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.

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

AIMTo investigate the effect of resveratrol on EMMPRIN expression of macrophages.

METHODSHuman monocytic cell line THP-1 cells were co-cultured with EMMPRIN-highly-expressed MCF-7 cells; MMP-9 production was assayed by zymography. THP-1 cells were induced by PMA, expression of EMMPRIN was assayed by Western blotting. Cells were treated with resveratrol or PPARgamma agonist--pioglitazone during differentiation, EMMPRIN expression and MMP-9 activity were assayed. U937 cells were co-transfected with PPARy expression and luciferase-coding reporter vector, then cultured with pioglitazone or resveratrol, the activating capability of resveratrol on PPARgamma was evaluated by measuring the luciferase activity. THP-1 cells were pretreated with PPARgamma antagonist--GW9662 before pioglitazone or resveratrol treatment, then assayed for EMMPRIN expression and MMP-9 production.

RESULTSEMMPRIN expression was greatly increased during the differentiation from monocytes to macrophages; co-culturing with MCF-7 cells significantly increased MMP-9 production by monocytes. Both resveratrol and pioglitazone markedly inhibited EMMPRIN expression during monocytes differentiation. Resveratrol significantly activated PPARgamma and GW9662 greatly decreased the effect of resveratrol on EMMPRIN and MMP-9.

CONCLUSIONEMMPRIN expression is greatly up-regulated from monocytes to macrophages, which may play a role in inducing MMPs production by monocytes/macrophages. Resveratrol can significantly inhibit EMMPRIN expression via activating PPARgamma, which may be the underlying mechanism of its inhibitory effect on MMPs production by monocytes/macrophages.

Anilides ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Basigin ; biosynthesis ; genetics ; Blotting, Western ; Breast Neoplasms ; metabolism ; pathology ; Cell Differentiation ; drug effects ; Cell Line ; Cell Line, Tumor ; Coculture Techniques ; Dose-Response Relationship, Drug ; Female ; Humans ; Luciferases ; genetics ; metabolism ; Macrophages ; cytology ; drug effects ; metabolism ; Matrix Metalloproteinase 9 ; biosynthesis ; Monocytes ; cytology ; drug effects ; metabolism ; PPAR gamma ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism ; Stilbenes ; pharmacology ; Thiazolidinediones ; pharmacology ; U937 Cells

BACKGROUNDIntertrochanteric femur fracture is common in elderly population. Though multiple treatment options are available, the choice of implant remains controversial. The reverse less invasive stabilization system (LISS) plating was introduced for treatment of a patient with ipsilateral intertrochanteric and midshaft femoral fractures. The aim of this research was to compare such technique to intramedullary nailing (proximal femoral nail, PFN) for intertrochanteric fractures.

METHODSFifty-six patients with an age of at least sixty-five years and an AO/OTA type-A1 or A2 fractures were included and divided into LISS and PFN treatment group.

BACKGROUNDparameters, fracture and surgery details were documented. Follow-up time was at least 12 months. Radiology, complication, Harris Hip Score and Rapid Disability Rating Score (RDRS) were recorded to evaluate fixation status and hip function for each patient during follow-up.

RESULTSThere was no significant difference between the two groups in surgical time ((48.0 ± 8.6) minutes, vs. (51.8 ± 10.8) minutes, P = 0.3836) and intraoperative blood loss ((149.1 ± 45.1) ml vs. (176.4 ± 25.4) ml, P = 0.0712). The LISS group had less postoperative haemoglobin (Hb) reduction ((10.2 ± 4.5) g/L Hb, vs. (15.1 ± 5.9) g/L Hb, P = 0.0475). There was no complication observed in PFN group. All 31A1 type fracture in LISS group showed 100% maintenance of reduction. One nonunion with locking screw breakage and 2 varus union were found in the LISS group. Postoperative hip function was similar between the two groups.

CONCLUSIONSThough reverse LISS plating may not be recommended as a routine fixation method for elderly unstable intertrochanteric fractures compared to PFN, it may possibly be reserved for rapid fixation and damage control in polytrauma patients and ORIF of subtrochanteric and reverse oblique intertrochanteric fractures.

Aged ; Aged, 80 and over ; Female ; Femoral Fractures ; surgery ; Femur ; surgery ; Fracture Fixation, Intramedullary ; methods ; Hip Fractures ; surgery ; Humans ; Male ; Prospective Studies ; Treatment Outcome

OBJECTIVETo investigate the risk of Alzheimer's disease (AD) associated with life style, early exposure to magnetic fields, family history of dementia and other risk factors.

METHODSWe conducted a case-control study among the inpatients of Chinese PLA General Hospital in 2000 - 2003. Sixty-two AD cases and 124 controls were selected and matched for age. Univariate and multivariate analyses were conducted using logistic regression model.

RESULTSAll subjects were males aged 66 to 102. In univariate analysis, lack of social activities, more physical exercises, early exposure to magnetic fields, suffering from negative life events and family history of dementia were statistically different between two groups (P < 0.05). Multivariate analysis showed that after adjusting for potential confounders, suffering from negative life events, family histories of dementia increased the risk of AD with odds ratio (OR) and 95% confidence interval (CI) 3.27 (1.53 - 6.97) and 5.78 (1.39 - 24.10). Early exposure to magnetic fields seemed a possible risk factor for AD, with OR (95% CI) 2.49 (0.96 - 6.45). The amount of social activities, cigarette smoking and history of cancers were negatively correlated with AD and their ORs (95% CI) were 0.81 (0.72 - 0.92), 0.46 (0.21 - 1.00) and 0.31 (0.12 - 0.82) respectively.

CONCLUSIONThe study demonstrated that suffering from negative life events and family history of dementia were risk factors for AD, and the early exposure to magnetic fields might also play a role.

Aged ; Aged, 80 and over ; Alzheimer Disease ; epidemiology ; etiology ; Case-Control Studies ; China ; epidemiology ; Electromagnetic Fields ; adverse effects ; Humans ; Logistic Models ; Male ; Middle Aged ; Military Personnel ; Occupational Exposure ; Risk Factors ; Smoking ; adverse effects

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

OBJECTIVE Despite the status of cisplatin (DDP) as a classical chemotherapeutic agent in the treatment of cancer, the development of multidrug resistance often leads to a failure of DDP therapy.Traditional Chinese medicine(TCM)as adjuvant chemotherapy of cancer drugs in China has been widely used in cancer treatment.ZuoJin WAN (ZJW),a TCM formula,was proved reversing drug resistance in gastric cancer,but its exact mechanism was still unclear. METHODS CCK-8 assay was used to detect the cell viability. The levels of proteins and mRNA were evaluated using Western blot and q-PCR. Mitochondrial membrane potential was measured by fl ow cytometry. Depolymerisa-tion of F-actin and translocation of G-actin(gamma-actin)from the cytoplasm to the mitochondria was detected using an immuno fl uorescence assay. RESULTS phosphorylated coflin-1 (p-coflin-1) was overexpressed in the DDP-resistant human gastric cancer cell lines SGC7901/DDP and BGC823/DDP, relative to the respective parent cell lines(SGC7901 and BGC823),and DDP induced the dephosphory-lation of p-coflin-1 in both parent lines but not in the DDP-resistant lines. However, ZJW could induce the dephosphorylation of pcoflin-1 and promote coflin-1 translocation from the cytoplasm into the mito-chondria in both SGC7901/DDP and BGC823/DDP cells. This mitochondrial translocation of coflin-1 was found to induce the conversion of flamentous actin to globular-actin, activate mitochondrial dam-age and calcium overloading, and induce the mitochondrial apoptosis pathway. These effects of ZJW on DDP-resistant human gastric cancer cell lines could be reversed via transfection with coflin-1-specifc siRNA,or treatment with a PP1 and PP2A inhibitor.CONCLUSION ZJW can be used as an inhibitor of chemoresistance in gastric cancer, which may partly be due to dephosphorylation of p-coflin-1 via the activation of PP1 and PP2A.

Objective Diminished ovarian reserve (DOR) severely affects the life of women and the estrogen replacement therapy for it has obvious adverse effects. This article aimed to study the effect of polygoni multiflori radix preparata (PMRP) on DOR in rats and provide a therapeutic option for clinical medication. Methods Sixty female SD rats were randomly divided into six groups of equal number,normal control,DOR model control,high-dose PMRP (4 g/kg),medium-dose PMRP (2 g/kg),low-dose PMRP (1 g/kg),and positive control. The DOR model was established by gavage of tripterygium glycosides as 75 mg/kg every morning,followed by administration of PMRP in the PMRP groups,Estradiol valerate at 0.18 mg/kg in the positive control group and distilled water in the model control group in the afternoon,all for 30 consecutive days. The estrous cycle of the rats was observed,the levels of serum estradiol (E2),follicle-stimulating hormone (FSH),luteinizing hor-mone (LH),anti-Müllerian hormone (AMH) and inhibin-B (INH- B) were determined by ELISA,the ovarian and uterine indexes were obtained,and the ovarian morphology was observed by HE stai-ning,and the counts of follicles at different stages were recorded. Results Compared with the normal controls,the DOR model rats showed modeling time-related lengthening,irregularity and even disorder of the estrous cycle,with a few epithelial cells or keratino-cytes and leucocytes on the vaginal smear at 11-30 days. The estrous cycle was normal in the PMRP and positive control groups at 1-10 days and relatively prolonged at 11-30 days. In comparison with the normal control group,the DOR model rats exhibited a signifi-cantly decreased levels of serum E2 ([302.6±42.9] vs [155.7±46.8] pg/mL,P<0.05) and INH-B ([494.5±84.1] vs [299.2± 106.8] pg/mL,P<0.05) but increased levels of FSH ([7.2±0.5] vs [21.7±1.2] mIU/mL,P<0.05) and LH ([17.4±1.2] vs [25.0±1.0] mU/mL,P<0.05). The INH-B level was markedly elevated in the PMRP and positive control groups as compared with that in the DOR models (P<0.05). The counts of follicles and corpora lutea were remarkably lower in the DOR model rats (P<0.05) while that of developing follicles markedly higher in the PMRP and positive control groups than in the normal control group (P<0.05). The numbers of atretic follicles+corpora lutea were significantly increased in the high-dose PMRP group but decreased in the low-dose PMRP group (P<0.05) and positive controls (P<0.05). The counts of primordial and developing follicles were dramatically higher in the PMRP and positive control groups than in the DOR model controls (P<0.01) and so were the numbers of atretic follicles+corpora lutea in the high-and medium-dose PMRP groups (P<0.05). Conclusion Polygoni multiflori radix preparata can effectively protect the reproductive function of female rats by inhibiting tripterygium glycosides-induced toxicity to the ovary.