Aim To research the synergistic effect of hyperlipoproteinemia and Aβ in the processing of Alzheimer′s disease.Methods Seventy SD rats were randomly divided into seven groups, and dealt with D-gal(hypodermic injection), hyperlipemia diet, microinjection into both side of CA1 section in hippocampus, independently.Morris water maze(MWM) test was used to evaluate the spatial memory impairments.Tau and tau(pThr181) pathology in the hippocampus were detected using Western blot and immunohistochemistry.Nissl′s staining was used to detect cell apoptosis.Results Aβ25-35-treated rats showed significant impairments of spatial memory in MWM test, especially in the group of D-gal+Aβ25-35+HLD(P<0.01).Furthermore, these rats treated with Aβ25-35, D-gal, and hyperlipemia diet, exhibited significantly increased phosphorylation of tau, particularly in the Thr181 site.Conclusion Hyperlipoproteinemia is the risk factor for older person, which could strengthen the toxic effect of Aβ, and promote phosphorylation of tau.

Objective To investigate the effect of macrophage polarization on tubulointerstitial fibrosis of mouse unilateral ureteral obstruction(UUO) model.Methods Twelve male C57BL/6J mice were employed,each of which with an age of 8 to 10 weeks.UUO model was established with these mice with the method of unilateral ureteral ligation.Mice were then sacrificed on the 7th and 14th day respectively after operation,and renal tissue specimens were obtained.The authors detected collagen deposition by Masson staining,and alpha smooth muscle actin (alpha SMA) as well as collagen type Ⅰ (Coll-1) mRNA by real-time quantitative PCR.The authors also detected the degree of renal interstitial macrophages infiltration and expression changes of polarization by immunofluorescence staining.Results Compared with the mice that were observed on the 7th day after operation,the degree of renal interstitial fibrosis in mice observed on the 14th day after operation was comparatively serious,the difference shown by semi-quantitative results was statistically significant (P ＜ 0.05).Moreover,mice observed on the 14th day after operation have more M2 macrophages,the difference between two groups of mice was statistically significant (P ＜ 0.05).On the contrary,there was no statistically significant difference in the degree of M1 macrophages infiltration between these two groups of mice.Conclusions In the renal interstitial fibrosis model induced by UUO,the degree of macrophage infiltration increased significantly,mainly resulted from M2 macrophage infiltration,suggesting that M2 macrophages were involved in the formation of renal fibrosis.

OBJECTIVE: To analyze the hematological phenotypes of Hb J-Bangkok and concomitant thalassemia. METHODS: In total 72 397 samples were screened by using capillary electrophoresis. Samples with Hb J-Bangkok were identified by DNA sequencing and analysis of red blood cell parameters. Gap-PCR and PCR-reverse dot blotting (PCR-RDB) were used for analyzing the thalassemia genes. RESULTS: Thirty one cases of Hb J-Bangkok were identified, all of which were heterozygotes. The hematological phenotype index (Hb, mean corpuscular volume, mean corpuscular hemoglobin, Hb J-Bangkok, Hb A CONCLUSION Hb J-Bangkok heterozygotes have normal hematological phenotypes, though they may show different hematological characteristics when concomitant with different types of thalassemia, for which genetic counseling should be provided accordingly.
Female ; Hemoglobins, Abnormal/genetics* ; Heterozygote ; Humans ; Male ; Phenotype ; Thailand ; beta-Thalassemia/genetics*

Objective:To observe the efficacy and safety of radium-223 in metastatic castration resistant prostate cancer (mCRPC) with bone metastasis.Methods:The clinical data of 48 patients with mCRPC treated with radium-223(55 kBq/kg, once every 4 weeks, planned to use for 6 cycles)from February 2021 to May 2022 were analyzed retrospectively. All patients had symptomatic bone metastasis without visceral metastasis, which the number of bone metastasis was more than one site.They were all classified as IVb stage. The average age was 70.5 (ranging 49-90) years. The median PSA was 44.70(ranging 0.15-1 864.00) ng/ml. The median ALP was 162 (ranging 43-1 589) U/L. The median time from mCRPC diagnosis to radium-223 use was 10 (ranging 3-47) months. 9, 18 and 11 patients had received first-line, second-line and third-line treatment for mCRPC before enrollment respectively, 10 patients had received at least fourth-line treatment. 38 (79.1%), 31 (64.5%), 30 (62.5%) and 7 (14.6%) patients had used abiraterone, enzalutamide, docetaxel and olaparib before enrollment. The probability of PSA level decrease >30%, ALP level decrease >30%, symptom improvement rate, median overall survival (OS), as well as the occurrence of treatment-related adverse reactions and the reasons for withdraw treatment were analyzed.Results:The median follow-up time was 8 (ranging 1-16) months. 11 patients completed all 6 courses of treatment. The median number of completed courses was 4 (ranging 1-6). 27 patients (56.2%) received radium-223 and bone protection drugs (Bisphosphate/ Denosumab). PSA decreased by >30% was recorded in 10 patients (20.8%) and ALP decreased by >30% was recorded in 25 patients (52.1%). 23 cases (47.9%) reported bone pain relief during treatment. Among the 9 patients who had received first-line of mCRPC previously, 6 cases (66%) had relief of bone pain symptoms, and 4 cases (44%) had a decrease of PSA >30%. Among the 18 patients who had previously received second-line mCRPC treatment, 11 cases (61%) had relief of bone pain symptoms, and 4 cases (22%) had a decrease of PSA >30%. Among the 21 patients who had received third-line or more mCRPC treatment in the past, 6 (28.5%) had symptom relief, and 2 (9.5%) had PSA decrease >30%. The median overall survival (OS) was not reached, and the OS was estimated to be 12.5 months using the Kaplan-Meier method. The most common hematological adverse effects were thrombocytopenia (15 cases, 31.2%; grade 3 in 6 cases and grade 4 in 0), followed by leucopenia (11 cases, 22.9%; grade 3 in 4 cases and grade 4 in 1 case) and anemia (8 cases, 16.7%; grade 3 in 3 cases and grade 4 in 0). Non-hematological adverse reactions included fever in 1 case (2.1%), constipation in 4 cases (8.3%), nausea and vomiting in 10 cases (20.8%), diarrhea in 7 cases (14.6%), dizziness in 1 case (2.1%) and fatigue in 11 cases (22.9%). Seven cases were discontinued due to intolerable adverse reactions (median 2 courses), 14 cases were discontinued due to disease progression or death (median 2 courses), and 5 cases were discontinued due to other reasons (median 1 course).Conclusions:Radium-223 has a good performance in symptom control for mCRPC patients who have previously received first-line or second-line therapy. Due to the high incidence of hematological adverse reactions, more attention should be paid to the changes of hemogram during the treatment, and timely treatment should be carried out to improve the drug tolerance of patients.

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2 macrophages infiltration. In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease.