There is an increasing demand for neonatal and juvenile animal toxicity studies during the research and development of new drugs. In this paper,we discussed general evaluation parameters of pediatric non-clinical safety with pediatric drugs,such as growth and development and food intake,and paramenters of other organs and systems, such as the central nervous system,reproductive system, behavior evaluation in combination with our own experience. In addition,the characteristics of non-clin?ical safety evaluation of new traditional Chinese medicine materia medica used for juvenile animals were analyzed. This paper is intended reference for non-clinical safety evaluation of pediatric drugs and to gain some experience related to formulation of new guidelines.

Objective To study the clinical application of midazolam combined with remifentanil in spinal anesthesia.Methods80 cases of vertebral fractures in Jiaxing hospital, Zhejiang armed police corps from February 2014 to December 2016 were selected as the research object in this study.They were randomly divided into two groups: control group and experimental group, each group had a total of 40 cases.Patients in the control group were treated with midazolam anesthesia, the experimental group was treated with midazolam combined with remifentanil anesthesia.Comparative analysis of the experimental group and control group of patients with vital signs and anesthesia recovery time and anesthetic effect indicators.ResultsAfter the corresponding anesthesia, the respiratory frequency and heart rate of the experimental group were significantly higher than those of the control group, with statistical difference (P<0.05).There was no significant difference between the control group and the experimental group, no statistical significance.The recovery time, the time of open eyes and extubation time of the experimental group were significantly lower than those of the control group (P<0.05).The excellent rate of anesthesia in the experimental group was 95.0%, and the excellent rate of anesthesia in the control group was 75.0%.As a result, the excellent rate of anesthesia in the control group was significantly lower than that in the experimental group, the OAAS score of the experimental group was significantly higher than that of the control group, with statistical difference (P<0.05).ConclusionThe application of midazolam combined with remifentanil in anesthesia of spinal fracture surgery, anesthesia effect is good, the patient's recovery time is faster, with the clinical significance of further promotion and application.

Objective To investigate the effects of gliquidone on the AGEs (advanced glycation end products) -induced RANTES(Regulated upon activation,normal T-cell expressed and secreted) expression of human renal mesangial cells (HRMC). Methods AGEs were prepared by incubation of bovine serum albumin (BSA) with high concentration of glucose at 37℃ in vitro. HRMC was cultured in the presence of AGE-BSA (glucose at 50 mmol/L) with or without gliquidone. RANTES mRNA was analyzed by semi-quantity RT-PCR. The concentration of RANTES in the supernatant was quantified by ELISA. Results Gliquidone significantly inhibited the expression and secretion of RANTES induced by AGE-BSA. The inhibition of RANTES expression and secretion was in dose and time dependent manners. Conclusions AGEs is a potential toxin to induce expression of RANTES in HRMCs, which is inhibited by gliquidone.

Objective To investigate the effects of gliquidone on the AGEs (advanced glycation end products) -induced RANTES(Regulated upon activation,normal T-cell expressed and secreted) expression of human renal mesangial cells (HRMC). Methods AGEs were prepared by incubation of bovine serum albumin (BSA) with high concentration of glucose at 37℃ in vitro. HRMC was cultured in the presence of AGE-BSA (glucose at 50 mmol/L) with or without gliquidone. RANTES mRNA was analyzed by semi-quantity RT-PCR. The concentration of RANTES in the supernatant was quantified by ELISA. Results Gliquidone significantly inhibited the expression and secretion of RANTES induced by AGE-BSA. The inhibition of RANTES expression and secretion was in dose and time dependent manners. Conclusions AGEs is a potential toxin to induce expression of RANTES in HRMCs, which is inhibited by gliquidone

Objective To develop a non-invasive method for diagnosis of esophageal varices in patients with cirrhosis induced by viral hepatitis.Methods The clinical data,including results of blood routine,liver function,blood coagulation and color ultrasonography,of patients with cirrhosis induced by viral hepatitis from the First Affiliated Hospital of Zhengzhou University during December 2011 and December 2012 were retrospectively analyzed.Patients with hematopoietic diseases and portal vein thrombosis were excluded,and no patients received beta-blocker,endoscope band ligation,and splenectomy treatment.According to gastroscopic results,all patients were divided into no/mild group and mid/serious group.Correlations between clinical data and esophageal varices were analyzed by Logistic regression method,and receiver operating characteristic (ROC) curve was used to evaluate their values for diagnosis of esophageal varices.Results Totally 96 patients were enrolled in the study,30 without or with mild esophageal varices,and 66 with mid/serious esophageal varices.There were significant differences on platelet (PLT),plateletcrit (PCT),platelet distribution width (PDW),alanine aminotransferase (ALT),aspartate aminotransferase (AST),spleen thickness (ST) and PLT/ST between no/mild group and mid/ serious group (Z/t =-2.842,-3.151,-2.549,-3.463,-3.601,-4.360and 11.877,P＜0.05 or P ＜ 0.01).Multivariate logistic regression analysis showed that only ST was statistically different between two groups (OR =1.127,OR 95％ confidence interval (CI):1.012-1.256,P =0.030).The area under the curve (AUC) was 0.728,and 95％ CI:0.628-0.827.With the cut off value of 52.5 mm,the sensitivity,specificity,and Youden index of ST in diagnosis of esophageal varices were 53.0％,90.0％ and 0.43,respectively.Conclusion ST measured by color ultrosonography can be used for early diagnosis of mid/serious esophageal varices.

Objective To study T lymphocyte subsets levels in acute zoster patients and investigate its relation to the zoster associated pain.MethodsAccording to the visual analogue scales(VAS) in the acuter phase, 60 patients with herpes zoster were divided into two groups: group A (VAS≤6) and group B (VAS＞6). According to the follow-up results, patients were divided into another two groups: group C (PHN not developed) and group D (PHN developed). 25 healthy volunteers with a similar age and gender range as the patients were recruited as control group. T lymphocyte subsets were detected by fluorescence-activated cell sorter (FACS). ResultsThere was no significant difference in gender and age between groups (P＞0.05). T lymphocyte subsets were significantly decreased in four groups compared with the control group (P＜0.05), and the CD4 +subsets in group B were significantly decreased compared with group A (P＜0.05). The CD4 +/CD8 + ratios were significantly higher in group A and C than in control group, higher in group A than B and higher in group C than in group D (P＜0.05). The visual analogue scales(VAS) in group D were significantly higher than in group C (P＜ 0.05).Conclusions Cellular immunity function is decreased with the lower percent of the T lymphocytes subsets in the elderly patients with acute herpes zoster, especially in severe patients. The CD4 +/CD8 + ratios and the visual analogue scales may be associated with the the risk of post herpetic neuralgia.

In current research and development of new drugs,the demand for toxicological study using neonatal and juvenile animals is becoming increasingly urgent. In this paper,we discussed the characteristics,importance and necessity of nonclinical safety evaluation for pediatric drugs,considerations for research design,selection of animal species and age,route and duration of drug administration and evaluation indexes. In addition,the characteristics of nonclinical safety evaluation of new traditional Chinese materia medica used for children were analyzed. It is hoped that these studies will not only provide support and reference for nonclinical safety evaluation of pediatric drugs but help accumulate material in formulating relevant guidelines.

Objective To evaluate the therapeutic efficacy of acupuncture based on syndrome differentiation for functional dyspepsia (FD), and to explore the plausible action mechanism.Method Seventy-two eligible FD patients were randomized into a treatment group (36 cases) and a control group (36 cases). In the treatment group, the FD patients were divided into four types, liver-qi stagnation, spleen-stomach qi-deficiency, liver-qi affecting stomach, damp-heat accumulated in stomach, to receive acupuncture at the corresponding points based on syndrome differentiation in addition to the basic points including Zhongwan (CV12), Tianshu (ST25), Zusanli (ST36), and Neiguan (PC6); the control group was given Itopride hydrochloride tablets. Before and after intervention, the symptomatic efficacy index and the MOS 36-Item Short-Form Health Survey (SF-36), as well as serum Gastrin (GAS) content were observed in the two groups.Result The total effective rate was 94.1% in the treatment group, significantly higher than 63.9% in the control group (P＜0.01); after intervention, the improvement of symptomatic efficacy index in the treatment group was markedly better than that in the control group (P＜0.01); the improvements of the SF-36 component scores in the treatment group were markedly higher than those in the control group (P＜0.05).Conclusion Acupuncture based on syndrome differentiation can obviously improve the symptoms of FD patients, gastrointestinal function, and the quality of life, which is possibly realized by regulating serum GAS, and thus this treatment protocol is proper to be the optimal protocol in clinic for FD.

BACKGROUND:Schatzker V, VI fracture often causes the injuries to cruciate ligament, col ateral ligaments and meniscus. Moreover, the col apse and shifting were severe. The locking plate on one side cannot support the weight or obtain satisfactory reduction. OBJECTIVE:To compare the effects and stability of the dual-incision double-plate fixation and knee midline incision locking plate fixation in the treatment of Schatzker V, VI tibial plateau fracture. METHODS:A total of 76 patients with Schatzker V, VI tibial plateau fracture were respectively treated with locking plate fixation (n=38) and dual-incision double-plate fixation (n=38). Fracture reduction and healing were assessed using anteroposterior and lateral radiographs. Varus angle and medial caster angle of tibial plateau received biomechanical measurement. RESULTS AND CONCLUSION:Hospital stay and postoperative load time were significantly less in the dual-incision double-plate fixation group than in the locking plate fixation group (P<0.05). No significant difference in healing time was detected between locking plate fixation and dual-incision double-plate fixation groups (P>0.05). The number of complications, such as ankylosis, fracture delayed union, pin tract infection, delayed union, varus deformity, was significantly fewer in the dual-incision double-plate fixation group than in the locking plate fixation group (P<0.05). There were no significant differences in the fracture of loosening, knee instability, wound infection, skin necrosis, bone necrosis and nonunion between the dual-incision double-plate fixation and locking plate fixation groups (P>0.05). Postoperative Rasmussen classification was significantly better in the dual-incision double-plate fixation group than in the locking plate fixation group (P<0.05). Experimental results indicated that the clinical efficacy of the dual-incision double-plate fixation is superior to that of the anterior cruciate midline incision locking plate fixation in the treatment of Schatzker V, VI type tibial plateau fractures. The dual-incision double-plate fixation has more biomechanical stability.

Elements, including experimental personnel, facili-ties, equipment, apparatus, technology and skills, are essential to carrying out pre-clinical reproductive toxicity research. As to a study , authenticity , normativity , scientificity and innovativeness guarantee the success. These four elements are independent of each other,but mutually supported. Authenticity and scientificity are the footstone and soul, respectively, for drug non-clinical re-productive toxicity research. Normativity guarantees authenticity and scientificity, and innovativeness relies on authenticity. Nor-mativity and scientificity ensure the reliability and dynamics of experimental results which perhaps is an effective way accessing innovation.