Objective To investigate the efficacy of butylphthalide on elderly patients with acute cerebral infarction and its effect on serum uric acid,c-reactive protein,and hemorheology.Methods Elderly patients (86 cases) with acute cerebral infarction in Xi'an No.1 Hospital from January 2015 to December 2015 were randomly divided into two groups.The control group was treated with conventional symptomatic treatment of acute cerebral infarction,observation group added with butylphthalide soft capsules.The NIHSS score and efficacy of the two groups,the serum uric acid,c-reactive protein,and the change of hemorheology before and after treatment were compared.Results The effective rate of observation group was 90.70％,significantly higher than that of control group 72.09％ (P ＜ 0.05);The NIHSS score,serum uric acid and c-reactive protein levels,blood viscosity and platelet aggregation rate of two groups after treatment were significantly lower (P ＜ 0.05),the Barthel index were significantly increased (P ＜ 0.05),and the change of observation group were more significant (P ＜ 0.05).Conclusion Butylphthalide has high curative effect on elderly patients with acute cerebral infarction,can reduce the level of serum uric acid,c-reactive protein and the degree of nerve function defect,improve the hemorheology and life self-care activities ability,which can protect the brain.

Intraperitoneal administration of timosaponin A-III (TA-III) has therapeutic effects on high-fat diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD), but oral administration has no effect. This suggests that gut microbiota may affect the oral bioavailability of TA-III. Metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory subtype of MASLD. To investigate the therapeutic effect of different administration modes of TA-III on MASH and its relationship with gut microbiota metabolism. In this study, a MASH mouse model was induced by choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Comparing the therapeutic effect of intraperitoneal injection (10 mg·kg^-1, ip) and intragastric administration (100 mg·kg^-1, ig) of TA-III. The concentration of TA-III in serum of rats under the two administration modes was analyzed. On this basis, the metabolic effect of gut microbiota on TA-III in mice was verified by the experiment of metabolism of gut microbiota in vitro. The pharmacokinetic experiment of combined antibiotic intervention in mice further verified the metabolism of TA-III by gut microbiota in mice. Finally, the concentration of TA-III in serum of mice after the administration of TA-III by intragastric administration under different antibiotic intervention conditions was compared, and 16S rRNA sequencing analysis was combined to find the key bacteria that may participate in the metabolism of TA-III. The animal welfare and experimental procedures in this paper were in accordance with the provisions of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine. The ethics approval number is PZSHUTCM2307030004 and PZSHUTCM2310200003. The results showed that TA-III (10 mg·kg^-1, ip) had definite therapeutic effect on MASH mice, but TA-III (100 mg·kg^-1, ig) was ineffective. The analysis showed that the prototype concentration of TA-III in serum and liver of mice in TA-III (100 mg·kg^-1, ig) was significantly lower than TA-III (10 mg·kg^-1, ip), suggesting that the oral administration of TA-III may be metabolized by gut microbiota. The concentration of TA-III in serum of streptomycin (Str) treated mice was higher than normal mice. Combined with 16S rRNA gene sequencing analysis, it was found that the abundance of Akkermansia_muciniphila (A. muciniphila) was significantly reduced in the Str group. In vitro experiments showed that A. muciniphila could metabolize TA-III. In conclusion, gut microbiota is an important factor affecting the efficacy of TA-III administration through the gastrointestinal tract, in which A. muciniphila may play an important role.

The biological activity of ADCC by anti-CD20 monoclonal antibody was determined by BioGlo™ Luciferase Assay System using Jurkat/NFAT-luc+FcγRIIIa cell line as effector cell and WIL2-S cell line as target cell. The developed method was verified for specificity, precision and accuracy. Anti-CD20 monoclonal antibody showed a dose-response mode by the developed method, and the determination result complied with the following four-parameter equation: y = (A-D)/[1 + (X/C)(B)] + D. The optimized parameters of the method were determined including the antibodies diluted concentration (18,000 ng·mL(-1)), dilution rate (1:5), the ratio of effector cell and target cell (6:1), and induction time (6 h). The values of eight independent tests have passed a statistical test for curve regression analysis, linear or parallelism, which showed the method possessed good specificity. Four different dilute groups of recovery rates sample were determined for 3 times, and the result showed mean relative potencies of (44.39±3.93)%, (72.74±2.78)%, (128.28±7.01)% and (168.19±2.70)% respectively, with a variation coefficient of less than 10%, and the recoveries of (88.78±7.85)%, (96.99±3.70)%, (102.63±5.61)% and (112.12±1.80)% respectively. A novel reporter gene method for determination of biological activity of ADCC by anti-CD20 monoclonal antibody was successfully developed, which showed strong specificity, good reproducibility and high accuracy, and might be used routinely.
Antibodies, Monoclonal, Murine-Derived ; pharmacology ; Antibody-Dependent Cell Cytotoxicity ; Antigens, CD20 ; immunology ; Genes, Reporter ; Humans ; Reproducibility of Results ; Rituximab

OBJECTIVETo study the effect of Tangshenkang Granule (TG) containing serum on renal mesangial cells' (RMCs) proliferation and TGF-β1/Smad2/3 pathway in the high glucose condition.

METHODSTwelve SD rats were randomly divided into four groups, i.e., the low dose TG group, the middle dose TG group, the high dose TG group, and the blank control group, 3 in each group. After 7-day gastrogavage via portal vein blood, rats were sacrificed and their serum samples were collected. RMCs were cultured in common rat serum and TG containing serum respectively. The proliferation of mesangial cells was determined by methly thiazolyl tetrazolium (MTT) assay to determine the optimal TG containing serum concentration. Expression levels of TGF-β1 mRNA and protein were determined by real time quantitative PCR and ELISA. Smad2/3 protein expression and phosphorylation were determined by Western blot and immunofluorescence.

RESULTSTG containing serum at different doses could inhibit high glucose induced RMC cells' proliferation, TGF-β1 over-expression and Smad2/3 phosphorylation.

CONCLUSIONTG containing serum could inhibit high glucose induced RMC cells' proliferation, and its mechanism might be possibly associated with inhibiting TGF-β1/Smad2/3 signaling pathway.

Animals ; Cell Proliferation ; Drugs, Chinese Herbal ; pharmacology ; Glucose ; Mesangial Cells ; Phosphorylation ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Serum ; Signal Transduction ; Smad2 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

This paper reports the determination of the drug antibody ratio in an antibody-drug conjugate with two methods, i.e. LC-MS and UV/VIS, and to provide a reliable method to scientifically evaluate and effectively control the drug antibody ratio. Deglycosylated sample was analyzed with C4 column followed by MS, and the number of conjugated drugs in the antibody was determined by the molecular weight increase due to the addition of different number of drugs to the antibody, and then drug antibody ratio was calculated by weighted average of different number of drugs conjugated to the antibody. Optical density at 252 and 280 nm was measured with UV/VIS, and due to the difference of extinction coefficients between the antibody and the drug, the drug antibody ratio was calculated from linear equation with two unknowns. The drug antibody ratio was 3.21 and 3.25 respectively measured by the two methods, and the results were similar with the two methods. Our study indicated that both methods, LC-MS and UV/VIS, could be applied to the analysis of drug antibody ratio of the antibody drug conjugate.
Antibodies ; analysis ; chemistry ; Gas Chromatography-Mass Spectrometry ; methods ; Glycosylation ; Immunoconjugates ; analysis ; chemistry ; Maleimides ; analysis ; chemistry ; Molecular Weight ; Pharmaceutical Preparations ; analysis ; chemistry ; Spectrophotometry, Ultraviolet ; methods

OBJECTIVETo evaluate wave intensity (WI) on left ventricular (LV) performance in the different hypertensive remolding hearts.

METHODS105 hypertensive and 98 control subjects were underwent noninvasive evaluation of carotid arterial wave intensity, LV structure and function.

RESULTS(1) There were increasing trends in the levels of blood pressure, LV end-diastolic diameter and LV mass index in the control, normal geometry group, concentric remodeling group, concentric and eccentric hypertrophy group. LV ejection fraction increased in the concentric hypertrophy group and decreased in the eccentric hypertrophy group in which mid-wall fractional shortening showed a decreasing trend. LV diastolic filling pressure presented increased progression accompanied by LV remodeling (P < 0.05). (2) Transient acceleration wave intensity (W1) in hypertensive subjects were higher than that in the control (P < 0.05). Transient deceleration wave intensity (W2) was lower than that in the control (P < 0.05). (3) W1 in the concentric hypertrophy group was higher and lower in the eccentric hypertrophy, compared with that in the control group, normal geometry group and concentric remodeling group (P < 0.05). W2 was lower in concentric hypertrophy group and eccentric hypertrophy group than that in the control, normal geometry group and concentric remodeling group (P < 0.05).

CONCLUSIONWI is a noninvasively obtained, clinically useful parameter for evaluation of LV performance.

Aged ; Blood Flow Velocity ; physiology ; Carotid Artery, Common ; physiopathology ; Case-Control Studies ; Female ; Humans ; Hypertension ; physiopathology ; Male ; Middle Aged ; Pulsatile Flow ; physiology ; Ventricular Function, Left ; physiology ; Ventricular Remodeling

OBJECTIVETo evaluate transient deceleration wave intensity (W2) of carotid artery on left ventricular diastolic function.

METHODS40 patients with hypertension and 43 healthy volunteers were enrolled and W2 of carotid artery of the both sides were measured. The parameters of left ventricular diastolic function by traditional and tissue Doppler imaging and NT-proBNP (N-terminal probrain natriuretic peptide) were measured.

RESULTS(1) W2 is not different between two sides of carotid artery. W2 in hypertension was lower than the control, especially in left side(1126 +/- 996 mmHg x m/s3 vs 1690 +/- 1126 mmHg x m/s3, P < 0.01). (2) The correlation of W2 and else parameters were analyzed. There were notably decreasing in left ventricular diastolic function of the hypertensive group than the control, for example, the ratio of peak velocity of early filling of mitral flow to peak early diastolic motion velocity of mitral annulus (E/Em, 9.37 +/- 3.32 vs 7.39 +/- 1.83, P < 0.01) and NT-proBNP (94.6 +/- 48.5 vs 45.2 +/- 13.8, P < 0.01). (3) The correlation analysis showed negative relation between W2 and E/Em (r = - 0.46, P < 0.05) and negative relation between W2 and NT-proBNP (r = -0.21, P < 0.05).

CONCLUSIONNew carotid W2 by non-invasive technology for hemodynamics is a deserving parameter in early evaluating left ventricular diastolic function.

Adult ; Carotid Artery, Common ; physiopathology ; Female ; Humans ; Hypertension ; physiopathology ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Ventricular Dysfunction, Left ; diagnosis ; physiopathology ; Ventricular Function, Left

OBJECTIVETo establish a method for the determination of the papaverine content in Qiangli Pibalu by HPLC.

METHODA C18 column with a solvent system of acetonitrile-0.02 mol x L(-1) sodium dihydrogen phosphate (0.2% triethylamine, phosphoric acid, at pH 3) (25:75) and UV detection 240 nm were used. The flow rate was 1.0 mL x min(-1). The column temperature was maintained at 40 degrees C.

RESULTThere was a good linear relationship between the absorption value and the concentration in the range of 0.020 2-0.100 5 microg for papaverine. The average recovery rates were 99.1% (RSD 2.3%).

CONCLUSIONThe method is simple, accurate and can be used to determine the contents in Qiangli Pibalu.

Antitussive Agents ; chemistry ; pharmacology ; Chromatography, High Pressure Liquid ; methods ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Eriobotrya ; chemistry ; Expectorants ; chemistry ; pharmacology ; Papaver ; chemistry ; Papaverine ; analysis ; Plants, Medicinal ; chemistry ; Quality Control ; Reproducibility of Results

OBJECTIVETo develop a LC-MS method for the determination of senkyunolide I (SI) in rat plasma, in order to observe whether there is significant change in the pharmacokinetics parameters of complex prescriptions of Huoluoxiaolingdan (HLXL) and single herbal extracts from Ligusticum chuanxiong Hort. in rats, and assess the effect of other components in HLXL on the pharmacokinetics of SI.

METHODTwelve male Sprague-Dawley (SD) rats were randomly divided into two groups, and orally administered with extract from HLXL and L. chuanxiong (both equal to SI 4.53 mg x kg(-1)). Their blood was collected at different time points for LC-MS, in order to detect the plasma concentration of SI. The pharmacokinetic parameters of SI were calculated by DAS 2.0 software. SPSS 16.0 software was used for independent-sample T-test and Nonparametric T-test.

RESULTA linear relationship of SI ranged from 6.750 to 675.0 microg x L(-1), and with the lowest limit of detection being 6.750 microg L(-1). Both of the plasma concentration-time curves of SI were fitted with the two-compartment model for extract of HLXL and L. chuanxiong. The detected AUC and Cmax of SI showed significant difference, with no significant difference in other parameters.

CONCLUSIONThe LC-MS determination method established in this experiment was so exclusive, accurate and sensitive that it is suitable for pharmacokinetic studies on extracts of HLXL and SI from L. chuanxion. The experiment results show that other ingredients of HLXL have noticeable effect on the absorption of SI in rat plasma.

Administration, Oral ; Animals ; Area Under Curve ; Benzofurans ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Male ; Metabolic Clearance Rate ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for patients with locally advanced rectal cancer. Controversy on whether patients should receive radical surgery after pathological complete response (pCR) after neoadjuvant chemoradiotherapy has remained since pCR patients have shown favorable long-term outcome. Progress in multidisciplinary modalities has been made, including MRI, PET/CT imaging studies, genetic expression profiling, etc. The methods of predicting pCR response are inspiring. In this article, we review the methods for prediction and prognostic effect of pCR response when patients with locally advanced rectal cancer are treated with neoadjuvant chemoradiotherapy.
Chemoradiotherapy ; Humans ; Neoadjuvant Therapy ; Rectal Neoplasms ; therapy ; Remission Induction ; Treatment Outcome