An introduction to the classified management of such trials and clinical application,documents submission for ethical review,operating procedures and review key points,as well as the problems found in the review.These efforts aim to provide guidance to the review of medical technique clinical trials,and to promote ethical supervision for new medical techniques.

AIM: To observe the protein expression of vascular endothelial growth factor 1 (VEGF-1) in pulmonary arterial endothelial cells and VEGF-1 gene expression in lung tissue in rats with hypoxia-induced pulmonary hypertension and treated with heparin. METHODS: Twenty four male adult SD rats were randomly divided into three groups (8 rats each): a control group (group A), a group with hypoxia for 4 weeks (group B) and a group with hypoxia for 4 weeks and injected with heparin to abdominal cavity simultaneously (group C). Mean pulmonary arterial pressure (mPAP), right ventricle hypertrophy index (RVHI) and vessel morphometry were measured. The morphology of pulmonary artery was observed by HE staining. The expression of VEGF-1 protein in pulmonary arterial endothelial cells was determined by immunohistochemistry. The level of VEGF-1 mRNA in lung tissue was measured by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: mPAP, RVHI, pulmonary artery remodeling parameters, VEGF-1 protein expression in pulmonary arterial endothelial cells and VEGF-1 gene expression in lung tissue of the three groups from high to low were group B, group C and group A. It was statistically significant when compared between either two groups of the three (P<0.01). Linear correlation analysis showed that VEGF-1 protein was positively correlated with pulmonary artery remodeling parameters (r=0.974, P<0.01), and VEGF-1 mRNA was positively correlated with VEGF-1 protein (VEGF 120 mRNA, r=0.919, P<0.01; VEGF164 mRNA, r=0.896, P<0.01). CONCLUSION: Heparin may down-regulate the expression of VEGF-1 at the levels of transcription and translation, resulting in the inhibitory effect on rats with hypoxia-induced pulmonary hypertension.

Objective To evaluate the neurotoxicity induced by multiple exposures to sevoflurane anesthesia in the neonatal rats.Methods Thirty-two healthy SPF Sprague-Dawley rats of both sexes,aged 7 days,weighing 15-20 g,were randomly divided into 2 groups (n=16 each) using a random number table:control group (group C) and multiple exposures to sevoflurane anesthesia group (group Sev).On postnatal day 7,14 and 21,2.6％ sevoflurane was inhaled for 2 h in group Sev,while the mixed gas of oxygen and air was inhaled instead of sevoflurane in group C.Morris water maze test was carried out on postnatal day 32-36 to assess the cognitive function.On postnatal day 21 and 36,8 rats in each group were selected and anesthetized,and the cerebrospinal fluid was collected for determination of the concentrations of amyloid β-protein by enzyme-linked immunosorbent assay.Results Compared with group C,no significant change was found in the escape latency,movement time spent in the effective region of the platform,movement distance,the number of entries into the effective region,percentage of residence time,percentage of movement distance,and percentage of the number of entries (P＞0.05),and the concentrations of amyloid β-protein in the cerebrospinal fluid were significantly increased on postnatal day 36 in group Sev (P＜0.05).Conclusion Multiple exposures to sevoflurane anesthesia can induce central neurotoxicity,but do not induce changes in the cognitive function in the neonatal rats.

Objective To evaluate the effect of situational health education in glycemic control in type 2 diabetes patients.Methods A total of 98 patients with type 2 diabetes was randomly assigned to the control(n=49)and the study group(n=49).The control group received conventional diabetes education,while the study group received situational health education.Fasting blood glucose(FBG),2-hour plasma glucose (2 hPG),HbAlc and the self-care behaviors were observed at baseline and 1-year after the intervention.Paired t test was used for data analysis.Results FPG,2hPG,HbA1c and self-care behavior scores were not significantly different between the two group at baseline.After 1-year intervention,FPG,2hPG and HbA1c of the two groups were significantly decreased,and FPG,2hPG and HbA1c of the study group were significantly lower than those of the control group(t values were 2.71,3.35 and 2.90,respectively; all P＜ 0.05).In comparison with the control group,self-care scores of the study group were increased(t values were 7.36,6.51,5.24,5.07,6.57 and 6.77,respectively; all P＜0.05).Conclusion Situational health education could improve self-management and glycemic control of type 2 diabetic patients.

Obj cetive A large number of recent studies show that sevoflurane anesthesia may cause learning and memory dysfunction.The aim of this study was to explore changes of learning and memory ability and hippocampal volume in infantile rats after neonatal interrupted and repeated inhalation of 2.6% sevoflurane through detecting the learning and memory ability by Morris water maze and the hippocampus volume by MRI.Method s Thirty two neonatal SD rats were randomly devided into two groups (n=16):experimental group and control group.Rats inhalated 2.6%sevoflurane in the experimental group and 1 L/min O2 +1 L/min Air in the control group at the postnatal days of 7, 14 and 21 (P7, P14, P21). The learning and memory ability was determined by the Morris water maze test from P31 to P37;The brains of rats were scanned by mag-netic resonance imaging ( MRI) machine under anesthesia with 1%sodium pentobarbital at P37, and the brain and bilateral hippocampal volumes were measured. Results ①In the place navigation test, the escape latency had no significant difference between the two groups (P>0.05).In the spatial probe test, the dwelling time, movement distance and number of entering times in platform quadrant decreased slightly in experimental group compared with those in the control group, while there was no significant difference (P>0.05).②The brain volume [(1.53 ±0.18) cm3 vs (1.60 ±0.13) cm3] and right hippocampal volume [(16.15 ±1.76)mm3 vs(16.46 ±1.71)mm3] had no significant difference between the two groups (P>0.05).The left hippocampal volume [(16.46 ±1.71)mm3] was decreased in the experimental group compared with the control group [(18.10 ±2.53)mm3](P<0.05). Conclusion The learning and memory ability has no significant changes in in-fantile rats after neonatal interrupted and repeated sevoflurane inhalation and MRI examination of hippocampal volume is not sufficient for the diagnosis of cognitive dysfunction.

BACKGROUND:There is a close relationship between epilepsy and apoptosis. The appearance of epilepsy can lead to the loss of neurons in the hippocampus, triggering a series of programmed cel death. OBJECTIVE:To investigate the effect of bone marrow stromal stem cel transplantation on apoptosis in epilepsy. METHODS:After modeled to be of epilepsy 45, Sprague-Dawley model rats were randomly divided into three groups, fol owed by given no intervention (moldel group), normal saline (normal saline group) or bone marrow stromal stem cel transplantation (transplantation group). At 1, 2 and 4 weeks after modeling, the number of Bax-positive cel s, Bcl-2-positive cel s and Bax/Bcl-2 were detected by immunohistochemistry. RESULTS AND CONCLUSION:The number of Bax-positive cel s, Bcl-2-positive cel s and Bax/Bcl-2 presented no obvious changes in the normal saline group at different time points. However, the number of Bax-positive cel s and Bax/Bcl-2 in the transplantation group was significantly decreased, while the number of Bcl-2-positive cel s significantly increased compared with the other two groups at 1, 2 and 4 weeks after modeling (P<0.05). Moreover, the above indicators varied significantly in the transplantation group at different time points after modeling (P<0.05). These results show that bone marrow stromal stem cel transplantation can affect the apoptosis and effectively reduce the apoptosis in rats with epilepsy by up-regulating the number of Bax-positive cel s and down-regulating the number of Bcl-2-positive cel s.

Objective To determine the off -label use of antibacterial agents,we investigated and analyzed the current status about off -label use of antibacterial agents.Methods The random sampling was conducted to select the outpatient prescription including antibacterial agents from January to April in 2016.According to drug instructions,the off -label drug use of prescription was analyzed.Results 1 264 prescriptions involving 58 kinds of drugs were analyzed.The main categories of off -label drug use were no pediatric and elderly information(23.42%), indication(4.1 5%),dosage (6.31 %),dosage range (62.95%)and administration route (3.1 5%).Conclusion The off -label use of antibacterial agents is common in our hospital.It's in need to regulate off -label drug use.

Objective To investigate the role of interleukin-1 receptor type 1 (IL-1R1) signaling in H1N1 influenza virus infection. Methods IL-1R1 knockout ( IL-1R1-/-) mice and wild type ( WT) mice were infected intranasally with 2×104 TCID50(50% tissue culture infective dose) of influenza virus H1N1 PR8. Changes in clinical signs, survivals and bodyweights of those mice were monitored daily for 14 consecutive days. Three mice from each group were sacrificed at 3, 7 and 14 days post infection (d. p. i), from which whole lungs were harvested. A part of the lobes was fixed in 4% paraformaldehyde for histopatho-logical assessment and the rest were split and stored at-80 centigrade for further analysis. Real-time quanti-tative PCR and cytometric bead array ( CBA) were performed to detect viral loads in lungs and inflammatory cytokines in supernatants of lung homogenates. Results The mice in both groups showed severe symptoms after the infection of PR8. The maximum bodyweight loss of IL-1R1-/- mice [(24. 22±0. 80) % at 8 d. p. i] was lower than that of WT mice [(28. 03±1. 51)% at 9 d. p. i] (P<0. 05). The IL-1R1-/- mice with PR8 infection showed a higher survival rate (90%) as compared with that of the control group (40%) (P<0. 05). No statistical differences in virus loads were observed between the two groups at 3, 7 and 14 d. p. i. The lung weight to body weight ratio of IL-1R1-/-mice [(1. 42±0. 03) %] was lower than that of WT mice [(1. 79±0. 08) %] at 3 d. p. i (P<0. 05). Pathological changes in IL-1R1-/- mice were less severe than those in WT mice. CBA detection assay revealed that the proinflammatory cytokines in lungs of IL-1R1-/-mice were less than those in WT mice. Conclusion IL-1R1 signaling plays a pathogenic role in mice infec-ted with 2×104 TCID50 of influenza virus PR8 by promoting inflammatory responses.

Objective:To summarize the clinical features and experience in diagnosis and treatment of subglottic cysts in children.Methods:The clinical data of 5 children with subglottic cysts admitted in Qilu Children′s Hospital of Shandong University from April 2018 to June 2019 were retrospectively analyzed.Results:Among the 5 patients, 2 cases were premature infants and 3 cases were full term infants.All patients had an endotracheal intubation history.One patient was asymptomatic.Four patients had laryngeal stridor, 2 cases of whom were accompanied by hoarseness and dyspnea.These 2 patients were used to be misdiagnosed with laryngomalacia, laryngitis, etc.Bronchoscopy revealed subglottic gray-white cyst-like lesions, and enhanced CT showed low density without enhancement.All patients were treated with laser and forceps, and bronchoscope was applied in the follow up period for 5-12 weeks.There was no recurrence or subglottic stenosis.Conclusions:Laryngeal stridor in children with a history of endotracheal intubation must be examined by bronchoscopy in time to find out whether there is subglottic cysts.Laser therapy is an effective treatment for subglottic cysts.

Objective To investigate the feasibility of new criteria for evaluating the radiotherapeutic effect on esophageal cancer by barium meal (BM) combined with CT scans.Methods A total of 189 patients who were diagnosed with esophageal cancer (confirmed by biopsy) from January 2004 to December 2010 were enrolled as subjects.All patients underwent BM and CT scans before and after radiotherapy.The maximal esophageal wall thickness (EWT) and changes in the volumes of regional lymph nodes measured by CT scans were analyzed.New criteria for evaluating the short-term radiotherapeutic effect on esophageal cancer was studied considering the analysis results as well as the BM-based criteria for evaluating short-term radiotherapeutic effect and follow-up results.Results The BM-based evaluation criteria were still useful,but had certain limitations.There were 115 patients who had regional lymph node metastasis as detected by CT scans before radiotherapy,and they were divided into complete remission (CR) group and partial remission (PR) group according to BM results after radiotherapy; the local control rate (LCR) of CR group was significantly higher than that of PR group,but there was no significant difference in survival rate (SR) between the two groups.There were 65 patients who had no regional lymph node metastasis,and they were also divided into CR group and PR group according to BM results after radiotherapy;the LCR and SR of CR group were significantly higher than those of PR group.In summary,the patients who had a CR as evaluated by BM and had the maximal EWT of ≤ 1.20 cm and the volumes of residual lymph nodes of ≤ 1.00 cm3 on CT were defined as CR ; the patients who had a PR as evaluated by BM or had the maximal EWT of ＞ 1.20 cm or those who had a CR evaluated by BM and had the maximal EWT of ≤ 1.20 cm and the volumes of residual lymph nodes of ＞ 1.00 cm3 on CT were defined as PR.The cases evaluated by BM as no remission (NR) or showing metastasis were defined as NR or progressive disease.There were significant differences in LCR and SR between the CR group and PR group determined by the new criteria.Conclusions Simply using BM to evaluate the short-term radiotherapeutic effect on esophageal cancer has certain limitations; instead,the evaluation based on both BM and CT scans is more accurate.