Objective To investigate the clinical data,brain pathology and molecular genetic characteristics of retinal vascular disease families with leukoencephalopathy and systemic damage.Methods The clinical data of two families of RVCL-S(retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations,RVCL-S)were collected and family maps were drawn to analyze the clinical manifestations,imaging,brain pathology and molecular genetic characteristics.Results Family 1:there were 3 male cases and the age of onset was 10 years,29 years and 40 years,respectively.Family 2:there was one male case and the age of onset was 32 years.Both families presented with retinal vascular disease,leukoencephalopathy and multi-system damage,the latter including liver,kidney and digestive tract involvement.There were 4 asymptomatic carriers in two families.The cranial CT of family 1-Ⅱ2 showed lamellar low density near the posterior corner of the left ventricle with multiple intracranial high density calcification.Brain MRI plain scan showed lateral ventricle lesions.The brain MRI plain and enhancement scans of family 1-I5 showed frontotemporal cortex lesions with peripheral edema and space occupying effect,and the ring enhancement was remarkable.The brain MRI plain scan and enhancement scan of family 2-Ⅱ1 showed the right and left frontal lobe lesions,accompanied by peripheral edema and enhancement,and the occupying effect was obvious.The operative pathology of brain tissue from family 1-I5 showed endothelial cell hyperplasia.The pathological manifestations of family 2-Ⅱ1 encephalopathy were consistent with"cerebral infarction"after two operations.The small blood vessels in the small intestinal wall showed endothelial cell proliferation.Molecular genetics:TREX1 D272Rfs heterozygous mutation was present in family 1-Ⅱ2,and his offspring including two daughters and one son were asymptomatic mutation carriers.TREX1 S246Ifs heterozygous mutation was detected in the 2-Ⅱ1 gene of the family which was not found in either the father or the mother found the mutation,and the son was asymptomatic carrier of the mutation.Conclusion The main clinical manifestations of RVCL-S are retinal vascular disease,nervous system involvement and multi-system damage.Imaging findings showed that intracranial lesions were space-occupying,accompanied by peripheral edema and enhancement.The pathological features were small vessel endothelial cell proliferation and lumen stenosis.Genetic results confirmed the presence of TREX1 gene mutation.

Objective:To investigate the clinical application of 68Ga-cyclo( L-arginylglycyl- L-α-aspartyl- D-tyrosyl-N6-(((4, 7-bis(carboxymethyl)-1, 4, 7-triazonan-1-yl)acetyl))- L-lysyl) (NODAGA-RGD) PET/CT to evaluate short-term efficacy of tyrosine kinase inhibitor (TKI) in distant metastatic differentiated thyroid cancer (dmDTC). Methods:From October 2019 to March 2023, 13 dmDTC patients (5 males, 8 females; age: 68(65, 69) years) from Nanjing First Hospital were retrospectively enrolled, of which 9 were clinically confirmed as radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and 4 were dmDTC without radioactive iodine treatment. All patients underwent 68Ga-NODAGA-RGD PET/CT to assess neovascularization of the target lesions (TL), and the SUV max and target background ratio (T/B) were recorded. After 3 months of TKI treatment (anrotinib ( n=9) or apatinib ( n=4)), change rates of the maximum diameter of TL and thyroglobulin (Tg) were measured. The correlation of SUV max, T/B and the change rate of the maximum diameter of TL were analyzed by Spearman rank correlation analysis. ROC curve analysis was performed for the effectiveness of the T/B and TKI therapy, and the difference of the remission rate of lesions was analyzed by Fisher exact test. Results:In 13 patients, 36 TL were measured by 68Ga-NODAGA-RGD PET/CT with SUV max of 5.44(3.43, 7.56) and T/B of 5.25(4.50, 7.23). The change rate of the maximum diameter of TL was -30%(-39%, -21%) and the change rate of Tg was -68%(-96%, -52%). T/B was negatively correlated with the change rate of the maximum diameter of TL after TKI therapy ( rs=-0.46, P=0.005), while SUV max was not correlated with the change rate of the maximum diameter of TL ( rs=0.03, P=0.883). ROC curve analysis showed that the optimal cut-off value for T/B was 4.95, with the AUC of 0.698, the sensitivity of 87.5%, and the specificity of 60.0%. Compared to lesions with T/B<4.95, those with T/B≥4.95 showed higher remission rate (2/14 vs 63.6%(14/22); P=0.006). After 3 months of TKI treatment, the disease control rate was 12/13. Conclusion:68Ga-NODAGA-RGD PET/CT can effectively reflect tumor neovascularization, predict efficacy of TKI therapy, and provide powerful imaging evidence for TKI therapy in dmDTC.

Objective:To explore the normal ranges of perfusion parameters between cerebral hemisphere, cerebellar hemisphere and brain anatomical subregions (56 pairs) in different gender and age groups with multiple post labeling delay time (Multi-PLD) arterial spin labeling (ASL) imaging.Methods:From November 2020 to December 2020, 42 healthy adult volunteers (Male 25, Female 17) were recruited to perform 7 PLD ASL imaging, including 21 young adults (15 males and 6 females, aged 23—35 years) and 21 seniors (10 males and 11 females, aged 36—74 years). The data was processed offline by Cereflow software to obtain arterial arrival time (ATT) and corrected cerebral blood flow (CBF) and cerebral blood volume (CBV) perfusion parameters. SimpleITK standardization function was used to standardize the calculated perfusion image according to the anatomical automatic labeling (AAL) template. Therefore, CBF, ATT, CBV perfusion values of brain subregions were obtained. Paired samples t test, Wilcoxon rank sum test, independent samples t test and Mann-Whitney U test were used to compare the differences of perfusion parameters in the cerebral hemisphere, the cerebellar hemisphere, brain subregions depending on side, gender and age. Pearson correlation analysis was used to compare the correlations of perfusion parameters with age. Results:CBF in 62.5% (35/56) subregions and CBV in 44.6% (25/56) subregions were higher in right side than those in left side. ATT in most brain anatomical subregions (16/56) were higher in left side. The CBF [(35.30±8.31) vs. (34.34±7.53) ml·100g -1·min -1, P=0.021], CBV [(0.47±0.11) vs. (0.45±0.09) ml/100g, P<0.001], ATT [(1.30±0.10) vs. (1.24±0.11) s, P<0.001] in left cerebellar hemisphere were higher than that of right side. The CBF (28/56) of cerebral hemisphere, cerebellar hemisphere and brain subregions was higher in females than that in males, while ATT in 83.9% (47/56) subregions was lower than that in males (all P<0.05). CBV in female subjects was higher only in 5 brain regions (superior occipital gyrus, middle occipital gyrus, inferior occipital gyrus, superior parietal gyrus and cerebelum_7b) (all P<0.05). In young subjects, CBF in 44.6% (25/56) subregions and CBV in 33.9% (19/56) subregions were higher than those in the senior group (all P<0.05). The ATT in most subregions in young group were lower than those in senior group, but the difference was statistically significant only in rectus gyrus ( P=0.026) and paracentral lobule ( P=0.006). The CBF ( r=-0.430, P=0.005) and CBV ( r=-0.327, P=0.035) of cerebral hemisphere were negatively correlated with age. The CBF (24/25, r range:-0.497 —-0.343, all P<0.05) and CBV (16/19, r range:-0.474 —-0.322, all P<0.05) in most subregions were negatively correlated with age, while ATT was positively correlated (gyrus rectus: r=0.311, P=0.045; paracentral lobule: r=0.392, P=0.010). Conclusions:Multi-PLD ASL imaging could be applied for quantitative analysis of brain perfusion. The perfusion parameters of anatomical subregions are different depending on side, gender, and age.

To report a typical case of Morvan syndrome with positive anti-leucine rich glioma-inactivated 1(LGI1) and contactin-associated protein 2 (CASPR2) antibodies in serum and cerebrospinal fluid. A 39-years-old female initially presented weakness of extremeties. The main symptoms included paroxysmal limb pain, wheezing, itching, muscle twitching, epilepsy, hypomnesia, dysphoria, apathy, intractable insomnia, salivation and sweating. Tests of electrolytes found hypokalemia (2.7-3.1 mmol/L) and hyponatremia (130-136 mmol/L). Arterial blood gas analysis showed hypoxemia (oxygen saturation 50%-70%). Total thyroxine (TT4) was elevated to 207 nmol/L with positive thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab). LGI1and CASPR2 antibodies (CBA method) were positive in both serum and cerebrospinal fluid, and the remaining antibodies related to autoimmune encephalitis and paraneoplastic syndrome were negative. Head MRI was almost normal, while mild abnormalities were found in electroencephalogram. Electromyography showed slightly increased voltage of left quadriceps motor unit potential. After treated with corticosteroids, IVIG and mycophenolate mofetil, the patient completely improved. Cognitive function scores recovered from MoCA/MMSE (16/24) to MoCA/MMSE (26/29). Positivity of LGI1/CASPR2 antibodies both in serum/cerebrospinal fluid are rarely seen in patients with Morvan syndrome. Steroids and immunosuppressants are suggested for treatment as early as possible.

Objective To determine the prevalence of human immunodeficiency virus (HIV) primary drug resistance (HIV-PDR) in newly reported HIV-infected individuals in Dehong Prefecture,Yunnan Province in 2015.Methods Newly reported HIV-positive patients who had viral load ≥ 1 000 copies/mL from January to November in 2015 were tested for HIV-PDR by reverse transcriptionpolymerase chain reaction (RT-PCR) and HIV pol gene sequencing.HIV-PDR was determined according to the Surveillance Drug Resistance Mutations (SDRM) list of Stanford University,which was recommended by World Health Organization (WHO) in 2009.Results A total of 322 newly reported HIV-infected cases whose pol gene was successfully amplified were included in the final analysis.Of them,211 (65.5％) were male,and 229 (71.1％) were sexually transmitted.A total of 152 (47.2％) were Chinese.A total of 29 HIV subtypes were found,including type B (12.1％),type C (28.0％),type CRF01_AE (24.5％),type CRF07_BC (5.9％),type CRF08_BC (5.6％),type 62_BC (7.5％),type BC-new breakpoint (3.4％) and other subtypes (13％).Six patients (1.9％) were defined as primary resistance to HIV according to the WHO standard.Conclusions The prevalence of HIV-PDR is 1.9％ among newly reported HIV-infected individuals,which is relatively low in the studied area.But HIV-PDR surveillance should be strengthened in this area with the scaling up of antiretroviral therapy.

Objective To understand the epidemiological characteristics of newly reported HIV infections in Chinese and Burmese residents during 2012-2016 in Dehong Dai and Jingpo Autonomous Prefecture of Yunnan province (Dehong) and to provide evidence for the development of related programs on prevention and control.Methods All the HIV infections who were newly reported during 2012-2016 in Dehong,were recruited as the study subjects,with epidemiological characteristics of the cases analyzed by using the software SPSS 22.0.Results A total of 5 692 HIV infections were newly reported between 2012 and 2016 (including 5 592 in this study),in which the Chinese patients accounted for 43.3％ (2 419) and the rest 56.7％ (3 173) were Burmese.Differences in age,gender and other social characteristics of these newly reported HIV infections were statistically significant between the Chinese and the Burmese (all p-values ＜0.05).Most cases were males and between the age of 20-49 years old.Other characteristics of the patients would include:having had primary school education,married,being farmers,and with CD4+ T cells counts ≥350 cells/μl.HIV infection was mainly transmitted through sexual contact among the Chinese patients but through injecting drug use among the Burmese patients.Conclusions Epidemiological characteristics of the newly reported HIV infections were different between the Chinese and the Burmese,between 2012 and 2016 in Dehong.Targeted prevention and control programs should be taken.

Objective To assess the role of 68Ga-N,N′-bis(2-hydroxy-5-(carboxyethyl)benzyl) ethylenediamine-N,N′-diacetic acid(HBED-CC)-(Ahx)Lys-CO-Glu(PSMA-11) PET/CT on the detection of metastatic lesions from castration-resistant prostate cancer (CRPC).Methods Sixteen patients with CRPC who underwent 68Ga-PSMA-11 PET/CT between January 2015 and November 2015 were recruited in this study.Mean age of patients was (72±9) years.The PSA levels were 4-12 356 μg/L, Gleason score was 7-10.PET/CT was performed at 1 h postinjection of 68Ga-PSMA-11.Patient-based analysis and lesion-based analysis were performed.ROI analysis was used to calculate the tumor uptake (SUVmax).Final diagnosis was based on histopathology and results of other imaging examinations(99Tcm-MDP imaging, MRI).χ2 test was used to compare the diagnostic efficiencies of PET and CT.Results No adverse effects were observed in patients.68Ga-PSMA-11 PET/CT showed moderate physiologic uptake in salivary glands and proximal small intestine, with predominant tracer clearance by the kidneys.All patients were positive on 68Ga-PSMA-11 PET/CT.Bone metastasis was found in 16 patients, liver metastasis in 2 patients (5 lesions), and lymph node metastasis in 4 patients (26 lesions).The SUVmax of liver, lymph node and bone metastases were 15.06±2.77, 7.54±5.20, 19.01±16.96, respectively.The diagnostic sensitivity, specificity and accuracy on bone metastasis with 68Ga-PSMA-11 PET and CT were 96.30%(52/54) vs 61.11%(33/54), 3/3 vs 1/3, 96.49%(55/57) vs 59.65%(34/57).The sensitivities and accuracies of the two modalities were significantly different(χ2=19.943, 22.593, both P<0.01).Conclusions 68Ga-PSMA-11 PET/CT could precisely detect both primary and metastatic lesions of CRPC, suggesting that it is of great value for the clinical management and treatment.

Objective To investigate the value of integrin αvβ3 targeted microSPECT/CT imaging with 99 Tcm-3P4-RGD2 as a radiotracer in tumor anti-angiogenesis therapy .Methods Animal models bearing glioma and prostate cancer xenografts were established by subcutaneously injecting tumor cells U87MG and PC-3 in nude mice.Anti-angiogensis therapy with Avastin was administered via intraperitoneal injection when the tumor diameter reached 6 to 7 mm while saline was served as control group . MicroSPECT/CT imaging was performed with 99 Tcm-3P4-RGD2 as radiotracer one day before and 3, 5, 10, 15 days after Avastin administration .Tumor volume and tumor uptake of 99 Tcm-3P4-RGD2 , expressed as percentage of injected dose (%ID) or %ID per gram (%ID/g) were measured and calculated based on microSPECT/CT.Mice basic condition was monitored and tumor xenograft was harvested in one tumor bearing nude mouse after its sacrifice at each imaging time point .Results Tumor volume of U87MG glioma in the administration group was significantly smaller than that of non-administration control group at 10 d after Avastin adminstration ( t=5.81, P<0.05), while no significance was observed between the administration group and its control group of PC-3 tumor (P >0.05).The uptake of 99Tcm-3P4-RGD2 (%ID/g) in U87MG group was higher than that in PC-3 group before Avastin administration ( t=10.48, P<0.05), and it decreased to a value less than control ( t =3.26, P <0.05) at 3 d after Avastin administration and continually reduced at longer time after administration .PC-3 tumor had less uptake of 99 Tcm-3P4-RGD2 in both Avastin administration group and its control group .The pathologic results revealed on that the decrease of tumor integrin β3 expression in U87MG treatment group was mainly on the endothelial cells of the neovessel .Linear relationship was verified between tumor uptake (%ID/g ) and integrin β3 expression (y=0.499 1x-0.243 8, R2 =0.811 7).Conclusions Complete inhibition of integrin is demonstrated early after Avastin administration .99 Tcm-3P4-RGD2 microSPECT/CT imaging, assessing the expression level of integrin αvβ3 level by quantification of tumor uptake of 99 Tcm-3P4-RGD2 , is probably an important method to reflect the early therapeutic effect of tumor anti -angiogensis .

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.

Objective To assess the role of 68Ga-N,N'-bis (2-hydroxy-5-(carboxyethyl) benzyl) ethylenediamine-N,N'-diacetic acid(HBED-CC)-(Ahx) Lys-CO-Glu(PSMA-11) PET/CT on the detection of metastatic lesions from castration-resistant prostate cancer (CRPC).Methods Sixteen patients with CRPC who underwent 68Ga-PSMA-11 PET/CT between January 2015 and November 2015 were recruited in this study.Mean age of patients was (72±9) years.The PSA levels were 4-12 356 μg/L,Gleason score was 7-10.PET/CT was performed at 1 h postinjection of 68Ga-PSMA-11.Patient-based analysis and lesionbased analysis were performed.ROI analysis was used to calculate the tumor uptake (SUVmax).Final diagnosis was based on histopathology and results of other imaging examinations(99Tcm-MDP imaging,MRI).x2 test was used to compare the diagnostic efficiencies of PET and CT.Results No adverse effects were observed in patients.68Ga-PSMA-11 PET/CT showed moderate physiologic uptake in salivary glands and proximal small intestine,with predominant tracer clearance by the kidneys.All patients were positive on 68Ga-PSMA-11 PET/CT.Bone metastasis was found in 16 patients,liver metastasis in 2 patients (5 lesions),and lymph node metastasis in 4 patients (26 lesions).The SUVmax of liver,lymph node and bone metastases were 15.06±2.77,7.54±5.20,19.01± 16.96,respectively.The diagnostic sensitivity,specificity and accuracy on bone metastasis with 68Ga-PSMA-11 PET and CT were 96.30％(52/54) vs 61.11％(33/54),3/3 vs 1/3,96.49％ (55/57) vs 59.65％ (34/57).The sensitivities and accuracies of the two modalities were significantly different(x2=19.943,22.593,both P＜0.01).Conclusions 68Ga-PSMA-11 PET/CT could precisely detect both primary and metastatic lesions of CRPC,suggesting that it is of great value for the clinical management and treatment.