Prognostic value of pretreatment 18F-FDG PET/CT in patients with metastatic melanoma treated with anti-PD1 immunotherapy / 中华核医学与分子影像杂志

Objective:To assess the prognostic value of pretreatment 18F-FDG PET/CT metabolic parameters in patients with metastatic malignant melanoma treated with anti-programmed cell death-1 (PD1) immunotherapy. Methods:A retrospective analysis of 29 patients (15 males, 14 females, age (59.1±13.0) years) with pathologically diagnosed metastatic malignant melanoma in Nanjing Drum Tower Hospital between June 2017 and October 2020 was conducted. Anti-PD1 immunotherapy were performed in all patients after 18F-FDG PET/CT imaging. 18F-FDG PET/CT parameters including SUV max, bone marrow-to-liver SUV max ratio (BLR), spleen-to-liver SUV max ratio (SLR) were obtained. Total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) of primary lesions were measured automatically using the thresholds of 40%SUV max. The median value of each PET parameter was regarded as the threshold value and was used to divide patients into 2 groups (≥ and < the median value, respectively). Kaplan-Meier survival curve and Cox proportional risk model were used to analyze the overall survival (OS) differences between groups. Results:The median follow-up time was 15.0 months and 13 patients died. The median OS was 26.0(95% CI: 20.4-31.6) months. The median SUV max, TMTV, TLG, BLR and SLR were 6.2, 8.2 cm 3, 38.6 g, 0.82 and 0.84 respectively. Kaplan-Meier method and log-rank test showed that differences of OS between SUV max≥6.2 and <6.2 groups, TLG≥38.6 g and <38.6 g groups, BLR≥0.82 and <0.82 groups, SLR≥0.84 and <0.84 groups were not significant ( χ2 values: 0.01-0.35, P values: 0.061-0.929), while patients with TMTV≥8.2 cm 3 suffered from poorer OS compared with those with TMTV<8.2 cm 3 ( χ2=5.90, P=0.015). Cox multivariate analysis showed that TMTV (hazard risk ( HR)=6.347, 95% CI: 1.039-38.789) was a significant predictor of OS ( P=0.045). Conclusion:18F-FDG PET/CT parameter TMTV is the independent predictive factor of OS in metastatic melanoma treated with anti-PD1 immunotherapy.

Surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multi-disciplinary diagnosis and treatment / 中华消化外科杂志

Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.

Esketamine induced apoptosis in human breast cancer cell line MDA-MB-468 and its mechanism / 中华内分泌外科杂志

Objective:To explore whether esketamine (ESK) can inhibit the proliferation and induce apoptosis of breast cancer cells, and explore the mechanism.Methods:CCK-8 assay was used to detect the inhibitory effect of ESK on the proliferation of breast cancer cells. Annexin V/PI staining was used to detect the morphological changes of cells; Apoptosis and reactive oxygen species were detected by flow cytometry. Western blot was used to detect apoptosis and pathway expression.Results:CCK-8 experiment results proved that ESK could inhibit the proliferation of breast cancer cells in a time-dependent manner. The survival rate of MDA-MB-468 cells treated with ESK at 20 μM was (35.47±2.61) %, which was statistically different from that treated with vinorelbine at the same concentration ( P<0.05). The IC50 value of ESK on MDA-MB-468 cells was (14.54±2.12) μM. After treatment with ESK, the mitochondrial membrane potential was significantly reduced. In the protein level, the expression of Cytochrome C, Bax and Caspase-3 was up-regulated, and the expression of Bcl-2 was down regulated, which induced the mitochondrial dependent apoptosis of MDA-MB-468 cells. ESK could up regulate the level of reactive oxygen species in MDA-MB-468 cells and regulate the expression of PI3K/AKT signaling pathway. Conclusions:ESK can inhibit the proliferation and migration of breast cancer cells and induce them to play a mitochondrial dependent apoptosis. Its mechanism is achieved by up regulating the level of ROS in breast cancer cells, thereby regulating the PI3K/AKT signaling pathway, which provides a theoretical basis for the development and utilization of Aln.

A cohort study on the correlation between serum uric acid trajectory and the progression of renal function in patients with Type 2 diabetes mellitus / 中南大学学报(医学版)

OBJECTIVES@#Diabetic kidney disease is one of the most serious complications of diabetes mellitus (DM), and it is a main cause for chronic kidney disease and end-stage kidney disease (ESRD). It is important to find out the factors that cause the progression of renal function. The study aims to explore the relationship between serum uric acid (SUA) trajectory and the progression of renal function in patients with Type 2 diabetes mellitus (T2DM).@*METHODS@#A total of 846 patients with T2DM, who were admitted to the Department of Nephrology and Endocrinology, the Third Xiangya Hospital of Central South University, from January 2009 to December 2021 and met the criteria of baseline estimated glomerular filtration rate (eGFR)≥60 mL/(min·1.73 m2), were selected as the research subjects. The SUA data of multiple measurements were collected and identified as different SUA trajectories by group-based trajectory modeling (GBTM). According to the SUA trajectories, the patients were divided into a low trajectory group (105 cases), a middle trajectory group (396 cases), a middle high trajectory group (278 cases), and a high trajectory group (67 cases). Cox regression analysis was used to examine the effect of SUA trajectory on the progression of renal function in patients with T2DM. Subgroup analysis was performed by sex, age, course of disease, body mass index (BMI) and hemoglobin A1c (HbA1c).@*RESULTS@#The median follow-up was 4.8 years. At the end of follow-up, 158 patients had different degrees of decline in renal function. After adjusting for multiple confounding factors by Cox regression analysis, the risks of eGFR<60 mL/(min·1.73 m2), eGFR reduction rate≥50%, serum creatinine (Scr) doubling and composite endpoint (eGFR reduction rate≥50%, Scr doubling or ESRD) in the high trajectory group were significantly higher than those in the low trajectory group, with HR of 3.84 (95% CI 1.83 to 8.05), 6.90 (95% CI 2.27 to 20.96), 6.29 (95% CI 2.03 to 19.52), and 8.04 (95% CI 2.68 to 24.18), respectively. There was no significant difference in the risk of ESRD among the above 4 groups (all P>0.05). Subgroup analysis showed that: compared with the low trajectory group, the risks of eGFR<60 mL/(min·1.73 m2) in patients with high trajectory in the subgroup of male, female, age<65 years, course of disease<10 years, BMI≥24 kg/m2 and HbA1c≥7% were increased (all P<0.05). The SUA trajectory had no interaction with sex, age, course of disease, BMI and HbA1c (all interactive P>0.05).@*CONCLUSIONS@#The high SUA trajectory increases the risk for progression of renal function in patients with T2DM. Long-term longitudinal changes of SUA should be paid attention to.

Prognostic value of pretreatment 18F-FDG PET/CT in patients with primary malignant melanoma / 中华核医学与分子影像杂志

Objective:To assess the prognostic value of pretreatment 18F-FDG PET/CT metabolic parameters in patients with primary melanoma. Methods:A retrospective analysis comprised of 35 patients (21 males, 14 females, age: 35-85 years; from January 2014 to August 2019; Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School) who were newly-diagnosed primary melanoma with preoperative 18F-FDG PET/CT was conducted. 18F-FDG PET/CT metabolic parameters including SUV max, SUV mean, peak of SUV (SUV peak) were obtained. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary focus were measured automatically using the threshold of 40%SUV max. The optimal thresholds of PET parameters were obtained by using ROC curve analysis. The associations between melanoma-specific survival (MSS), progression-free survival (PFS) and PET/CT metabolic parameters were assessed using Kaplan-Meier method and Cox proportional hazards model. Results:The median follow-up was 15.4 months, and 20 patients showed disease progression and 7 died. The cut-off values for SUV max, SUV mean, SUV peak, MTV and TLG were 3.95, 2.45, 2.65, 3.60 cm 3 and 14.85 g, respectively (AUCs: 0.742, 0.790, 0.728, 0.655, 0.693; P values: 0.016, 0.004, 0.022, 0.121, 0.053). Kaplan-Meier method and log-rank test showed that SUV max, SUV mean, SUV peak, MTV and TLG were predictors of PFS ( χ2 values: 4.06-8.35, all P<0.05). Multivariate analysis showed that MTV (hazard ratio ( HR)=3.09, 95% CI: 1.08-8.86, P=0.036) and TLG ( HR=3.36, 95% CI: 1.11-10.14, P=0.031) were significant predictors of PFS but not for MSS ( HR=5.14, P=0.080). Conclusions:SUV max, SUV mean and SUV peak of primary focus may help for predicting PFS of patients with primary melanoma. MTV and TLG of primary focus may be the best to predict PFS of primary melanoma.

Knockout of farnesoid X receptor gene aggravates cisplatin-induced kidney injury / 中南大学学报(医学版)

OBJECTIVES@#Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand activated transcription factors and belongs to bile acid receptor. Studies have shown that the expression of FXR in renal tissue can reduce renal injury via regulation of glucose and lipid metabolism, inhibition of inflammatory response, reduction of oxidative stress and renal fibrosis. However, it is unclear whether FXR is involved in autophagy in renal diseases. This study aims to investigate the role of FXR in cisplatin-induced acute renal injury and whether its mechanism is related to autophagy regulation.@*METHODS@#Twelve male WT or FXR-KO mice at 12 weeks were randomly divided into a WT group, a WT+cisplatin group, a FXR-KO group, and a FXR-KO+cisplatin group, with 6 mice in each group. The WT+cisplatin group and the FXR-KO+cisplatin group were intraperitoneally injected with cisplatin (20 mg/kg), and the WT group and the FXR-KO group were intraperitoneally injected with equal volume of cisplatin solvent. Seventy-two hours later, the mice were killed and blood and renal tissue samples were collected. The levels of SCr and BUN were detected by immunoturbidimetry. After the staining, the pathological changes of renal tissue were observed under optical microscope. The protein levels of LC3 and p62 were detected by Western blotting and immunohistochemistry. The clearance of damaged mitochondria and the accumulation of lysosomal substrate were observed under electron microscope. The apoptosis of renal tubular epithelial cells was detected by TUNEL.@*RESULTS@#Compared with the WT group or the FXR-KO group, both SCr and BUN levels in the WT+cisplatin group or the FXR-KO+cisplatin group were significantly increased (P<0.01 or P<0.001), and SCr and BUN levels in the FXR-KO+cisplatin group were significantly higher than those in the WT+cisplatin group (both P<0.05). Under the light microscope, there were no obvious pathological changes in the renal tissue of mice in the WT group and the FXR-KO group. Both the WT+cisplatin group and the FXR-KO+cisplatin group had vacuolar or granular degeneration of renal tubular epithelial cells, flat cells, lumen expansion, brush edge falling off, and even exposed basement membrane and tubular formation. The scores of renal tubular injury in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the score in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05). Under the transmission electron microscope, the mitochondria of mouse tubular epithelial cell in the WT+cisplatin group and the FXR-KO+cisplatin group was swollen, round, vacuolated, cristae broken or disappeared; the lysosome was uneven and high-density clumps, and the change was more obvious in the FXR-KO+cisplatin group. Western blotting showed that the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased in the WT+cisplatin group compared with the WT group and the FXR-KO+cisplatin group compared with FXR-KO group (P<0.05 or P<0.01); compared with the FXR-KO group, the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased significantly in the FXR-KO+cisplatin group (both P<0.05). Immunohistochemistry results showed that the expression of total LC3 and p62 in renal cortex of the WT+cisplatin group and the FXR-KO+cisplatin group was increased significantly, especially in the FXR-KO+cisplatin group. TUNEL results showed that the mice in the WT group and the FXR-KO group had negative staining or only a few apoptotic tubular epithelial cells, and the number of apoptotic cells in the WT+cisplatin group and the FXR-KO+cisplatin group were increased. The apoptosis rates of renal tubular epithelial cells in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the apoptosis rate in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05).@*CONCLUSIONS@#Knockout of FXR gene aggravates cisplatin induced acute renal injury, and its mechanism may be related to inhibiting autophagy and promoting apoptosis.

Comparison of 18F-FDG PET/CT and digestive endoscopy findings in gastric mucosa-associated lymphoid tissue lymphoma / 中华核医学与分子影像杂志

Objective:To investigate 18F-fluorodeoxyglucose (FDG) PET/CT imaging manifestations and digestive endoscopy of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and evaluate whether maximum standardized uptake value (SUV max) can reflect the tumor proliferation activity and diagnose the diffuse large B cell transformation. Methods:18F-FDG PET/CT of 36 untreated histologically confirmed gastric MALT lymphoma patients (19 males, 17 females, age (46.4±18.1) years) between December 2012 and January 2019 in Nanjing Drum Tower Hospital were reviewed retrospectively. A positive or negative PET was defined based on visual analysis. 18F-FDG uptake above surrounding tissues in the regions of interest defined by the nuclear physician was considered positive, while negative was definited if the 18F-FDG uptake below surrounding tissues. Types of uptake included focal uptake and diffuse uptake. The characteristic findings of 18F-FDG PET/CT and digestive endoscopy (3 types: chronic gastritis-like type, depressed type and protruding type) in the consecutive patients were evaluated. The region of interest was drawn and the maximum standardized uptake value (SUV max) was measured. One-way analysis of variance and the least siginficant difference t test were used to compare the SUV max of 3 types of lesions and Mann-Whitney U test was used for comparison of SUV max between lesions with/without diffuse large B cell transformation. The correlation between SUV max and Ki-67 was assessed by Spearman rank correlation analysis. Receiver operating characteristic (ROC) curve analysis was performed to calculate the optimal cut-off value for the diagnosis of diffuse large B cell transformation. Results:Positive 18F-FDG PET/CT were found in 15 patients and the diagnostic accuracy was 41.7%(15/36). 18F-FDG uptake results were positive for all protruding tumors (5/5) mainly with focal uptake (4/5), but only 4/16 for chronic gastritis-like type tumors and 6/15 for depressed type tumors. SUV max of protruding type tumors (10.7±6.4) was significantly higher than chronic gastritis-like type tumors (2.1±0.8) and depressed type tumors (2.7±1.4; F=13.010, all P<0.05). SUV max (2.7(1.8, 5.0)) was associated with Ki-67 (10%(15%, 40%); rs=0.345, P=0.039). SUV max of tumors with diffuse large B cell transformation in 36 patients was significantly higher than that with no transformation (9.4(3.1, 14.8) vs 2.3(1.7, 3.9); z=-3.044, P=0.002), and the cut-off value of SUV max was 6.5 (area under the curve: 0.788, P=0.011). Conclusions:18F-FDG PET may be a useful method for evaluating protruding type gastric MALT lymphoma but not appropriate for chronic gastritis-like type or depressed type tumors. SUV max may be a useful biomarker for tumor proliferation activity and can be used for diffuse large B cell transformation diagnosis in gastric MALT lymphoma patients.

Role of interim 18F-FDG PET/CT combined with Bcl-2/MYC protein dual expression status in risk stratification for patients with primary gastrointestinal diffuse large B-cell lymphoma / 中华核医学与分子影像杂志

Objective:To explore the potential value of interim 18F-fluorodeoxyglucose (FDG) PET/CT combined with B-cell lymphoma-2 (Bcl-2)/MYC protein dual expression (DE) status in the prognostic stratification for patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL). Methods:Forty-six patients (21 males, 25 females; age 20-83 years) with newly diagnosed PGI-DLBCL from June 2012 to May 2019 in Nanjing Drum Tower Hospital were enrolled in this retrospective study. Immunohistochemistry for Bcl-2 and MYC protein expression was performed. All patients underwent baseline and interim (after 2-4 cycles of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP) regimen) 18F-FDG PET/CT scans for assessment. Interim 18F-FDG PET/CT results were determined based on Deauville 5-point scale (DS) and changing rate of maximum standardized uptake value (ΔSUV max%) in 18F-FDG PET/CT images. Kaplan-Meier survival analysis, Cox proportional hazards regression model (single factor, multiple factors analysis) were used to analyze the prognosis (3-year progression free survival (PFS) and overall survival (OS) rates). Results:Patients were followed up for 6-84 months, and 14 showed disease progression and 9 died. The PFS rate and OS rate were 69.6% and 80.4%, respectively. DE, DS as well as ΔSUV max% were significant predictors of PFS (hazard ratio ( HR) values: 3.280, 5.120, 9.167, all P<0.05); lactate dehydrogenase (LDH), MYC protein expression, DS and ΔSUV max% were significant predictors of OS ( HR values: 4.091, 9.618, 7.697, 11.151, all P<0.05). Multivariate analysis revealed that DS and ΔSUV max% were independent predictors of PFS and OS ( HR values: 4.370-9.244, all P<0.05). In the DS negative (-) group, patients with DE positive (+ ) had lower PFS and OS rates than those with DE- (PFS rate: 50.0% vs 88.9%; OS rate: 66.7% vs 96.3%; χ2 values: 6.050, 4.966, both P<0.05). In ΔSUV max%<90% group, patients with DE+ had lower PFS rate than those with DE- (12.5% vs 68.8%; χ2=6.649, P=0.01). Conclusions:Interim PET/CT analysis using DS and ΔSUV max% is able to predict survival in PGI-DLBCL patients. The combination of DS, ΔSUV max% and DE can risk-stratify PGI-DLBCL patient more effectively.

Radiographic features of 18F-FDG PET/CT in the assessment of disease activity in adult-onset Still′s disease / 中华核医学与分子影像杂志

Objective:To investigate the characteristic findings of 18F-fluorodeoxyglucose (FDG) PET/CT in patients with adult-onset Still′s disease (AOSD) and the correlation between the maximum standardized uptake value (SUV max) and clinical disease activity score as well as laboratory data. Methods:Twenty-two patients (6 males, 16 females, age range: 19-73 (41.5±16.3) years) with AOSD according to criteria set by Yamaguchi between May 2015 and June 2018 in Nanjing Drum Tower Hospital were recruited in the retrospective study. The characteristic findings of 18F-FDG PET/CT in the consecutive AOSD patients were evaluated. The correlation between SUV max and clinical disease activity score as well as laboratory data was assessed with Spearman rank correlation analysis. Results:PET/CT results contributed to the diagnosis of AOSD in all the 22 patients (100%). The accumulation of 18F-FDG was showed in lymph nodes of 21 patients(95.5%), and the spleen and bone marrow uptake were observed in all the 22 patients (100%). Besides, 18F-FDG uptake was found in shoulder joint ( n=6, 27.3%), submaxillary glands ( n=9, 40.9%) and parotid glands ( n=7, 31.8%). The SUV max of lymph nodes were significantly correlated with the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) ( r s values: 0.622, 0.538, both P<0.05). The SUV max of spleen was significantly correlated with CRP and ESR levels ( r s values: 0.543, 0.475, both P<0.05). The SUV max of bone marrow was significantly correlated with the level of CRP and neutrophils(%) ( r s values: 0.497, 0.431, both P<0.05). However, there was no correlation between the SUV max and clinical disease activity score ( r s values: 0.008, 0.102, 0.210, all P>0.05). Conclusions:Characteristics findings of 18F-FDG PET/CT imaging can provide useful information for differential diagnosis as well as extent assessment for AOSD, and play an important role in the diagnosis process of AOSD. 18F-FDG PET/CT scan may be a helpful imaging technique for evaluation of disease activity in patients with AOSD but prospective study with large cohort of individuals are needed.

Diagnostic value of glomerular filtration rate, microalbuminuria, β2-microglobulin and cystatin C for renal function in patients with diabetic nephropathy / 中华核医学与分子影像杂志

Objective To investigate the clinical value of GFR, microalbuminuria (mAlb), serum β2-microglobulin (MG) and cystatin C (CysC) for the evaluation of renal function in patients with DN.Methods A total of 150 patients with type 2 DM diagnosed by WHO standard (1999) from December 2012 to December 2015 were retrospectively analyzed.Thirty-three kidney transplantation donors during the same time were chosen as the control group.The urine mAlb, Cr, albumin/Cr ratio(ACR) and SCr, serum β2-MG, CysC, urea, uric acid(UA), fasting blood glucose (FBG), hemoglobin A lc (HbA1c) and C-reactive protein (CRP) were measured.99Tcm-DTPA renal dynamic imaging was performed.The Gates method was used to calculate GFR, and the modification of diet in renal disease (MDRD) method was used to calculate the estimated GFR (eGFR).The relative equation between GFR and eGFR was studied.The clinical stages of renal function in type 2 DM patients were evaluated by Mogenesen standard method.Two-sample t test was used for data analysis.ROC curve analysis was performed to study the diagnostic value of GFR in DN.Results The patients were divided into merely type 2 DM group, early stage DN (Ⅰ, Ⅱ, Ⅲ), and clinical DN(Ⅳ) groups by Mogenesen standard method.GFR and eGFR in the DNⅠstage were higher than those of the merely type 2 DM group (t values:-7.502,-3.629, both P0.05), but the renal function indicators were different (t values:-5.090-2.209, all P<0.01).Compared with the normal CRP group, the FBG, HbA1c and renal function indicators were statistically different in high CRP group (t values:-6.114-7.386, all P<0.01).Conclusions GFR and eGFR show a linear relationship in type 2 DM.GFR is a sensitive, specific diagnostic index in DN Ⅰ period.β2-MG, CysC, mAlb and ACR are conducive to the early diagnosis of DN.High UA is an independent risk factor for the onset of DN, and high CRP is an inflammatory damage factor in DN.

Vitamin D/vitamin D receptor, autophagy and inflammation relevant diseases / 中南大学学报(医学版)

The biological effects mediated by vitamin D and vitamin D receptor (VDR) are involved in the regulation of multiple pathophysiologic processes,including calcium phosphorus metabolism,immune regulation,anti-inflammation,anti-infection and cancer prevention,etc.Autophagy is a eukaryotic cell lysosome-mediated catabolic pathway,which is classified into 3 different types:macroautophagy,microautophagy,and chaperone-mediated autophagy.Since autophagy is vital to maintain energy and metabolism in cells,autophagy dysfunction is closely associated with various pathological processes such as inflammation,infection and tumor.Studies have shown that vitamin D/VDR can affect the different stages of autophagy and regulate inflammation in autophagy.Moreover,vitamin D/VDR and autophagy play an important role in autoimmune disease,diabetes,cardiovascular disease,cancer and other inflammatory diseases.

A prospective study on the prognosis of biopsy-confirmed cervical intraepithelial neoplasia grade 1 and the relationship with high-risk human papillomavirus / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the prognosis of cervical intraepithelial neoplasia grade 1 (CIN1) at different follow-up time points in Chinese women and the relationship with high-risk human papillomavirus (HR-HPV) infection.</p><p><b>METHODS</b>Biopsy-confirmed CIN1 women were followed up from cervical cancer screening cohorts established during 1999 to 2008 in Xiangyuan county, Yangcheng county, Qinxian county and Wuxiang county, Shanxi Province.In each follow-up visit, participants were examined by visual inspection with acetic acid, liquid-based cytology and HR-HPV DNA testing. Those with any positive results received colposcope and biopsies. The cumulative incidence rates of CIN grade 2 or worse (CIN2+) and CIN grade 3 or worse (CIN3+), regression rates and persistent rates were calculated using pathological findings as a gold standard. The risks of progression related with HR-HPV were evaluated stratified by baseline and follow-up HR-HPV status.</p><p><b>RESULTS</b>A total of 228, 224, 261 and 105 CIN1 women received the 1-year, 2-year, 6-year and 11-year follow-up exams, respectively. The cumulative incidence rate of CIN2+ among baseline HR-HPV positive women was 4.8% (6/126), 10.7% (16/150), 16.9% (29/172) and 35% (19/55) in the above follow-up visits, respectively, and their risk of progression was 2.7(95%CI:0.3-22.0), 2.9 (95%CI:0.7-12.1), 12.0 (95%CI:1.7-86.2) and 30.6 (95%CI:1.9-493.5) times higher than baseline HR-HPV negative women. Moreover, the cumulative incidence of CIN2+ among women with positive HR-HPV both at baseline and follow-up visit was 11% (6/55), 14% (6/42), 17% (10/60) and 50% (13/26) in the above follow-up visits, respectively.No new CIN2+ cases were found among those with negative HR-HPV both at baseline and follow-up visits.</p><p><b>CONCLUSION</b>Given that CIN1 progression is related to HR-HPV infection, different follow-up intervals and strategies for CIN1 should be taken according to HR-HPV infection status.</p>

Noninvasive observation of atherosclerosis in mice with 7.0T MR and Micro-PET / 中国医学影像技术

Objective To explore the feasibility of detecting atherosclerosis with 7.0T MR and Micro-PET. Methods Ten 46-week-old ApoE-/- mice with high lipid diet for 6 months were selected to establish atherosclerosis models. Among them, 5 mice underwent MRI before and 12 h, 24 h, 36 h after injection of SPIO, respectively, and the other 5 mice were injected with ~(18)F-fluorodeoxyglucose (~(18)F-FDG) through tail vein and observed with Micro-PET after 1 h, 2 h and 3 h. The specimens of abdominal aorta were taken for pathologic examination. Results Atherosclerotic plaques were observed in all animals with 7.0T MRI after 6 months high lipid diet. Thirty-six hours after the injection of SPIO, the high signal rings were thinner and the lumen of blood vessels were wider than those before injection on T2WI. Radioactive concentration was observed in abdominal aorta and both sides of iliac artery 3 h after the injection of ~(18)F-fluorodeoxyglucose (~(18)F-FDG). Pathological examination showed the formation of atherosclerotic plaques and the aggregation of the macrophages. Conclusion 7.0T MRI and Micro-PET can be used to observe the macrophage-rich plaque and to judge the vulnerability of plaque, thus provide theoretical basis for early detection, diagnosis and treatment of atherosclerosis.

Research advancement of the stem cells of the bone marrow interstitial substance differentiating into islet cells / 介入放射学杂志

Type I diabetes mellitus (T_1DM) is a chronic metabolic disease liable to teenagers all over the world. Its mechanism is due to the attack of auto-immune system on the body's own islet cells leading to hyperglycemia with great damages to the body. The implantation of islet cells is an effective way of curing T_1DM. The authors reviewed in detail the research advancement of islet cell source from stem cells of the bone marrow interstitial substance.

IN VITRO TRANSDIFFERENTIATION OF RAT BONE MARROW MESENCHYMAL STEM CELLS INTO INSULIN-SECRETING CELLS / 解剖学报

Objective To investigate the possibility of bone marrow mesenchymal stem cells to transdifferentiate into insulinf-secreting cells or islet progenitors,and to demonstrate whether these islet-like cells can generate insulin and glucagon. Methods BMSCs were isolated from tibia or thighbone of 6-8 weeks normal SD rat,purified on the basis of their ability to adhere to matrix,and expanded through their self-renewal.Two-step strategy was adopted,BMSCs were induced to generate nestin-positive cells under diffferentiation culture medium 1(added 20??g/L bFGF,10??g/L EGF and 2% B-(27) in DMDM/F-(12) medium) in step one;Nestin-positive cells were differentiated and developed into islet-like cells or islet progenitors under complexed culture medium 2(added 10??g/L Betacellulin,10??g/L HCF,10??g/L Activin A,10?mmol/L nicotide and 2% B27 serum-free in HG-DMEM medium) in step two.The differentiated cells were tested by Dithiazone staining;Immunocytochemistry was carried out using standard protocols in which the cells were incubated with Rb-Rat insulin monoclone antibody,mouse-human glucogan polyclone antibody and Rb-Rat nestin monoclone antibody and assessed by examining the cells under a Zeiss microscope.Insulin secretion in response to insulin secretagogues(glucose) was assayed by radioimmunoassay(RIA). Results After 5 days,BMSCs were expressing nestin,a marker shared with neural stem cells and pancreatic stem cells.Dithiazone staining was positive(bright orange).The differentiated cell masses were containing insulin and glycagon as indicated by immunocytochemistry.RIA demonstrated that these cell mass could generate insulin,the responsibility to glucose was weak.Conclusion BMSCs can be induced to differentiate into insulin-secreting cells or islet progenitors by adding various different cell growth factors and the strategy is repeatable.This study may present a potential approach for the treatment of insulin-depended diabetes by interventional therapy.