OBJECTIVES: To investigate the therapeutic effect of Exocarpium Citri Grandis formula granules (ECGFG) on fatty liver disease (FLD) in zebrafish and explore the underlying mechanism. METHODS: Nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (ALD) models were established in zebrafish larvae at 3 days post fertilization (dpf), in which the treatment efficacy of 16, 32, or 64 μg/mL ECGFG was evaluated by examining zebrafish survival and liver pathologies and using whole-fish oil red O staining and RT-qPCR. The therapeutic mechanism of ECGFG for FLD was investigated using Prussian blue staining, DCFH-DA probe, MDA content detection, RT-qPCR assay and immunohistochemical staining for CAV1. RESULTS: In zebrafish models of NAFLD and ALD, treatment with ECGFG significantly reduced lipid accumulation and the expression levels of FASN, SREBP1, HMGCRA, TNF-α and IL-6, increased the expressions of Apoa1 and PPARα, and reduced iron deposition and the contents of MDA and ROS in the liver. In zebrafish models of NAFLD, treatment with ECGFG at the 3 doses significantly increased hepatic expressions of Tf, TfR, FPN and SLC7A11, and at the doses of 32 and 64 μg/mL, ECGFG obviously increased hepatic expression of GPX4. ALD fish models showed significantly increased hepatic expressions of Tf, TfR and FPN, which were effectively lowered by treatment with ECGFG at the 3 doses. ECGFG did not obviously affect the expression of SLC7A11, but its high dose (64 μg/mL) caused significant elevation of GPX4 expression. Both zebrafish models of NAFLD and ALD showed obviously increased CAV1 expression level in the liver, which was significantly reduced by treatment with 32 and 64 μg/mL ECGFG. CONCLUSIONS In zebrafish models of NAFLD and ALD, ECGFG can alleviate lipid accumulation and inflammatory response and lower the expression level of CAV1 to restore iron homeostasis and suppress lipid peroxidation and ferroptosis in the liver.
Animals ; Zebrafish ; Ferroptosis/drug effects* ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Iron/metabolism* ; Disease Models, Animal ; Lipid Peroxidation/drug effects* ; Homeostasis ; Fatty Liver/drug therapy* ; Liver/metabolism* ; Lipid Metabolism/drug effects* ; Drugs, Chinese Herbal/pharmacology*

To investigate the executive function impairment in CBS patients and its relationship with the microstructural integrity of white matter fiber tracts. MethodsEleven CBS patients and 17 cognitively normal subjects who visited our hospital from November 2018 to November 2019 were evaluated for executive function，including forward digit span，reverse digit span，correct line of TMT-A line，and correct line of TMT-B line. Diffusion tensor imaging（DTI）scans were performed in the CBS control group to compare the fractional anisotropy（FA）value，mean diffusivity（MD）value，axial diffusivity（AD）and radial diffusivity（RD）values of the fiber bundles with changed microstructure with executive function scores. ResultsExcept for CBS digit span forward score（P=0.446），reverse digit span（P<0.001），correct line of TMT-A line（P<0.001）and correct line of TMT-B line（P<0.001），the differences were statistically significant. Compared with the HC group，the FA values of the left corticospinal tract，anterior thalamic radiation，cingulate fasciculus，superior longitudinal fasciculus，inferior longitudinal fasciculus，and corpus callosum were reduced in the CBS group compared with the HC group，and the difference was not statistically significant（P>0.05）. The MD values，AD values，and RD values of the left corticospinal tract，anterior thalamic radiation，cingulate tract，superior longitudinal tract，inferior longitudinal tract，and corpus callosum were increased in the CBS group（lesion side）and the HC group compared with the HC group，and the differences were statistically significant（P<0.05）. The reverse digit span was negatively correlated with the RD value of the superior longitudinal fasciculus of the lesion（r=-0.741，P=0.036），and the reverse digit span was negatively correlated with the RD value of the superior longitudinal fasciculus of the lesion. ConclusionPatients with CBS have executive dysfunction and changes in the integrity of white matter fiber tracts；executive dysfunction in patients with CBS is related to changes in the integrity of white matter fiber tracts in addition to frontotemporal atrophy；abnormal structural connectivity of white matter fibers may be one of the causes of executive dysfunction in patients with CBS.

Objective To analysis long-term effects and safety of arsenic trioxide (ATO)-based induction and maintenance therapy in newly diagnosed acute promyelocytic leukemia (APL). Methods Retrospective analysis induction remission and post-remission treatment of 62 newly diagnosed APL patients was performed. These cases were followed up for 5 and 7 years. Results The complete remission (CR) rate was similar in ATO/all-trans retinoic acid (ATRA) induction group and ATRA/chemotherapy induction group.However, the former group has the shorter time to CR. The negative rate of PML-RARα fusion gene after induction without ATO was less than that of ATO group (86.2 % vs 56.3 %, P ＜0.05). After CR, the 5-year overall survival (OS) between ATO-base rotation maintenance group and chemotherapy-base rotation maintenance group showed that the former was (94.4±5.4) %, the latter is (45.5±10.2) %; 7-year OS was (52.5±23.7) % and (27.3±9.3) %; 5-year disease free survivals (DFS) was (94.7±5,5) % and (41.3±10.1) %; 7-year DFS was (52.6±23.7) % and (27.5±9.4) %. There was significant different in 5-year or 7-year OS and DFS between two groups (P ＜0.05). The relapse rates of the two groups in post-remission treatment were 14.7 % and 37.0 % (P ＜0.05). Conclusion ATO combined ATRA induction therapy increased the negative rate of PML-RARα fusion gene. ATO-base rotation maintenance improved long-term outcome and decreased the rate of relapse. Furthermore, ATO appeared to be generally safe and well tolerated.

Purpose: To evaluate the clinical efficacy of V AD regimen in the treatment of newly diagnosed stage III multiple myeloma (MM). Methods:26 patients with newly diagnosed stage Ⅲ multiple myel oma were treated with VAD regimen. VAD solution consisted of vincristine (VCR) , doxorubicin(ADR),dexamethasone (Dex).Three continuous treatments in one treatm ent course were considered evaluable.Evaluation included results of serum myelom a protein(M-protein); renal function; proteinuria of 24-hours; bone marrow ; per ipheral blood et al.The side reactions were recorded. The clinical efficacy eval uation was divide into complete response(CR),partial response(PR),minimal-respon se(MR), no change(NC) , plateau progression.Results:5 cases achieved CR(19.3%), 13 cases PR(50%),6 case s MR (23%), 2 cases no change (7.7%). Overall response rate was 92.3%, median su rvival duration was 7 to 84 months (29.6?17months). Conclusions:Achieved marked clinical efficacy with VAD agent in newly diagnosed stage III multiple myeloma. Especially,the patients with renal failure and serious clinical manifestation improved rapidly and significantly.