Objective:To investigate factors influencing 18F-FDG PET/CT SUVmax,T/MB ratio and Ki-67 expression in non-Hodgkin's lymphoma(NHL),to analyze their correlations with lymphoma aggressiveness and their potential advantages in predicting therapeutic efficacy.Methods:A retrospective analysis was conducted to investigate correlations between tumor SUVmax,T/MB ratio,and Ki-67 expression with NHL aggressiveness and clinical characteristics in 99 patients;whether SUVmax,T/MB ratio and Ki-67 served as independent prognostic factors influencing therapeutic efficacy was examined,and potential utility of ΔSUVmax and ΔT/MB as biomarkers for treatment response assessment were evaluated.Results:Aggressive NHL demonstrated significantly higher SUVmax,T/MB ratio and Ki-67 level compared to indolent NHL and aggressive/indolent NHL(P<0.05).A pretreatment SUVmax≥9.05,T/MB≥5.115 or Ki-67≥55%could predict clinical remission in NHL patients post-treatment,while post-treatment reductions of ΔSUVmax≥22.65%or ΔT/MB≥34.85%were associated with achieved clinical remission.Conclusion:SUVmax,T/MB ratio and Ki-67 are closely associated with aggressiveness of NHL,which can be predicted whether NHL will be relieved after treatment.ΔSUVmax and ΔT/MB can assess whether NHL has been relieved after treatment.

Objective:To investigate factors influencing 18F-FDG PET/CT SUVmax,T/MB ratio and Ki-67 expression in non-Hodgkin's lymphoma(NHL),to analyze their correlations with lymphoma aggressiveness and their potential advantages in predicting therapeutic efficacy.Methods:A retrospective analysis was conducted to investigate correlations between tumor SUVmax,T/MB ratio,and Ki-67 expression with NHL aggressiveness and clinical characteristics in 99 patients;whether SUVmax,T/MB ratio and Ki-67 served as independent prognostic factors influencing therapeutic efficacy was examined,and potential utility of ΔSUVmax and ΔT/MB as biomarkers for treatment response assessment were evaluated.Results:Aggressive NHL demonstrated significantly higher SUVmax,T/MB ratio and Ki-67 level compared to indolent NHL and aggressive/indolent NHL(P<0.05).A pretreatment SUVmax≥9.05,T/MB≥5.115 or Ki-67≥55%could predict clinical remission in NHL patients post-treatment,while post-treatment reductions of ΔSUVmax≥22.65%or ΔT/MB≥34.85%were associated with achieved clinical remission.Conclusion:SUVmax,T/MB ratio and Ki-67 are closely associated with aggressiveness of NHL,which can be predicted whether NHL will be relieved after treatment.ΔSUVmax and ΔT/MB can assess whether NHL has been relieved after treatment.

The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes. Progestin and adipoQ receptor 3 (PAQR3), a key regulator of inflammation and metabolism, can negatively regulate the PI3K/AKT signaling pathway. Here, we report that gentiopicroside (GPS), the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa, decreased lipid synthesis and increased glucose utilization in palmitic acid (PA) treated HepG2 cells. Additionally, GPS improved glycolipid metabolism in streptozotocin (STZ) treated high-fat diet (HFD)-induced diabetic mice. Our findings revealed that GPS promoted the activation of the PI3K/AKT axis by facilitating DNA-binding protein 2 (DDB2)-mediated PAQR3 ubiquitinated degradation. Moreover, results of surface plasmon resonance (SPR), microscale thermophoresis (MST) and thermal shift assay (TSA) indicated that GPS directly binds to PAQR3. Results of molecular docking and cellular thermal shift assay (CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH₂-terminus including Leu40, Asp42, Glu69, Tyr125 and Ser129, and spatially inhibited the interaction between PAQR3 and the PI3K catalytic subunit (P110α) to restore the PI3K/AKT signaling pathway. In summary, our study identified GPS, which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway, as a potential drug candidate for the treatment of diabetes.

Objective To study the effect of comprehensive Chinese medicine therapy,including Chinese herbal medicine fumigation,massage,and quadriceps exercise,on adipokines of visfatin and chemerin content in joint fluid of patients with knee osteoarthritis (KOA),and to explore its possible therapeutic mechanism for KOA.Methods A total of 60 cases of KOA patients were randomly divided into treatment group and control group,30 cases in each group.The treatment group was treated with comprehensive Chinese medicine therapy,and the control group was treated with Chinese medicine fumigation alone.After treatment for 2 weeks,the clinical efficacy of both groups was evaluated,and the changes in the scores of the Western Ontario and McMaster Universities Arthritis Index (WOMAC)were observed.Moreover,the contents of visfatin and chemerin in jointfluid were examined.Results (1) The total effective rate of the treatment group was 96.7％ and that of the control group was 83.3％,the difference being significant (P ＜ 0.01).(2) After treatment,WOMAC scores of both groups were obviously decreased(P ＜ 0.01 compared with those before treatment),and the decrease in the treatment group was superior to that in the control group (P ＜ 0.01).(3) The contents of visfatin and chemerint in joint synovial fluid of both groups were decreased (P ＜ 0.01 compared with those before treatment),and the decrease in the treatment group was superior to that in the control group(P ＜ 0.05).Conclusion The comprehensive Chinese medicine therapy of Chinese herbal medicine fumigation,massage and quadriceps exercise is effective for the treatment of KOA,and can decrease the contents of visfatin and chemerin in joint fluid of KOA patients,which may be one of its therapeutic mechanisms.

Objective To evaluate the risk of locoregional recurrence (LRR) and the influencing factors for long-term survival in patients with epithelial-myoepithelial carcinoma (EMCa).Methods A retrospective analysis was performed for 18 EMCa patients, who received initial therapy or initial adjuvant therapy in our hospital from 1999 to 2015, to investigate their survival.Among these patients, 8(44%) underwent surgery alone, 9(50%) received adjuvant radiotherapy, and 1(6%) received radical concurrent chemoradiotherapy.Locoregional recurrence-free survival (LRFS) and overall survival (OS) rates were compared between these groups.The Kaplan-Meier mtthod was used to calculated survival rates and log-rank test was used to compare the LRFS.Results With a median follow-up time of 46 months, 5 patients developed LRR, and the 5-year LRFS and OS rates were 69% and 93%, respectively.The patients treated with radiotherapy had a significantly higher 5-year LRRFS rate than those not treated with radiotherapy (71% vs.57%, P=0.569).Conclusions LRR is the main failure mode of EMCa treatment, and further improving local control is the key to improved survival.

AIM:To investigate the effect of short-chain acyl-CoA dehydrogenase ( SCAD) on collagen expres-sion and proliferation of rat cardiac fibroblasts and to explore the relationship between SCAD and cardiac fibrosis . METHODS:The model of proliferation and collagen expression of rat cardiac fibroblasts induced by angiotensin II was es -tablished.After treatment with siRNA-1186, the expression of SCAD at mRNA and protein levels , fatty acids beta oxida-tion rate, ATP, the enzyme activity of SCAD and free fatty acids in the rat cardiac fibroblasts were determined . RESULTS:The mRNA and protein expression of SCAD was decreased in the rat cardiac fibroblasts induced by angiotensin II compared with the control cells , and the expression of collagen I and collagen III was significantly upregulated .Com-pared with negative control group , SCAD expression and activity , fatty acid beta-oxidation rate and ATP significantly de-creased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the rat cardiac fibroblasts , and the expression of collagen I and collagen III was significantly up-regulated.CONCLUSION:The expression and synthesis disorder of collagen may be triggered by down-regulation of SCAD .SCAD may be a promising therapeutic target for myocar-dial fibrosis .

AIM:To investigate the change of short-chain acyl-CoA dehydrogenase (SCAD) expression during cardiomyocyte apoptosis and to explore the relationship between SCAD and cardiomyocyte apoptosis .METHODS: The neonatal rat cardiomyocytes treated by tert-butyl hydroperoxide (tBHP) were used as the model of cardiomyocyte apoptosis . The cell viability , the expression of SCAD at mRNA and protein levels , the activity of SCAD and the content of free fatty acids were determined .RESULTS:The mRNA and protein expression of SCAD decreased in the cardiomyocyte apoptosis model.Compared with negative control group , SCAD expression and activity were both significantly decreased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the cardiomyocytes .Meanwhile, SCAD siRNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP .CONCLUSION: Down-regulation of SCAD may play an important role in primary cardiomyocyte apoptosis .Increase in the expression of SCAD may become an impor-tant part in intervening cardiomyocyte apoptosis .

[ABSTRACT]AIM:ToinvestigatethedifferenteffectsofERK1/2/PPARα/SCAD(short-chainacyl-CoAdehy-drogenase) signal pathways on the cardiac hypertrophy induced by insulin-like growth factors 1 ( IGF-1) or phenylephrine ( PE) .METHODS:The neonatal rat cardiomyocytes induced by IGF-1 were used as the model of physiological cardiac hypertrophy , and those induced by PE were used as the model of pathological cardiac hypertrophy .The surface area of the cardiomyocytes, the expression of p-ERK1/2, PPARαand SCAD, the activity of SCAD and the content of free fatty acid in the cardiomyocytes were measured .RESULTS:Compared with the control cells , the surface area of the cardiomyocytes in-duced by IGF-1 and PE were both increased .Compared with the controls , the expression of SCAD and PPARα, and the activity of SCAD in the cardiomyocytes induced by IGF-1 were increased , while the expression of p-ERK1/2 was de-creased.However, the cardiomyocytes treated with PE showed decreased expression of SCAD and PPARα, decreased activ-ity of SCAD and increased expression of p-ERK1/2.Meanwhile, the decrease in free fatty acid in IGF-1-induced cardio-myocytes and the increase in PE-induced cardiomyocytes indicated that the fatty acid utilization was increased in the cardio -myocytes induced by IGF-1, but decreased in the cardiomyocytes induced by PE .CONCLUSION: The changes of p-ERK1/2, PPARαand SCAD in the cardiac hypertrophy induced by IGF-1 or PE indicate that the effects of ERK 1/2/PPARα/SCAD signal pathways are different between physiological cardiac hypertrophy and pathological cardiac hypertro -phy , and that SCAD may be a molecular marker of these 2 different cardiac hypertrophies and a potential therapeutic target for pathological cardiac hypertrophy .

Objective To discuss the surgical treatment and its effects for hepatocellular carcinoma (HCC) in late pregnancy. Methods Clinical data of 3 patients with HCC in late pregnancy who were admitted in Department Hepatobiliary Surgery, the First People's Hospital of Foshan from November 2011 to December 2011 were analyzed retrospectively. The age of the patients was 23, 33 and 26 years old respectively. Case 1 with 35 weeks pregnancy was admitted to hospital for 3+weeks of progressive jaundice in skin and sclera after caesarean, and the alpha-fetoproteins (AFP) was 49 096μg/L. Case 2 with 29+4 weeks pregnancy was admitted to hospital after 1 week of ifnding a giant occupying lesion in the right lobe of liver, and the AFP was 973μg/L. Case 3 with 30+6 weeks pregnancy was admitted to hospital for 1 month of right upper quadrant abdominal dull pain after 2 d of ifnding a giant occupying lesion in the right lobe of liver, and the AFP was>1 210μg/L. The patients who had a history of viral hepatitis B began to take obstetrical examinations from 3+month of pregnancy, but not including the upper abdomen ultrasonic scan. All of them were diagnosed with HCC by ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI). The informed consents of 3 patients were obtained and the ethical committee approval was received. Case 1 underwent percutaneous transhepatic cholangial drainage (PTCD) to reduce jaundice, then underwent right hemihepatectomy by anterior approach+thrombectomy through choledochotomy+left hepatic duct-jejunum end-to-side anastomosis. Case 2 delivered a healthy baby girl by caesarean after 2 weeks of conservative treatment, then underwent right hemihepatectomy by anterior approach+hepatic segmentⅣnodulectomy. Case 3 delivered a healthy baby boy naturally after 1 week of conservative treatment, then underwent segmentⅥ,Ⅶ,Ⅷhepatectomy by anterior approach. Results Case 1 recovered well after operation and was found with multiple intrahepatic metastasis in January 2013. Then transcatheter arterial chemoembolization (TACE) was performed. Case 2 was discharged from hospital with improvement 10 d after operation. Multiple hepatic and pulmonary metastasis was found 4 months after operation, and then treatments of targeted therapy of sorafenib combined with local radiofrequency ablation were given to the patient. Case 3 suffered bile leakage, bile duct and right subphrenic infection, and pancreatic tail infection and necrosis after operation and was discharged from hospital with improvement 93 d after treatments of repeated anti-infection, percutaneous peritoneal drainage, enternal nutrition support and so on. And then multiple pulmonary metastasis was found in February 2013. All the patients survived till this article was submitted. Conclusions Once the diagnosis of HCC in late pregnancy is conifrmed, the patient is suggested to keep pregnant till 32 weeks in order to save baby’s life and undergo hepatectomy as early as possible. Most of the patients are late HCC and the curative effect is poor.

OBJECTIVETo investigate the apoptosis inducing effects of ponicidin (PON) on leukemic K562 cells and its mechanisms of action.

METHODK562 cells in culture medium in vitro were given different concentrations of PON (10-50 micromol x L(-1)) for 24, 48 and 72 h. The inhibitory rate of the cells was measured by MTT assay, cell apoptotic rates were detected by flow cytometry (FCM) using Annexin V staining after K562 cells were treated with different concentrations of PON for 72 hours, and cell morphology was observed by Wright-Giemsa staining. Western blot was used to detect caspase-3 and poly(ADP-ribose) polymerase (PARP) expression, and the protein levels in mitogen-activated protein kinase signaling pathways (MAPKs, p-P38, p-ERK and p-JNK) as well as p-AKT and p-P85 in PI3K/AKT signaling pathways were also detected.

RESULTPON (over 30 micromol x L(-1)) could inhibit the growth of K562 cells in both time- and dose-dependent manner. FCM analysis revealed that apoptotic cells were gradually increased in a dose-dependent manner after treatment for 72 hours, and that marked morphological changes of cell apoptosis such as condensation of chromatin was clearly observed by Wright-Giemsa staining after treatment by 50 micromol x L(-1) PON. Western blot showed cleavage of the caspase-3 zymogen protein (32 kD), with the appearance of its 17 kD subunit, and a cleaved 89 kD fragment of 116 kD PARP was also found. Furthermore, Western blotting also showed that expression of p-AKT and p-P85 in PI3K/AKT signaling pathways was downregulated dramatically whereas the expression of p-P38 as well as p-ERK and p-JNK remained unchanged after the cells were treated by PON for 48 h.

CONCLUSIONThe results demonstrate that PON exhibits in vitro anti-leukemia effect by induction of apoptosis in K562 cells, and that PON induced apoptosis in K562 cells mainly related to activation of caspase-3 as well as inactivation of PI3K/AKT signaling pathway via down regulation of the expression of p-AKT and p-P85 protein levels. These results provide strong laboratory evidence for further anti-leukemia trials of PON.

Apoptosis ; drug effects ; Blotting, Western ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Diterpenes ; pharmacology ; Humans ; Poly(ADP-ribose) Polymerases ; metabolism ; Signal Transduction ; drug effects