Scientific research training program is an important component in the 8-year medical education program. It focuses on the training of scientific research thinking and research methods. It is necessary to establish an effective evaluation system in order to achieve the learning outcomes of scientific research training program. PUMC has established an effective evaluation system which involves research project selecting,supervising,formative assessment,oral defense. This paper introduces the evaluation system of scientific research training program at PUMC.

Objective To characterize the nasal resonance of children with spastic cerebral palsy by comparing it with that of ordinary school-age children.Methods The mean nasalance scores (MNSs) of 90 normal school-age children and 62 school-age children with spastic cerebral palsy were measured and compared.Results (1) Age has significant effects on the MNS of/a/,/i/and/m/ in ordinary children,but has almost no effect on the MNS of/u/.The MNS of/a/,/i/,/u/ and/m/ in children with spastic cerebral palsy does not change with age.(2) Sex only has a significant relationship with the MNS of/i/ in ordinary children,but does not significantly predict the other MNSs.(3) The MNS of/a/ of children with spastic cerebral palsy is significantly lower than that of ordinary children,and their MNS of/i/ and /u/ is significantly greater than those of ordinary children.Conclusions The MNS of /a/,/i/and /u/first increases and then decreases with age in ordinary children,while the MNS of/m/ increases gradually.Children with spastic cerebral palsy did not show the same trends and demonstrated a state of retardation of nasal resonance.Children with spastic cerebral palsy are more likely to display hypernasality than ordinary children.

SUMMARY National Institutes of Health (NIH) released the biomedical research project NIH Roadmap Initiatives, including 3 themes, new pathways to discovery,research teams of the future,and re-engineering the clinical research enterprise. The purpose of the project is to catalyze to transform our new scientific knowledge into tangible benefits for people. Now,Mostly of the Project have begin to carry into practice.

Objective To investigate the changes of serum osteocalcin and bone micro-structure in ovariectomized mice exposed to low-iron environment.Methods Twenty-four 12-week-old female C57BL/6 mice were divided equally into sham operation (SHAM) group,model(OVX) group,and low iron(OVX+DFO) group.In low-iron group,deferoxamine(DFO) was injected 3 times per week for 5 weeks after operation ; the other groups were injected with the same dose of 0.9％ normal saline for 5 weeks.The serum,left femur,uterus were harvested after five weeks of treatment.The serum osteocalcin and ferritin levels were measured by ELISA kit,the weight of the uterus was recorded by analytical balance.A high resolution micro-CT was used to scan the left femur for cortical bone and cancellous bone analysis.Results (1) The serum osteocalcin and serum ferritin levels in low-iron group were significantly lower than those in the other 2 groups (P＜0.01) ; (2) Compared with the sham group and ovx group,there were significant decrease of the BMD、BV/TV and Tb.N,but increase of Tb.Th and Tb.Sp in low-iron group (P＜0.01).Conclusion A certain dose of DFO (30 mg/kg) can decrease the serum ferritin levels as well as the bone formation index in ovariectomized mice.

Organ-specific tumor cell adhesion to extracellular matrix (ECM) components and cell migration into host organs often involve integrin-mediated cellular processes. Direct integrin-mediated cell adhesion to ECM components in the space of Disse appears to be required for the successful liver metastatic formation of colon cancer. In the present study, human colon cancer HT-29 cells were transfected by liposome with integrin-beta(1) antisense oligodeoxynucleotide (ASODN). The integrin-beta(1) gene expression in HT-29 cells was significantly down-regulated. The migration of HT-29 cells was assayed using transwell cell culture chambers in vitro. The number of migrating HT-29 cells in experimental group was far less than that in control group (P<0.05). The models of hepatic metastasis in nude mice were established by the intrasplenic injection of transfected HT-29 cells. Thirty days later, the nude mice were killed and the average number of hepatic metastases (4.00+/-0.93 per mouse), average volume (10.10+/-6.50 mm(3) per mouse), average weight (0.0440+/-0.0008 g per mouse) in experimental group were remarkably reduced as compared with those in control group (P<0.05). Integrin-beta(1) expression in the hepatic metastasis was studied by immunohistochemistry (SP). Positive cell percentage of hepatic metastases in experimental group was markedly decreased as compared with that in control group (P<0.05). It was concluded that integrin-beta(1) may take part in hepatic metastasis, and down-regulation of integrin-beta(1) expression may play a key role in decreasing migration and hepatic metastasis of human colon carcinoma cells (HT-29).

Objective:To investigate the relationship of polymorphism of leptin receptor gene Gln223Arg with asthma and metabolic syndrome.Methods: Collected 120 asthma patients,92 metabolic syndrome patients,54 asthma combined metabolic syndrome patients and 81 normal controls.According to the severity,the asthma patients were divided into mild-medium group and severe group.The serum leptin level was measured by ELISA,the genotypes of leptin receptor were analyzed by the method of polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP),and statistcs of each subject′s MBI,blood pressure,lung function and fasting blood glucose were collected.Results: ①There were significant differences in genotype and allele frequency in leptin receptor gene Gln223Arg between the metabolic syndrome group,asthma combined metabolic syndrome group and normal control group(P<0.05).②The allele frequency and genotype in leptin receptor gene Gln223Arg were significant different between the severe asthma group and normal control group(P<0.05).③The serum leptin level,BMI and systolic blood pressure of AA+AG genotype group were significiant higher than GG genotype group(P<0.05),while the value of FEV1% and FEV1/FVC of lung function were lower than GG genotype group(P<0.05).Conclusion: Leptin receptor gene Gln223Arg polymorphism is correlated with asthma and metabolic syndrome,and by causing leptin resistance,the A allele might be the genetic factor that contribute to individual susceptibility for asthma and metabolic syndrome.

The purpose of the study is to construct R8 peptide (RRRRRRRR) and pH sensitive polyethylene glycols (PEG) co-modified liposomes (Cl-Lip) and utilize them in breast cancer treatment. The co-modified liposomes were prepared with soybean phospholipid, cholesterol, DSPE-PEG2K-R8 and PEG5K-Hz-PE (pH sensitive PEG). The size and zeta potential of Cl-Lip were also characterized. The in vitro experiment demonstrated that the Cl-Lip had high serum stability in 50% fetal bovine serum. The cellular uptake of Cl-Lip under different pre-incubated conditions was evaluated on 4T1 cells. And the endocytosis pathway, lysosome escape ability and tumor spheroid penetration ability were also evaluated. The results showed the particle size of the Cl-Lip was (110.4 ± 5.2) nm, PDI of the Cl-Lip was 0.207 ± 0.039 and zeta potential of the Cl-Lip was (-3.46 ± 0.05) mV. The cellular uptake of Cl-Lip on 4T1 cells was pH sensitive, as the cellular uptake of Cl-Lip pre-incubated in pH 6.0 was higher than that of pH 7.4 under each time point. The main endocytosis pathways of Cl-Lip under pH 6.0 were micropinocytosis and energy-dependent pathway. At the same time, the Cl-Lip with pre-incubation in pH 6.0 had high lysosome escape ability and high tumor spheroid penetration ability. All the above results demonstrated that the Cl-Lip we constructed had high pH sensitivity and is a promising drug delivery system.

Objective To observe the expression of neural nicotinic acetylcholine receptor subunit α3 (α3nAChR) and extracellular regulated protein kinases (ERK1/2),c-Jun N-terminal kinase (JNK),p38 kinases of mitogen-activated protein kinase (MAPK) pathway in human neuroblastoma cell line SH-SY5Y overexposed to fluoride,and try to investigate the molecular mechanism of cell damage caused by overexposure of fluoride.Methods The SH-SY5Y cell with low expression of α3nAChR suppressed by silence interference RNA served as α3nAChR silence group;the normal SH-SY5Y cell served as control group,and the effect of silencing of αt3nAChR gene in SHSY5Y was detected by Western blotting and real-time PCR;SH-SY5Y cell was treated with different concentrations of fluoride (0.000,0.005,0.050,0.500,1.000,2.500,5.000 mmol/L),the safe concentration of fluoride in SHSY5Y cell was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay;the SH-SY5Y cell of control group and α3nAChR silence group were treated with 4.000 mmol/L fluoride for 0,4,8,12,24,36,48 h according to the results of MTT assay;the expression of ERK1/2,JNK,p38 kinases of MAPK pathway in SH-SY5Y at protein levels was measured by Western blotting.Results The expression of α3nAChR mRNA (0.04 ± 0.03) and protein (12.0 ± 2.5) in α3nAChR silence group was decreased significantly compared with those of control group (1.00 ± 0.11,100.0 ± 11.3,t =24.58,28.80,all P ＜ 0.05).The viability of SH-SY5Y cell treated with 5.000 mmol/L fluoride (0.53 ± 0.15) was decreased significantly compared with that of SH-SY5Y cell treated with 0.000 mmol/L fluoride (1.05 ± 0.05,P ＜ 0.05).The increased expression of phospho-ERK1/2 was found in α3nAChR silence group and control group incubated with fluoride with time prolonged,and the expression of phospho-ERK1/2 increased significantly at time points 24,36 and 48 h (188.33 ± 7.33,200.00 ± 10.01,213.33 ± 11.55;125.33 ± 5.69,136.00 ± 4.52,155.33 ± 6.51) compared to 0 h in the same groups (100.00 ± 0.00,100.00 ± 0.00,all P ＜ 0.05),and the expression of phospho-ERK1/2 was higher significantly in α3nAChR silence group than those of control group (t =9.26,7.63,5.72,all P ＜ 0.05);no change of expression of total-ERK1/2 in the two groups was found with the passage of time.The gradually increased expression of phospho-JNK was found in α3nAChR silence group and control group,among which,the expression of phospho-JNK in o3nAChR silence group at time points 12,24,36 and 48 h (154.00 ± 6.25,149.00 ± 5.57,156.00 ± 6.08,141.67 ± 2.52) and in control group at 8,12,24,36,48 h (133.33 ± 10.69,173.00 ± 4.00,175.00 ± 11.79,200.67 ± 11.93,200.33 ± 18.58) was compared to those at 0 h in the same groups (100.00 ± 0.00,100.00 ± 0.00),and the difference was significant (all P ＜ 0.05);the higher expression of phospho-JNK was found in α3nAChR silence group other than control group at 8,12,24,36,48 h (t =-4.28,-5.02,-2.89,-8.33,-6.18,all P ＜ 0.05);no change of expression of total-JNK was found in the two groups (P ＞ 0.05).The increased expression of phospho-p38 was detected in control group at time points 24,36 and 48 h (120.33 ± 4.51,122.00 ± 7.55,119.67 ± 7.57) compared to 0 h in the same groups (100.00 ± 0.00,all P ＜ 0.05),and the expression of phospho-p38 was significantly higher than that in α3nAChR silence group at the same time points (93.33 ± 9.61,94.00 ± 5.01,98.33 ± 5.69,t =-4.01,-6.73,-5.59,all P ＜ 0.05);no change of expression of total-p38 was found in the two types of SH-SY5Y cells treated with fluoride (P ＞ 0.05).Conclusion When SH-SY5Y cells are exposed to fluoride;activation of ERK1/2 may be not depend on α3nAChR;α3nAChR may have protected the cell from apoptotic injury caused by activation of JNK pathway,and the activation of p38 may be depend on nAChRα3.

Objective To investigate the effect of endoscope assisted microincision cholelithotomy(EMC) in the treatment of gallstone. Methods The clinical data of 86 patients with gallbladder stone treated by EMC were analyzed retrospectively.Of them, 63 cases were follwed-up and studied. Results All eighty-six patients were successfully operated on and discharged, no operative complications occurred. Among 63 patient being followed up for 1～3 years,the recurrence rate of gallbladder stones was 3.2%(2/63). No recurrence was noted in 46 patients with single gallstone. In the other seventeen patients with multiple stones, gallstone recurrence was found in 2 patients, the recurrence rate was 11.8%(2/17). Conclusions If selection of the operation idications are strict, endoscope assisted microincision cholelithotomy for treatment of gallstone is simple, safe, effective and less trauma, and can preserves the function of gallbladder, but it can not replace the cholecystectomy.

AIM: To establish the method for determing four effective components in Qidan Capsules(total saponin of Radix et Rhizoma Notoginseng,total phenolic acids of Radix et Rhizoma Salviae Miltiorrhizae) by RPHPLC. METHODS: The contents of ginsenoside Rg1、ginsenoside Rb1,notoginsenoside R1 were simultaneously determined by an HPLC system with Lichrospher C18(150 mm ? 4. 6 mm,5 ?m). The mixture of acetonitrile and water was used as the mobile phase and the flow rate was 1. 0 mL/min. The detection wavelength was set at 203 nm. The content of salvianolic acid B was determined by an HPLC system with Lichrospher C18 (150 mm ? 4. 6 mm,5 ?m). The mobile phase was (formic acid-water)-(methanol-acetonitrile) = 62 ∶ 38. Formic acid-water (1 ∶ 59),Methanol-acetonitrile (30 ∶ 10),and the flow rate was 1. 0 mL/min and the detection wavelength was 286 nm. RESULTS: The linear ranges of notoginsenoside R1,ginsenoside Rg1,ginsenoside Rb1 and salvianolic acid B were 0. 472 1 - 2. 832 ?g(r = 0. 999 5),1. 734 - 10. 404 ?g (r = 0. 999 9),1. 732 - 10. 392 ?g (r = 0. 999 9),0. 4 - 4. 0 ?g (r = 0. 999 9) respectively. The average recoveries (n = 5) were 100. 32% ,99. 965% , 100. 285% and 101. 4% ,corresponding RSD were 1. 01% ,2. 53% ,2. 46% and 1. 88% respectively. CON-CLUSION: The results indicate that the HPLC method is simple,highly selective and reproducible; thus it can be used in the determination of the four components in Qidan Capsule.