1.Difference analysis of 18F-FMISO PET/CT hypoxia imaging in response to heavy ion radiotherapy in patients with non-small cell lung cancer
Mingyu LIU ; Ningyi MA ; Jian CHEN ; Caiyue REN ; Fuquan ZHANG ; Jingfang MAO ; Kailiang WU ; Guoliang JIANG ; Yun SUN ; Shaoli SONG ; Jingyi CHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(1):11-15
		                        		
		                        			
		                        			Objective:To explore the clinical value of 18F-fluoromisonidazole (FMISO) PET/CT hypoxia imaging in early response to heavy ion radiotherapy in patients with non-small cell lung cancer(NSCLC). Methods:From April 2018 to January 2021, the 18F-FMISO PET/CT images of 23 NSCLC patients (19 males, 4 females; age (64.9±10.3) years) who received heavy ion radiotherapy in Shanghai Proton and Heavy Ion Center were retrospectively analyzed. The evaluation parameters included tumor volume (TV), tumor to background ratio (TBR) before and after radiotherapy. Patients were divided into hypoxia group and non-hypoxia group with the baseline TBR value≥1.4 as hypoxia threshold. Wilcoxon signed rank test was used to compare the differences of TV and TBR before and after radiotherapy in 2 groups. Results:Of 23 NSCLC patients, 17 were hypoxia and 6 were non-hypoxia. Compared with the baseline, TV after the radiotherapy (59.44(22.86, 99.43) and 33.78(8.68, 54.44) cm 3; z=-3.05, P=0.002) and TBR after the radiotherapy (2.25(2.09, 2.82) and 1.42(1.24, 1.67); z=-3.39, P=0.001) of the hypoxia group were significantly lower, while TV (16.19(6.74, 36.52) and 8.59(4.38, 25.47) cm 3; z=-1.57, P=0.120) and TBR (1.19(1.05, 1.27) and 1.10 (0.97, 1.14); z=-1.89, P=0.060) of the non-hypoxia group decreased with no significant differences. Conclusions:Hypoxic NSCLC tumors are sensitive to heavy ion radiation. Compared with non-hypoxic tumors, hypoxic tumors respond more quickly, and a significant reduction in TV can be observed early after radiotherapy. Heavy ion radiation can significantly improve tumor hypoxia.
		                        		
		                        		
		                        		
		                        	
2.Study on ultrasonic characteristics of eccrine spiradenomas and diagnostic efficacy
Kailiang CHEN ; Size WU ; Kefeng YANG ; Changke HONG ; Meixi CHEN
Chinese Journal of Ultrasonography 2022;31(11):973-977
		                        		
		                        			
		                        			Objective:To investigate the ultrasonic characteristics of eccrine spiradenoma (ES) and to analyze the diagnostic value.Methods:Nineteen ES patients with 24 lesions confirmed by pathology in 3 grade-A tertiary hospitals from October 2011 to October 2021 were enrolled as study group, and in the same time, 46 patients with 46 masses in the skin and muscular tissues with clinical features of automatic pain and/or tenderness were selected as control group. The ultrasonographic characteristics of the two groups were analyzed retrospectively, including anatomical location, shape, boundary, internal echogenicity, echogenic distribution, calcification, posterior acoustic effect, and vascularity. The ultrasonographic characteristics of the two groups were compared, and the risk sonographic characteristics of ES were obtained by multivariate logistic regression analysis. The sensitivity and specificity of ultrasound characteristics for the diagnosis of ES were calculated.Results:The ultrasonic characteristics of the two groups had significant differences in lobulated shape, boundary, internal echogenicity and posterior acoustic effect (χ 2=32.65, 15.65, 5.77, 13.63; all P<0.01). Multivariate logistic regression analysis showed that lobulated shape and posterior acoustic enhancement were the risk ultrasonic characteristics of ES. The sensitivity and specificity of lobulated shape and posterior acoustic enhancement characteristics in the diagnosis of ES were 79.17%, 89.13%, 95.83% and 47.83%, respectively; and the sensitivity and specificity of the combination of lobulated shape and posterior acoustic enhancement characteristics in the diagnosis of ES were 79.17% and 97.83%, respectively. Conclusions:The lobulated shape and posterior acoustic enhancement characteristics are important for the identification of ES, which have higher diagnostic efficacy for ES.
		                        		
		                        		
		                        		
		                        	
3.A successfully treated case of colchicine poisoning with lethal dose
Yuxia SUN ; Yulong YAO ; Kailiang XU ; Lin YUAN ; Gang CHEN ; Weifang YUAN ; Ming LEI
Chinese Critical Care Medicine 2020;32(2):240-242
		                        		
		                        			
		                        			At present, there is no specific antidote for colchicine intoxication, and 0.8 mg/kg is its lethal dose.The prognosis of colchicine intoxication patients is closely related to the dosage, but the individual difference is very great. A 38-year-old man with colchicine poisoning was admitted to the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, who had ingested 80 mg colchicine tablets (1.19 mg/kg) orally for 4 hours. He was immediately put on gastric lavage, enema, and catharsis. Continuous blood purification was performed for 34 hours and 22 minutes, with a combination of hemoperfusion (HP) and continuous veno-venous hemofiltration dialysis (CVVHDF). He also received a large dose of the glucocorticoid with 80 mg of methylprednisolone injected intravenously every 8 hours and organ function support. The patient was hospitalized for 2 weeks and discharged with improvement. The successful treatment of this case was reported for reference.
		                        		
		                        		
		                        		
		                        	
4.Experimental study on the mechanism of glycogen synthase kinase-3β inhibitor on acute kidney injury of acute necrotizing pancreatitis in rats
Kailiang ZHAO ; Xiaojia YANG ; Chen CHEN ; Liang ZHAO ; Fangchao MEI ; Yupu HONG ; Weixing WANG
Chinese Critical Care Medicine 2019;31(6):719-724
		                        		
		                        			
		                        			Objective To explore the protective mechanism of glycogen synthase kinase-3β(GSK-3β) inhibitor TDZD-8 on acute necrotizing pancreatitis (ANP) associated kidney injury in rats. Methods SPF male Wistar rats were randomly divided into four groups (n = 20): sham operation group (Sham group), ANP model group, TDZD-8 intervention group and TDZD-8 control group. The rat ANP model was prepared by retrograde injection of 5% sodium taurocholate into the bile duct; the same volume of normal saline was injected into the pancreatic duct of the Sham group. The TDZD-8 intervention group and the TDZD-8 control group were injected with GSK-3β inhibitor TDZD-8 (1 mL/kg) via the femoral vein 30 minutes before the model or sham operation; the ANP model group and the Sham group were injected equal volume of 10% dimethyl sulfoxide (DMSO). Rats in each group were sacrificed at 12 hours after operation to measure the serum amylase (AMY), blood lipase (LIPA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels and to observe the pathological changes of pancreatic tissues and kidney tissues. Ultrastructural change of renal cells was analyzed by transmission electron microscopy. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were evaluated by enzyme linked immunosorbent assay (ELISA). The activation of nuclear factor-κB p65 (NF-κB p65) was evaluated by immunohistochemistry assay. The protein expressions of GSK-3β, phospho-GSK-3β (Ser 9), tumor necrosis factor -α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and interleukin-10 (IL-10) in the kidney were determined by Western Blot. Results Compared with the Sham group, the serum and inflammatory factors levels of the ANP model group were significantly increased, the pathological damage of the pancreas and kidney tissues were severe, the histopathological score was significantly increased, the expression of NF-κB p65 was enhanced in the nucleus of the kidney tissue, and the expressions of GSK-3β, TNF-α, ICAM-1 and iNOS were significantly enhanced, and the expressions of p-GSK-3β(Ser 9) and IL-10 were significantly attenuated. Compared with the ANP model group, TDZD-8 pretreatment significantly reduced serum and inflammatory factor levels in the ANP model group [AMY (kU/L): 5.60±0.30 vs. 10.07±0.34, LIPA (U/L): 1 111.0±110.8 vs. 2 375.0±51.1, SCr (μmol/L): 47.38±1.48 vs. 72.50±2.43, BUN (mmol/L): 17.6±1.0 vs. 26.0±1.0, IL-1β (ng/L):195.90±5.50 vs. 332.40±38.29, IL-6 (ng/L): 246.10±26.74 vs. 385.30±32.19, all P < 0.01]; pathological damage of pancreas and kidney tissue (histopathological score: 7.1±0.4 vs. 12.1±0.3, 301.2±7.5 vs. 433.5±13.8, both P < 0.01) and ultrastructural damage of renal cells were alleviated; the expression of NF-κB p65 in the nucleus was significantly decreased; the expression of p-GSK-3β(Ser 9) was significantly increased, and blocking GSK-3β activity could inhibit the expressions of TNF-α, ICAM-1, iNOS and increase the expression of IL-10, while the expression of GSK-3β in renal tissues was not statistically significant. There were no significant differences between the TDZD-8 control group and the Sham group. Conclusions Blockade of GSK-3βactivity by TDZD-8 exerts the protective effect against kidney injury by inhibiting the inflammation signaling pathway in ANP. It can alleviate histopathological and ultrastructural changes in kidney injury, which protection mechanism is mediated by NF-κB and its related inflammatory mediators.
		                        		
		                        		
		                        		
		                        	
5.The effects of different GSK-3β inhibitors and dose-response relationship in severe acute pancreatitis associated kidney injury in rats
Zhoujun CUI ; Weixing WANG ; Kailiang ZHAO ; Chen CHEN ; Hongbo LI ; Yuhua MOU ; Jing SUN
Chinese Journal of Emergency Medicine 2018;27(9):960-966
		                        		
		                        			
		                        			Objective To observe the dose-response relationship of the GSK-3β inhibitor TDZD-8 in severe acute pancreatitis (SAP) associated kidney injury in rats. In order to identify the most effective class of GSK-3β inhibitor and its effective and reasonable safe dose in SAP associated kidney injury model in rats by comparing three kinds of frequently-used GSK-3β inhibitor TDZD-8, lithium chloride (LiCL), SB216763 in this model. Methods Totally 96 SPF male Wistar rats were randomly(random number) divided into 8 groups (n=12): sham operation group (SO group), severe acute pancreatitis group (SAP group), TDZD-8 pretreatment groups (TD group, marked TD1, TD2, TD3 and TD4 group, respectively) at different dosage (0.25, 0.5, 1.0 and 2.0 mg/kg), LiCL pretreatment groups (L group, 40 mg/kg), and SB216763 pretreatment group (SB group, 1 mg/kg). SAP model was induced by retrograde infusion of 5% sodium taurocholate into the biliopancreatic duct. Rats in each group were sacrificed at 12 h after operation. Then the mortality, quantity of ascites, serum AMY, Cr, BUN and ALT were recorded, and the pathological changes of pancreatic tissues and kidney tissues were observed. Results Compared with the SO group, the levels of ascites, serum AMY, Cr, BUN, ALT and pancreatic and renal pathologic score in the SAP group were all significantly increased (P<0.05). Compared with the TD1 group, quantity of ascites, serum AMY, Cr, BUN,ALT and pancreatic tissue pathological grading were reduced in different degrees in the TD2, TD3 and TD4 groups with statistically significant difference (P<0.05); ALT values were reduce in different degrees in the TD2 and TD3 groups as compared with the SAP group (P<0.05), while ALT value in the TD4 group was similar to that in the SAP group; compared with the TD2 group, all the indexes in the TD3 group were significant better (P<0.05); Compared with TD3 group (the best group in TD group), the levels of ascites and serum ALT in the L group and SB group had no significant difference (P>0.05), but the levels of AMY, Cr, BUN, ALT, pancreatic and renal pathologic score were significantly reduced in the TD3 group than those in the L and SB groups (P<0.05); compared with the SB group, the values of Cr, BUN, pancreatic and renal pathologic score in the L group were lower (P<0.05). GSK-3βprotein expression in all groups showed no obvious difference (P>0.05), while p-GSK-3β ser9 protein expression in the SAP group was lower than that in the SO group (P<0.05), and p-GSK-3β ser9 protein expression in the TD3, L and SB groups were stronger than that in the SAP group. Among them, p-GSK-3βser9 protein expression was highest in the TD3 group, followed by the L group, finally the SB group, and the differences were statistically significant (P<0.05). Conclusions Among the three different GSK-3βinhibitors, TDZD-8 is the most effective GSK-3β inhibitor for SAP associated with kidney injury in rats. The GSK-3β inhibitor TDZD-81 mg/kg administered intravenously is safe, effective and optimal dosage for attenuating the severity of severe acute pancreatitis associated with kidney injury.
		                        		
		                        		
		                        		
		                        	
6.The relationship of sarcopenia in patients undergoing pancreaticoduodenectomy with outcome
Qin CAO ; Youming DING ; Mengrong CHEN ; Bin WANG ; Xiaoyan CHEN ; Kailiang ZHAO ; Chen CHEN ; Jianhui GE
Chinese Journal of Clinical Nutrition 2018;26(1):40-45
		                        		
		                        			
		                        			Objective To explore the prognostic value of sarcopenia in patients undergoing pancreati-coduodenectomy.Method Clinicopathologic data and follow-up information of 116 patients undergoing pancre-aticoduodenectomy at Renmin Hospital of Wuhan University between March 2011 and August 2016 were collected for statistical analysis.Results Among the 116 patients,the prevalence of sarcopenia was 42.2% (n =49).When compared to the rest of the patients who did not have sarcopenia,the sarcopenia group had longer recovery time [(17.33±6.54) d vs.(13.46±9.32) d,P=0.013] and increased risk of complications (complications in general,59.2% vs.38.8%,x2 =4.714,P =0.030;Clavien-Dindo ≥ 3:26.5% vs.10.4%,x2 =5.130,P=0.024).Both the Kaplan-Meier survival analysis (P<0.05) and the Cox proportional hazard model (overall survival:hazard ratio =2.285,95% CI =1.521-3.431;recurrence-free survival,hazard ratio =2.167,95% CI=1.445-3.248) indicated sarcopenia as the risk factor for poorer overall survival and recurrence-free survival.Conclusions Sarcopenia was an independent predictor of poor prognosis for patients undergoing pancreaticoduodenectomy.Patients with sarcopenia had higher risk of developing complications after surgery and lower overall survival rate and recurrence-free survival rate.
		                        		
		                        		
		                        		
		                        	
7.Expression of glycogen synthase kinase-3β in renal damage of acute necrotizing pancreatitis and its mechanism
Kailiang ZHAO ; chen CHEN ; Qiao SHI ; liang ZHAO ; Fangchao MEI ; ping WANG ; Weixing WANG
Chinese Journal of Pancreatology 2017;17(5):302-306
		                        		
		                        			
		                        			Objective To observe the changes of tissue morphology and ultrastructure of kidney in the rat model of acute necrotizing pancreatitis (ANP),and to investigate the protein expression of glycogen synthase kinase-3β(GSK-3β) and phosphorylated GSK-3βin renal tissue.Methods Sixty SPF male SD rats were randomly divided into 5 groups (n =12 for each group) according to random number method,including control group,ANP 3 h,6 h,12 h,24 h groups.ANP model was established by retrograde infusion of 5% sodium taurocholate solution into the biliopancreatic duct.Rats were sacrificed at corresponding time points to collect pancreatic and left renal tissue.Serum amylase (AMY),lipase (LIPA),creatinine (Cr) and urea nitrogen (BUN) levels were detected.Pancreatic and renal tissues were routinely pathologically examined.Rephrocytes' ultrastructure changes were observed by projection electron microscope.GSK-3β protein expression and phosphorylated GSK-3β(p-GSK-3β) in kidney tissue were quantified by Western-blot.Results Serum AMY,LIPA,Cr,Bun and pathological scores for pancreatic and renal tissues in ANP groups were obviously higher than those in control group,which increased gradually with the progress of pancreatitis.In ANP rats,it was observed that the microvilli on the surface of the epithelial cells of renal tubules were swelling and irregularly arranged,the nucleus was condensed and broken,the nuclear chromatin was condensed and separated from the nuclear membrane,the mitochondria was condensed,swelling and vacuolated.The expression levels of GSK-3β protein in the renal tissue of the control group and ANP 3 h,6 h,12 h,24 h groups were 0.702± 0.044,0.876± 0.017,0.872± 0.034,0.855± 0.035 and 0.852± 0.032,respectively.The expression levels of p-GSK-3β were 0.626 ± 0.029,0.790 ± 0.029,0.616 ± 0.021,0.448 ±0.028 and 0.439 ± 0.017.GSK-3β protein expression was higher in ANP group than in control group,and the difference was statistically significant (all P < 0.05).But there was no statistically significant difference at different time points in ANP group.p-GSK-3β protein expression increased at 3 h after modeling,and then gradually decreased.p-GSK-3β protein expression was higher in ANP 3 h group than control group and other ANP groups,which in ANP 12 h,24 h group was obviously lower than control group and ANP 3 h,6 h group,and the difference was statistically significant (P < 0.05).Conclusions GSK-3β expression in the kidney of ANP rats began to increase at 3 h after modeling and maintain a high level.p-GSK-3β was transiently increased at 3 h after modeling and then gradually decreased to a level obviously lower than control group.It indicated that these changes may play a crucial role in ANP associated kidney injury.
		                        		
		                        		
		                        		
		                        	
8.Effects of rosiglitazone on hyperlipidemic rats with severe acute pancreatitis secondary to lung injury
Kailiang ZHAO ; Chen CHEN ; Jia YU ; Xiaoyan CHEN ; Liang ZHAO ; Peng HU ; Weixing WANG
Chinese Journal of Emergency Medicine 2016;25(11):1418-1423
		                        		
		                        			
		                        			Objective To explore the effects of rosiglitazone (ROSI),a peroxisome proliferator-activated receptors-gamma (PPAR-γ) ligand,on hyperlipidemia in rats with severe acute pancreatitis (SAP) associated with lung injury.Methods A total of 120 male SD rats received intragastric administration of high fat diet for two weeks to induce experimental hyperlipemia.The hyperlipidemic rats were randomly (random number) divided into six groups:hyperlipidemia (HL) group (n =20),hyperlipidemia with SAP (HP) group (n =20),hyperlipidemia with rosiglitazone intervention (HRP) group (n =20),hyperlipidemia with rosiglitazone and antagonist to rosiglitazone (HRGP) group (n =20),rosiglitazone control (HR) group (n =20) and antagonist control (HG) group (n =20).The SAP was induced by a retrograde infusion of 5% sodium tauroholate into bile-pancreatic duct,and the SAP was established in HP group,HRP group and HRGP group.In HL group,HR group and HG group,equivalent volume of normal saline was used instead of sodium taurocholate.In HRP group and HR group,ROSI (6 mg/kg) was administered via the femoral vein 1 hour prior to the administration of sodium taurocholate.In HRGP group,GW9662 (0.3 mg/kg),an antagonist to PPRA-gamma,was given via the femoral vein 30 min prior to the administration of ROSI.In HG group,only GW9662 (0.3 mg/kg) was given via the left femoral vein 30 min prior to pretend SAP modeling.Rats from each group were sacrificed by exsanguination 12 h after SAP modeling.Blood samples were taken from all subjects to measure serum amylase (AMY),total cholesterol (TC),triglycerides (TG),Successive sections of the paraffin embedded tissue from pancreas and lung were taken for pathological examination with hematoxylin-eosin (HE) staining.Histopathological changes of pancreatic and pulmonary tissues observed under light microscope were evaluated.In pulmonary tissue,nuclear factor-kappa B (NF-κB) p65 expression was assayed by immunohistochemistry.Intercellular adhesion molecule (ICAM-1) protein and tumor necrosis factor-α (TNF-γ) protein levels were studied using Western blot analysis.Results The serum levels of TC and TG in HL group and HP group were significantly higher than those in HR group and HRP group (1.24 ± 0.28,1.14 0.08 vs.0.41 ±0.17,0.58±0.12;14.86±1.47,12.42±0.96 vs.6.52±2.04,7.36±0.95,allP< 0.05);The levels of serum AMY,W/D ratio,pancreas pathologic score,lung pathologic score,expression of NF-κB p65,ICAM-1 and TNF-α in pancreas in the HP group and HRGP group were significantly higher than those in HL group,HR group,and HG group (6 501.9 ±3 770.0,5 922.2 ±925.9 vs.1 139.3 ± 35.6,1 070.8 ±67.0,1 012.4 ±94.7;3.14±0.16,3.06±0.12vs.1.81 ±0.13,1.76±0.23,1.83 ± 0.18;all P <0.05);Compared with the HP group and HRGP group,the levels of serum AMY,TC and TG were significantly decreased in HR group and HRP group,ameliorating pancreas and lung pathological damage,and down-regulating the expression of NF-κB p65,ICAM-1 and TNF-α in pulmonary tissue (all P < 0.05).While there were no statistically significant differences in above biomarkers between HP group and HRGP group (all P > 0.05).Conclusions Our study demonstrates that ROSI exerts anti-hyperlipidemic effect and anti-inflammatory effect on hyperlipidemia in rats with sodium taurocholate-induced severe acute pancreatitis associated with lung injury by inhibiting NF-κB and down-regulating the expression of TNF-α and ICAM-1.
		                        		
		                        		
		                        		
		                        	
9.Inhibition of autophgay enhances resveratrol-induced apoptosis of human chondrosarcoma cells
Kailiang ZHOU ; Kai WU ; Xiaolei ZHANG ; Yongli WANG ; Haidong JIN ; Naifeng TIAN ; Zhaojie CHEN ; Huazi XU
Chinese Journal of Pathophysiology 2015;(8):1401-1406
		                        		
		                        			
		                        			AIM:Toinvestigatewhetherautophagyisup-regulatedwhenresveratrol(Res)inducesapoptosis in chondrosarcoma , and to study the effects of autophagy inhibitor combined with Res on chondrosarcoma .METHODS:SW1353 cells were divided into 4 groups: control group, Res group, 3-methyladenine (3MA) group, and Res +3MA group.Electron microscopy was used to observe the autophagyosomes in control group and Res group .At the same time, the viability of the cells in the 4 groups was detected by CCK-8 assay.TUNEL staining and Western blotting (for determi-ning the levels of cleaved caspase-3, Bax and Bcl-2) were used to reflect levels of apoptosis in all groups .The expression of autophagy-related proteins Beclin 1, LC3-Ⅱ and p62 was detected by Western blotting .RESULTS: Exposure of the cells to Res resulted in a decrease in cell viability and an increase in the level of apoptosis ( P<0.05 ) .Compared with control group, the level of apoptosis was increased but the autophagy was decreased (P <0.05).Compared with Res group, the cell viability and the level of autophagy were decreased and the level of apoptosis was increased ( P<0.05 ) . CONCLUSION:Resveratrol induces apoptosis and autophagy , and inhibition of autophgay enhances resveratrol-induced apoptosis in chondrosarcoma .
		                        		
		                        		
		                        		
		                        	
10.Lung protective and ventilatory management strategies in potential lung donor patients after brain death: report of two cases
Huiqing GE ; Ye SHEN ; Jingyu CHEN ; Kailiang DUAN ; Xianyin SANG ; Meiqi ZHANG ; Wenwei CAI
Chinese Journal of Organ Transplantation 2015;36(5):265-270
		                        		
		                        			
		                        			Objective To investigate the effect of lung protective and ventilatory management strategies for brain death donors on eligibility and availability of lungs for transplantation.Method The clinical data of two brain dead patients who accepted lung protective ventilatory management strategies from Feb.2015 to Mar.2015 were retrospectively analyzed.Two cases of brain-dead patients,due to severe cerebral trauma,accepted the aggressive lung protective ventilatory management strategies and airway management for 9 days and 4 days respectively.PaO2/FiO2,chest imaging manifestations,surface of the lung harvested and pulmonary rehabilitation of recipients after operation were observed.Result Two lung recipients were liberated from ventilation and pulmonary function improved significantly after double lung transplantation.Conclusion The application of lung protective ventilatory strategies in potential organ donors with brain death can increase the number of eligible and harvested lungs.
		                        		
		                        		
		                        		
		                        	
            
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