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.

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

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.

Objective To study the effect of CO 2 pneumoperitoneum and enteric disturbance on serum ?-endorphin (?-EP) in SD rats, in order to investigate their influence on peri-operative stress responses in SD rats. Methods A total of 120 SPF-grade male SD rats were randomly divided into four groups with 30 rats in each group. The four groups received CO 2 pneumoperitoneum (Group A), a 5 cm abdominal incision (Group B), a 5 cm abdominal incision with gastroenteric disturbance (Group C), and intraperitoneal anesthesia (Group D or Control Group), respectively. Concentrations of serum ?-EP of these groups were measured 10 min, 20 min, and 40 min after the beginning of surgery, respectively. Results Concentrations of serum ?-EP in the Group A 10 min, 20 min, and 40 min after the beginning of surgery were 274 7?66 6 pg/dl, 157 3?63 8 pg/dl, and 163 9?74 5 pg/dl, respectively, which were all extremely significantly higher than those in the Control Group ( P

Objective To investigate the expression and clinical significance of Bmi-1,Podoplanin and p53 in human thymic epithelial tumor(TET) according to new histological classification of World Health Organization. Methods One hundred and ten TET tissue chips were prepared,and the expressions of Bmi-1,Podoplanin and p53 were detected by NovoLinkTM Polymer detection systems. Results The positive expressions of Bmi-1,Podoplanin and p53 were 68.2%,41.8% and 42.7%,respectively.The positive expressions of Bmi-1,Podoplanin and p53 were significantly associated with pathologic histological classification,Masaoka staging and clinic pathological grading(P

The causes of iatrogenic injury in choledo-cho-pancreatico-duodenai junction include iatrogenic factors, anatomic factors and pathological factors. T-tube, methylthionine chloride and fiber choledochoscopy are useful methods for early diagnosis. Accurate exploration of the injury site and reasonable choice of management were significant in dealing with the iatrogenie injury and can lead to a satisfactory result. Choledo-chojejunostomy and Oddi sphincteroplasty are not recommended unless the patients had distal bile duet stricture or the stones can not be removed. Accurate detection of the injury site, evaluation of the severity, and proper choice of the surgical method are important for the prognosis of the patients.

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.

BACKGROUND:Although core decompression can contribute to the reconstruction of necrotic bone, its single use appears to have some deficiencies and cannot completely realize the reconstruction of the femoral head.
OBJECTIVE:To explore the effect of arthroscopic core decompression with autologous bone marrow induction material combined with titanium rod in the repair of stage II femoral head necrosis
METHODS:A retrospective analysis was performed on clinical data of 79 cases of stage II femoral head necrosis admitted at the South Branch of Tongchuan People’s Hospital from February 2011 to February 2013. According to the therapeutic methods, these cases were divided into control group (40 cases) and observation group (39 cases), and were given conventional core decompression and arthroscopic core decompression with autologous bone marrow induction material combined with titanium rod. Patients were fol owed up for 24 months, and the range of hip flexion and Harris scores on hip function and adverse events were observed and compared between two groups.
RESULTS AND CONCLUSION:Al the 79 patients successful y completed the 24-month fol ow-up. By the last fol ow-up, the range of hip flexion and Harris score were significantly higher in the observation group than the control group (P<0.05). There was no failure case due to surgical material rejection. To sum up, arthroscopic core decompression with autologous bone marrow induction material combined with titanium rod is safe and effective for repair of stage II femoral head necrosis.