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Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.
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Multi-centre clinical trials on PET/CT brain imaging are complex to organize and require careful co-ordination and management. This article describes considerations, which are necessary when designing and starting a multi-centre clinical trial on PET/CT brain imaging, based on guidelines and multi-center clinical brain imaging studies, providing references for further studies.
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To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.
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@#Objective To explore the feasibility and clinical value of free-of-puncture positioning in three-dimension-guided anatomical segmentectomy for ground-glass nodule (GGN) compared with percutaneous positioning. Methods Clinical data of 268 enrolled patients undergoing anatomical pulmonary segmentectomy from October 2018 to June 2019 were retrospectively collected, including 75 males and 193 females with an average age of 56.55±12.10 years. The patients were divided into two groups, including a percutaneous positioning group (n=89) and a free-of-puncture positioning group (n=179). Perioperative data of the two groups were compared. Results The average CT scan times of the percutaneous positioning group was 3.01±0.98 times, and the numerical rating scale (NRS) score of puncture pain was 3.98±1.61 points. Pulmonary compression pneumothorax (≥30%) occurred in 7 (7.87%) patients and intercostal vascular hemorrhage occurred in 8 (8.99%) patients after puncture. Lung nodules were successfully found and removed in both groups. There was no statistically significant difference between the two groups in the location of nodules (P=0.466), operation time (151.83±39.23 min vs. 154.35±33.19 min, P=0.585), margin width (2.07±0.35 cm vs. 1.98±0.28 cm, P=0.750), or the number of excised subsegments (2.83±1.13 vs. 2.73±1.16, P=0.530). Conclusion Anatomical segmentectomy with three-dimensional navigation avoids the adverse consequences of puncture, which has the same clinical efficacy and meets the requirements of oncology compared with percutaneous positioning. The free-of-puncture positioning method can be used for GGN located in the central region of pulmonary segment/subsegment or adjacent to intersegment veins instead of percutaneous positioning.
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The combination of chemotherapy and photodynamic therapy provides a promising approach for enhanced tumor eradication by overcoming the limitations of each individual therapeutic modality. However, tumor is pathologically featured with extreme hypoxia together with the adaptable overexpression of anti-oxidants, such as glutathione (GSH), which greatly restricts the therapeutic efficiency. Here, a combinatorial strategy was designed to simultaneously relieve tumor hypoxia by self-oxygenation and reduce intracellular GSH level to sensitize chemo-photodynamic therapy. In our system, a novel multi-functional nanosystem based on MnO
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OBJECTIVE@#To investigate the feasibility of a novel molecular probe of Zn-DPA-PSS794 to monitor the efficiency of doxorubicin to ovarian cancer and compare with Cy5.5-annexin V.@*METHODS@#Efficiency of doxorubicin to OVCAR-8 cells in vitro was measured by MTT assay and flow cytometry. The in vivo studies were performed on an OVCAR-8 xenograft tumor model. Mice were divided into a control group and a treatment group. Each group was divided into 2 subgroups, DPA and annexin V. In the treatment group, the mice were treated with doxorubicin for 2 doses. All mice were performed optical imaging by Zn-DPA-PSS794 or Cy5.5-annexin V, respectively and then sacrificed. The tumor was separated and stained by HE. The expression of caspase-3 protein was measured by Western blot.@*RESULTS@#The IC50 of doxorubicin to OVCAR-8 was 6 μmol/L. The percentage of apoptosis and dead cells was 35% after doxorubicin treatment. In the optical image, photons accumulated in the tumor either by Zn-DPA-PSS794 or Cy 5.5-annexin V in the treatment group. That was negative in the control group. The fluorescence intensity had significant difference between the 2 groups(P<0.001). The nuclei were big and stained with deep color after the cells were stained with HE. The caspase-3 expression was high in the treatment group, while it was low in the control group.@*CONCLUSION@#Zn-DPA-PSS794 as a probe used by optical imaging can monitor the efficiency of doxorubicin to OVCAR-8 xenograft tumor, which is similar to Cy5.5-annexin V.
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Animals , Female , Humans , Mice , Apoptosis , Carbocyanines , Cell Line, Tumor , Doxorubicin , Pharmacology , Fluorescent Dyes , Infrared Rays , Mice, Nude , Molecular Imaging , Organometallic Compounds , Ovarian Neoplasms , Pathology , Picolines , Spectroscopy, Near-Infrared , MethodsABSTRACT
Objective To evaluate the PSD-007-mediated photodynamic effect on mouse osteosarcoma cell line LM-8, both in vitro and in vivo. Methods LM-8 cells were incubated with different concentrations of PSD-007 for 4 hours and then followed different laser irradiations. After photodynamic therapy (PDT), cell viability was measured using MTT assay and the optical density in each experiment was measured at 450 nm with a micro plate reader. The inhibition rate of cell growth was calculated. Four-week-old female C3H mice were used for implantation of LM-8 cells. When the diameter of tumor reached up to 7-8 mm, the mice were randomly divided into following groups: 1) control group, including untreated control, saline with laser irradiation, PSD-007 without laser irradiation; 2) PDT group, PSD-007 (5 and 10 mg/kg) was injected intravenously into the mice, and the tumor site was irradiated with laser light 6 hours after injection. Seven days after PDT, the size and weight of the tumors were measured. The inhibition rate of tumor was calculated, and all tumor specimens were taken for pathologic examination. After the diameter of tumor was 10-12 mm, the tumors were performed a marginal resection and subsequently followed 3 different treatments: without PDT (control), PDT with 240 J/cm2 or 360 J/cm2 laser irradiation. After 4 weeks treatment, the tumor recurrence rates were analyzed. Results MTT assay revealed that the cytotoxic effect of PDT on the LM-8 cells was positively correlated with the concentration of PSD-007 and the level of laser irradiation. When the concentration exceeded 4μg/ml, and the energy exceeded 6 J/cm2, the inhibition ratio was over 50%. No anti-tumor effect was observed in the cells treated with only laser irradiation or PSD-007 injection. Compared with the control group, the size and weight of the tumors were obviously decreased after PDT. PDT performed after marginal resection of the tumor reduced the rate of local recurrence. Conclusion PDT with PSD-007 showed cytotoxic effect on the LM-8 cells, and which performed after marginal resection of the tumor reduced the rate of local recurrence.
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Objective To discuss the relations between optimal surgical margin and local recurrence and the impact of preserving segment of sacral nerve root on neural functions based on the clinical and pathological features of giant cell tumor(GCT).Methods From August 1996 to August 2008,48 patients with sacral GCT undergoing tumor resection were respectively analyzed,including 20 males and 28 females with an average of 34.7 years(range,19-74).The tumors were located in S1-S5 in 4 patients,S1-S4 in 7,S1-S3 in 15,S1,2 in 12,S2-S5 in 8,and S3-S5 in 2.Surgical methods included single posterior approach in 29 cases,combined anterior-posterior approach in 19.The surgical margins adopted were en-bloc in 2 patients,marginal in 15,marginal and curettage in 25,and curettage in 9.Results Forty-one of 48 cases were successfully followed up,the average time was 43.5 months(range,18-115).The average blood loss during surgery was 3560 ml(range,550-12 000).Benign lung metastasis occurred in one case 6 years after operation,2 patients died of malignant transformation.Local recurrence occurred in 15 cases.The recurrence rates in patients with en-bloc resection,marginal resection,marginal resection combined with curettage,and curettage were 0,18.2%,40.9%,66.7%,respectively.The recurrence rate of marginal group was significantly lower than that of the curettage group.Of 27 cases with bilateral S3 nerve root preservation,2 sufiered from urine or fetal dysfunction.with an incidence rate of 7.4%.While 4 of 12 patients with unilateral S3 nerve root preservation suffered from sphincter disturbance,with an incidence rate of 33.3%.The significant difference between groups in nerve root preservation was confirmed.Conclusion Optimal surgical margin for sacral GCT is of great importance to local control of tumor recurrence,the surgical procedure of sacral GCT should aim at the marginal resection on the basis of rational sacral nerve roots preservation;preservation of bilateral S3 nerve roots contributes to the recovery of sphincteral function in most patients.
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OBJECTIVE@#To compare the efficiency of human bone marrow mesenchymal stem cells (hBMSCs) with rat BMSCs (rBMSCs) transfected by modified adenovirus containing fiber 35 (AdF35)-enhanced green fluorescence protein(eGFP).@*METHODS@#We separated hBMSCs and rBMSCs from the bone marrow of humans and rats, respectively, and osteogenesis and adipogenesis were induced. eGFP was carried by modified AdF35, which was transfected to hBMSCs and rBMSCs with different multiplicity of infections (MOIs). Activity of the cells was detected by MTT. The transfected cells were observed under fluorescent microscope. The transfection efficiency was measured by flow cytometer. The expression of coxsackie and adenovirus receptor (CAR) and CD46 mRNA in the cells was inspected by real time PCR.@*RESULTS@#hBMSCs and rBMSCs induced osteogenesis and adipogenesis successfully after being separated from human and rat bone marrow respectively. The activity of the cells was inhibited when MOI was 1,000 PFU/mL. hBMSCs with strong green fluorescence were observed but few rBMSCs were seen under fluorescence microscope 48 h after being transfected by AdF35-eGFP. The transfective efficiency was (84.8±7.1)% and (3.3±1.1)%, respectively. The expression of CD46 was high while that of CAR was low in hBMSCs. The expression of CAR was very high and that of CD46 was low in rBMSCs (P<0.01).@*CONCLUSION@#AdF35 may be the ideal vector to carry the target gene to transfect hBMSCs effectively but not to transfect rBMSCs.
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Animals , Humans , Rats , Adenoviridae , Genetics , Bone Marrow Cells , Cell Biology , Metabolism , Genetic Vectors , Green Fluorescent Proteins , Genetics , Mesenchymal Stem Cells , Cell Biology , Metabolism , TransfectionABSTRACT
Objective To investigate the feasibility of rat sodium/iodide symporter (rNIS) as a reporter gene monitoring rat bone marrow mesenchymal cells (rBMSC) transplanted to rat myocardium in vivo.Methods Recombinated adenovirus vector was constructed by rNIS/enhanced green fluorescence protein (EGFP) (Ad-rNIS/EGFP).rBMSC transfected by Ad-rNIS/EGFP were studied using fluorescence microscope.Fifteen rats were transplanted with rBMSC and randomly divided into three groups:rNIS group (with rNIS transfection), blocked group (with rNIS transfection) by oral intake of perchloric sodium before planar imaging(GE Millennium MPR SPECT), and control group (without rNIS transfection).All rats underwent 99Tcm-pertechnetate planar imaging.The biological distribution of 99Tcm-pertechnetate was studied.The expressions of rNIS gene and protein in myocardium were measured by real time polymerase chain reaction (PCR) and western blot, respectively.The expressions of CD29, CD44, CD90, CD11b, CD34 and CD45 were measured by immunohistochemistry.Results rBMSC transfected by Ad-rNIS/EGFP showed EGFP expression under fluorescence microscope.The transplanted rat myocardium could be visualized on 99Tcm-pertechnetate planar imaging in rNIS group.The relative uptake ratio( Rheart/Rhmb, RUR) was 6.7 ±0.4.RUR in control group (3.0 ±0.2) was lower than that in rNIS group (t =2.78, P=0.03).The percentage injection dose per gram of tissue (% ID/g) of the transplanted myocardium was 60.2 ± 20.8 in rNIS group,which was higher than that (2.5 ± 0.4) % ID/g of control group ( t = 7.13, P＜0.001 ).rNIS gene and protein were highly expressed in transplanted myocardium in rNIS group but less expressed in control group.The expressions of CD29, CD44 and CD90 were positive, CD45 and CD45 negative CD11b mildly positive in the myocardium transplanted with infective rBMSC.Conclusion rNIS can efficiently monitor rBMSC transplanted to rat myocardium.
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<p><b>OBJECTIVE</b>To screen and identify the peptides that specifically bind to CD13 on monocytes.</p><p><b>METHODS</b>The phages capable of specific binding to CD13 were screened in the phage-displayed 12-peptide library. The affinity of the selected phages with CD13 was verified with enzyme-linked immunosorbent assay (ELISA). The sequences of the peptides bound to the phages were deduced according to the phage DNA sequences, and the functional peptides aligned using the BLASTP on the Website NCBI were synthesized. To analyze the biological function of the screened peptides, the location of the peptides bound to THP-1 cells was detected using immunofluorescence assay. The blocking effect of WM15 on the peptide binding to THP-1 cells was assessed by immunofluorescence assay.</p><p><b>RESULTS</b>The phages that specifically bound to CD13 were effectively enriched to approach saturation after 4 rounds of panning. The recovery rate in the fourth round was 30 times that in the first round. Twenty selected phages were verified by ELISA, and the signals of 10 phages were higher than the control. The sequences of the peptides P9 and P7 showed 83% and 100% identity with those of human cytomegalovirus (HCMV) UL38 and UL105, respectively. The peptides bound to the cell membrane of THP-1 cells as shown by immunofluorescence assay. The binding of the peptides P9 and P7 to THP-1 cells was blocked by CD13-specific monoclonal antibody WM15 at different levels.</p><p><b>CONCLUSION</b>Two peptides (P7 and P9) that can specifically bind to CD13 have been screened successfully, and these two peptides show specific binding to CD13 on the membrane of THP-1 cells.</p>
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Humans , Amino Acid Sequence , Binding, Competitive , CD13 Antigens , Metabolism , Cell Line , Molecular Sequence Data , Peptide Library , Peptides , Metabolism , Protein BindingABSTRACT
OBJECTIVE@#To investigate the effects of intravenous anesthetics on LPS-induced inflammatory responses of primary cultures of rat glial cells in vitro.@*METHODS@#The primary cultures of rat glial cells were stimulated with lipopolysaccharide( LPS) to produce inflammatory responses. Glial cells were divided into 8 groups (n=4): blank control (Group C), LPS(Group L), 100micromol/L ketamine with LPS(Group K1), 1000micromol/L ketamine with LPS (Group K2), 30micromol/L propofol with LPS (Group P1), 300micromol/L propofol with LPS (Group P2), 3micromol/L midazolane with LPS (Group M1), and 30micromol/L midazolane with LPS (Group M2). TNF-alpha released into the culture media was measured by radioimmunity assay.@*RESULTS@#Compared with the blank control Group C, LPS-induced TNF-alpha productions in Group L, K1, K2, P1, P2, M1 and M2 increased significantly. The levels of TNF-alpha in Group K1 and K2 were significantly lower than those in Group L (P<0.05), but TNF-alpha productions in Group P1, P2, M1 and M2 were not significantly different as compared with that in Group L.@*CONCLUSION@#Ketamine can reduce LPS-induced TNF-alpha production of glial cells, thereby inhabiting some of the inflammatory responses. Propofol and midazolam have no effect on the production of TNF-alpha from LPS-stimulated glial cells.