Objective To evaluate the effects of midazolam pretreatment on inflammatory responses and cell apoptosis during intestinal ischemia-reperfusion (I/R) in mice.Methods Thirty healthy male Kunming mice,weighing 18-22 g,were equally and randomly divided into 3 groups using a random number table:sham operation group (S group),I/R group,and midazolam pretreatment group (M group).Intestinal I/R was produced by occlusion of the superior mesenteric artery for 20 min followed by reperfusion.In group M,midazolam 1 mg/kg was injected intraperitoneally,and intestinal I/R was produced 30 min later.At 24 h of reperfusion,the mice were sacrificed,and intestinal tissues were removed for microscopic examination and for determination of the expression of interleukin-6 (IL-6),tumor necrosis factor-alpha (TNF-α) and caspase-3.Intestinal damage was assessed and scored according to Chiu.Results Compared with group S,Chiu's scores were significantly increased,and the expression of IL-6,TNF-α and caspase-3 was significantly up-regulated in I/R and M groups (P＜0.05).Compared with group I/R,Chiu's scores were significantly decreased,and the expression of IL-6,TNF-α and caspase-3 was significantly down-regulated in group M (P＜0.05).Conclusion Midazolam pretreatment can reduce intestinal I/R injury,and the mechanism is related to inhibition of inflammatory responses and cell apoptosis in mice.

The present study was to evaluate feasibility of a limited sampling strategy (LSS) in the prediction of inhibited hepatic CYP3A activity with systemic clearance of midazolam (MDZ), a hepatic CYP3A activity phenotyping probe. Rats were pretreated with a serial doses of ketoconazole, a selective inhibitor on CYP3A. Blood samples were collected and detected for MDZ at specified time points after intravenous injection of MDZ. Stepwise regression analysis and a Jack-knife validation procedures were performed in one group of rats as training set to establish the most informative LSS model for accurately estimating the clearance of MDZ. Another group of rats with same treatment was used as validation set to estimate the individual clearance based on predictive equations derived from the training set. Bland-Altman plots showed a good agreement between the systemic clearance calculated from DAS (CLobs) and corresponding parameter that was derived from three LSS models (CLest). LSS models derived from two or three sampling time points, including 60, 90 min, 30, 60, 90 min and 30, 60, 120 min, exhibited a good accuracy and acceptable error for estimating the CLobs of MDZ to evaluate hepatic CYP3A activity, especially the 60, 90 min LSS model is most accurate and convenient. The results supported that limited plasma sampling to predict the systemic clearance of MDZ is easier than the usual method for estimating CYP3A phenotyping when the hepatic activity of CYP3A is reduced in the rat. The present study provided theoretical basis and laboratory evidence for LSS to clinically evaluate metabolizing function of liver and
Animals ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; genetics ; metabolism ; Cytochrome P-450 CYP3A ; genetics ; metabolism ; Cytochrome P-450 CYP3A Inhibitors ; Dose-Response Relationship, Drug ; Enzyme Inhibitors ; pharmacology ; Injections, Intravenous ; Ketoconazole ; administration & dosage ; pharmacology ; Male ; Metabolic Clearance Rate ; Midazolam ; blood ; pharmacokinetics ; Phenotype ; Random Allocation ; Rats ; Rats, Wistar

The present study was to estimate pharmacokinetic parameters of metformin hydrochloride in 20 Chinese healthy volunteers with a limited sampling strategy (LSS), which will provide scientific data for bioequivalence and clinical application. A single dose of metformin was administrated to 20 healthy volunteers. The concentration of metformin in whole blood was determined by validated high performance liquid chromatography (HPLC) method. Multi-linear regression analysis was performed to establish a model to estimate AUC(0-24 h) and Cmax of metformin by LSS method. The LSS models were validated by the Jackknife method. The result indicated: the linearity relationship between AUC(0-24 h) or Cmax and single concentration point was poor. Several models for metformin AUC(0-24 h) or Cmax, estimation were better (r2 > 0.9, P < 0.05). Validation tests indicated that most informative sampling points (C2, C6 for AUC(0-24 h), C1.5, C2 for Cmax) provided accurate estimations of these parameters. So, a multi-linear regression model for estimation pharmacokinetic parameters of metformin by using LSS method is feasible.
Adult ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Humans ; Hypoglycemic Agents ; administration & dosage ; pharmacokinetics ; Linear Models ; Male ; Metformin ; administration & dosage ; pharmacokinetics ; Sample Size ; Therapeutic Equivalency ; Young Adult

To observe the influence of tumor necrosis factor-alpha (TNF-alpha) on differentiation of rat mesencephalic neural stem cells (NSCs), the numbers of neurons, astrocytes and oligodendrocytes generated from NSCs were analyzed after differentiation for 3 days by using immunocytochemistry technique. The results show that: (1) TNF-alpha enhanced the proportions of neurons and oligodendrocytes in progeny of NSCs; and (2) TNF-alpha induced the proliferation of oligodendrocytes derived from NSCs, but the proliferation of astrocytes was not influenced by TNF-alpha. We conclude that the TNF-alpha could influence the application of NSCs.
Animals ; Animals, Newborn ; Astrocytes ; cytology ; Cell Differentiation ; physiology ; Cell Proliferation ; Mesencephalon ; cytology ; Neural Stem Cells ; cytology ; Neurons ; cytology ; Oligodendroglia ; cytology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; physiology

OBJECTIVETo investigate the fibrogenetic effects induced by rush-mat dust in rats.

METHODSSD rats were treated with 50 mg of rush-mat dust per rat by intra-tracheal instillation, sacrificed 3, 6, and 12 months respectively after exposure. The lung tissue and lung lymph-node were taken out for pathological and electron microscopic examination. The content of collagen and ceruloplasmin (CP) in lung tissues were also determined.

RESULTSAfter treatment for 12 months, fresh wet lung weight in rush-mat dust group [(2.69 +/- 0.22) g] was higher than those in saline group [(1.87 +/- 0.25) g], TiO(2) group [(2.25 +/- 0.26) g], but lower than that in SiO(2) group [(11.41 +/- 1.63) g]; dry lung weight in rush-mat dust group [(0.47 +/- 0.03) g] was higher than those in saline group [(0.32 +/- 0.03) g], TiO(2) group [(0.41 +/- 0.08) g], but lower than that in SiO(2) group [(2.06 +/- 0.28) g]; lung collagen content in rush-mat dust group [(103.08 +/- 14.79) mg] was higher than those in saline group [(75.96 +/- 13.91) mg, TiO(2) group [(85.84 +/- 17.62) mg], but lower than that in SiO(2) group [(497.50 +/- 100.80) mg]; CP content in rush-mat dust group [(18.03 +/- 1.87) U/L] was higher than those in saline group [(15.05 +/- 2.24) U/L], TiO(2) group [(16.92 +/- 1.67) U/L], but lower than that in SiO(2) group [(25.37 +/- 3.58) U/L], P < 0.05 or P < 0.01. Pathological examination showed lung macrophage alveolitis, broadening of alveolar interval, one to two grade of silicotic nodes and increased amount of type II epithelial cell in alveolar as well as slight collagenous fibrosis in lung tissue of rush-mat dust group. Under electron microscope, primary and secondary lysosome and medullary sheath-like phagocytic residual body were found in lung tissue of rush-mat dust group, meanwhile the amount of type II alveolar epithelial cell and collagen fiber were slightly increased but these changes were less than those of quartz group.

CONCLUSIONThe rush-mat dusts have slight pulmonary fibrogenetic effect on rat.

Animals ; Ceruloplasmin ; analysis ; Dust ; Environmental Pollutants ; toxicity ; Fibrillar Collagens ; analysis ; Lung ; chemistry ; pathology ; ultrastructure ; Male ; Microscopy, Electron ; Pulmonary Fibrosis ; etiology ; pathology ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; toxicity ; Titanium ; toxicity

Purpose: Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. Materials and Methods: Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. Results: Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. Conclusion The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

AIM: To establish a sensitive and rapid liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method for the quantitative analysis of dehydrated puerarin in rat plasma, and its application for pharmacokinetic studies. METHODS: A plasma sample was pretreated by one-step protein precipitation by the addition of five volumes of methanol. The chromatographic separation was achieved on a Zorbax SB-C18 column (4.6 mm × 150 mm I.D. 5.0 μm, Agilent, USA) at 40 °C at a flow rate of 0.6 mL·min(-1) by an isocratic elution consisting of 10 mmol·L(-1) ammonium acetate in methanol and water containing 0.1% formic acid in a ratio of 20 : 80 (V/V). Detection was performed on a triple quadrupole mass spectrometer in multiple-reaction monitoring (MRM) mode. An atmospheric pressure chemical ionization (APCI) interface in positive ionization mode was used by monitoring the transitions from m/z 399.1→281.0 (dehydrated puerarin) and m/z 271.0→215.0 (internal standard, IS). RESULTS: Calibration curves were linear in the concentration range from 1.50 to 5400 ng·mL(-1), and the lower limit of quantification (LLOQ) was 1.50 ng·mL(-1) in rat plasma. The accuracy and precision values, which were calculated from three different sets of quality control samples analyzed in sextuplicate on three different days, ranged from 95.73% to 103.18%, and from 4.33% to 7.86%, respectively. CONCLUSION The method was successfully applied to assess the pharmacokinetics of dehydrated puerarin after oral administration in rats.
Animals ; Chromatography, High Pressure Liquid ; methods ; Drug Stability ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; metabolism ; pharmacokinetics ; Female ; Isoflavones ; administration & dosage ; blood ; metabolism ; pharmacokinetics ; Male ; Pueraria ; chemistry ; Rats ; Rats, Wistar ; Tandem Mass Spectrometry ; methods

OBJECTIVE: To observe the effect of ginger-partitioned moxibustion on digestive tract reaction, quality of life and white blood cell count after chemotherapy in advanced malignant bone tumors patients. METHODS: A total of 64 patients were randomly divided into an observation group and a control group, 32 cases in each group. Both groups were treated with adriamycin combined with cisplatin (AP) chemotherapy. The patients in the control group were treated by tropisetron hydrochloride intravenous on preventing the vomiting 1 h before receiving chemotherapy. On the basis of the control group, the patients in the observation group were treated with ginger-partitioned moxibustion at Neiguan (PC 6), Zusanli (ST 36), Shenque (CV 8), and Zhongwan (CV 12) 2 h after chemotherapy, once a day, 30 min each time. The course of chemotherapy, ginger-partitioned moxibustion and tropisetron hydrochloride intravenous was 5 days. The digestive tract reaction rating, quality of life score and white blood cell count were compared 1 d before chemotherapy, 2 d after chemotherapy and 7 d after chemotherapy between the two groups. RESULTS: The number of 0 grade in digestive tract reaction 2 d and 7 d after chemotherapy in the observation group was significantly higher than that in the control group ( CONCLUSION Ginger-partitioned moxibustion can prevent and treat vomiting after chemotherapy in advanced malignant bone tumors, and improve the quality of life and white blood cell count of patients.
Acupuncture Points ; Bone Neoplasms/drug therapy* ; Ginger ; Humans ; Moxibustion ; Quality of Life ; Vomiting/etiology*

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications