[ ABSTRACT] AIM:To investigate the effects of maternal limb ischemic preconditioning ( LIP) on the mitochon-drial structures and functions of the hippocampal neurons induced by reoxygenation in the intrauterine distress fetal rats. METHODS:Pregnant rats (n=40) were randomly divided into 4 groups: sham (S) group, LIP group, fetal distress ( FD) group and LIP+FD group.Intrauterine ischemia model was established through the experimental design.The ultra-structure of the mitochondria in CA1 area of the hippocampus was observed .The mitochondrial membrane potential and re-active oxygen species ( ROS) were measured .The content of ATP and MDA in the hippocampus tissue was detected.The activity of Mn-SOD was observed.RESULTS:Compared with sham group, the ultrastructure of mitochondria in CA1 area of the hippocampus was damaged in FD group and LIP+FD group.The mitochondrial membrane potential, the content of ATP and the activity of Mn-SOD were decreased.However, the content of ROS and MDA was increased.Compared with FD group, the ultrastructure of mitochondria in CA1 area of the hippocampus was intact in LIP+FD group.Furthermore, the reduced mitochondrial membrane potential and ATP content were inhibited.The activity of Mn-SOD was increased, but the content of ROS and MDA was decreased in LIP+FD group.CONCLUSION:Limb ischemia preconditioning inhibits the damage the mitochondria of fetal hippocampal neurons induced by reoxygenation in the intrauterine distress fetal rats.

Objective To investigate the effect of maternal limb ischemic preconditioning on the expression of caspase-3 in neurons in brain tissues after reoxygenation in the fetal rats with intrauterine distress.Methods Forty Sprague-Dawley rats at 19 days of gestation were randomly divided into 4 groups (n=10 each) using a random number table:sham operation group (group S),limb ischemic preconditioning group (group LIP),fetal rat distress group (group FD),and limb ischemic preconditioning + fetal rat distress group (group LIP+FD).Distress/reoxygenation model was established by clamping the uterine and ovarian arteries and veins with a micro-artery clamp for 15 min followed by removal of the clamp to permit reperfusion.Limb ischemic preconditioning was induced by 3 cycles of occlusion of the lower limb blood flow at the site of the right groin for 5 min with a tourniquet followed by 5 min unclamping.In group LIP+ FD,the uterine and ovarian arteries and veins were clamped,and limb ischemic preconditioning was performed at the same time.Cesarean section was performed on 2 days after the end of treatments in each group,and the fetal rat mortality rate was calculated.The fetal rats alive were sacrificed,and the hippocampi were isolated for determination of neuronal apoptosis (by TUNEL) and expression of caspase-3 protein and mRNA (by Western blot and real-time reverse transcriptase polymerase chain reaction,respectively) in hippocampal CA1 region.Apoptosis index was calculated.Results Compared with group S,the fetal rat mortality rate and apoptosis index were significantly increased,and the expression of caspase-3 protein and mRNA in hippocampal CA1 region was significantly up-regulated in FD and LIP+FD groups (P＜0.05 or 0.0l),and no significant change was found in the parameters mentioned above in group LIP (P＞0.05).Compared with group FD,the fetal rat mortality rate and apoptosis index were significantly decreascd,and the expression of caspase-3 protein and mRNA iu hippocampal CA1 region was significantly down-regulated in group LIP+FD (P＜0.05 or 0.01).Conclusion The mechanism by which maternal limb ischemic preconditioning inhibits apoptosis in neurons after reoxygenation is related to down-regulation of the expression of caspase-3 in the fetal rats with intrauterine distress.

OBJECTIVE:To investigate the characteristics of pediatric drug-induced liver injury (DILI) in China,and to provide reference for reducing ADR.METHODS:Using"liver injury liver damage hepatotoxicity hepatitis liver disease""drug induced children" as keywords,related domestic literatures were retrieved from CNKI and Wanfang database during 2007-2016,clinical information of DILI children in literatures were recorded in detail and analyzed comprehensively.RESULTS:A total of 363 literatures were retrieved,including 13 effective literatures and 665 children in total.There were 424 boys (63.76％)and 241 girls (36.24％),with ratio of 1.76 ∶ 1.The youngest child was 1 month old,the oldest child was 14 years old;the average age was 7.87 years,337 children aged more then 7 years old,accounting for 50.68％.Top 3 primary diseases were respiratory tract infection (40 cases,31.50％),hematologic diseases (29 cases,22.83％) and tumor (14 cases,11.02％).Top 3 pediatric DILI-inducing drug types were antibiotics (245 cases,34.41％),TCM (143 cases,20.08％) and antipyretic analgesics (113 cases,15.87％).DILI usually happened within 4 weeks (332 cases,82.18％).The most common clinical classification was hepatocellular type (382 cases,65.30％).The severity of liver injury was mainly mild and moderate (505 cases,86.32％),and 80 cases were severe (13.68％),including 31 cases of hepatic failure (5.30％).Clinical symptoms mainly manifested as anorexia,jaundice,nausea,vomiting,hypodynamia and abdominal discomfort.After drug withdreawd and treatment,96.54％ of the patients were recovered or cured,and 4 cases died (0.60％).CONCLUSIONS:Under the premise of rational use of drugs,it is necessary to carry out medication education and supervision for antibiotics,TCM and antipyretic analgesics which mainly induce pediatric DILI,pay attention to allergic history and evaluate the progress of extrahepatic symptoms.When ADR occurred,the timely and drug withdrawal intervention are conducted to improve good prognosis.

Objective To observe the effects of Jianpi Qutan Huayu Prescription on oxidative stress and inflammatory response in mini-pigs with atherosclerosis(AS);To explore its mechanism based on the NOX5-ERK1/2 signaling pathway.Methods Twelve Bama mini-pigs were randomly divided into control group,model group,and Jianpi Qutan Huayu Prescription low-and high-dosage groups,with 3 pigs in each group.A high-fat diet was used to feed for 24 weeks to construct an AS model,and the treatment group was also supplemented with Jianpi Qutan Huayu Prescription in the feed.The general condition of mini-pigs(body length,abdominal circumference,body mass,food intake,and fecal water content)was measured at week 0,16,and 24 of administration,HE staining was used to observe the morphology of aortic tissue,while oil red O staining was used to observe lipid deposition in aortic and myocardial tissue,transmission electron microscopy was used to observe the ultrastructure of aortic tissue,and a fully automated biochemical analyzer was used to detect serum contents of TC,HDL-C,and LDL-C.ELISA was used to detect the contents of serum reactive oxygen species(ROS),interleukin(IL)-6,IL-10,tumor necrosis factor(TNF)-α,hypersensitivity-C-reactive protein(hs-CRP),vascular cell adhesion molecule-1(VCAM-1),and intercellular adhesion molecule-1(ICAM-1).Western blot was used to detect the expressions of NADPH oxidase 5(NOX5),extracellular signal regulated kinase 1/2(ERK1/2),p-ERK1/2,VCAM-1,and proliferating cell nuclear antigen(PCNA)proteins.Results Compared with the control group,the abdominal circumference,body mass,and food intake of mini-pigs in the model group increased at 16 and 24 weeks(P<0.01),there was significant thickening of the inner membrane of aorta,destruction of endothelial cells,lipid deposition,edema of smooth muscle cells,and significant swelling of mitochondria,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,VCAM-1,and ICAM-1 increased,while the content of HDL-C decreased(P<0.01);the expressions of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue increased(P<0.01).Compared with the model group,Jianpi Qutan Huayu Prescription low-and high-dosage groups showed a decrease in abdominal circumference,body mass,and food intake at 16 and 24 weeks(P<0.05,P<0.01),the plaque area and lipid deposition were reduced,and the damage to endothelial cells was alleviated,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,ICAM-1,and VCAM-1 decreased,and the content of HDL-C increased(P<0.01,P<0.05);the expressiond of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue decreased(P<0.01,P<0.05).Conclusion Jianpi Qutan Huayu Prescription can effectively alleviate AS in mini-pigs,and its mechanism may be related to inhibiting the activation of the NOX5-ERK1/2 signaling pathway and alleviating oxidative stress-induced inflammatory response.

Objective: To preliminarily evaluate the clinical efficacy of endoscopic argon plasma coagulation (APC) combined with sub-mucosal injection of norepinephrine saline in the treatment of radiation proctitis (RP), especially for refractory RP. Methods: Clinical data of 22 RP patients were retrospectively analyzed. The severity of RP was evaluated by a modified endoscopy scoring system (A) or Sherman′s classification (B). The criteria of successful treatment are the improvement of clinical symptoms or the cessation of bleeding (or only occasional traces of blood on the stools that do not need further treatment). Results: All 22 patients were successfully treated. Among them, 18 patients (82%) had no bleeding. According to the classification of A, 15 patients (68%) had mild proctitis and 7(32%) experienced severe proctitis. Based on B classification, 9 patients (41%) were categorized as mild proctitis and 13(59%) as severe proctitis. Using the classification of A, the number of treatment sessions was significantly correlated with the endoscopic grade (or endoscopic total score)(Spearman’s r=0.86, P<0.001). Conclusions Preliminary evidence demonstrates that endoscopic APC combined with sub-mucosal injection of norepinephrine saline is not only effective for mild and moderate RP, but also maintains long-term efficacy for refractory RP. Modified endoscopy scoring system (A) assessment is more suitable for clinical application compared with B assessment.

Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.