Objective To observe the effect of fluvastatin(Flu) on differentiation and induction of human promyelocytic leukemia HL-60 cells and provide the theoretical foundation for treatment of human promyelocytic leukemia.Methods The cultured HL-60 cells were treated with 20 ?mol?L-1 Flu,the morphological changes of the cell differentiation were examined.The NBT reduction capability was detected in HL-60 cells treated with Flu for 72 h.After HL-60 cells were treated with 20 ?mol?L-1 Flu for 5 d,they were stained with non-specific esterase and the percentage of differentiation cells was analyzed.Results The HL-60 cells treated with Flu showed smaller cell body,reducing proportion of nucleus to cytoplasm,the nucleus tortuosity,fold or sublobe.There were specific granules and vacuoles in cytoplasm,displaying that some cells had differentiated to relative mature cells.As compared with control group,the NBT reduction capability in HL-60 cells treated with Flu for 72 h was significantly higher than that in control cells(P

OBJECTIVE Toexplorethecredibityoftwoimprovedmodelsofsyntheticvascular dementia(VD)rats.METHODS OneimprovedmodelofVDratswasestablishedbyligatuingthebilat-eral common carotid artery twice at 3 d (improved 2-VO),while the other was established by blocking the middle cerebral artery on the left side by separating pterygopalatine arteria (i mproved MCAO/R). The learning and me mory ability was determined by escape latency in Morris water maze directional navi-gation test and cross-over ti mes in target areas in spatial probe test and the search strategy.The organi-zational structure in CA1 area of the hippocampus was observed and analyzed under a microscope after HEstaining.RESULTS Thelearningandmemoryabilitydecreasedsignificantlyin2modelgroupsat 20 d after the operation.The escape latency was much longer in improved 2-VO group and improved MCAO/R group than that in sham group(P<0.05)especially in improved 2-VO group.41 d after the operation,no difference between MCAO/R and sham group (P <0.05 ).The differences between improved 2-VO group and sham group remained significant(P<0.01 ),and difference between improved 2-VO group and improved MCAO/R group was significant(P<0.01 )at 41 d.The cross-over times in the target area in spatial probe test decreased more significantly in 2 model groups than in sham group. 41 d after the operation,improved MCAO/R group was not different from sham group(P<0.05). Search strategy results showed that swimming trajectory in the improved 2-VO groupwas mostly edge and random type,but was of tendency type and straight type in the improved MCAO/R group.In the organization structure of hippopal CA1 area of rats,the nu mber of cells was reduced,their arrange ment was sparse and chaotic,the morphology of cells was inco mplete,the structure of cells was abnormal, cytoplasmwasscarce,andnucleoliwereinconspicuous.CONCLUSION TwoimprovedVDmodelscan lead to behavior and pathological changes in rats.The i mproved 2-VO model,si mple and stable,is suitable for drug efficacy research.The improved MCAO/R model is the ideal short-term efficacy study.

Humans ; Lung ; Lung Diseases ; rehabilitation ; Pneumoconiosis ; rehabilitation ; Respiratory Therapy

Objective To explore the mechanisms of trafficking and signaling of serotonin 1A receptor(5-HT_(1A))and its spatiotemporal distribution in living cells.Methods The mouse 5-HT_(1A) gene amplified by RT-PCR was recombined into pEGFP-N1 vector and the EGFP coding sequence was located in-frame at the C-terminal end of the 5-HT_(1A) receptor.The 5-HT_(1A)-EGFP was transfected into neuron-like PC12 cells as well as HEK293.The transfected cells were visualized using confocal microscopy,the mobility of 5-HT_(1A)-EGFP was monitored by live measurements and fluorescence recovery after photobleaching.Results The 5-HT_(1A) gene was identitical with the published gene sequence NM_008308.4 and a 5-HT_(1A)-EGFP fusion construct was created.After stable transfection of the plasimd into a PC12 cell line and analysis with a confocal laser scanning microscopy,the EGFP-tagged 5-HT_(1A) was predominantly associated with the plasma membrane,but some intracellular vesicles in the perinuclear region also contained the fusion protein.The predominant localization of 5-HT_(1A)-EGFP at the plasma membrane was confirmed in transiently transfected HEK293 cells.Bleached fluorescence was partialy recovered in 100 seconds,indicating that the 5-HT_(1A)-EGFP was mobiled on the membrane.Conclusion Spatiotemporal distribution and mobility of 5-HT_(1A) tagged with EGFP can be monitored in the 5-HT_(1A)-EGFP stable PC12 cell line,which could be an excellent neuron-like experimental cell model for research of 5-HT_(1A) trafficking and signaling.

Aim To investigate the effects of the alco-hol extract from Coreopsis tinctoria Nutt. on urinary metabolomics of spontaneous hypertension rats ( SHR) . Methods SHR were fed with normal diet for 1 week and then, they were randomly divided into six groups:untreated control, the high, middle, low dos-age group of the alcohol extract(3.2 g·kg-1 ,1.6 g· kg-1,0.8 g·kg-1) , captopril group(4 mg·kg-1) and Duzhong tablet group(187.5 mg·kg-1). The u-rine of normal rats and SHR hypertension model rats was collected on 1,2,3,4 weeks. The metabolic pro-files were analyzed using 1 H-NMR. PLS-DA methods were used to discriminate the difference and the bio-markers. Results Compared with model group, the blood pressure of all groups was significantly lowered after 4 weeks ( P <0.01 ) . The alcohol extract from Coreopsis tinctoria Nutt. could significantIy reduce blood pressure, and the urinary metabolic profiles trea-ted with Coreopsis tinctoria Nutt. were changed signifi-cantly such as IIL,creatine,β-glucose,etc. Conclusion The alcohol extract from Coreopsis tinctoria Nutt. could significantIy reduce blood pressure and change the urinary metabolomics profiles of SHR rats.

Objective To discuss the clinical features of trachea and bronchial tuberculosis and estimate the efficacy of the diagnosis of trachea and bronchial tuberculosis by fiberoptic bronchoscopy. Methods Clinical presentations and examination of fiberoptic bronchoscopy findings of 216 patients diagnosed by Olympus electric or fiberoptic bronchoscopy were retrospectively investigated. Results Male of the 216 patients were 95, female were 121, with 1.27 times higher incidence noted in female than in male subjects. An activator dry cough was the most complain in 72.7% , intermittent hemoptysis was in 34.7% , absenting of typical clinical poisoning symptoms of tuberculosis. Atelectasis and shape in lung were the most common chest roentgenographic presentations respectively in 31.0 % and 24.1 %. Chest roentgenographic presentations of 16.7% were normal. Bronchoscopic findings showed that main pathologic changes included 36.1% granulation, 31.0% mucosa inflammation, 24.1% ulceration (or necrosis) and 8. 8% cicatricial stenosis, left lung (56. 2%) was more often affected than right lung (37.6%), left bronchi (26.9% ) was in the first. The pathologic changes affected all of leaf, segment bronchi. One hundred and seventy-eight cases (82.4%) were diagnosed by bronchoscopic biopsy, 68 cases (31.5%) were diagnosed by bronchoscopic brushing examination for acid - fast bacillus. Conclusion The clinical features of trachea and bronchial tuberculosis are non - specific and easy to be misdiag-nosed. It is the main reason to be misdiagnosed that bronchial biopsy is neglected by clinical doctors. Bronchial biopsy should be the most reliable and accurate step to get the definite diagnosis.

The aim of this study is to investigate the effect of echinacoside (ECH) on cholinergic neurotransmitter extracellular of hippocampus and striatum and its possible mechanisms of neuro-protective effect against vascular dementia rats. In this study brain microdialysis technique combined with HPLC-IMER-ECD (high-performance liquid chromatography-immobilized enzyme reactor-electrochemical detector) was used. The bilateral common carotid arteries occluded in two times operation at 72 h interval for vascular dementia model rats were used and the successful vascular dementia model rats were examined by Morris water maze. The content of acetylcholine (ACh) and choline (Ch) of microdialysate extracellular of hippocampus and striatum was determined by HPLC-IMER-ECD and the AChE activity in the hippocampus was measured. The results showed that the success rate of vascular dementia model was 83.08% after six weeks; the results also showed that echinacoside and galantamine could increase the content of ACh and reduce the content of Ch extracellular of hippocampus and striatum significantly and the AChE activity increased significantly compared with that of the model group. The results suggested that echinacoside could promote the recovery of cholinergic neurotransmitter levels in vascular dementia rats' brain, which may be one of the mechanisms of neuro-protection.

FLASH radiotherapy (FLASH-RT) is a treatment modality that delivers ultra-high dose rate and ultra-fast radiation for cancer treatment. Compared to conventional dose rate radiotherapy, FLASH-RT can yield similar efficacy for tumors and achieve normal tissue protection, translating to an increased therapeutic window. Due to this unique feature, FLASH-RT is attracting increasing attention from the radiotherapy community, both academia and industry. Due to its unique Bragg peak as well as intrinsic high dose rate, application of FLASH has more value and profound significance in proton therapy while achieving highly conformal dose deposition simultaneously. This article reviews research progress on FLASH-RT, relevant cell and animal studies, experimental conditions and results. Moreover, this article also investigates the potential biological mechanisms, technical challenges for implementation and potential clinical applications of FLASH-RT.

Objective This study aims to elucidate the structure-activity domain of LBP1C-2 targeting Kvβ.2 through an exploration of the structure-activity relationship.This study may also provide the scientific basis for the development of drug candidate with anti-early-onset dementia activity.Methods After partial acid hydrolysis,various structural fragments were obtained and subjected to monosaccharide composition and molecular weight analysis.Potential target proteins were selected using a protein chip,followed by validation of the targeting specificity of each structural fragment using surface plasmon resonance(SPR)technology.Results Through high-throughput screening using the HuProtTM human protein array,potential target protein Kvβ.2 was identified for LBP1C-2.SPR experiments revealed a strong binding affinity between LBP1C-2 and Kvβ.2 protein,with a binding constant(KD)of 1.9×10-7 M.The various structural fragments of LBP1C-2 exhibited different binding strengths with the target protein Kvβ.2.Among them,the segment LBP1C-2-1I(18.1 k Da)with a molar ratio of rhamose to galecturonic acid of 1:1 showed a binding strength to Kvβ.2 similar to that of the polysaccharide LBP1C-2,with a KD of approximately 3.3×10-7 M.Structural analysis indicates that the structure of LBP1C-2-1I contains 1,2-linked Rha and 1,4-linked GalA which are alternatively linked.The acid-hydrolyzed extracellular portion corresponding to this segment,LBP1C-2-1O may also bind to Kvβ.2.However,compared to other segments,it demonstrated a higher tendency to dissociate from the protein.Knockdown of the KCNAB2 gene(Kvβ.2)in BV2 cells inhibited the uptake of Aβ in BV2 cells,suggesting that protein Kvβ.2 may be a functional protein in the development of Alzheimer's disease.Conclusion LBP1C-2-1I has been identified as the primary active domain through which LBP1C-2 targets Kvβ.2.This suggests that the active domain of LBP1C-2 predominantly resides on the main chain rather than the side chain.This study provides crucial insights for a deeper understanding of the anti-early-onset dementia activity of LBP1C-2 and lays an experimental foundation for the design and development of targeted drugs for anti-early-onset dementia based on Lycium barbarum polysaccharides.

Objective:To understand the clinical phenotype and spectrum of ATP7B gene mutation in children with Wilson’s disease (WD). Methods:A total of 55 cases diagnosed with WD at the Children's Hospital Affiliated to Nanjing Medical University from June 2012 to June 2018 were taken as the research subject. ATP7B gene point mutation was detected by direct sequencing after PCR amplification. Heterozygous mutation in children was discovered by sequencing. Furthermore, the long segment mutation of exon was analyzed by multiplex ligation-dependent probe amplification (MLPA). Results:All 55 WD children had varying degree of liver damage symptoms. Among them, 2 cases had combined neurological symptoms. The positive rates of K-F ring (21%), 24-hour urine copper (97.7%), and ceruloplasmin were all abnormal. The results of ATP7B gene had identified 8 homozygous, 41 compound heterozygous and 6 heterozygous in 55 cases. Direct sequencing method had detected ten cases of ATP7B heterozygotes. In addition, MLPA analysis showed that other allele in four cases had a deletion of the ATP7B gene exon. In all cases, 35 different ATP7B gene mutations were detected, including 23 missense mutations, 3 frameshift mutations, 4 nonsense mutations, 3 exon deletions and 2 splicing changes. The most common allele mutation was c.2333G > T/p.R778L in exon 8, with an allele frequency of 36.54%, followed by c.2975C > T/p.P992L in exon 13, with an allele frequency of 14.42%. Conclusion:ATP7B gene c.2333G > T/p.R778L and c.2975C > T/p.P992L mutations are the most common mutations in children with WD in China. WD patients report shows that there are three long deletion mutations in the exon of the ATP7B gene. For WD children whose DNA sequencing is heterozygous ATP7B gene, it is suggested to further use MLPA method to detect deletion mutations of exons.