Objective:To explore the impacts of 131I-NaI radiotherapy on the promotion of glycolysis and 18F-fluorodeoxyglucose ( 18F-FDG) uptake in pancreatic cancer cells via the induction of proviral integration moloney murineleukemia virus 2 (PIM2) and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3). Methods:In the cell experiments, human pancreatic carcinoma cells-1 (PANC-1) were randomly divided into four groups: a control group, an HJ-PI01 group, a 131I-NaI group, and an HJ-PI01 + 131I-NaI group. Their aerobic glycolysis capacity was assessed by measuring glucose uptake, lactate production, and extracellular acidification rate (ECAR). In vivo animal experiments, 12 nu/nu female nude mice were given 100 μl (1 × 10 7 cells) of cell suspension through subcutaneous injection into the left lower limbs. When the tumor volume reached approximately 60 mm 3, these mice were divided into four groups (a control group, a HJ-PI01 group, a 131I-NaI group, and an HJ-PI01+ 131I-NaI group) using a random number table, with three mice in each group. After 14 days of treatment, 18F-FDG PET/CT imaging was performed to calculate the maximum standardized uptake value (SUV max) of the xenografts. Following PET/CT imaging, the tumor tissues were harvested and analyzed for PIM2, PFKFB3, and Ki-67 expressions using immunohistochemistry. Results:In cell experiments, compared to the control group, the HJ-PI01 group exhibited significant reduction in glucose uptake, lactate production, PFKFB3 protein expression, and ECAR in PANC-1 cells ( t = 4.59-13.98, P < 0.05). In contrast, the 131I-NaI group showed significant increases in these parameters ( t = 3.36-13.97, P < 0.05). Compared to the 131I-NaI group, the HJ-PI01+ 131I-NaI group showed significant reduction in glucose uptake, lactate production, PFKFB3 protein expression, and ECAR ( t = 5.14-20.87, P < 0.05). In the animal experiments, compared to the control group, the three groups displayed significant decrease in SUV max of 18F-FDG uptake in tumors ( t = 16.48, 22.49, 32.64, P < 0.001). Moreover, the HJ-PI01 + 131I-NaI group exhibite significantly lower SUV max than the 131I-NaI group ( t = 10.16, P < 0.001). Immunohistochemical analysis revealed that the HJ-PI01+ 131I-NaI group, compared to the 131I-NaI group, showed significantly lower Ki-67 expression and the PIM2/PFKFB3 signaling pathway in tumor tissues ( t = 3.27, 10.73, 14.85, P < 0.05). Conclusions:Glycolysis enhancement of PANC-1 cells, mediated by the PIM2/PFKFB3 signaling pathway inhibition, can significantly improve the anticancer capacity of 131I-NaI, providing a novel strategy for radiotherapy in pancreatic cancer.

Objective:To explore the impacts of 131I-NaI radiotherapy on the promotion of glycolysis and 18F-fluorodeoxyglucose ( 18F-FDG) uptake in pancreatic cancer cells via the induction of proviral integration moloney murineleukemia virus 2 (PIM2) and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3). Methods:In the cell experiments, human pancreatic carcinoma cells-1 (PANC-1) were randomly divided into four groups: a control group, an HJ-PI01 group, a 131I-NaI group, and an HJ-PI01 + 131I-NaI group. Their aerobic glycolysis capacity was assessed by measuring glucose uptake, lactate production, and extracellular acidification rate (ECAR). In vivo animal experiments, 12 nu/nu female nude mice were given 100 μl (1 × 10 7 cells) of cell suspension through subcutaneous injection into the left lower limbs. When the tumor volume reached approximately 60 mm 3, these mice were divided into four groups (a control group, a HJ-PI01 group, a 131I-NaI group, and an HJ-PI01+ 131I-NaI group) using a random number table, with three mice in each group. After 14 days of treatment, 18F-FDG PET/CT imaging was performed to calculate the maximum standardized uptake value (SUV max) of the xenografts. Following PET/CT imaging, the tumor tissues were harvested and analyzed for PIM2, PFKFB3, and Ki-67 expressions using immunohistochemistry. Results:In cell experiments, compared to the control group, the HJ-PI01 group exhibited significant reduction in glucose uptake, lactate production, PFKFB3 protein expression, and ECAR in PANC-1 cells ( t = 4.59-13.98, P < 0.05). In contrast, the 131I-NaI group showed significant increases in these parameters ( t = 3.36-13.97, P < 0.05). Compared to the 131I-NaI group, the HJ-PI01+ 131I-NaI group showed significant reduction in glucose uptake, lactate production, PFKFB3 protein expression, and ECAR ( t = 5.14-20.87, P < 0.05). In the animal experiments, compared to the control group, the three groups displayed significant decrease in SUV max of 18F-FDG uptake in tumors ( t = 16.48, 22.49, 32.64, P < 0.001). Moreover, the HJ-PI01 + 131I-NaI group exhibite significantly lower SUV max than the 131I-NaI group ( t = 10.16, P < 0.001). Immunohistochemical analysis revealed that the HJ-PI01+ 131I-NaI group, compared to the 131I-NaI group, showed significantly lower Ki-67 expression and the PIM2/PFKFB3 signaling pathway in tumor tissues ( t = 3.27, 10.73, 14.85, P < 0.05). Conclusions:Glycolysis enhancement of PANC-1 cells, mediated by the PIM2/PFKFB3 signaling pathway inhibition, can significantly improve the anticancer capacity of 131I-NaI, providing a novel strategy for radiotherapy in pancreatic cancer.

Objective To explore the effects of graphene oxide (GO)-polyethylene glycol (PEG)-folic acid (FA)-pyrenemethylamine hydrochloride (PyNH2)-mediated RNA interference (RNAi) of hypoxia-inducible factor-1α (HIF-1α) on the biological behaviors of human pancreatic cancer Patu8988 cells.Methods GO-PEG-FA-PyNH2 and RNAi targeting HIF-1α gene (GO-PEG-FA-PyNH2-HIF-1α-RNAi)was constructed.The expressions of HIF-1α and glucose transporter 1 (Glut-l) in Patu8988 cells were determined after knockdown of HIF-1α by RNAi.The invasive ability,the proliferation and the cell cycle of Patu8988 cells were investigated.The effect of HIF-1α knockdown on the uptake of 18F-fluorodeoxyglucose (FDG) in Patu8988 cells was also detected.Comparison of data was conducted by one-way analysis of variance and least significant difference t test.Results The GO-PEG-FA-PyNH2 was successfully constructed,and no cytotoxicity was found.Under the hypoxia or normoxia state,the mRNA and protein levels of HIF-1α and mRNA level of Glut-1 in cells transfected with GO-PEG-FA-PyNH2-HIF-1α-RNAi (study group) were lower than those in cells transfected with GO-PEG-FA-PyNH2 (negative group) and cells transfected with Opti-minimal essential medium (Opti-MEM,control group;F=30.25-32.58,t=3.66-5.81,all P＜0.05);the numbers of migrated cells in the study group were much lower than those in the negative group and the control group (F=38.63 and 41.35,t=20.51-35.25,all P＜0.01);the cell proliferation in the study group was significantly lower than that in the negative group and the control group (F=35.19 and 38.11,t =15.11-22.19,all P＜0.05).The proportions of G0/G1 cells in the study group were higher than those in the negative group and the control group (F=34.60 and 34.83,t=11.55-34.56,all P＜0.05);the 18 F-FDG uptake in the study group was lower than that in the negative group and control group (F=29.85 and 31.69,t =3.35-4.35,all P＜0.05).Conclusion GO-PEG-FA-PyNH2-mediated HIF-1α RNAi inhibits the expression of HIF-1α in pancreatic cancer cells,leading to changes in related biological behaviors.

Objective To investigate the relationship between the biochemical markers of bone turnover and renal osteodystrophy (ROD) in patients with primary nephrotic syndrome (PNS).Methods A total of 30 patients with PNS and 50 healthy subjects (controls) were included in the study.The BMD of lumbar vertebrae and femur was measured by dual-energy X-ray absorptiometry.The levels of total procollagen type Ⅰ amino-terminal propeptide (TP Ⅰ NP),β-isomerized carboxyterminal propeptide (β-CTx),intact PTH (iPTH),serum calcium,serum phosphorus,ALP,25-OH-Vitamin D3 (25-OH-VD3),β2-micro-globulin(β2-MG),and ratio of urinary to creatinine (UA/Cr) were measured and calculated.The risk factors related to ROD in PNS patients were analyzed.Two-sample t test,multiple linear regression and partial correlation analysis were used to analyze data.Results The BMD values of lumbar vertebrae and femur in the PNS group were significantly decreased compared with those in controls (t =6.162,5.583,3.891 (＜40 years),5.923,5.324,3.129 (≥40 years),all P＜0.05) and the serum levels of TPⅠNP,β-CTx,iPTH,ALP,β2-MG and UA/Cr in the PNS group were significantly higher than those in controls (t:2.738-10.129(＜40 years),3.226-12.581 (≥40 years),all P＜0.05),and the levels of serum calcium and 25-OH-VD3 in the PNS group were significantly lower than those in controls (t =3.624,7.223 (＜40 years),2.011,2.564 (≥40 years),all P＜0.05).But there was no significant difference for serum phosphorus between the 2 groups (t=0.811,0.513,both P＞0.05).TP Ⅰ NP was positively correlated with β-CTx,iPTH,ALP,UA/Cr,β2-MG(r:0.512-0.682,all P＜0.01),and TP Ⅰ NP was negatively correlated with serum calcium and 25-OH-VD3(r=-0.314,-0.562,both P＜0.01)in the PNS group.β-CTx was positively correlated with iPTH,ALP,UA./Cr,β2-MG(r:0.459-0.618,all P＜0.01),and negatively correlated with serum calcium and 25-OH-VD3(r=-0.212,-0.589,both P＜0.01).The iPTH was positively correlated with ALP,UA/Cr and β2-MG (r =0.410,0.606,0.508,all P＜0.05),and negatively correlated with serum calcium and 25-OH-VD3(r=-0.315,-0.516,both P＜0.05).Conclusions The BMD in PNS patients is lower than that in healthy subjects.Combined measurement of TP Ⅰ NP,β-CTx and the BMD is helpful for the diagnosis of ROD in PNS patients.

Objective To evaluate the significance of tumor markers CEA and CA15-3,and biochemical markers of bone turnover (total procol]agen type Ⅰ amino-terminal propeptide (TP I NP),β-isomerized carboxyterminal propeptide (β-CTx),ALP and PTH) in the diagnosis of bone metastasis from breast cancer.Methods A total of 78 patients (all females) with mean age (56.72 ± 10.76) years,who were diagnosed with breast cancer,were included in this study.The patients were divided into two groups based on radionuclide bone imaging:with bone metastasis (n =32) and without bone metastasis (n =46).The serum concentrations of CEA,CA15-3,TP I NP,[β-CTx,PTH,ALP were measured.Gleason scores were evaluated.The diagnostic value was evaluated by ROC curve.The two groups were compared using two-sample t test.The correlations between bone metastasis and tumor markers,bone metastasis and biochemical markers of bone turnover were analyzed with Pearson correlation and logistic analysis.Results The serum levels of CEA,CA15-3,TPINP,β-CTx,PTH and ALP were significantly higher in the group with bone metastasis than those in the group without bone metastasis (t:4.16-7.56,all P ＜ 0.05).For the diagnosis of bone metastasis from breast cancer,the AUC of CEA,CA15-3,TPINP,[β-CTx,PTH and ALP was 0.815,0.887,0.869,0.852,0.844,0.731,respectively.Using the cut-off values of 4.18 μg/L for CEA,0.04 U/L for CA15-3,49.70 μg/L for TP I NP,0.47 pg/L for β-CTx,54.90 ng/L for PTH and 49.90 U/L for ALP,the sensitivities were 56.3％ (18/32),75.0％ (24/32),78.1％ (25/32),81.3％ (26/32),78.1％ (25/32),68.8％ (22/32) and the specificities were 80.4％ (37/46),84.8％ (39/46),76.1％ (35/46),78.3％ (36/46),69.6％ (32/46),58.7％ (27/46),respectively.CEA,CA15-3,TPINP,β-CTx,PTH,ALP and Gleason score were positively correlated with the presence of bone metastasis (r:0.267-0.636,all P ＜ 0.05).CEA,CA15-3,TP I NP,β-CTx,PTH and Gleason score were independent predictors for bone metastasis of breast cancer (odds ratios:2.45,3.44,1.24,1.54,1.11,2.22,all P ＜0.05).The total coincidence rate of regression model was 81.3％ (26/32) in patients with bone metastasis.Conclusions The diagnostic values of CEA,CA15-3,TP I NP,β-CTx and PTH are comparable.Combined use of these parameters may be helpful for the early diagnosis of bone metastasis from breast cancer.

Thirty-two patients with Meniere disease were treated by acupuncture therapy,Baihui(GV 20),Fengfu(GV 16),bilateral Fengchi(GB 20),Shenshu(BL 23),Taixi(KI 3),and Xuanzhong(GB 39)were selected.Of the 32 cases,8 cases was totally under control,12 cases were generally under control,9 cases were partly under control and 3 cases were out of control,the totaI effective rate was 90.6%.