ObjectiveTo investigate the effects of Saposhnikovia divaricata extract combined with arsenic trioxide (ATO) on the proliferation and apoptosis in chronic myelogenous leukemia K562 cells. MethodsSaposhnikovia divaricata extract was prepared.Cultured K562 cells were treated with different concentration of Saposhnikovia divaricataextract or/and ATO for 48h. Cell proliferation was determined using the MTT assay. Apoptosis and cell cycle were detected using flow cytometry.ResultsThe MTT assay showed that Saposhnikovia divaricata extract of 750,1 000,1 250,1 500 μg/ml had a significantly proliferation inhibitory effect compared with control group, the inhibitory rates were 23.29% ± 3.31%, 48.30% ± 2.50%, 79.62% ± 3.41% and 88.94% ± 0.06%, respectively (allP<0.05); Saposhnikovia divaricata extract of 500 μg/ml combined with ATO of 1.0, 0.5 μg/ml significantly increased inhibitor rates compared with ATO of 1.0, 0.5 μg/ml (64.99% ± 5.18%vs. 44.48% ± 3.31%,38.59% ± 3.88%vs.26.30% ± 5.03%; allP<0.05). FCM showed that Saposhnikovia divaricata extract of 500 μg/ml combined with ATO of 2.0, 1.0, 0.5 μg/ml significantly increased apoptotic rate compared with ATO group of 2.0, 1.0, 0.5 μg/ml (33.97% ± 0.59%vs.20.97% ± 2.17%, 13.53% ± 0.47%vs.9.77%±0.64%、6.63%±&0.40%vs.4.00%±0.46%; allP<0.05 ). Cell cycle results showed that Saposhnikovia divaricata extract of 500μg/ml combined with ATO of 2.0,1.0, 0.5μg/ml significantly increased the rate of S phase compared with ATO group of 2.0, 1.0, 0.5 μg/ml (60.25 ± 2.59%vs.55.61 ± 1.28%, 60.89 ± 1.53%vs.37.96 ± 1.02%, 47.76 ± 0.87%vs.39.90 ± 0.92%; allP<0.05).ConclusionsSaposhnikovia divaricataextract could obviously inhibit the proliferation of K562 cells and enhance the apoptotic effect of ATO. ATO could induce a G2/M phase arrest, while Saposhnikovia divaricata extract combined with ATO could induce a S phase arrest in K562 cells.

Objective To observe the changes of serum superoxide dismutase (SOD) levels in typeⅡdiabetic patients with peripheral arterial disease (PAD) before and after interventional therapy, and to investigate the effects of oxidative stress level and interventional treatment on serum SOD level. Methods During the period from July 2011 to December 2012 at authors’ hospital, a total of 40 patients with type Ⅱ angiography together with balloon dilation and/or stenting was carried out in 24 patients (group B, with Fontaine stage of Ⅱb - Ⅲ). Of the 24 patients in group B, lower limb arterial angiography together with balloon dilation was employed in 16 (group B1) and lower limb arterial angiography together with balloon dilation and stenting was adopted in 8 (group B2). Twenty healthy clinical subjects were used as control group (group C). Before interventional treatment, elbow venous blood samples of patients in group A and B were collected to determine serum lipid, HbA1c and SOD levels. The same tests were also carried out in the subjects of group C. During percutaneous lower extremity arterial intervention , through arterial sheath 3 ml arterial blood specimen was collected in all patients of both group A and B before intervention started. Twenty-four hours after the treatment, venous blood specimen was also collected in all patients to determine serum SOD levels. The results were statistically analyzed. Results Lower limb arterial angiography showed that no obvious arterial stenosis was seen in the patients of group A. The interventional procedures were all successfully completed in all patients of group B. SOD levels of group A, B and C were (46.1 ± 3.13)U/ml, (35.37 ± 3.58)U/ml and (60.50 ± 6.99)U/ml respectively. SOD levels of both group A and B were significantly lower than that of group C (t = 8.420, P < 0.01; t = 14.324, P < 0.01). The level of SOD in group A was significantly higher than that in group B (t = 10.092, P < 0.01). The ankle-brachium indexes (ABI) of group A, B and C were (0.70 ± 0.12), (0.58 ± 0.13) and (1.15 ± 0.07) respectively. ABI of group A and B was significantly lower than that of group C (t = 14.324, P < 0.01; t = 17.392, P < 0.01). ABI of group B was significantly lower than that of group A (t=3.027, P<0.05). SOD level bore a negative correlation with HbA1c level (r=-0.541, P<0.01). In both group A and group B, no significant difference in SOD level existed between the venous blood and arterial blood. The preoperative arterial SOD levels in group B1 and group B2 were (35.70 ± 3.04)U/ml, and (36.07 ± 2.14)U/ml respectively, and the difference between the two groups was not statistically significant. The preoperative SOD levels in the ischemic arterial region in group B1 and group B2 were (32.95 ± 3.52)U/ml and (33.59 ± 2.64)U/ml respectively, and the difference between the two groups was not statistically significant although these levels were significantly lower than the preoperative arterial SOD levels(t=2.741, P<0.05; t=2.704, P<0.05). After the interventional treatment, the SOD levels in the ischemic arterial region in group B1 and group B2 were (29.40 ± 5.49)U/ml and (26.68 ± 2.31)U/ml respectively, and the difference between the two groups was not statistically significant although these levels were significantly lower than the preoperative SOD levels in the ischemic arterial region (t = 2.536, P < 0.05; t = 5.005, P < 0.01). No statistically significant differences in SOD levels at each corresponding site existed between group B1 and group B2. Conclusion No significant difference in SOD level exists between the venous blood and the arterial blood. Serum SOD level carries a negative linear correlation with HbA1c level. Before interventional treatment , the SOD level in ischemic region is low, which becomes lower after the interventional procedure, which may be caused by the enhanced oxidative stress reaction that is resulted from the damage of the vascular wall due to interventional manipulations. The enhanced oxidative stress reaction may play an important role in the occurrence of restenosis.

Objective:To evaluate the safety of cardiac catheterization intervention therapy and transthoracic small incision surgery in the occlusion bydomestic occluder under echocardiography guiding in patients with atrial septal defect (ASD).Methods:A total of 1 080 patients with ASD in the occlusion by domestic occluder were analyzed retrospectively,and the interventional treatment were performed in 734 cases through cardiac catheterization intervention therapy and 346 cases through transthoracic small incision surgery.The patients undergone cardiac catheterization intervention therapy were guided under the digital substraction angiography (DSA) and were monitored by transthoracic echocardiography (TTE) in the whole interventional process,and the efficacy was evaluated with TTE.The occlusion of transthoracic small incision surgery was guided under the transesophageal echocardiography (TEE),which was used to monitor the position of occluder and evaluate the efficacy immediately.Results:Two kinds of intervention in the occlusion by domestic occluder had achieved satisfactory results in patients with ASD.There was no statistically difference in the longest size of ASD between the 2 intervention methods,while there were statistically differences in the ratio between ASD longest diameter and atrial septal length,and the size of the occlusion,and the disparity between the size of the occluder and ASD longest diameter (D value),respectively (all P＜0.05).When the size of arithmetic mean of the ASD was ＜30 mm,the success rate of the 2 methods was both 100％.When the size of arithmetic mean of the ASD was ≥ 30 mm,the success rate was 100％ in the transthoracic small incision surgery and 50％ in the cardiac catheterization intervention therapy.Conclusion:Domestic occluder is safe.Compared with the imported one,its cost is lower.When the size of the defects is same,the occlusion is smaller in the transthoracic small incision surgery compared with that in the cardiac catheterization intervention therapy.When the size of arithmetic mean of the ASD is ≥ 30 mm,the success rate of the transthoracic small incision surgery is higher compared with the cardiac catheterization intervention therapy.When the cardiac catheterization intervention therapy fails,the transthoracic small incision surgery may be a better choice.

Objective To study the effect of black granule capsules(BGCs) on growth of transplanted mouse hepatocarcinoma cells, cell proliferation cycle and apoptosis.Methods KM mouse were subcutaneously inoculated with Hepatocarcinoma cells (H22) and randomly divided into the model control group, the positive control group, the low, medium and high does of BGC group after 24h. The positive control group received intraperitoneal injection with 30 mg/kg cyclophosphamide. Mice of BGC groups were intragastricaly with different dosage of BGC (400, 800, 1 600 mg/kg). The model control group received intragastricaly with normal saline. The drugs were administrated once a day for seven days. The tumor inhibition rate was calculated at 24 h after the last administration. Flow cytometry was used to detect changes of cell cycle and apoptosis in harvested H22 tumor cells.Results The group of high does showed significant inhibitory effect on the growth of transplanted H22 tumor cells withthe inhibitory rate 38.78% (male) and 43.57% (female). Compared with model control group, groups of different dosages decreased time of G0-G1 phase (58.06% ± 9.65%, 55.10% ± 5.89%, 61.36% ± 15.95%vs. 74.47% ± 2.63%), increased tiem of Sphase (33.96% ± 11.90%, 32.67% ± 4.04%, 33.89% ± 9.82%vs. 14.37% ± 4.92%), and increased the apoptosis rate (31.12% ± 1.85%, 31.89% ± 2.16%, 40.64% ± 0.55%vs.21.75% ± 2.64%).Conclusion BGC has antitumor effect on mouse hepatocarcinoma H22 tumor cells, and its mechanism was to regulate cell proliferation cycle and induce the apoptosis.

Nucleocapsid protein (NPs) of negative-sense single-stranded RNA (-ssRNA) viruses function in different stages of viral replication, transcription, and maturation. Structural investigations show that -ssRNA viruses that encode NPs preliminarily serve as structural building blocks that encapsidate and protect the viral genomic RNA and mediate the interaction between genomic RNA and RNA-dependent RNA polymerase. However, recent structural results have revealed other biological functions of -ssRNA viruses that extend our understanding of the versatile roles of virally encoded NPs.
Animals ; Capsid ; metabolism ; Humans ; Lassa virus ; chemistry ; physiology ; Nucleocapsid Proteins ; chemistry ; metabolism ; Orthobunyavirus ; chemistry ; physiology ; RNA Viruses ; chemistry ; physiology

Novel coronavirus pneumonia (COVID-19) is currently raging worldwide, and the prevention and control situation is very grim. Gratifying achievements of organ donation have been made in China since its implementation. Due to the characteristics of potential donors, such as complicated personnel structure, sudden onset and critical illness, it is necessary for multi-department to contact with the donors and their families during the work link of donor evaluation, family communication, donor transportation, organ function maintenance and organ procurement, which raises higher requirement for the screening and management of potential donors under COVID-19 epidemic. During the outbreak, Beijing Youan Hospital, Capital Medical University has completed 9 cases of organ donation, formulated the relevant screening process, established the prevention and control requirements, and gained certain experience and effects, which benefits the orderly and smooth development of organ donation under the COVID-19 epidemic.

Dehydration is one of the key steps in the biosynthesis of mycolic acids and is vital to the growth of Mycobacterium tuberculosis (Mtb). Consequently, stalling dehydration cures tuberculosis (TB). Clinically used anti-TB drugs like thiacetazone (TAC) and isoxyl (ISO) as well as flavonoids inhibit the enzyme activity of the β-hydroxyacyl-ACP dehydratase HadAB complex. How this inhibition is exerted, has remained an enigma for years. Here, we describe the first crystal structures of the MtbHadAB complex bound with flavonoid inhibitor butein, 2',4,4'-trihydroxychalcone or fisetin. Despite sharing no sequence identity from Blast, HadA and HadB adopt a very similar hotdog fold. HadA forms a tight dimer with HadB in which the proteins are sitting side-by-side, but are oriented anti-parallel. While HadB contributes the catalytically critical His-Asp dyad, HadA binds the fatty acid substrate in a long channel. The atypical double hotdog fold with a single active site formed by MtbHadAB gives rise to a long, narrow cavity that vertically traverses the fatty acid binding channel. At the base of this cavity lies Cys61, which upon mutation to Ser confers drug-resistance in TB patients. We show that inhibitors bind in this cavity and protrude into the substrate binding channel. Thus, inhibitors of MtbHadAB exert their effect by occluding substrate from the active site. The unveiling of this mechanism of inhibition paves the way for accelerating development of next generation of anti-TB drugs.
Amino Acid Sequence ; Bacterial Proteins ; chemistry ; metabolism ; Catalytic Domain ; Enzyme Inhibitors ; chemistry ; pharmacology ; Flavonoids ; chemistry ; pharmacology ; Hydro-Lyases ; antagonists & inhibitors ; chemistry ; Molecular Sequence Data ; Mycobacterium tuberculosis ; drug effects ; enzymology ; Protein Binding ; drug effects ; Protein Multimerization ; drug effects ; Protein Structure, Secondary ; Sequence Alignment

Fusarium graminearum (sexual stage: Gibberella zeae) is the causative agent of Fusarium Head Blight (FHB), which is one of the most destructive plant disease of cereals, accounting for high grain yield losses, especially for wheat and maize. Like other fungal pathogens, several extracellular enzymes secreted by G. zeae are known to be involved in host infection. Among these secreted lipases, G. zeae lipase (GZEL), which is encoded by the FGL1 gene, was demonstrated to be crucial to G. zeae pathogenicity. However, the precise mechanism of GZEL remains unclear due to a lack of detailed structural information. In this study, we report the crystal structure of GZEL at the atomic level. The structure of GZEL displays distinct structural differences compared to reported homologues and indicates a unique "double lock" enzymatic mechanism. To gain insight into substrate/inhibitor recognition, we proposed a model of GZEL in complex with substrate and the lipase inhibitor ebelactone B (based on the reported structures of GZEL homologues), which defines possible substrate binding sites within the catalytic cleft and suggests an "anti sn-l" binding mode. These results pave the way to elucidating the mechanism of GZEL and thus provide clues for the design of anti-FHB inhibitors.
Amino Acid Sequence ; Catalytic Domain ; Crystallography, X-Ray ; Gibberella ; enzymology ; Lactones ; chemistry ; Lipase ; chemistry ; metabolism ; Models, Molecular ; Molecular Sequence Data ; Oleic Acid ; chemistry ; Protein Binding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Sequence Alignment ; Sequence Homology, Amino Acid ; Substrate Specificity ; Surface Properties

PURPOSE: The lecture is a technique for delivering knowledge and information cost-effectively to large medical classes in medical education. The aim of this study was to analyze teaching quality, based on triangle analysis of video recordings of medical lectures, to strengthen teaching competency in medical school. METHODS: The subjects of this study were 13 medical professors who taught 1st- and 2nd-year medical students and agreed to a triangle analysis of video recordings of their lectures. We first performed triangle analysis, which consisted of a professional analysis of video recordings, self-assessment by teaching professors, and feedback from students, and the data were crosschecked by five school consultants for reliability and consistency. RESULTS: Most of the distress that teachers experienced during the lecture occurred in uniform teaching environments, such as larger lecture classes. Larger lectures that primarily used PowerPoint as a medium to deliver information effected poor interaction with students. Other distressing factors in the lecture were personal characteristics and lack of strategic faculty development. CONCLUSION: Triangle analysis of video recordings of medical lectures gives teachers an opportunity and motive to improve teaching quality. Faculty development and various improvement strategies, based on this analysis, are expected to help teachers succeed as effective, efficient, and attractive lecturers while improving the quality of larger lecture classes.
Consultants ; Education, Medical ; Humans ; Lectures ; Quality Improvement ; Self-Assessment ; Students, Medical ; Video Recording

Rituximab, a chimeric monoclonal antibody directed against CD20, has become a part of the standard therapy for patients with non-Hodgkin's lymphoma either in combination with other drugs or as a single agent. The CD20 antigen is expressed on 95% of B-cell lymphoma cells and normal B-cells but, is not found on precursor B-cells or stem cells. Rituximab is now approved for patients with diffuse large B-cell lymphoma when combined with standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone) or patients with follicular lymphoma who have failed first line chemotherapy. The monoclonal antibody is generally well tolerated. Most of the adverse events are infusion-associated, mild to moderate non-hematological toxicities. Severe respiratory adverse events have been infrequent. Here, we report two patients with non-Hodgkin's lymphoma in whom interstitial pneumonitis developed with rituximab therapy.
Prednisolone/therapeutic use ; Methylprednisolone/therapeutic use ; Male ; Lung Diseases, Interstitial/*chemically induced/diagnosis/drug therapy ; Humans ; Antineoplastic Agents/*adverse effects ; Antibodies, Monoclonal/*adverse effects ; Aged