With the advantage of clear target and little side effect, antibody drug has attracted widely attention of worldwide pharmaceutical companies. However, large scale mammalian cell culture and antibody quality analysis are the bottlenecks of antibody drug industrialization in China. Especially due to the significant effect of cell culture conditions on antibody heterogeneity. Therefore, it is extremely urgent to optimize cell culture conditions to favor the demands of antibody drug development. This review summarized the most recent advances in the effect of cell culture conditions on antibody quality, followed by addressing the key issues that might be strategically important for domestic antibody drug development.
Animals ; Antibodies, Monoclonal ; biosynthesis ; isolation & purification ; Antibody Formation ; Cell Culture Techniques ; methods ; trends ; Genetic Heterogeneity ; Protein Stability ; Quality Control

This study is to report the establishment of an UPLC-MS/MS method for the determination of plasma concentration of UA carried in self-microemulsifying drug delivery system (SMEDDS) and its pharmacokinetics in rats. It was used for determination and analysis when serum with internal standard was extracted from C18 solid-phase column. Acquity UPLC BEH C18 column (100 mm x 2.1 mm, 1.7 microm) was used for separation. The mobile phase was acetonitrile -0.1% ammonia with gradient elution at the flow rate of 0.2 mL x min(-1). The column temperature was 40 degrees C and the detection wave length was 210 nm. It was detected by negative ion using electrospray ionization source (ESI) and scanned by multiple reaction ion monitoring (MRM) mode. The liner relationship of UA was very good in the range of 1.19-3 815.00 ng x mL(-1) (r = 0.999 0). Recovery rate of different concentrations were 87.42%-89.95%. The precision of inter-day and intra-day were less than 11%. The method developed in our study was proved to be sensitive, rapid and simple. It is suitable for the pharmacokinetic study of UA-SMEDDS in rats.

Objective:This study aimed to compare rectal cancer tumor volume parameters measured by MRI sequences (T1WI, T2WI, and DWI) and/or CT with those by pathological specimen. Methods:Twenty-two patients with rectal cancer were prospectively enrolled. MRI sequences including T1WI, T2WI, and DWI, and/or CT of the pelvis were performed before operation. Volume parameters, such as tumor length along the rectal axis, maximum tumor width perpendicular to rectal axis, and tumor actual area in that perpendicular plane, were measured on T1WI, T2WI, DWI, and CT, respectively, for each patient. The respective pathological parameters were further measured in surgical specimen after total mesorectal excision. The two kinds of parameter values measured in imaging and pathology were statistically compared and accuracy appraisal was performed. Results:The mean Lpath-L was 4.06±1.14 cm. The mean LT1-L, LT2-L, LDWI-L, and LCT-L were 3.91± 1.51, 4.62±1.41, 3.39±1.05, and 3.94±1.23 cm, respectively. Correlation coefficients were 0.688, 0.635, 0.688, and 0.720 (P<0.05). An average 6 mm overestimation was found in T2WI, and 1 to 6 mm underestimation in T1WI, DWI, and CT in length values compared with those measured in surgical specimen. The mean Lpath-W was 2.56 ±0.94 cm. The mean LT1-W, LT2-W, LDWI-W, and LCT-W were 3.62±0.99, 3.66±0.76, 3.23±0.58, and 3.64±1.04 cm, respectively. The magnitude of mean overestimation ranged from 5.1 to 11.1 mm. The Apath was 4.30 ±2.83 cm2. AT1, AT2, ADWI, and ACT were 8.98±3.90, 8.99±3.43, 8.41±3.09, and 9.63±4.40 cm2, respectively, which double overestimated the tumor area in the perpendicular rectal plane. Conclusion:The difference in longitudinal length between MRI sequences/CT and pathological specimen was in the range of?6 mm to 6 mm. The mean maximum tumor width and areas in the maximum tumor perpendicular plane were overestimated. This study indicated that gross tumor volume delineation based on CT or MRI for rectal cancer irradiation should be conservative in the axial images of rectum, and meticulous consideration is required along the rectum.

AIM: In this study,we tested the hypothesis that remote postconditioning induced by a single 5-min episode of femoral artery occlusion and reperfusion applied immediately before the onset of coronary artery reperfusion protects the myocardium from reperfusion injury.METHODS: Thirty healthy New Zealand white rabbits were randomly divided into three groups(n=10 in each group): control,myocardial ischemic postconditioning(MIP) and Limb ischemic postconditioning(LIP).Myocardial infarct size and tissue myeloperoxidase(MPO) activity were determined at the end of the experiment.Plasma creatine kinase(CK) activity and malondialdehyde(MDA) levels were measured at baseline,the end of ischemia,and after 180 min of reperfusion,respectively.RESULTS: Myocardial infarct size was significantly reduced in MIP and LIP as compared to control(P

Objective:To define more information for familial hematuria by genetic screening in a pedigree with familial hematuria.Methods:This was a 4 generation pedigree included 20 family members. The clinical data and laboratory manifestations of the family members were reviewed and collected from medical records. Meanwhile, the peripheral blood samples of 11 family members of the pedigree were collected, and then DNA samples were extracted by salting out method for genetic analysis. For genetic analysis, firstly, three family members including the proband were selected for whole exome sequencing, and the genetic variations were screened according to the sequence variation interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) for diagnostic sequence interpretation. Then PCR and Sanger sequencing were used to verify the identified pathogenic variants in all family members in the pedigree.Results:In the pedigree, 6 female members had persistent hematuria. Among them, 2 died due to end-stage renal disease, 2 died due to non-renal diseases, and 2 maintained stable renal function. One of the two members with stable renal function was diagnosed as IgA nephropathy by renal biopsy. Moreover, diffuse basement membrane lesions were identified in her renal biopsy sample after the electron microscope examination, which resulted in the suspected diagnosis of Alport syndrome. Genetic testing in this pedigree revealed two novel mutations in COL4A4 gene (NM_000092), c.G446T:p.G149V in exon 7 and c.G1249A:p.G417R in exon 20. Conclusion:Two novel mutations of COL4A4 gene (c.G446T:p.G149V in exon 7 and c.G1249A:p.G417R in exon 20) in a hematuria pedigree are related with phenotype of familial hematuria.

Pharmaceutical standard system which belongs to an important part of national drug policies is an inevitable result of the development of pharmacy. There was a long standing of pharmaceutical standard system in China whose germination could be traced back to Qin and Han dynasties, and it had laid a solid foundation for the establishment and improvement of modern pharmaceutical standard system by continual accumulation from the past dynasties. Since the founding of new China, distinguished achievements had been obtained on pharmaceutical standardization working,and currently it is in a new developing stage. There was a brief description in this paper on the development history of pharmaceutical standard system in China.
China ; Dosage Forms ; standards ; Education, Pharmacy ; history ; History, 20th Century ; History, 21st Century ; History, Ancient ; Humans ; Pharmaceutical Preparations ; history ; standards ; Pharmaceutical Services ; history ; standards ; Pharmacy ; history ; standards ; Quality Control

Objective To leam the clinical features and management of Rowell's syndrome (RS).Methods The clinical information of patients with RS who were admitted to the First Affiliated Hospital of Zhengzhou University from December 2010 to December 2016 was retrospectively analyzed.Results Seven cases,6 women,1 man;with the average age at onset of (40±11) years were reported.Only one patient had clear history of seafood intake.Skin lesions presented as generalized targeted lesions,coupling with some papules.Histopathological examination revealed hyperkeratinization,partial dyskeratocytes,focal areas of basal cell liquefaction,and perivascular infiltration of lymphocytes in the upper dermis.Six of them were treated with prednisone at a dose of 0.7-1.1 mg ·kg-1 ·d-1,one was treated with methylprednisolone at a dose of 80 mg/d while in hospital and at a dose of 1.2 mg ·kg-1 ·d-1 after discharge.During the process of glucocorticoid tapering,hydroxychloroquine was administered at a dose of 0.2-0.4 g/d in 4 patients,and 1 was treated with cyclophosphamide at 0.4 g per week.Glucocorticoid could be tapered once the symptoms were relieved,4 patients without relapse while others relapsed.Conclusion RS is a rare clinical syndrome with relative special immunological presentations.No specific therapy strategy has developed for this disease.Glucocorticosteroids tapering should be slower than in those who with lupus erythematosus,and the prognosis is variable.

Objective To analyze the effect of dominant accessory atrioventricular pathways (AP) on the end vector of ventricular depolarization. Methods All patients had single AP confirmed by radiofrequency cathteter abalation (RFCA) and were free from organic heart disease (including 102 cases of dominant accessory AP and 38 cases of concealed AP). The AP was divided into posterior septal(P3) ,mediate septal (MS) ,anterior septal (AS), left posterior free wall (LP), left anterior free wall (LA), right posterior free wall (RP) and right anterior free wall (RA). Results The end 40 ms vector of QRS wave changed in 102 patients with manifested AP and in 4 patients with concealed AP (P < 0. 05). Conclusion The end 40 ms vector of QRS wave of any site manifested AP can change and the changes have the specihty of leads.

Objective Clinical evidence has suggested that ATI receptor blocker (ARB) could prevent the development of heart failure. Decreased sareoplasmic reticulum(SR) Ca2+ content, which is due to reduced SR calcium reuptake by SERCA2a, is responsible for defective systolic function in failing heart. To better understand how ARB could improve cardiac systolic dysfunction, we studied the effects of Valsartan on calcium reuptake of SR and its regulatory proteins in heart failure rabbits. Methods Thirty rabbits were divided into three groups: sham rabbits(controls, n= 11), rabbits with heart failure treated with Valsartan (n= 11) and rabbits with heart failure but without Valsartan treatment (n=8).Rabbit heart failure model was established by volume plus pressure overload. Cardiac function was measured by echocardiography. SR calcium uptake was determined by measuring extra vesicular free [Ca2+] changes in a fluores-cence spectrophotometer. SERCA2a, Serl 6-phosphorylated phospholamban (p-PLB), PKA and PP1a protein abundance were deter-mined by use of Western blot analysis. Results Compared to control rabbits, the ejection fractions in the HF rabbits were significantly decreased (P<0.05), these changes could be significantly attenuated by Valsanan treatment (P<0.05).Calcium reuptake of SR, activity of SERCA2a and PKA decreased in heart failing myocytes (P<0.05), with down regulations of p-PLB, SERCA2a and PKA, but up regulation ofPP1αin ventricular samples from the failing rabbits (P<0.05). All of these changes were attenuated by Valsartan treatment (all P<0.05). Conclusion Valsartan improved cardiac function in volume plus pressure overload induced heart failure of rabbits possibly by restoring the SR calcium uptake resulted from attenuating the activities and expressions of SERCA2a and its regulatory proteins.

Objective:To evaluate the application value of three-dimensional shear wave elastography(3D-SWE) with quantitative parameters and qualitative analysis of stiff rim sign in differentiating benign and malignant breast masses.Methods:One hundred and seventeen female patients (121 breast masses) admitted to the First Affiliated Hospital of Soochow University from January 2020 to February 2021 were examined by conventional ultrasound, two-dimensional shear wave elastography (2D-SWE) and 3D-SWE. Surgical or puncture pathology were used as the gold standard, the ROC curves of 2D-SWE and 3D-SWE were drawn to obtain the optimal qualitative and quantitative indicators. Afterwards, BI-RADS category was adjusted according to the optimal indicators, which could be used to evaluate the diagnostic value in differentiating benign and malignant breast masses.Results:The area under ROC curve (AUC) of BI-RADS category was 0.846, the sensitivity and specificity were 89.6% and 79.6%, respectively. The AUC value of mass-to-fat elasticity ratio(Eratio) of coronal plane was 0.869, which was the highest among all quantitative parameters and was significantly higher than that of 2D-SWE ( P<0.05). In addition, the AUC value of stiff rim sign of coronal plane was significantly higher than those of 2D-SWE, sagittal plane and transverse plane (All P<0.05). The AUC of combination of stiff rim sign of coronal plane and conventional US was 0.901, which was significantly higher than that using conventional ultrasound alone( P<0.05). Conclusions:Compared with 2D-SWE, Eratio and stiff rim sign of coronal plane of 3D-SWE yield better diagnostic efficiency.Adjusting stiff rim sign coronal plane to BI-RADS category can effectively improve the diagnostic efficiency.