OBJECTIVETo investigate the effects of different concentrations of lipopolysaccharide (LPS), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), dexamethasone (Dex), and insulin on the mRNA and protein expressions of GPR54 in the MCF7 cell line in vitro.

METHODSMCF7 breasr cancer cells were cultured and treated with different concentrations of LPS (10 and 20 µg/ml), TNFα (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L). Those treated with culture fluid only served as controls. The mRNA and protein expressions of GPR54 were measured by real-time PCR and Western blot, respectively, after 6, 24, 48, and 72 hours of treatment.

RESULTSCompared with the blank con- trol, LPS (10 and 20 µg/ml), TNFα (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L) significantly increased the expressions of GPR54 mRNA (P < 0.05) and protein (P < 0.05).

CONCLUSIONLPS, TNFα, IL-6, Dex, and insulin evidently increase the expression of GPR54 in the MCF7 cell line, indicating their influence on the function of gonads by regulating the GPR54 level.

Blotting, Western ; Dexamethasone ; administration & dosage ; pharmacology ; Glucocorticoids ; administration & dosage ; pharmacology ; Gonads ; drug effects ; metabolism ; Humans ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; Insulin ; administration & dosage ; pharmacology ; Interleukin-6 ; administration & dosage ; pharmacology ; Lipopolysaccharides ; administration & dosage ; pharmacology ; MCF-7 Cells ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, G-Protein-Coupled ; drug effects ; genetics ; metabolism ; Receptors, Kisspeptin-1 ; Time Factors ; Tumor Necrosis Factor-alpha ; administration & dosage ; pharmacology

Objective · To evaluate the efficacy and safety of prophylactic phenylephrine in parturients prone to develop spinal hypotension.Methods · Fifty parturients undergoing elective cesarean delivery whose preoperative positional mean arterial pressure (MAP) change from supine to right lateral position were bigger than 8 mmHg (1 mmHg=0.133 kPa) were randomly allocated into 2 groups, i.e. high-risk prevented group (group A) and high-risk control group (group B). Another 25 parturients whose positional MAP change were smaller than 8 mmHg were allocated into low-risk prevented group (group C). After spinal anesthesia, phenylephrine (50 μg bolus and 50 μg/min infusion) was given immediately to group A and C, and the pump speed was adjusted to 25 μg/min 10 min later till fetuses were removed. Normal saline with the same volume and pump speed was given to group B. The incidences of hypotension, reactive hypertension, and bradycardia, the occurrence of nausea and vomiting, and Apgar scores at 1 min and 5 min of three groups were compared. Results · The incidence of hypotension in group A was 28%, 76% in group B, and 16% in group C. Group A and C were significantly lower than group B (P<0.01). The reactive hypertension rate was 4% in group A and 28% in group C. There was a difference between these two group (P=0.015). There were no significant differences among 3 groups in Apgar scores at 1 min and 5 min (P>0.05). Conclusion · Prophylactic phenylephrine in the paturients prone to develop spinal hypotension reduces the incidence of spinal hypotension without obvious adverse effects on the paturients and neonates.

Objective To evaluate the value of quantitative 3T dynamic contrast enhanced MRI in the diagnosis of breast lesions. Methods One-hundred and eighteen patients suspected of breast lesions underwent MRI examination. A 3.0 T MR scanner was used to obtain the quantitative MR pharmacokinetic parameters: Ktrans( volume transfer constant), Kep (exchange rate constant) and Ve (extravascular extracellular volume fraction). The mean Ktrans, Kep and Ve of malignant, benign and normal glandular tissues were calculated and compared each other using LSD method. Independent sample t test was used between invasive ductal carcinoma and ductal carcinoma in situ (microinvasion included). Finally, the areas under the ROC curve (AUC) of Ktrans, Kep and Ve between malignant and benign lesions were compared. Results The mean Ktrans, Kep and Ve of malignant lesions (n=87) were (1.010±0.580) min-1, (1.634 ± 1.481) min-1 and (0.735 ±0.273); the mean Ktrans, Kep and Ve of benign lesions (n=23) were (0.331±0.192) min - 1, (0.417±0.324) min - 1 and (0.847±0.291); and the mean Ktrans, Kep and Ve of normal glandular tissues (n =83) were (0.051 ±0.028) min-1, (0.133±0.125) min-1 and (0.597±0.354), respectively. There were significant differences between normal glandular tissues and benign lesions, normal glandular tissues and malignant lesions, benign and malignant lesions in Ktrans (t=9.681, 11.189, 5. 590, respectively, P ＜ 0. 01 ), normal glandular tissues and malignant lesions, benign and malignant lesions in Kep(t =5. 287, 3. 874, P＜0. 05). There were a statistic differences between normal glandular tissues and benign lesions, normal glandular tissues and malignant lesions in Ve(t =2. 932, 2. 562 ,P ＜0. 05). There were no significant differences between normal glandular tissues and benign lesions in Kep, benign and malignant lesions in Ve ( t = 0. 760, 0. 832, P ＞ 0.05 ),invasive ductal carcinoma and ductal carcinoma in situ (microinvasion included) in Ktrans, Kep and Ve(t =0.834,0.075,0.454,P＞0.05). The areas under the ROC curve (AUC) of Ktrans, Kep and Ve between malignant and benign lesions were 0. 934, 0. 941 and 0. 659. The sensitivity of Ktrans, Kep and Ve were 77.01% ,91.95% ,56. 32% and the specificity of Ktrans, Kep and Ve were 95. 65%, 86. 96%, 78.26% for the differential diagnosis of breast lesions if taken the maximum Youden's index as cut-off. Conclusion The differential diagnosis of benign and malignant breast lesions by Ktrans, Kep is applicable.

Animal models with kidney disease are generally divided into two types. One belongs to the models which imitate human kidney disease by the artificial operations, such as anti-glomerular basement membrane antibody nephritis, Heymann nephritis, anti-Thyl. 1 antibody nephritis, BSA nephritis and puromycin nephropathy. The other one pertains to the models which make themselves kidney disease, and appear the pathological characteristics naturally as like as human, such as HIGA mice with IgA nephropathy and NZB/WF1 and MRL/1pr mice with lupus nephritis. In addition,the transgenic animal models with kidney disease can also be established by the modern molecular biologic techniques including gene knockout and siRNA transfection. As for the studies related with kidney disease in pharmacodynamics and pharmacology of Chinese herbal medicine (CHM), it is important to understand deeply the features of each animal model with kidney disease, and select accurately the proper models according to the different experimental objectives, and then, build the special models provided with the combination of disease with syndrome in traditional Chinese medicine (TCM). Therefore,it is the developmental direction for the further study to establish animal models with kidney disease, which should possess the characteristics of syndrome in TCM.
Animals ; Diabetic Nephropathies ; etiology ; Disease Models, Animal ; Humans ; Kidney Diseases ; etiology ; Medicine, Chinese Traditional ; Mice ; Streptozocin

ObjectiveTo investigate the effects of diet-induced obesity on the developmental process of testes in pubertal Sprague Dawley (SD) rats and explore the possible reversibility. MethodsSixty one-month-old male SD rats were randomly divided into a control group ( n =10) and a model group ( n =50 ), which were fed on a normal diet and a high-fat diet, respectively. After 8 weeks, all the rats in the control group and 10 rats randomly picked out from the model group were killed. The serum testosterone and estradiol levels were measured by enzymelinked inununosorbent assay. Their left testes sections were stained by HE method, and the histology was observed under optical microscope and the spermatogenic activity was evaluated by Johnsen scoring system. The remaining 40 rats in the model group were further randomly divided into 3 subgroups: continued high-fat diet subgroup ( n =13), resume normal diet subgroup (n =13), and weight-loss subgroup (n =14). The continued high-fat diet subgroup was fed by high-fat diet, while the other two subgroups were fed by normal diet. Rats in weight-loss group took normal diet with running 20 min/d. After 6 weeks, the same parameters were assessed using the same methods. ResultsAfter 8 weeks, compared with the control group, the testosterone level of the model group significantly decreased (P =0.024) and the estradiol level significantly increased ( P =0. 017). The result of HE staining showed that the spermatogenic cell layers decreased, with part of seminiferous tubule experiencing atrophy.The number of Leydig cell also decreased and lipo vacuole was seen in the interstitial tissue of testis. The Johnsen score of the model group was significantly lower than that of the control group (P =0.000). The testosterone level was significantly lower in the continued high-fat diet subgroup than that in resume normal diet subgroup ( P =0.001 ) and weight-loss subgroup ( P =0.000), and was significantly lower in resume normal diet subgroup than that in weight-loss subgroup ( P =0.001 ). The estradiol level was significantly higher in continued high-fat diet subgroup than that in resume normal diet subgroup ( P =0.001 ) and weight-loss group ( P =0.000 ), and was significantly higher in resume normal diet subgroup than that in weight-loss group ( P =0.001 ). HE staining showed that, pathological changes aggravating and worsening compared with the control group, the model group had significantly decreased seminiferous tubule cell layers, with some seminiferous tubules experiencing atrophy.The Johnsen score was significantly higher in weight-loss subgroup than that in the other two subgroups ( P =0.000and 0.001, respectively). The Johnsen score was negatively correlated with body weight ( r =- 0.962, P =0.000), and positively correhted with the serum testosterone level ( r =0.916, P =0.000 ). Conclusions High-fat diet can induce pubertal obesity in male SD rats, which is featured by testicular hypoplasia, decreased spermatogenesis, and endocrine dysfunction. Physical exercise may improve the conditions. The degree of obesity may be negatively correlated with the spermatogenic function.

Aim To study pharmacokinetics and bioavailablity of domestic penicillin V dispersion tablet in healthy volunteers. Methods According to the crossover design, each volunteer in two groups was orally given a single dose ( 0.75 g ) of domestic penicillin V dispersion tablet or imported penicillinV tablet alternately and the plasma concentrations were determined by RP HPLC. The pharmacokinetic parameters were obtained by using ATPK program and calculated on the basis of open single compartment model. Results After a single oral dose( 0.75 g ), the t 1/2(ke) was ( 0.75 ? 0.10 ) h and ( 0.70 ? 0.14 ) h ,the c max was( 8.44 ? 2.40 ) mg?L -1 and ( 8.75 ? 3.04 ) mg?L -1 at ( 0.56 ? 0.11 ) h and ( 0.63 ? 0.17 ) h and AUC 0～4 was( 8.44 ? 2.40 ) mg?h?L -1 and ( 8.75 ? 3.04 ) mg?h?L -1 for two formulations, respectively. Relative bioavailability of domestic penicillin V dispersion tablet was ( 90.50 ? 8.84 )%. Conclusion The result shows that the two formulations are bioequivalent.

Objective To explore the role ofpostsynaptic density 95 (PSD-95) in Parkinsonian rat models receiving chronic L-dopa treatment. Methods The hemi-parkinsonian rat models were established by stereotaxically injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of 60 rats. Thirty-two of them were successfully induced into models with PD and equally randomized into PD group, L-dopa plus physiological saline treatment group, L-dopa plus PSD-95antisense oligonucleotide treatment group and L-dopa plus TE treatment group (n=8). The rats in the PD group were treated intraperitoneally with 0.2% ascorbic acid physiological saline water. The rats in the for 22 d. On the following 3 days, the rats were performed intraperitoneal injection of physiological saline water, injection of PSD-95 antisense oligodeoxynucleotide and TE buffer in the striatum,respectively. Another 8 rats were chosen as normal control group, only given solvent. Rotational reaction time and the largest number of revolutions within 5 minutes of rotation were estimated on the 25th d of injection. After rats being sacrificed, Mrna and protein expressions of PSD-95 at the corpus striatum were observed by RT-PCR and Western blotting, repectively. Results After chronic treatment with L-dopa methylester, the rotational reaction time was prolonged and the the largest number of revolutions within 5 minutes of rotation of PD rats was decreased in the L-dopa plus PSD-95 antisense oligodeoxynucleotide group on the 25th d, as compared with those in the L-dopa plus physiological saline water group and L-dopa plus TE group (P＜0.05). In the lesioned striatum of PD rats, the abundance of PSD-95 Mrna and protein expressions were statistically and evidently reduced as compared with those in the control group (P＜0.05). After chronic treatment of PD rats with L-dopa, the abundance of PSD-95mRNA and protein expressions were statistically and evidently increased as compared with that in the PD group (P＜0.05). Pretreatment with PSD-95 antisense oligodeoxynucleotide statistically and obviously reduced the abundance of PSD-95 protein expression as compared with pretreatment with chronic L-dopa (P＜0.05). Conclusion PSD-95 may play a significant role in the pathogenesis of motor complications of rats with PD receiving chronic L-dopa treatment.

OBJECTIVETo demonstrate the effects and mechanisms of Huangkui capsule (HKC) on renal fibrosis in rats with diabetic nephropathy (DN).

METHODRats were randomly divided into 5 groups, the sham-operated group (Sham group, n = 5), the vehicle-given group (Vehicle group, n = 7), the low dose of HKC-treated group (L-HKC group, n = 7), the high dose of HKC-treated group (H-HKC group, n = 7) and the lipoic acid (LA)-treated group (LA group, n = 7). DN models were induced by intraperitoneal injection of streptozotocin (STZ,35 mg x kg(-1)) twice and unilateral nephrectomy. After models were successfully established, the rats in HKC and LA groups were daily administrated with HKC suspensions (0.75, 2 g x kg(-1)) or LA suspensions (60 mg x kg(-1)) respectively, and at the same time, the rats in Vehicle group were daily administrated with distilled water (2 mL) for 8 weeks. All rats were sacrificed at the end of week 8 to collect blood and renal tissues. UAlb, renal function, renal fibrotic morphologic characteristics, as well as oxidative stress (OS)-related markers, the protein expressions of the key signaling molecules in p38 mitogen-activated protein kinase (p38MAPK) signaling pathway, fibrogenic cytokines and inflammatory factors were examined respectively.

RESULTHKC, similar to LA, improved the general state of health, body weight, UAlb, BUN, UA and Alb in DN model rats. Of note, renal fibrosis was ameliorated in HKC groups,especially in H-HKC group which was better than that in LA group. In addition, HKC not only improved the main indexes of OS in the kidney like LA, but also down-regulated the protein expressions of phosphorylated-p38MAPK (p-p38MAPK), transforming growth factor (TGF)-β1 and tumor necrosis factor(TNF)-α in the kidney, whereas, LA only decreased the protein expression of TNF-α in the kidney in DN model rats.

CONCLUSIONHKC, similar to LA, has the actions of anti-OS in vivo. Moreover, HKC could attenuate renal fibrosis by suppressing the activation of p38MAPK signaling pathway and the protein expressions of fibrogenic cytokines and inflammatory factors in the kidney in DN model rats, which is different from LA.

Abelmoschus ; chemistry ; Animals ; Capsules ; Diabetic Nephropathies ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Fibrosis ; Kidney ; drug effects ; pathology ; MAP Kinase Signaling System ; drug effects ; Male ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors

OBJECTIVETo explore the effects and mechanisms of multi-glycoside of Tripterygium wilfordii (GTW) on improving glomerular inflammatory lesion in rats with diabetic nephropathy (DN).

METHODDN model was induced by unilateral nephrectomy and intraperitoneal injection of STZ (35 mg x kg(-1)) twice. The rats were randomly divided into 3 groups, the sham-operated group (Sham group, n = 5), the vehicle-given group (Vehicle group, n = 5 ) and GTW-treated group (GTW group, n = 5). After the model was successfully established, the rats in GTW group were daily oral administrated with GTW suspension (50 mg x kg(-1) x d(-1)), meanwhile, the rats in Vehicle group were daily oral administrated with distilled water (2 mL) for 8 weeks. From the beginning of the administration, all rats were killed 8 weeks later. Blood and renal tissues were collected,and then UAlb, renal function, glomerular morphology characteristics and glomerular macrophages (ED1 + cells) infiltration, as well as the protein expressions of inflammatory cytokines including tumor necrosis factor(TNF)-α and interleukin(IL)-lβ, and the key molecules in p38MAPK signaling pathway including p38 mitogenactivated protein kinase (MAPK), phosphorylated p38 (p-p38MAPK) and transforming growth factor(TGF)-β1 were investigated respectively.

RESULTGTW not only ameliorated the general state of health and body weight,but also attenuated UAlb, glomerulosclerosis, the infiltration of glomerular ED1 + cells and the protein expressions of TNF-α, IL-1β, p-p38MAPK and TGF-β1 in the kidney in DN model rats.

CONCLUSIONBy means of DN model rats, we demonstrated that GTW has the protective effect on renal inflammatory damage in vivo via inhibiting inflammatory cells infiltration and inflammatory cytokines expression. Furthermore, GTW could improve renal inflammatory lesion through down-regulating the expressions of the key signaling molecules in p38MAPK pathway such as p-p38MAPK and TGF-β1 ,and inhibiting the activation of p38MAPK signaling in the kidney.

Animals ; Diabetic Nephropathies ; drug therapy ; Disease Models, Animal ; Glomerulonephritis ; drug therapy ; Glycosides ; pharmacology ; MAP Kinase Signaling System ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; analysis ; Tripterygium ; chemistry ; p38 Mitogen-Activated Protein Kinases ; physiology

This paper uses the data collected from 138,477 patient discharge records of 37 Shanghai tertiary public hospitals in December 2013 and classifies all the records into different groups by using a localized diagnosis re-lated group tool.The coefficient of variation index ( CV) of each group was used to analyze the dispersion of average hospital cost per inpatient day for each group, in order to evaluate the suitability of diagnosis related group systems and to set the coefficients of difficulty ( relative weights) for each disease.The study has found that severity-based di-agnosis related group systems are more suitable and consistent.However, future studies should collect more detailed information on health costs in order to reflect the value of health professionals and technologies and therefore further improve diagnosis related classification and develop new systems that can be adapted to local conditions by applying the weights of different groups.