Objective To assess the memory function of hyperthyroid patients at different disease durations and investigate the value of cerebral blood flow (CBF) imaging in the detection of memory dysfunction in related regions.Methods Thirty-seven hyperthyroid patients (10 males,27 females; mean age (39.27± 10.58) years) and 28 healthy volunteers (8 males,20 females; mean age (35.80±9.41) years) were enrolled into this prospective study.The patients were divided into two subgroups: short duration group (duration ≤ 6 months; n =15),long duration group (duration ＞6 months ; n =22).Wechsler memory scale was used for memory assessment,and cancellation test was used for attention assessment.Self-rating depressions scale (SDS) and self-rating anxiety scale (SAS) were used for mood disorder assessment.99Tcm-ECD SPECT CBF imaging was performed at rest for all patients and controls on the same day.SPM 2.0 was used to investigate the differences of rCBF between the two groups.Two independent samples t test was used for the comparisons of memory and attention scores between patients and controls,also between patients with short and long disease durations.Multiple stepwise regression was used for factor analysis of memory state.Results Scale total score (92.27±17.50 vs 101.75±11.70; t=-2.476)and memory quotient (91.32±17.76 vs 100.29±9.43 ; t =-2.421) were significant different between patients and controls (both P＜0.05).The scale total score and memory quotient in patients with long disease duration were significant lower than those of controls(88.77±16.69 vs 101.75±11.70,t=-3.231; 86.18±16.73 vs 100.29±9.43,t=3.770,both P＜0.05).The memory quotient was significant lower in patients with long disease duration than those with short disease duration(86.10± 17.13 vs 98.87± 17.00; t =2.212,P＜0.05).There was no significant difference in memory quotient and scale total score between short duration group and controls (t=-0.754,0.910,both P＞0.05).CBF was reduced in the limbic system of hyperthyroid patients and the involved area was larger in patients with long disease duration.Age,attention score,serum FT4 level and reduced CBF in left pulvina nuclei,left lateral geniculate body and right amygdale were the statistically significant factors for impaired memory function in hyperthyroid patients (b=-0.393-0.685,all P＜0.05).Conclusions Memory impairment could be significant in hyperthyroid patients with long disease duration.CBF imaging could reflect the degree of dysfunction at specific brain regions responsible for memory impairment in these patients.

Objective To establish a mouse model of lung adenocarcinoma brain metastasis with human luc+-PC?9 cells stably expressing luciferase and to compare the evaluation values of bioluminescence imaging and18 F?FDG ( 18 F?flu?orodeoxyglucose) SPECT/CT in these models. Methods Suspension of luc+?PC?9 cells was injected into the left ventri?cle of BALB/c nude mice to establish a mouse model of brain metastasis from lung cancer. Bioluminescence imaging and18 F?FDG SPECT/CT were used to evaluate the metastasis of tumors as compared with HE?staining pathology as a golden standard. Results The success rate of brain metastases was 85% through injecting luc+?PC?9 cells into the left ventricle. The number of tumor cells was positively related to the intensity of light, with a linear correlation (R2 =0. 96). Fluores?cence was observed in the brain, spine and femur by bioluminescence imaging, and the metastases were confirmed by H&E pathological examination. 18 F?FDG SPECT/CT observed abnormal density collective foci in the spine or femur but not in the brain. Conclusions Injection of tumor cell suspension into the mouse left ventricle is a good method to establish a brain metastasis of lung cancer. Bioluminescence has a higher sensitivity and specificity in detecting brain metastasis and bone metastasis, with advantages of real?time, dynamical and non?invasive detection of tumor metastasis growth. 18 F?FDG SPECT/CT does not have superiority in detection of brain metastases but is suitable for detecting bone metastasis.

Objective:To explore the imaging features of 18F-fluorodeoxyglucose (FDG) PET/CT (high-resolution CT, HRCT) imaging in focal organizing pneumonia (FOP). Methods:Patients with solid nodular FOP ( n=45; 33 males, 12 females, age (58±9) years) and early peripheral non-mucinous solid lung adenocarcinoma ( n=47; 21 males, 26 females, age (63±10) years) confirmed by postsurgical pathology between May 2012 and December 2018 in Zhongshan Hospital, Fudan University were retrospectively analyzed. All patients underwent 18F-FDG PET/CT (HRCT) imaging followed by surgery within 3 weeks. The imaging findings and characteristics of the lesions were recorded. Differences of the maximum standardized uptake value (SUV max) and maximum diameter between FOP and adenocarcinoma were analyzed by Mann-Whitney U test or t′ test. Spearman correlation or Pearson correlation analysis was performed to analyze the relation between SUV max and maximum diameter. Binary logistic regression analysis was performed to identify the predictive factors for FOP. Finally, the receiver operating characteristic (ROC) curve analysis was used for evaluation of diagnostic efficiency. Results:The SUV max of FOP was lower than that of lung adenocarcinoma (3.1(1.7, 4.9) vs 6.5(3.8, 9.3); z=-4.598, P<0.01), and the maximum diameter of FOP was smaller than that of lung adenocarcinoma ((18.0±6.3) mm vs (21.8±4.3) mm; t′=-3.424, P<0.01). The SUV max was positively correlated with the maximum diameter in FOP group ( r s=0.509, P<0.01), while the SUV max of lung adenocarcinoma was not correlated with the lesion size ( r=0.076, P>0.05). HRCT of the PET/CT system showed the fusiform shape were more common in FOP ( χ2=9.549, P<0.05). Multivariate regression analysis identified that SUV max≤7.1, diameter≤18.3 mm, and fusiform shape were independent factors to predict FOP, with odds ratio ( OR) of 10.585, 4.674, 9.073, respectively (all P<0.05). ROC curve analysis showed that the area under the curve (AUC) of SUV max≤7.1 combined with diameter≤18.3 mm and fusiform nodule was 0.860, and the sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 97.8%(44/45), 70.2%(33/47), 75.9%(44/58), 97.1%(33/34), and 83.7%(77/92), respectively. Conclusion:SUV max≤ 7.1 combined with maximum diameter≤ 18.3 mm and fusiform shape may predict solid nodular FOP.

OBJECTIVETo analysis the pathological demography in Chinese patients undergoing renal biopsy from our nephrology center.

METHODSBetween January 1979 and October 2000 in Jinling Hospital, Nanjing, China, 10,002 attempts of percutaneous renal were performed in patients with renal disease from 33 provinces of China. The pathological classifications were made according to the WHO criteria of 1982 for renal pathology or the modified WHO criteria of 1995 by a panel of pathologists and nephrologists during routine clinical-pathological rounds. The pathological demography between those specimens collected from 1979 - 1989 and those from 1990 - 1999 was compared.

RESULTSThe mean age of the 10,002 subjects undergoing renal biopsy was 31.4 +/- 13.0 years (ranging from 1 to 78 years), with a male to female ratio of 1.3:1; for the 592 renal transplant recipients, the mean age was 37.5 +/- 9.1 years (ranging from 16 to 66 years), with a male to female ratio of 2.36:1. Primary glomerular diseases (PGD) accounted for 71% of the total patients undergoing renal biopsies, secondary glomerular nephritis (SGN) 23%, tubular-interstitial diseases 3.2%, unclassified renal diseases 1.3%, hereditary and congenital renal diseases 1.0%, end stage renal diseases 0.96%, and recently realized or rare renal diseases 0.15%. IgA nephropathy (IgAN) was the most frequent pathological pattern (40%) of PGD, followed by mesangial proliferative lesion (MsPL) (30%), membranous nephropathy (MN) (10%), and focal segmental glomerulosclerosis (FSGS) (6%). Lupus nephritis (LN) was the most pathology common seen (74%) in SGN. During the 22 years of the study period, there was a steady increase in patients with SGN discovered during pathological evaluation of renal disorders. A rise in prevalence was found in IgA nephropathy, MN (both P < 0.001), crescentic glomerulonephritis (P < 0.0001), anti-GBM disease, and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura related renal damages (both P < 0.001). There was a decrease in endocapillary proliferative glomerulonephritis (P < 0.001) and IgM nephropathy (IgMN) (P < 0.01) from 1990 - 1999 as compared to 1979 - 1989. Infrequent renal pathological entities were also diagnosed in this group, including Niemann Pick disease, Fabry's disease, POEMS syndrome, and lipoprotein glomerulonephropathy.

CONCLUSIONSThis is the largest series of renal biopsy data in China, and therefore may reflect the demographic picture of renal diseases in this country. Changes in prevalence of renal pathological entities were reflected in this group of patients over the last 22 years. In primary glomerular diseases, IgA nephropathy is still the most frequently observed pathological pattern. In SGN, LN appeared the most often. Increased prevalence was found in anti-GBM nephritis and HUS/TTP.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Japan ; epidemiology ; Kidney Diseases ; epidemiology ; pathology ; Male ; Middle Aged ; Prevalence

OBJECTIVE To study the effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m on cutaneous squamous cell carcinoma. METHODS Using human cutaneous squamous cell carcinoma A431 and Colo-16 cells as research subjects， CCK-8 assay was used to detect the effects of different concentrations of 3m （5， 10， 20， 40， 80 μmol/L） on the proliferation of A431 and Colo-16 cells after 24， 48 and 72 hours； the median inhibitory concentration （IC50） was calculated at 48 h of treatment. A431 and Colo-16 cells were divided into control group， 3m low-concentration and high- concentration groups （15， 30 μmol/L）. After treated with relevant drugs or culture medium for 48 h， the morphological changes of cells in each group were observed by inverted microscope. Clone formation rate， migration rate and number of cell invasions， cell cycle distribution and apoptosis rate were detected. The phosphorylation， or expression of Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway related proteins [JAK2， STAT3， B-cell lymphocyte-2 （Bcl-2）， Bcl-2- associated X protein （Bax）]， and their mRNA expression in cells were detected. RESULTS 3m could significantly inhibit the proliferation of A431 and Colo-16 cells after treated for 24， 48， 72 h （P＜0.01）， and IC50 of them were 20.36， 23.72 μmol/L， respectively. After 48 hours of treatment， compared with control group， A431 and Colo-16 cells arranged sparsely and loosely connected in 3m low-concentration and high-concentration groups. The clone formation rate， migration rate， number of cell invasions， mRNA expressions of JAK2， STAT3 and Bcl-2， the phosphorylation of JAK2 and STAT3， protein expression of Bcl-2 were significantly decreased/weakened （P＜0.01）. Proportion of cell cycle in G2 phase， apoptosis rate， protein and mRNA expression of Bax were increased significantly （P＜0.01）； and all the above effects were in dose-dependent manner. CONCLUSIONS 3m can inhibit the proliferation， clone formation， migration and invasion abilities of cutaneous squamous cell carcinoma A431 and Colo-16 cells in a dose-dependent manner， the mechanism of which may be associated with inhibiting the activity of JAK2/STAT3 signaling pathway， and inducing cell apoptosis.

OBJECTIVE：To stud y the effects of sinapine thiocyanate （ST） on the proliferation ，epithelial mesenchymal transformation（EMT）and metastasis of human cutaneous squamous cell carcinoma SCL- 1 cells，and to investigate its possible mechanism. METHODS ：Human cutaneous squamous cell carcinoma SCL- 1 cells were divided into blank control group （0.1％ DMSO） and ST different concentration groups （5，10，20 μmol/L）. CCK- 8 assay，5-ethynyl-2′-deoxyuridine（EDU）test， scratch test and Transwell chamber invasion test were adopted to test the proliferation ，migration and invasion ability. The expression of N-cadherin and E-cadherin were detected by Western blot and immunofluorescence assay . Other SCL- 1 cells were collected and divided into blank control group （0.1％ DMSO），ST group （20 μmol/L），ST+NSC228155 group [ 20 μmol/L ST+100 μmol/L NSC228155（EGFR agonist ）] and ST+SC 79 group [ 20 μmol/L ST+20 μmol/L SC79（PI3K/Akt agonist ）]. The proliferation ，migration and invasion ability of SCL- 1 cells in each group were detected by CCK- 8 assay，scratch test and Transwell chamber invasion assay. The expression of epidermal growth factor receptor （EGFR），phosphatidylinositol 3 kinase（PI3K），phosphorylated phosphatidylinositol 3 kinase（p-PI3k），protein kinase B （Akt）and phosphorylated protein Akt （p-Akt）protein of cells in blank control group and ST different concentration groups（5，10，20 μmol/L）were determined by Western blot assay so as to validate the relationship between ST effect and EGFR/ PI3K/Akt signaling pathway. SCL- 1 cells and human normal skin fibroblasts cell WS 1 were divided into blank control group （0.1％ DMSO），ST group （20 μmol//L），ZD1839 group（positive control ，20 μmol//L，EGFR inhibitor ）and LY 294002 group（positive control，20 μmol//L，PI3K/Akt inhibitor ）. CCK- 8 assay was used to detect the cell proliferation in order to evaluate the cells cytotoxicity of ST. RESULTS ：Compared with blank control group ，the proliferation ，migration and invasion ability of SCL- 1 cells were significantly decreased in 5，10，20 μmol/L ST groups（P＜0.05）. Western blot and immunofluorescence assay showed that the expression of N-cadherin in SCL- 1 cells were decreased significantly in 5，10，20 μmol/L ST groups（P＜0.05），while the protein expression of E-cadherin was increased significantly （P＜0.05）；the protein expressions of EGFR ，p-PI3K and p-Akt were significantly decreased （P＜0.05）. Compared with ST group ，the proliferation ，migration and invasion ability of SCL- 1 cells were increased significantly in ST + NSC 228155 group and ST + SC 79 group （P＜0.05）. Compared with blank control group ，the proliferation ability of WS 1 cells had no significant change in ST group ，while the proliferation ability of SCL- 1 cells was decreased significantly （P＜0.05）；the proliferation ability of the two kinds of cells were decreased significantly in ZD 1839 group and LY 294002 group（P＜0.05）. Compared with ST group ，the proliferation ability of WS 1 cells was decreased significantly in ZD1839 group and LY 294002 group（P＜0.05），but there was no significant difference in the proliferation ability of SCL- 1 cells （P＞0.05）. CONCLUSIONS ：ST may inhibit the proliferation ，EMT and metastasis of SCL- 1 cells through inhibiting the activation of EGFR/PI 3K/Akt signaling pathway ，and its side effects are few.

ObjectiveTo investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1， 2019 to March 31， 2021， and all patients received camrelizumab monoclonal antibody treatment， among whom 84.8% also received targeted therapy. According to the age of the patients， they were divided into elderly group （≥65 years） and non-elderly group （<65 years）. The two groups were assessed in terms of overall survival （OS）， progression-free survival （PFS）， objective response rate （ORR）， disease control rate （DCR）， and immune-related adverse events （irAE）. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the independent samples t-test was used for comparison of normally distributed continuous data， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used for survival analysis， and the log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months. ResultsA total of 99 HCC patients were enrolled， with 27 in the elderly group and 72 in the non-elderly group. The elderly group had an OS rate of 67.8%， an ORR of 44.4%， and a DCR of 74.1% at 12 months and a median PFS of 6.4 （95% confidence interval ［CI］： 3.0‍ ‍—‍ ‍12.4） months， with no significant differences compared with the non-elderly group （all P>0.05）. The median OS was unavailable for the elderly group， while the non-elderly group had an OS of 18.9 （95%CI： 13.0‍ ‍—‍ ‍24.8） months； there was no significant difference between the two groups （P=0.485）. The univariate and multivariate Cox regression analyses showed that major vascular invasion （MVI） was an independent risk factor for PFS （hazard ratio ［HR］=2.603， 95%CI： 1.136‍ ‍—‍ ‍5.964， P=0.024） and DCR （HR=3.963， 95%CI： 1.671‍ ‍—‍ ‍9.397， P=0.002） at 6 months， while age， sex， etiology of HBV infection， presence of extrahepatic metastasis， Child-Pugh class B， and alpha-fetoprotein>400 ng/mL were not associated with PFS or DCR at 6 months. For the elderly group， the incidence rates of any irAE and grade 3/4 irAE were 51.9% and 25.9%， respectively， with no significant differences compared with the non-elderly group （P>0.05）， and skin disease was the most common irAE in both groups （39.4%）. ConclusionCamrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged ≥65 years and those aged <65 years. MVI is associated with suboptimal response to immunotherapy and poor prognosis.