With the in-depth study of related substances and the development of consistency evaluation of generic drugs, relative correction factors are gaining increasing attention. By analyzing the domestic and foreign literature on correction factors in recent years, this paper describes the correction factor component, the current measurement method and its application. The rules and key points of use of an impurity correction factor and its determination and application are described, and some problems in its determination and application are discussed, providing a reference and basis for the standardization of research on impurity correction factors in the future.

The change of kirenol, darutigenol and darutoside in Siegesbeckia and its first to ninth processed products were studied, and the ten fingerprints were compared, which provided the experimental basis for the study of Siegesbeckia processing tech- nology. The samples were analysed by HPLC on a SunFire-C18 column (4.6 mm x 150 mm, 5 μm) with gradient elution of acetonitrile (0.1% formic acid)-water (0.1% formic acid) at a flow rate of 1.0 mL x min(-1). Column temperaturewas 30 °C and the detected wavelength was 215, 320 nm. The calibration curves of kirenol, darutigenol and darutoside were linear in the range of 2.180-26.16, 2.900-34.80, and 1.012-6.072 mg x L(-1), respectively, and the average recoveries were 96.4%, 97.2% and 96.3% wit RSD 2.2%, 1.7% and 2.4%. This method was simple, the result was stable and had good repeatability, recovery and precision. The re- sult was the basis of the chemical contents variation in the processing of Siegesbeckia Herbs and further clarifying the effect of the changing.
Asteraceae ; chemistry ; Chemistry, Pharmaceutical ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Temperature

Objective To study the ratio of anti-drug antibody(ADA) produced by tumor necrosis factor alpha (TNF-α) monoclonal antibody in Chinese healthy adult volunteers,and to analyze its influencing factors.Methods This is a parallel,randomized,double-blind,controlled study.Three sets of test totally included 164 cases of Chinese healthy adult volunteers.Trial one:56 cases of Chinese healthy adult volunteers were randomized into six groups,given 10,20,35,50,65,75 mg of L00653 test drugs in abdominal subcutaneous injection way.Trial two:64 cases of Chinese healthy adult volunteers were divided into six groups,given 5,15,30,50,75,100 mg of the test drug L02151 by abdominal subcutaneous injection.Trial three:48 cases of Chinese healthy adult volunteers were randomized into four groups,The volunteers in each group were given L00)048 and primary research drugs by intravenous infusion according to 1∶1 proportion as controlled trials.The levels of ADA were measured by ligand binding assay (LBA).Results A total of 164 healthy volunteers were performed in the study.Trail one:The positive rates of A,B,C,D,E,F groups were 17.00％,20.00％,40.00％,30.00％,0,30.00％,respectively.There was no significant difference between ADA positive rate and administration dose (P ＞ 0.05);Trail two:The positive rates of 5,15,30,50,75 and 100 mg groups were 100.00％,1000.00％,100.00％,100.00％,100.00％,70.00％,respectively.There was no significant difference in ADA positive rate between the groups and the dose of Administration (P ＞ 0.05);Trail three:Only two cases of ADA appeared.Conclusion The ADA produced in the body by TNF-o monoclonal antibody drug was associated with its source and structure,but without close relationship with drug doses.The research could be used to TNF-o monoclonal antibody drug research,providing experimental basis for clinical safe use.

OBJECTIVETo investigate the effects of two fluid resuscitations on the bacterial translocation and the inflammatory factors of small intestine in rats with hemorrhagic shock.

METHODSFifty SD healthy male rats were randomly divided into 5 groups (n equal to 10 per group): Group A (Sham group), Group B (Ringer's solution for 1 h), Group C (Ringer's solution for 24 h), Group D (hydroxyethyl starch for 1 h) and Group E ((hydroxyethyl starch for 24 h). A model of rats with hemorrhagic shock was established. The bacterial translocation in liver, content of tumor necrosis factor-alpha (TNF-alpha) and changes of myeloperoxidase enzyme (MPO) activities in small intestine were pathologically investigated after these two fluid resuscitations, respectively.

RESULTSThe bacterial translocation and the expression of TNF-alpha in the small intestine were detected at 1 h and 24 h after fluid resuscitation. There were significant increase in the number of translocated bacteria, TNF-alpha and MPO activities in Group C compared with Group B, significant decrease in Group E compared with Group D and in Group B compared with Group D. The number of translocated bacteria and TNF-alpha expression significantly decreased in Group E as compared with Group C.

CONCLUSIONSThe bacterial translocation and the expression of TNF-alpha in the small intestine exist 24 h after fluid resuscitation. 6% hydroxyethyl starch can improve the intestinal mucosa barrier function better than the Ringer's solution.

Animals ; Bacterial Translocation ; drug effects ; Fluid Therapy ; Hydroxyethyl Starch Derivatives ; administration & dosage ; pharmacology ; Intestine, Small ; metabolism ; Isotonic Solutions ; administration & dosage ; pharmacology ; Male ; Peroxidase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; therapy ; Tumor Necrosis Factor-alpha ; metabolism

This study was aimed to investigate the effects of peripheral blood Th17 cells, IL-17 and IL-21 in the occurrence and development of acute leukemia. 60 patients with acute leukemia (19 patients with ALL, 41 patients with AML) were divided into non-remission group (group A, n=24), remission group (group B, n=36); 25 healthy volunteers were used as control group (group C). In addition to this, these 60 patients were divided into infection group (n=32) and non-infection group (n=28) on the basis of infection status. The concentration of IL-17 and IL-21 in the peripheral blood mononuclear cell culture supernatant after stimulation with anti-CD3 and anti-CD28 mAb were determined with ELISA. The expression of CD4+ IL-17+ cells was determined by flow cytometry. The results showed that (1) the concentrations of IL-17 and IL-21, and proportion of Th17 cells in group A and group B were much lower than those in group C (p<0.05); (2) the expression levels of IL-17 and IL-21, and the proportion of Th17 cells in group A were lower than those in group B (p<0.05); (3) the expression levels of Th17 and IL-17 in infection group were lower than those in non-infection group (p<0.05). It is concluded that Th17 cells may play important roles in the occurrence and development of acute leukemia through secreting IL-17 and IL-21, and their functional level can partially reflect the status of leukemia and can be used to evaluate the risks of infection in patients with leukemia.
Adolescent ; Adult ; CD4-Positive T-Lymphocytes ; Case-Control Studies ; Female ; Humans ; Interleukin-17 ; metabolism ; Interleukins ; metabolism ; Leukemia, Myeloid, Acute ; metabolism ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; Th17 Cells ; secretion ; Young Adult

OBJECTIVETo observe the biocompatibility of new biomaterials porous calcium phosphate (CPC) and ectopic bone formation of CPC with bone marrow stromal cells (BMSCs).

METHODSThe BMSCs were cultured from Beagle dog and combined with the porous CPC with the best concentration after transfect green fluorescent protein (GFP). The adhesion and growth of BMSCs on CPC were observed under inversion, fluorescence and scanning electron microscopy. The ectopic bone formation were observed at the 8th week after CPC and BMSCs were implanted subcutaneously into nude mice.

RESULTSWhen BMSCs with CPC were cultured at the 1st day, cells were climbing out from CPC with normal morphology. At the 7th day cells can be seen protruding pseudopods, secretion of matrix. Bone formation could be seen histomorphologically at the 8th week.

CONCLUSIONPorous CPC has good biocompatibility and is an ideal scaffold material for bone tissue engineering.

Animals ; Biocompatible Materials ; Bone Cements ; Bone and Bones ; Calcium Phosphates ; Dental Cementum ; Dogs ; Mesenchymal Stromal Cells ; Mice ; Mice, Nude ; Tissue Engineering

Objective To assess the heritability of serum uric acid in adult,using the classic twin design.Methods Adult Twins were recruited from the Qingdao Twin Registry.Uric acid,height,weight were measured.Zygosity in all the same-sex twin pairs was determined by 16 polymorphic markers.Heritability was assessed by structural equation models,with age,gender and body mass index(BMI) included as covariates.Results In total,687 twin pairs were available for data analyses,including 420 pairs of monozygotic and 267 pairs of dizygotic twins.After logarithm transformed,uric acid in males ( 17.47±1.91 ) was significantly higher than in females ( 15.22±1.70,P＜0.0001 ).After adjustment on age,sex and BMI,intraclass correlations for uric acid were 0.70 for monozygotic twins and 0.40 for dizygotic twins.The sex-limitation AE model,combining additive genetic and unique environmental factors,could produce the best fit for the data.Heritability estimate for uric acid was 70.5% (95% CI:65.9-74.6),with the proportion of unique environmental effects as 29.5%(95%CI:25.4-34.2).Conclusion Additive genetic effects appeared to be the major contributor to the variation of uric acid in this twins sample being studied.

Objective:To discuss the topical action characteristics of the biological transmission of moxibustion heat via temperature collection and numerical modeling.Methods:Temperature of moxibustion was measured at multiple points at a distance of 3 cm to obtain the moxibustion temperature field nephograms by the high-accuracy temperature measure array.Finite element analysis was used to imitate the three-dimensional dynamic distribution of temperature in acupoint tissues.Results:Through numerical analysis,the one-dimensional,two-dimensional and three-dimensional distributions of temperature in human acupoint tissues at 5 min of moxibustion were established.The result showed that moxibustion heat mainly transmitted from the surface of the tissue to the internal,and the influence of moxibustion heat decreased with the depth of the tissue.The analysis of the nephograms of acupoint tissue temperature at 5,10,15 and 20 min of moxibustion showed that with the increase of the moxibustion time,the temperature in acupoint tissues constantly rose,and the transmission depth of moxibustion heat also further expanded inside acupoint.Conclusion:By establishing the three-dimensional dynamic model of heat transmission inside acupoint tissues with the biological parameters of human tissues and the temperature values obtained,this study used finite element analysis software ANSYS 14.0 and discovered the rules in the transmission of heat in body tissues during moxibustion,and the features in moxibustion heat transmission (from the proximal to the distant) and heat penetration (from the surface to the internal).This study provides theoretical and experimental support for the application of moxibustion in clinical practice.

With the development of science and technology, and the emergence of artificial intelligence, wearable technology is becom-ing a hot topic in the field of rehabilitation medicine. Wearable technology is characterized by miniaturization, intelligency and convenience, and has been widely researched and applied in many fields, such as neurological rehabilitation, orthopaedic rehabilitation, spinal cord injury rehabilitation and rehabilitation for senile degenerative diseases. The further research may focus on the reliability of signals under dynamic monitoring, the comfortable feeling during long-term use of wearable devices, the data security based on personal privacy, and so on.

OBJECTIVETo investigate the influence of pyrrolidine dithiocarbamate (PDTC) on the expression of transforming growth factor beta(1) (TGF-beta(1)), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor-1 of metalloproteinase (TIMP-1) in rats with pulmonary damage induced by paraquat (PQ).

METHODSFifty-four healthy male SD rats were randomly assigned into the control group (normal saline), the PQ-treatment groups (4 groups) and the PDTC treatment groups (4 groups). Except the rats in the control group, the rats in the PQ group were gavaged only with 40 mg/kg PQ, and PDTC group with 40 mg/kg PQ plus immediate injection 120 mg/kg PDTC (i.p). On the 3rd, the 7th, the 14th and 28th day after treatments, one group rats of each treatments were sacrificed and lung and blood samples were collected. The level of TGF-beta(1) protein in the plasma, the mRNA expression of TGF-beta(1), MMP-2 and TIMP-1 were evaluated using RT-PCR and real-time quantitative PCR, while pathological changes of lung were examined under optical microscope and electrical microscope.

RESULTSThe TGF-beta(1) protein, TGF-beta(1) and MMP-2 mRNA expression were increased significantly in the earlier stage and then decreased after PQ administration (P < 0.05 or P < 0.01), while the mRNA level of TIMP-1 was augmented continuously (P < 0.01) throughout the study compared to the control group. In comparison with the PQ group, in the PDTC treatment group, the TGF-beta(1) mRNA expression on the 3rd and the 14th day, 0.54 +/- 0.08 and 0.72 +/- 0.04 respectively, the MMP-2 mRNA expression on the 7th and 14th day, 1.62 +/- 0.50 and 1.97 +/- 0.34 respective-ly, and the TIMP-1 mRNA on the 7th and 21st day, 1.79 +/- 0.21 and 2.00 +/- 0.34 respectively, were significantly decreased (P < 0.05 or P < 0.01).

CONCLUSIONPDTC could attenuate paraquat-induced up-regulation of TGF-beta(1) and its mRNA expression, MMP-2 and TIMP-1 mRNA levels, which indicates that PDTC may exert its protective effects on paraquat-induced pulmonary damage by alleviating the earlier inflammation damage and adjust-ing the balance between MMPs and TIMPs. However, further studies are still warranted to investigate and clarify the underlying mechanisms involved in this complicated process.

Acute Lung Injury ; chemically induced ; metabolism ; pathology ; Animals ; Disease Models, Animal ; Lung ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Paraquat ; poisoning ; Pyrrolidines ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Thiocarbamates ; pharmacology ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism