Objective:To evaluate the efficacy and safety of switch from prednisone (AA+ P) to dexamethasone (AA+ D) in metastatic castration-resistant prostate cancer patients (mCRPC) progressing on abiraterone plus prednisone.Methods:Between November 2016 and December 2019, 46 mCRPC patients were switched to AA+ D after progression on AA+ P at Sun Yet-sen University Cancer center. Median age was 72 years(50 to 89 years), with median androgen deprivation therapy (ADT) duration 14.6 months(2.1 to 168.5 months). PSA level at the time of diagnosis, the initiation of AA+ P treatment, the time of switch were 258.9 ng/ml, 56.6 ng/ml, 25.1 ng/ml, respectively. 42 (91.3%), 12(26.1%), 7(15.2%) patients had bone metastasis, lymph node metastasis, visceral metastasis, respectively. 28 patients had Gleason score ≥8, and 11 patients had Gleason score<8. The primary endpoint was progression free-survival (PFS). Secondary endpoints included PSA response rate of PSA decline ≥50% and ≥30% and safety. Patients were divided into different risk level groups according to PSA level at the time of switch and PFS on AA+ P.Results:The median follow-up of 46 patients was 4.9 months, 40 patients progressed at the last follow-up, the treatment was terminated in 1 patient because of cerebral infarction, 5 patients were still on the treatment of AA+ D. Median PFS on AA+ D of 46 patients was 3.7 (1.6-24.1) months. A total of 12 (26.1%) patients showed a PSA decline≥50% after treatment with AA+ D, and 21 (45.7%) patients showed a PSA decline ≥30%. The median PFS was 8.5 (2.7-24.1) and 3.0 (1.6-17.8) months for patients with PSA decline≥50% and PSA didn’t decline ≥50%, respectively. Four factors below were significantly associated with a longer PFS on AA+ D after steroid switch in univariate analysis: lower PSA level at the time of switch (<30 ng/ml, HR=0.30, 95% CI 0.14-0.64, P=0.002), longer ADT sensitivity duration (≥18 months, HR=0.55, 95% CI 0.28-1.06, P=0.045), longer AA+ P treatment PFS (≥8 months, HR=0.36, 95% CI 0.18-0.72, P=0.004), and greater PSA decline on AA+ D (≥50%, HR=0.30, 95% CI 0.17-0.75, P=0.007). The above mentioned factors were also independent prognostic factors associated with better PFS on AA+ D after steroid switch in multivariate analysis. Treatment with AA+ D was well tolerated in all patients, with no grade 3/4 toxicity reported. Conclusions:Switching from prednisone to dexamethasone is effective and safe in mCRPC patients progressing on abiraterone plus prednisone. Patients with lower PSA level at the time of switch, longer ADT sensitivity duration, longer AA+ P treatment PFS and greater PSA decline on AA+ D might gain better efficacy.

The change in serum level of 8-hydroxy-deoxyguanosine (8-OHdG),an oxidative stress biomarker,in patients with active Graves' ophthalmopathy (GO) during corticosteroid treatment was observed.The serum level of 8-OHdG was significantly increased in patients with active GO as compared with that of normal controls and patients with Graves' disease (P ＜ 0.05).After systemic corticosteroid treatment,patients with GO showed significantly lowered 8-OHdG level as compared with that before treatment and patients with Graves' disease.These changes in serum 8-OHdG level were accompanied by decreases in clinical activity score (P ＜ 0.05) during corticosteroid treatment.Oxidative stress may play a role in the pathogenesis of GO.Serum 8-OHdG level may be used as an objective and quantitative parameter in patients with GO during immunosuppressive treatment.

Objective To investigate the therapeutic effect of liraglutide on glycemic control in metformin-treated patients with type 2 diabetes mellitus (T2DM).Methods Twenty patients with T2DM by maximum tolerated dose of mefformin in this study.For at least 3 months,participants were treated by addingliraglutide.After 1 week,the dosage of liraglutide was increased to 1.2 mg for 3 months from 0.6 mg.Patients' blood glucose,glycosylated hemoglobin(HbA1c),islet function,blood lipid and body weight were observed.Results Compared with before treatment,there were significant change of fasting blood glucose ((8.9 ± 1.4) mmol/L vs.(6.9 ± 1.0) mmol/L,t =5.951,P ＜0.01),postprandial blood glucose ((14.4 ±1.5) mmol/L vs.(10.4 ± 1.4) mmol/L,t =8.878,P ＜ 0.01)),HbA1 c ((8.7 ± 1.3) ％ vs.(7.6 ± 1.1) ％,t =4.860,P ＜0.01),fasting C peptide ((1.7 ±0.6) mg/L vs.(2.9 ± 1.1) mg/L,t =5.752,P ＜ 0.01) and postprandial2 h C peptide ((5.0 ±2.3) mg/L vs.(10.2 ±3.5) mg/L,t =5.667,P ＜0.01) after treatment.Significant change of blood liquid and body weight were also observed after treatment than before treatment (P ＜ 0.01).Conclusion Liraglutide treatment resulted in persistent better glycaemic control,weight reduction,improvements of blood lipid and function of pancreatic island successfully.Liraglutide was also associated with low risk of hypoglycemic and should be chosen by patients with T2DM.

To investigate the role played by 8-hydroxy-deoxyguanosine (8-OHdG) in patients with Graves'ophthalmopathy(GO),and the association between 8-OHdG and the disease activity of GO.Serum levels of 8-OHdG were tested in 48 cases with GO and 30 cases with Graves' disease(GD) without ophthalmopathy.30 healthy subjects participated in this study as controls.8-OHdG was detected by enzyme-linked immunosorbent assay (ELISA).Compared with the controls,the mean level of 8-OHdG in GO patients and GD patients was increased significantly [(2.98±1.33),(2.07±1.30) vs(0.72±0.93)ng/ml,P＜0.05].Mean 8-OHdG level in GO patients was markedly higher when compared to GD patients(P＜0.05).Pearson regression analysis showed that elevated levels of 8-OHdG were significantly correlated with the Clinical Activity Score of GO (r =0.54,P＜0.01).The serum level of 8-OHdG in GO patients was raised obviously,it implies that oxidative stress plays an important role in the pathogenesis of GO,and the serum level of 8-OHdG might act as an activity index of GO.

To investigate weather serum soluble intercellular adhesion molecule-1 (sICAM-1) and hyaluronic acid(HA) levels can be used in assessing the disease activity of Graves' ophthalmopathy (GO).Serum levels of sICAM-1 and HA were determined in 48 cases with GO and 30 cases with Graves' disease without GO (CON).Compared with the CON group,the levels of sICAM-1 and HA in GO cases were raised significantly( P＜0.05 ).sICAM-1 and HA levels in the subgroup of patients with active GO were markedly elevated when compared to those with stable GO(P＜0.05 ).Pearson regression analysis showed that elevated levels of slCAM-1 and HA were positively correlated with the Clinical Activity Score ( CAS ) of GO ( r =0.53,P ＜ 0.01 ; r =0.46,P ＜ 0.01 ) ; A significant correlation between sICAM-1 and HA( r=0.31,P＜0.05 ) was noted.The raised serum levels of sICAM-1and HA may serve as two activity markers of GO.

Objective To investigate the reliability of intramyocardial electrogram (IMEG) in monitoring acute rejection after human heart transplantation. Methods From June 2004 to March 2009, 32 patients underwent orthotopic heart transplantations. During the operation telemetric pacemakers were placed under the skin of the body with connected bipolar electrodes implanted into epimyocardium. Postoperative IMEGs, including the autonomous IMEG and ventricular evoked response (VER) were recorded routinely. The endomyocardium biopsy (EMB) was taken routinely and performed once again when positive IMEG results or other positive signs were observed. Results Totally 523 IMEGs has been produced, 41 of VERs were recorded together with autonomous IMEGs and EMBs, in which 17 EMB specimens were confirmed positive and 24 negative. AUC of QRS was 0.7537, Se was 88.24%, Sp was 62. 50%; AUC of Tslew was 0. 9081, Se was 94. 12%, Sp was 87. 50%. QRS and Tslew had significant difference in AUC of ROC, with x2 = 4. 22, P＜0. 05; AUC of combined diagnostic index (positive when either QRS or Tslew is positive and negative when both values are negative) was 0. 7917, Se was 100.00%, Sp was 58. 33%. Conclusion QRS amplitude of the autonomous IMEGs, Tslew of VERs and combined diagnostic index are reliable indexes for monitoring acute allograft rejection after human heart transplantation. Furthermore, Tslew has a better prognostic value than QRS.

Objective:To study the express levels of transcription factor nuclear factor-?B in diabetic rat retina. Methods: Sprague-Dawley rats were randomly divided into control groups of 1, 3 and 6 months, diabetic groupsof 1, 3 and 6 months, respectively. Diabetic model of rat was induced by injecting streptozotocin (STZ). The retinal morphology was observed in paraffin slide by microscope. The expression of NF-?B was detected by immunohistochemistry and electrophoretic mobility shift assay. Results: Histopathological changes were detected at 3 and 6 months. The changes were severer at 3 months than at 6 months. Activation of retinal NF-?B was detected by electrophoretic mobility shift assay and immunohistochemistry at 1 month, and the NF-?B remained activated at 3 and 6 months in diabetic rats. Conclusion: NF-?B is activated in retina in diabetes before histopathological changes can be seen, and remains activated for the duration when the retinopathy is developing.

Objective:Activation of the transcription factor nuclear factor-kappaB (NF-?B) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short activation of NF-?B , we observed a long-lasting activation of NF-?B and iNOS in the kidneys of diabetic rats. Methods:Sprague-Dawley rats were randomly divided into control group and diabetic group. The pathological changes in the kidneys of diabetic rats were observed at 1, 3 and 6 months respectively. The activity of NF-?B and iNOS was detected by immunohistochemistry. Results:The change of histopathology was severer at 6 months than at 3 months and 1 month in the kidneys of diabetic rats. A comparable increase in NF-?B p65 antigen was observed in the kidney cells especialy in vascular endothelial cells of diabetic rats, and the expression of iNOS in renal tissues of diabetic rats was higher than that of normal control. Conclusion:NF-?B and iNOS may play an important role in the pathoge-neis of diabetic rats, and the expression of them may be considered as a predictor of progressive renal in- jury in diabetic rats.

Diabetic cardiovascular autonomic neuropathy is the most common and troublesome complication of diabetes mellitus.Diabetic cardiovascular autonomic neuropathy contributes greatly to the morbidity,mortality.Factors in the pathogenesis of these complications are altered metabolism,vascular insufficiency,loss of growth factor trophism,and autoimmune destruction of nerves in a visceral and cutaneous distribution.There are studies in progress that suggest cardiovascular autonomic nerves can be induced to regenerate,and the future for patients with diabetic cardiovascular autonomic neuropathy is brighter.

At the present a clear account of pathogensis of autoimmune thyroid disease(AITD) cannot be given, although several pathogenic factors have been implicated in AITD. However patients way differ in these factors and mechanisms, which contributes to the clinical and pathological heterogeneity of AITD. This article focuses on recent research of possible genetic and environmental factors in AITD.