Purpose To explore the application value of combining 18F-FDG PET images with interpretable deep learning radiomics(IDLR)models in the differential diagnosis of primary Parkinson's disease(IPD)and atypical Parkinson's syndrome.Materials and Methods This cross-sectional study was conducted using the Parkinson's Disease PET Imaging Benchmark Database from Huashan Hospital,Fudan University from March 2015 to February 2023.A total of 330 Parkinson's disease patients underwent 18F-FDG PET imaging,both 18F-FDG PET imaging and clinical scale information were collected for all subjects.The study included two cohorts,a training group(n=270)and a testing group(n=60),with a total of 211 cases in the IPD group,59 cases in the progressive supranuclear palsy(PSP)group,and a group of 60 patients with multiple system atrophy(MSA).The clinical information between different groups were compared.An IDLR model was developed to extract feature indicators.Under the supervision of radiomics features,IDLR features were selected from the features collected by neural network extractors,and a binary support vector machine model was constructed for the selected features in images of in testing group.The constructed IDLR model,traditional radiomics model and standard uptake ratio model were separately used to calculate the performance metrics and area under curve values of deep learning models for pairwise classification between IPD/PSP/MSA groups.The study conducted independent classification and testing in two cohorts using 100 10-fold cross-validation tests.Brain-related regions of interest were displayed through feature mapping,using gradient weighted class activation maps to highlight and visualize the most relevant information in the brain.The output heatmaps of different disease groups were examined and compared with clinical diagnostic locations.Results The IDLR model showed promising results for differentiating between Parkinson's syndrome patients.It achieved the best classification performance and had the highest area under the curve values compared to other comparative models such as the standard uptake ratio model(Z=1.22-3.23,all P<0.05),and radiomics model(Z=1.31-2.96,all P<0.05).The area under the curve values for the IDLR model in differentiating MSA and IPD were 0.935 7,for MSA and PSP were 0.975 4,for IPD and PSP were 0.982 5 in the test set.The IDLR model also showed consistency between its filtered feature maps and the visualization of gradient-weighted class activation mapping slice thermal maps in the radiomics regions of interest.Conclusion The IDLR model has the potential for differential diagnosis between IPD and atypical Parkinson's syndrome in 18F-FDG PET images.

Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.

Objective:To investigate the influence of abnormal blood pressure circadian rhythms and the morning surge on aortic stiffness in elderly patients with isolated systolic hypertension(ISH).Methods:A total of 300 untreated elderly(≥60 years)patients with ISH were enrolled.24-hour ambulatory blood pressure was measured by using a non-invasive portable ambulatory sphygmomanometer with an inflatable cuff.Brachial-ankle pulse wave velocity(baPWV)and the ankle-brachial pressure index(ABI)were measured by using an automated device.Patients were divided into the dipper(n=95), no-dipper(n=177)and extreme dipper(n=28)groups according to the rate of nocturnal blood pressure reduction.They were also divided into the morning surge(n=88)and no morning surge(n=212)groups according to the morning blood pressure surge(MBPS). Differences between the groups were compared.Correlations between the parameters were calculated by partial correlation analyses.The effects on baPWV and ABI were calculated by multiple linear regression analyses.Results:baPWV was higher in the extreme dipper group than in the dipper and no dipper groups[(1 402±234)cm/s vs.(1 467±114)cm/s vs.(1 538±140)cm/s, P<0.01], while ABI values were lower in the extreme dipper group than in the dipper group(0.98±0.10 vs.1.05±0.12, P<0.01)and the no dipper group(0.98±0.10 vs.1.03±0.12, P<0.05). Moreover, baPWV[(1 508±170)cm/s vs.(1 430±163)cm/s, P<0.01]was higher while ABI values(0.98±0.13 vs.1.06±0.11, P<0.01)were lower in the morning surge group than in the no morning surge group.baPWV was positively correlated with daytime Systolic blood pressure(dSBP)( r=0.169, P<0.01), 24 hSBPCV( r=0.143, P<0.05), and MBPS( r=0.157, P<0.01), while ABI was negatively correlated with dSBP( r=-0.146, P=0.011)and MBPS( r=-0.321, P<0.01). Age( P<0.01), dSBP( P<0.05)and 24 h systolic blood pressure variation coefficient( P<0.05)were independent factors for baPWV, while dSBP and MBPS were independent factors for ABI(all P<0.01). Conclusions:Abnormal blood pressure circadian rhythms and the morning surge are associated with increased aortic stiffness in elderly patients with ISH.

A 66-year-old female patient received Gukang capsules and Jieguqili pills orally for 11 days for fracture. On day 6 after the drugs withdrawal, she developed weakness, anorexia, and yellow urine. Drugs above-mentioned were re-given and ibuprofen and codeine phosphate tablets were added. Five days later, her symptoms were aggravated. Laboratory tests showed alanine aminotransferase (ALT) 778 U/L, aspartate aminotransferase (AST) 782 U/L, alkaline phosphatase (ALP) 151 U/L, total bilirubin (TBil) 34.3 μmol/L, direct bilirubin (DBil) 24.0 μmol/L, and gamma-glutamyltransferase (γ-GT) 111 U/L. It was considered to be liver injury caused by Gukang capsules, Jieguqili pills, and ibuprofen and codeine phosphate tablets. All drugs above were withdrawn and the liver-protective and anti-jaundice treatments were given. After 21 days, laboratory tests showed ALT 24 U/L, AST 17 U/L, ALP 104 U/L, TBil 13.6 μmol/L, DBil 9.0 μmol/L, and γ-GT 52 U/L.

A 66-year-old female patient received Gukang capsules and Jieguqili pills orally for 11 days for fracture. On day 6 after the drugs withdrawal, she developed weakness, anorexia, and yellow urine. Drugs above-mentioned were re-given and ibuprofen and codeine phosphate tablets were added. Five days later, her symptoms were aggravated. Laboratory tests showed alanine aminotransferase (ALT) 778 U/L, aspartate aminotransferase (AST) 782 U/L, alkaline phosphatase (ALP) 151 U/L, total bilirubin (TBil) 34.3 μmol/L, direct bilirubin (DBil) 24.0 μmol/L, and gamma-glutamyltransferase (γ-GT) 111 U/L. It was considered to be liver injury caused by Gukang capsules, Jieguqili pills, and ibuprofen and codeine phosphate tablets. All drugs above were withdrawn and the liver-protective and anti-jaundice treatments were given. After 21 days, laboratory tests showed ALT 24 U/L, AST 17 U/L, ALP 104 U/L, TBil 13.6 μmol/L, DBil 9.0 μmol/L, and γ-GT 52 U/L.

Objective: To investigate the value of statistical parametric mapping (SPM) analysis of ¹⁸F-fluorodeoxyglucose (FDG) PET imaging in the differential diagnosis of Parkinsonism in single-case level. Methods: SPM software was used to retrospectively analyze the ¹⁸F-FDG PET images of 160 patients (104 males, 56 females, age: 30-82 years) who were suspected with Parkinsonism at baseline and were clinical confirmed by follow-up from April 2010 to December 2017. ¹⁸F-FDG PET images of patients was compared with those of age-matched healthy controls in single-case level using two-sample t test in SPM software to obtain the imaging diagnosis. By comparing imaging diagnosis with the final clinical diagnosis, the diagnostic accuracy of SPM in the overall cohort as well as the early subcohort (duration of disease less than 2 years (56 males, 22 females, age: 50-82 years)) were calculated respectively. Results: Among 160 patients with Parkinsonism, 146(91.2%) had the same ¹⁸F-FDG PET diagnosis as their final clinical diagnosis. The diagnostic sensitivity for Parkinson′s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and cortical basal ganglia degeneration (CBD) were 93.5%(86/92), 92.3%(24/26), 84.0%(21/25) and 15/17, respectively. The specificity were 95.6%(65/68), 95.5%(128/134), 96.3%(130/135) and 100%(143/143), respectively. In the early subcohort, the analysis also achieved similar differential diagnosis effectiveness(92.3%). Conclusion The single-case ¹⁸F-FDG PET imaging SPM analysis can be helpful in the early differential diagnosis of Parkinsonism effectively.

OBJECTIVE： To establish a method for simultaneous determination of matrine， oxymatrine， gallic acid， peoniflorin， costunolide and dehydrocostus lactone in Libiling tablets. METHODS： RP-HPLC method was adopted. The determination was performed on Agilent ZORBAX SB-C18 column with mobile phase consisted of methanol-0.1％ phosphoric acid （gradient elution） at the flow rate of 1.0 mL/min. The detection wavelengths were 210 nm （matrine， oxymatrine） and 225 nm （gallic acid， peoniflorin， costunolide， dehydrocostus lactone）. The column temperature was set at 30 ℃， and sample size was 5 μL. RESULTS： The linear ranges of matrine， oxymatrine， gallic acid， peoniflorin， costunolide， dehydrocostus lactone were 0.053-5.28 mg/mL（r＝0.999 8）， 0.125-12.54 mg/mL（r＝0.999 9）， 0.013-1.33 mg/mL（r＝0.999 8）， 0.169-16.94   mg/mL（r＝0.999 9）， 0.048-4.77 mg/mL（r＝0.999 8）， 0.072-7.16 mg/mL （r＝0.999 9）. The limits of quantitation were 4.08×10－4， 4.48×10－4， 3.12×10－4， 2.10×10－4， 1.36×10－4， 1.84×10－4 mg/mL， respectively. The limits of detection were 1.24×10－4， 1.50×10－4， 1.02×10－4， 6.20×10－5， 4.20×10－5， 6.40×10－5 mg/mL， respectively. RSDs of precision， stability and reproducibility tests were all lower than 2％ （n＝6）. The recoveries were 98.03％-101.43％ （RSD＝1.25％， n＝6）， 97.73％-102.26％ （RSD＝1.96％， n＝6）， 97.18％-101.41％ （RSD＝1.98％，n＝6）， 97.45％-102.11％ （RSD＝1.88％，n＝6）， 96.85％-101.07％ （RSD＝1.75％， n＝6）， 97.12％-102.64％ （RSD＝1.82％，n＝6）， respectively. CONCLUSIONS： Established method is simple， stable and rapid， and can be used for simultaneous determination of 6 components in Libiling tablets.

Objective To investigate the value of statistical parametric mapping (SPM) analysis of 18F-fluorodeoxyglucose (FDG) PET imaging in the differential diagnosis of Parkinsonism in single-case level.Methods SPM software was used to retrospectively analyze the 18F-FDG PET images of 160 patients (104males,56 females,age:30-82 years) who were suspected with Parkinsonism at baseline and were clinical confirmed by follow-up from April 2010 to December 2017.18F-FDG PET images of patients was compared with those of age-matched healthy controls in single-case level using two-sample t test in SPM software to obtain the imaging diagnosis.By comparing imaging diagnosis with the final clinical diagnosis,the diagnostic accuracy of SPM in the overall cohort as well as the early subcohort (duration of disease less than 2 years (56 males,22 females,age:50-82 years)) were calculated respectively.Results Among 160 patients with Parkinsonism,146(91.2％) had the same 18F-FDG PET diagnosis as their final clinical diagnosis.The diagnostic sensitivity for Parkinson's disease (PD),multiple system atrophy (MSA),progressive supranuclear palsy (PSP) and cortical basal ganglia degeneration (CBD) were 93.5％ (86/92),92.3％ (24/26),84.0％(21/25) and 15/17,respectively.The specificity were 95.6％(65/68),95.5％(128/134),96.3％ (130/135) and 100％(143/143),respectively.In the early subcohort,the analysis also achieved similar differential diagnosis effectiveness(92.3％).Conclmion The single-case 18F-FDG PET imaging SPM analysis can be helpful in the early differential diagnosis of Parkinsonism effectively.

Objective To investigate the protective effects of vascular endothelial growth factor-165 (VEGF165) transfected the endothelial progenitor cells (EPCs) mediated by lentivirus on acute lung injury (ALI) in rats. Methods The mononuclear cells from the male Sprague-Dawley (SD) rats were isolated and cultured to get the EPCs for study. The lentivirus vector carrying the human VEGF165 gene was constructed. According to the random number table method, 90 male SD rats were divided into ALI model group, phosphate buffer solution (PBS) group, EPCs treatment group, none transfected EPCs treatment group and VEGF165 transfected EPCs treatment group, and the rats in each group were subdivided into 4, 12 and 48 hours subgroups, with 6 rats in each subgroup. The rat model of ALI was reproduced by intravenous injection of oleic acid (0.15 μL/g). Then each treatment group was given PBS, EPCs, none transfected EPCs and VEGF165 transfected EPCs respectively with the same volume of 0.2 mL. For the groups with cells, about 1×106cells were contained. Abdominal aortic blood and lung tissue were harvested at 4, 12 and 48 hours. Arterial blood gas analysis was performed. The lung wet/dry weight ratio (W/D) was calculated. The expressions of induced nitric oxide synthase (iNOS), endothelin-1 (ET-1) and VEGF165 were determined by enzyme-linked immunosorbent assay (ELISA). After dyed with hematoxylin-eosin (HE), the lung tissue pathology was observed and the lung injury score was performed. Results Compared with the ALI model group, the arterial partial pressure of oxygen (PaO2) in EPCs, none transfected EPCs and VEGF165 transfected EPCs treatment groups was significantly increased from 4 hours, and lung W/D, expressions of iNOS and ET-1 were significantly decreased, and VEGF165 expression was significantly increased. Compared with the EPCs treatment group, the increase in PaO2, the decrease in lung W/D and expressions of iNOS and ET-1, and the increase in VEGF165 expression in VEGF165 transfected EPCs treatment group were more significant [4 hours: PaO2(mmHg, 1 mmHg = 0.133 kPa) was 82.84±10.69 vs. 72.34±9.36, lung W/D ratio was 4.83±0.23 vs. 5.55±0.37, iNOS (ng/mg) was 8.77±1.10 vs. 14.84±1.34, ET-1 (ng/mg) was 103.41±5.66 vs. 153.08±5.12, VEGF165 (ng/mg) was 130.56±12.16 vs. 83.03±5.95; 12 hours: PaO2(mmHg) was 91.67±6.81 vs. 78.5±8.81, lung W/D ratio was 4.44±0.35 vs. 5.32±0.25, iNOS (ng/mg) was 7.23±0.24 vs. 14.04±1.18, ET-1 (ng/mg) was 91.98±3.52 vs. 125.99±7.55, VEGF165 (ng/mg) was 164.49±5.71 vs. 96.61±6.12]; individual parameters reached valley value or peak value at 48 hours [lung W/D ratio was 4.26±0.30 vs. 4.89±0.15, iNOS (ng/mg) was 5.79±0.85 vs. 12.72±1.10, ET-1 (ng/mg) was 74.53±7.10 vs. 108.33±5.84, VEGF165 (ng/mg) was 237.43±10.79 vs. 134.24±11.99, all P < 0.05]. Over time, lung tissue injury in each group was gradually increased, and the lung injury score was gradually increased. The lung injury score at 48 hours in the EPCs, none transfected EPCs and VEGF165 transfected EPCs treatment groups were lower than that in the ALI model group. Compared with the EPCs treatment group, the VEGF165 transfected EPCs treatment group had a lower score at 48 hours (8.50±1.05 vs. 10.50±1.05, P < 0.05). Conclusion The transplantation of EPCs which were transfected with VEGF165 mediated by lentivirus could obviously improve the oxygen pressure, reduce the lung water seepage, decrease the iNOS and ET-1 expressions in lung tissue, and had obvious protective effects on ALI.

OBJECTIVETo establish a nude mouse model of orthotopic engineered gastric tumor for in vivo fluorescence imaging studies.

METHODSAn engineered gastric tumor was constructed in vitro using collagen as the scaffold and the human gastric cancer cell line BGC823-EGFP cells expressing enhanced green fluorescence protein (EGFP) as the seed cells. The engineered tumor was then implanted into the stomach of nude mice, and the tumor growth was observed with in vivo fluorescence imaging. The nude mice were sacrificed 6 weeks after the transplantation to assess the tumor growth and metastasis, and the tumor histology was evaluated.

RESULTSThe tumor cells in the engineered tumor model grew well in three-dimensional culture. The success rate of orthotopic gastric tumor implantation was 100% (10/10) in nude mice with metastasis in the abdominal organs. The isolated tumor mass, weighing 1.719∓0.349 g, showed a histological characteristic of poorly differentiated adenocarcinoma. In vivo fluorescence imaging detected EGFP-expressing tumors in the abdominal cavity of the nude mice, but not accurately.

CONCLUSIONThe nude mouse model bearing orthotopic engineered gastric tumor provides a simple animal model for the study of gastric cancer, but a stronger fluorescence than green fluorescence is more desirable for more effective observation in in vivo fluorescence imaging.

Animals ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Fluorescence ; Green Fluorescent Proteins ; analysis ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Optical Imaging ; Stomach Neoplasms ; Tissue Engineering