OBJECTIVES: To investigate the role of mitochondrial autophagy disorder caused by deletion of E3 ubiquitin ligase Parkin in neuroinflammation in a mouse model of MPTP-induced Parkinson's disease (PD). METHODS: Wild-type (WT) male C57BL/6 mice and Parkin^-/- mice were given intraperitoneal injections with MPTP or PBS for 5 consecutive days, and the changes in motor behaviors of the mice were observed using open field test. The effects of Parkin deletion on PD development and neuroinflammation were evaluated using immunofluorescence and Western blotting. The changes of the PINK 1/Parkin signaling pathway in the midbrain substantia nigra of the mice were examined to explore the molecular mechanism of Parkin-mediated regulation of mitochondrial autophagy and its effect on neuroinflammation in PD mice. RESULTS: Compared with their WT counterparts, the Parkin^-/- mice with MPTP injections exhibited significant impairment of motor function with decreased TH⁺ neurons, increased α-synuclein (α-syn) accumulation, and increased numbers of GFAP⁺ and I-ba1⁺ cells in the midbrain substantia nigra. Parkin deletion obviously affected PINK1/Parkin-mediated mitochondrial autophagy to result in significantly increased mtDNA and upregulated expressions of STING and NLRP3 inflammatosomes in the midbrain substantia nigra of MPTP-treated transgenic mice. CONCLUSIONS Parkin deletion causes mitochondrial autophagy disorder to accelerate PD progression and exacerbates neuroinflammation in mice by affecting the PINK1/Parkin signaling pathway, suggesting the important role of Parkin in early pathogenesis of PD.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mice ; Mice, Inbred C57BL ; Male ; Parkinson Disease/genetics* ; Protein Kinases/genetics* ; Mitochondria/metabolism* ; Disease Models, Animal ; Autophagy ; Signal Transduction ; Neuroinflammatory Diseases/metabolism* ; Mice, Knockout ; alpha-Synuclein/metabolism* ; Substantia Nigra/metabolism* ; Mitophagy ; Disease Progression

ObjectiveTo explore the correlation between dryness and energy metabolism of Atractylodis Rhizoma， and to analyze the difference of medicinal properties between Atractylodes lancea and A. chinensis. MethodA total of 110 healthy SD rats were randomly divided into 11 groups， including normal group， volatile oil of A. lancea 1-5 group （S1-S5 group， doses of 447， 473， 442， 489， 496 mg·kg^-1） and volatile oil of A. chinensis 1-5 group （N1-N5 group， doses of 197， 118， 281， 222， 185 mg·kg^-1）， the administration volume was 0.01 mL·g^-1 with intragastric administration for 21 days. Dryness effect of A. lancea and A. chinensis on rats was evaluated by comparing the body weight， drinking water volume， urine volume， whole blood viscosity and pathological sections of submandibular gland stained with hematoxylin-eosin （HE）. The expression of aquaporin 2 （AQP2） in rat kidney was measured by immunohistochemistry， the mRNA expressions of cytochrome C oxidase subunit 7A2 （COX7A2） and succinate dehydrogenase （SDH） complex subunit D （SDHD） in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The contents of SDH， lactate dehydrogenase （LDH） and sodium ion-potassium ion-adenosine triphosphatase （Na⁺-K⁺-ATPase） in rat plasma were determined by colorimetry. The quality of A. lancea and A. chinensis was evaluated by coefficient of variation method， and Pearson correlation coefficient was used to analyze the correlation between dryness and energy metabolism. ResultCompared with the normal group， the amounts of drinking water and urine in volatile oil of A. lancea group and volatile oil of A. chinensis group increased， and the submandibular gland acini atrophied， the whole blood viscosity of rats in the volatile oil of A. lancea group increased significantly （P<0.01）， the expression levels of COX7A2 and SDHD mRNA， the activities of SDH， LDH and Na⁺-K⁺-ATPase increased significantly （P<0.01）， and the expression of AQP2 in kidney decreased significantly （P<0.01）. Compared with the normal group， the expression level of COX7A2 mRNA， SDH activity and whole blood viscosity in the volatile oil of A. chinensis group increased （P<0.05， P<0.01）， the AQP2 and SDH mRNA expression levels， LDH and Na⁺-K⁺-ATPase activities had no significant difference. The comprehensive score analysis of each index showed that the effect of volatile oil of A. lancea on dryness and energy metabolism was stronger than that of volatile oil of A. chinensis， and there was a positive correlation between dryness index and energy metabolism index. ConclusionThe two indexes show that medicinal properties of A. lancea is stronger than that of A. chinensis， and energy metabolism is closely related to the dryness of Atractylodis Rhizoma. It is suggested that it is reasonable to evaluate the dryness effect of Atractylodis Rhizoma from the perspective of energy metabolism， which can further enrich the evaluation indexes of medicinal properties.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.
Asian Continental Ancestry Group ; B-Lymphocytes ; Cyclophosphamide ; Disease-Free Survival ; Doxorubicin ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell ; Prednisone ; Prognosis ; Rituximab ; Vincristine

Objective:To establish the fingerprint analysis method for the aqueous extracts of Eucommia ulmoides from Enshi by HPLC. Methods:The fingerprint of aqueous extracts of ten batches of Eucommia ulmoides from Enshi were analyzed by HPLC. The columnwasWondaSilC18(250mm×4.6mm,5μm). Themobilephaseconsistedofacetonitrile-0.1% phosphoricacidwithgradient elution. The flow rate was 1. 0 ml·min-1 , the detection wavelength was 230 nm, the column temperature was 25℃, and the injection volume was 10 μl. Results:The fingerprint consisted of 12 common peaks. The similarity range of ten batches of Eucommia ulmoides calculated by similarity evaluation system for the chromatographic fingerprint of TCM(Version 2004 A)was 0. 596-0. 997. The standard fingerprint of Eucommia ulmoides was established by HPLC. Conclusion: The established HPLC fingerprint analysis method for Eu-commia ulmoides from Enshi is simple, stable and reproducible, which can effectively control the quality of Eucommia ulmoides from Enshi.