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.

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.

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.

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.

Aim To observe the effects of liver cirrho-sis on the expression of transforming growth factor-β1 ( TGF-β1 ) and ColⅠin rat myocardium and interven-tion of erythropoietin ( EPO ) . Methods Thirty-six male Sprague-Dasley rats were randomly divided into three groups:control group, liver cirrhosis group and EPO group, then the cardic hemodynamic parameters in vivo and levels of serum lactate dehydrogenase ( LDH ) as well as creatine kinase isoenzyme ( CK-MB) were measured. With Masson′s trichrome stain, changes of collagen formation of myocardial tissue in different groups were observed. Also the mRNA ex-pressions of TGF-β1 and ColⅠin myocardium were de-tected by RT-PCR. Results In contrast to control group, rats in liver cirrhosis group showed a decline in systolic and diastolic function of left ventricule, rising myocardial enzyme, a distinct increase of cardiac colla-gen deposition, as well as an elevation of TGF-β1 and ColⅠmRNA expressions. In contrast to liver cirrhosis group, rats in EPO group demonstrated an improve-ment in systolic and diastolic function of left ventricule as well as in cardiac collagen deposition, and a de-crease in both myocardial enzyme and TGF-β1 and ColⅠmRNA expressions. Conclusion Liver cirrhosis can lead to the changes of myocardial structure and function in rats,and it can accelerate myocardial inter-stitial fibrosis; EPO can protect the myocardial injury in liver cirrhosis rats.

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: This study was designed to investigate the inhibition of tanshinone ⅡA on C6 glioma cell line and its mechanism. METHODS: MTT was used to measure the levels of the proliferation of C6 cultured with tanshinone ⅡA at different concentrations. The effects of tanshinone ⅡA on cell cycle of C6 were observed by FCM. The change of DNA was observed by Sepharose electrophoresis. The expression of proto-oncogenes c-myc was measured by RT-PCR. RESULTS: The proliferation of C6 was obviously inhibited by tanshinone ⅡA in a dose-dependent manner. The outcome of FCM showed that the apoptotic cell rate was 7.7%, when cultured with tanshinone ⅡA at 1.0 mg/L for 3 days. The apoptotic cell rate was 21.6%, when cultured with tanshinone ⅡA at 2.0 mg/L in 3 days. CONCLUSION: Tanshinone ⅡA inhibits the proliferation of C6 cells, induces apoptosis and inhibits the expression of proto-oncogene c-myc.

AIM: To investigate whether tumor necrosis factor ? (TNF?) pretreatment can inhibit mitochondrial permeability transition pore opening in isolated rat hearts subjected to hypoxia and reoxygenation. METHODS: Isolated perfused rat hearts were subjected to 30 min regional hypoxia (occlusion of left anterior descending artery) and 120 min reoxygenation. The infarct size, lactate dehydrogenase (LDH) release during reoxygenation and ventricular hemodynamic parameters were measured. RESULTS: Pretreatment with TNF? at concentration of 1?104 U/L for 7 min followed by 10 min washout reduced the infarct size and LDH release, and improved the left ventricular performance (left ventricular developed pressure and rate-pressure product) and left ventricular end-diastolic pressure during hypoxia and reoxygenation. Administration of atractyloside (Atr, an opener of mitochondrial permeability transition pore, 20 ?mol/L) for 20 min (last 5 min of hypoxia and first 15 min of reoxygenation) and paxilline (Pax, a calcium activated potassium channel antagonist, 1 ?mol/L) for 5 min before hypoxia attenuated the reduction of infarct size and LDH release and improved the left ventricular performance induced by TNF?. CONCLUSION: The findings indicate that in the isolated rat heart model, TNF? protects myocardium against hypoxia and reoxygenation injury via inhibiting mitochondrial permeability transition pore opening as well as activating calcium, activated potassium channel.

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.