Objective To develop quality control methods for the key quality properties of recombinant monoclonal antibodies against proprotein convertase subtilisin/Kexin 9(PCSK9). Methods According to the corresponding requirements of Chinese Pharmacopoeia(Volume Ⅲ,2020 edition)and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH),the PCSK9 monoclonal antibody was identified for the identity by reducing trypsin peptide fingerprint mapping analysis,identified for the specificity by ELISA,determined for the charge heterogeneity by imaging capillary isoelectric focusing electrophoresis(icIEF),detected for the variant purity by reducing/non-reducing capillary electrophoresis-sodium dodecyl sulfonate(CE-SDS),measured for the content of monomers,high molecular weight substances and low molecular weight substances by size-exclusion chromatography high performance liquid chromatography(SEC-HPLC),analyzed for the glycotype with N-glycan labeled with 2AB after carbohydrate cutting by Waters ACQUITY UPLC system with fluorescence detector,determined for the biological potency with HepG2 cell line and low-density lipoprotein(LDL),and detected for the content of polysorbate 20 by the liquid phase detection system(CAD detector). Results PCSK9 monoclonal antibody sample had characteristic peptide segments,and the peptide fingerprint was consistent with that of reference substance. The sample contained specific antibodies;The relative area percentages of main peak,acid peak and alkaline peak of the sample were(49. 27 ± 0. 38)%,(46. 44 ± 0. 35)% and(4. 28 ± 0. 04)%,respectively. The relative area percentages of“heavy chain + light chain”peak,non-glycosyl main peak and low molecular weight substance peak were(94. 16 ± 0. 82)%,(4. 11 ± 0. 76)% and(0. 85 ± 0. 20)%,respectively. The relative area percentages of main peak,nonglycosyl main peak and low molecular weight substance peak were(94. 27 ± 0. 22)%,(2. 85 ± 0. 08)% and(2. 88 ± 0. 15)%,respectively. The relative area percentages of monomer,high molecular weight substance and low molecular weight substance were(98. 30 ± 0. 03)%,(0. 75 ± 0. 01)% and(0. 96 ± 0. 02)%,respectively. The relative percentages of G0F,G1F,G2F and non-fucosylated(G0 + G1 + G2 + Man5)were(39. 31 ± 0. 54)%,(34. 69 ± 0. 41)%,(9. 09 ± 0. 14)% and(12. 61 ± 0. 50)%,respectively. The relative biological potency was(101. 64 ± 3. 61)% of the reference. The content of polysorbate 20 was(0. 012 ± 0. 000 3)%. Conclusion According to the key quality attribute of monoclonal antibody against PCSK9,the corresponding key quality control methods have been established,which can ensure the safety,effectiveness and quality controllability of the product.

Objective To explore the relationship between mean platelet volume(MPV),blood fibrinogen(Fg)level and carotid atherosclerosis in patients with cerebral infarction.Methods 50 patients with cerebral infarction were selected as the research objects,and divided into the carotid atherosclerosis group and without carotid atherosclerosis group depending on whether carotid atherosclerosis,each group 25 cases.The MPV and plasma Fg of the two groups were detected and compared.Results The levels of MPV and blood fibrinogen in the carotid atherosclerosis group[(12.99±1.45)fl,(4.59±1.05)g/L]were higher than those without carotid atherosclerosis group[(11.01±1.21)fl,(3.05±0.51)g/L](t=4.212,-0.387,P=0.000,0.001).Conclusion The relationship between MPV,Fg levels and carotid atherosclerosis in patients with cerebral infarction is close.

Carcinogens ; chemistry ; toxicity ; Chromium ; chemistry ; toxicity ; Chromium Compounds ; chemistry ; toxicity ; Humans ; Occupational Exposure ; analysis

Objective: To investigate the changes of vasoconstrictor and vasodilator functions of isolated thoracic aorta in the rats with obstructive jaundice, so as to study the mechanism for the functional changes of the aorta in rats with obstructive jaundice. Methods: Sixty male SD rats were randomly divided into bile duct ligation (BDL) group and sham operation (SO) group. The thoracic aortas were isolated at 3, 7 and 14 d after surgery and the vasoconstrictor responses induced by high potassium, norepinephrine (NE) and phenylephrine (PE) gradient and the vasodilator response to SNP were tested. Another 40 male SD rats were randomly divided into BDL three-day group, BDL seven-day group, BDL 14-day group and sham operation (SO) group. The expression of α1D-AR protein in the thoracic aorta was assessed by Western blotting. Results: The vasoconstrictor responses of thoracic aorta rings in high potassium, NE, PE, and BDL rats were weaker than those in the SO group. The vasodilator response induced by SNP in the BDL group was greater than that in the SO group. The expression of α1D-AR protein in the BDL group was weaker than that in the SO group, and the expression decreased with the prolongation of obstructive time. Conclusion: The systolic and diastolic functions of isolated thoracic aorta rings are changed in cholestatic rats; the weakened systolic function might be a result of decreased expression of α 1D-AR albumen.

We report a case of a 47-year-old man who firstly complained of throat pain for half a month accompanied with fever. Specialized examination showed tonsils' hypertrophy and the laryngoscope found his right vocal cord was swelling and hyperemia. The routine blood test counted white blood cell as 31 x 10(9)/L, lymphocyte as 30. 84 x 10(9)/L while prolymphocyte could be seen with microscope. After that B-ultrasound scan gave spleen hypertrophy and multi-lymphatic-node enlargement. Peripheral blood flowcytometry and bone marrow biopsy finally diagnosed the man as actue myelocytic leukemia.
Humans ; Leukemia, Myeloid, Acute ; complications ; diagnosis ; Male ; Middle Aged ; Pain ; etiology ; Pharynx

Objective To explore the effect of aspirin resistance on cardiovascular events in non-insulin-dependent diabetes melli-tus patients .Methods 496 patients with non-insulin-dependent diabetes mellitus received daily aspirin therapy (100mg/d) 4 weeks were recruited from Jun .2006 to Sept .2010 .Platelet aggregation was measured by light transmission aggregometry .The patients were divided into three groups :aspirin resistance group ,aspirin semi-resistance group and aspirin-sensitive group .The clinical bio-chemistry indications and the adverse cardiovascular events were collected .Results 11 .69% of patients were found to be resistant to aspirin therapy ,and 37 .90% of patients to be aspirin semi-responders .There were 67 .48% female in aspirin resistance group and aspirin semi-responders .The preprandial glucose of group AR and ASR was higher than that of group AS (P<0 .05) .The HbA1C and TG of group AR were higher than those of group AS(P<0 .05) .There was statistically significant difference of the rate of car-diovascular events .Conclusion The measure of platelet aggregation should be taken in the diabetic mellitus patients and pay atten-tion on the dose of aspirin recommended .Particular attention is should also devote to the incidence of adverse cardiovascular events .

Diastolic and systolic dysfunction of cerebral artery is an important pathophysioiogical basis of the occurrence and development of cerebrovascular diseases, and is also the presence of decreased cerebrovascular reserve capacity. Cerebrovascular myogenic and metabolic regulation abilities can be evaluated by different methods so as to reflect cerebrovascular reserve capacity, of those, transcranial Doppler ultrasonography is the most widely used one. Various diseases, such as hypertension, diabetes mellitus, and carotid atherosclerosis also have great effect on cerebrovascular reserve capacity.

Perihematomal edema is common after hypertensive intracerebral hemorrhage. It is one of the important causes influencing functional recovery. This article reviews the mechanisms of perihematomal brain edema formation after hypertensive intracerebral hemorrhage, particularly, the potential mechanisms of hypertension in the processes of brain edema formation, as well as therapeutic targets of brain edema.

Carotid stenosis is an important modifiable risk factor in ischemic stroke.The com prehensive diagnosis of carotid stenosis,including the comprehensive understanding of stenosis degree,plaque stability,and head and neck vessels,which has important guiding significance for the prevention and treatment of ischemic stroke.This article reviews the diagnostic values of digital subtraction angiography,sonography,magnetic resonance angiography and CT angiorgaphy in carotid stenosis.

OBJECTIVE: To establish the quality standard of l of Zengshi oral liquid. METHODS: Thin-layer chromatography(TLC) was employed for the qualitative determination of the Lycium barbarum,Cassia obtusifolia and schisandra chinensis. High performance liquid chromatography (HPLC) was applied for the determination of chrysophanol in Zengshi Oral Liquid. RESULTS: The quality standard of Zengshi oral liquid could be established through qualitative determination of the Lycium barbarum,Cassia obtusifolia and Schisandra chinensis.The linear range of Chrysophanol was 0.083～0.416?g (r=0.999 9). The average recovery was 98.38% and the RSD was 1.72%. CONCLUSION: The established standard can be used for the quality control of Zengshi oral liquid.