibitor addition (t values: 4.301-27.483, all P<0.05). 177Lu-PSMA-I&T was cleared from blood rapidly and predominantly excreted by kidneys. Significant radioactive uptake was observed in tumors with a long retention time.@*Conclusion@#177Lu-PSMA-I&T can be produced in a convenient and efficient procedure using iQS-TS automated module, with good biological properties and excellent affinity and targeting property towards prostate cancer cells, which making it a potential radiopharmaceutical for prostate cancer therapy.
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Objective To evaluate the changes of monocytes,dendritic cells(DC),myeloid dendritic cells (mDC)and plasma dendritic cells(pDC)of peripheral blood in diffuse large B-cell lymphoma(DLBCL)pa-tients after 3 courses of GM-CSF treatment.Methods 33 patients diagnosed with DLBCL in the hospital from October 2015 to February 2016 were enrolled in the study.All the patients were treated with GM-CSF for 3 courses.Before each course,3 mL venous blood samples were extracted and the monocytes,dendritic cells,my-eloid dendritic cells and plasma dendritic cells were analyzed by using flow cytometer within 24 h.All the data was analyzed with SPSS17.0 software.Results After 3 courses′ treatment,the monocytes decreased signifi-cantly,from(9.85 ± 2.31)% to(3.67 ± 0.78)%.Dendritic cells increased significantly,from(0.24 ± 0.04)% to(0.58 ± 0.13)%.mDCs increased significantly from(0.11 ± 0.02)% to(0.36 ± 0.08)%,however, pDCs only increased from(0.13 ± 0.03)% to(0.21 ± 0.04)% with no statistically significance.Conclusion After 3 treatment courses with GM-CSF,the monocytes decreased obviously while DCs especially mDCs in-creased obviously in DLBCL patients.GM-CSF might activate the anti-tumor immunity of DLBCL patients.
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Objective To verify the performance characteristics of the human SLCO1B1 & APOE gene detection kit (PCR-fluorescent probe technique).Methods The verification protocol for the human SLCO1B1 & APOE gene detection kit manufactured by Wuhan YZY Medical Science and Technology Co.,Ltd.was designed by referring to the requirements of professional standard and pertinent literatures,and its accuracy,specificity,lowest detection limit and anti-interference ability were compared with those of sequencing technique (gold standard).Results The results coincidence of 20 clinical samples from fluorescence PCR and sequencing technique was 100％,which met the requirement of accuracy.Forty clinical samples with wild type loci determined by fluorescence PCR were verified by sequencing and no any mutation was detected,which met the requirement of specificity.The lowest detection limit of the kit was 10 ng/μL.Three interfering substances,including hemoglobin,bilirubin and triglyceride,were individually added into the blood samples with known genotype,and the results determined by the kit were coincident with that without interfering substances,which met the requirement of anti-interference ability.Conclusion The verification parameters of the human SLCO1B1 & APOE gene detection kit are basically consistent with the manufacturer's statement,indicating that the kit meets the requirements of the relevant quality management and may be applied to the detection of clinical samples.
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Objective To investigate the clinical value of 18F-FDG PET/CT in diagnosing G3 NEN and compare it with 68Ga-DOTA-NOC PET/CT.Methods Twenty-three patients (12 males,11 females;average age (63± 12) years) diagnosed of NEN between January 2006 and November 2016 were retrospectively recruited in this study:11 patients with gastroenteropancreatic NEN (GEP-NEN),10 with G3 NEN in lungs,1 with malignant pheochromocytoma and 1 with G3 NEN of unknown primary site.All patients underwent 18F-FDG PET/CT for staging and evaluation of biological behavior,and 9 of them also underwent 68Ga-DOTA-NOC PET/CT within 1 week.Image interpretation was analyzed by visual and semi-quantitative analysis,and SUVmax was calculated.Results All 23 cases showed positive results on 18F-FDG PET/CT (100％,23/23),with primary tumor SUVmax 10.56±3.94.Compared with 18F-FDG PET/CT,the positive detection rate of 68Ga-DOTA-NOC PET/CT was lower (6/9 vs 9/9),with primary tumor SUVmax 14.24± 10.00.There were 22 patients with distant metastasis.The most frequent metastatic sites associated with G3 NEN in lungs were lymph nodes and bones,while those with GEP-NEN were lymph nodes and the liver.In one patient with non-functional NEN,some metastatic lesions showed negative results on 18F-FDG PET/CT but positive results on 68 Ga-DOTA-NOC PET/CT.Conclusions 18 F-FDG PET/CT has higher diagnostic ability for G3 NEN and may serve as a useful tool for evaluating biological behavior of G3 NEN.68Ga-DOTA-NOC PET/CT is valuable as a complementary diagnostic tool in a small proportion of high differentiated G3 NEN.
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In this retrospective cohort study conducted in 63 children with idiopathic thrombocytopenic purpura (ITP) in China; petechiae, bruises and bleeding were the major presentations. Most cases required therapy with one/more treatment options.
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Objective To investigate the antibiotics recipe in one third‐grade hospital from January to December 2012 and to pro‐vide reference for clinical rational use and effective management of antibiotics .Methods The defined daily dose(DDD) was treated as analysis unit ,and the total DDDs was calculated .The antibiotics use densities(AUD) were calculated by the value of DDD per 100 days person .Results The average value of AUD in 2012 was 49 .84 ,compared to the first half of the year ,the second half at‐tended to decrease .Qualification rate was 91 .8% for the investigated antibiotics recipe .Conclusion The use density of antibiotics was medium in the investigated hospital in 2012 .The date of usage of antibacterial drugs showed a steady trend and to be more rea‐sonable during the clinical use of antimicrobial agents special rectification activities .
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<p><b>OBJECTIVE</b>To assess whether the existing three types of pharmacogenetics-based Warfarin dosing algorithms appropriately predict the actual maintenance dose in Han Chinese mechanical heart valve replacement patients (n = 130).</p><p><b>METHODS</b>The patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by PCR-RFLP. The genotype of CYP2C9, VKORC1 and other information were used to calculate predicted doses. Accuracy of the models was assessed using the absolute value of the difference between predicted dose and actual dose, calculated on both an absolute and percentage basis. Actual weekly dose was also regressed on predicted weekly dose, from which we obtained R(2) values. Clinical accuracy of the predictions was assessed by computing the proportion in which the predicted dose was 20% or more below the actual dose (under dosed), within 20% of the actual dose (ideally dosed), or 20% or greater above the actual dose (over dosed).</p><p><b>RESULTS</b>The average absolute error is the smallest for the predictions made by the Wen model (3.74 mg/wk), followed by the Ohno model (4.07 mg/wk) and IWPC model (5.05 mg/wk). R(2) was 40.2% in the Wen model, 38.2% in the Ohno model and 26.7% in the IWPC model. When comparing the percentage of patients for whom the predicted doses were ideal, the Wen model works the best (50.0%) in low-dose group (≤ 21 mg/wk), but the Ohno model works the best (85.29%) in middle-dose group (21 - 49 mg/wk), followed by the Wen model.</p><p><b>CONCLUSION</b>The best accuracy is achieved by the Wen model and the best clinical accuracy is obtained by the Ohno model for predicting the actual maintenance dose in Han Chinese mechanical heart valve replacement patients.</p>
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Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Anticoagulants , Aryl Hydrocarbon Hydroxylases , Genetics , Asian People , Genetics , Cytochrome P-450 CYP2C9 , Drug Design , Genotype , NAD(P)H Dehydrogenase (Quinone) , Genetics , Pharmacogenetics , Polymorphism, Genetic , WarfarinABSTRACT
<p><b>OBJECTIVE</b>To investigate the outcome of orthotopic heart transplantation for patient with end-stage hypertrophic cardiomyopathy.</p><p><b>METHODS</b>This retrospective review analyzed the clinical data of nine patients (7 males) undergoing orthotopic heart transplantation for end-stage hypertrophic cardiomyopathy in our center. All patients received induced therapy protocols peri-operative and standard triple maintenance immunosuppressive therapy postoperative.</p><p><b>RESULTS</b>One recipients developed acute renal failure due to renal artery embolism and allograft rejection in the early posttransplantive course, symptoms and signs were improved under continuous renal replacement therapy and steroid-pulse therapy, this patient died of sudden cardiac arrest at 32 months post transplantation. Another recipient developed demyelinating disease in frontal and parietal lobe and finally recovered with medical therapy. Eight patients survived the operation with good quality of life and there was no episode of rejection or infection or chronic graft arteriosclerosis during follow-up time. Three recipients developed left ventricular hypertrophy and there were no signs of grapg-vessel diseases in the survivals.</p><p><b>CONCLUSION</b>Heart transplantation is the best therapeutic option for selected patients with end-stage hypertrophic cardiomyopathy.</p>
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Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Cardiomyopathy, Hypertrophic , General Surgery , Heart Transplantation , Postoperative Period , Retrospective Studies , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To summarize the surgical experience of type A aortic dissection.</p><p><b>METHODS</b>From January 2001 to December 2006, 54 cases were admitted for Standford type A aortic dissection, including 36 cases of acute aortic dissection and 18 cases of chronic. Thirty-five cases underwent emergence operation and 11 cases underwent selective/limited operation, while 8 cases received medical treatment According to the modus operandi of root of aorta, 9 cases underwent ascending aorta replacement merely, 11 cases for Bentall operation, 12 cases for Wheat operation and ascending aorta replacement, 14 cases for David operation and ascending aorta replacement. According to the modus operandi of aortic arch and descendens, 6 cases underwent right hemiarch replacement, 25 cases for total arch replacement with four branches aortic graft, 24 cases for stent-graft elephant trunk technique. One patient of coronary heart disease and 1 patient of right coronary fracture underwent coronary artery bypass grafting. Deep hyperthermic circulatory arrest and antegrade selective cerebral perfusion were applied with aortic arch operation. Surface cooling was applied with selective/limited operation.</p><p><b>RESULTS</b>Four patients died in operation group (8.7%) and 8 died in non-operation group (75.0%). Postoperative complication included 1 mental symptom, 3 pleural/pericardial effusion, 1 hoarseness, 1 sternal rupture and poor wound healing. All the complication were cured. The operative out-hospital patients were followed up (13.0 +/- 14.2) months and the quality of life was satisfied.</p><p><b>CONCLUSIONS</b>Standford type A aortic dissection should be operated aggressively. Expected outcome could be acquired with optimum modus operandi, proper cerebral protection and dealing with postoperative complication timely.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Aortic Dissection , General Surgery , Aorta , General Surgery , Aortic Aneurysm , General Surgery , Blood Vessel Prosthesis Implantation , Follow-Up Studies , Retrospective Studies , StentsABSTRACT
<p><b>OBJECTIVE</b>To report the preliminary experience of 21 orthotopic heart transplantations without early death.</p><p><b>METHODS</b>Between April 2002 and June 2005, 21 patients underwent orthotopic heart transplantation. Recipients' pulmonary vascular resistance ranged from 3.0 to 5.9 wood units [mean (4.3 +/- 1.4) wood units]; Stanford myocardial protective solution or HTK solution was perfused for donor heart myocardial preservation, donor heart cold ischemic period ranged from 52 to 310 min [mean (81 +/- 23) min]; Three patients had previous cardiac operations under cardiopulmonary bypass, conventional Stanford orthotopic cardiac transplantation in 20 cases and total heart technique in 1 case; Recipients received simulect preoperatively and cyclosporine A, cellcept and prednisone postoperatively for prevention of acute allograft rejection; Patients received appropriate medical control of hypertension, hyperglycemia, hypercholesterolemia and uricacidemia.</p><p><b>RESULTS</b>Acute right heart failure in 3 cases and pericardial effusion in 4 cases were observed at the early postoperative stage, but no any infection and acute rejection were found. All patients survived with good life quality.</p><p><b>CONCLUSIONS</b>Heart transplantation may produce satisfying early results. Suitable selection of recipients with low pulmonary vascular resistance, excellent donor heart conservation, practised anastomotic technique, proper immunosuppression treatment and efficient postoperative management are key measures of orthotopic heart transplantation with excellent early outcome.</p>