Objective To compare the effects of intermittent high blood glucose and consistent hilgh blood glucose on pancreatic islet β-cell function and β-cell apoptosis in GK rats.Methods Twenty-two male GK rats were randomly divided into 2 groups consisting of consistent hish blood glucose group(HG)and intermittent high blood glucose group(FG).Eleven male Wistar rats were used as normal glucose controls(NG).The fluctuating high blood glucose animal model was induced by intraperitoneal injection of insulin and glucose at different time for six weeks.Intraperitoneal injection glucose tolerance test and insulin release test were performed.The area under curve of glucose(AUCg).the area under carve of insulin(AUCi)/AUCg and the ratio of insulin increment to blood glucose increment 15 min after glucose load(Δ115'/ΔG15')were calculated routinely.Then the pancreatic slides were stained with insulin antibody.The apoptotic β cells in islets were detected and quantified by the TUNEL technique.Results(1)The fasting plasma glucose and 15,30,60,and 120 min plasma glucose levels after glucose loading in FG group were significantly higher than those in control group(all P<0.01),and AUCg was also markedly increased[(1 012.14±82.62 vs 813.60±56.70)ng·ml~(-1)·h~(-1)·10~4,P<0.01].Insulin levels of FG group at 15,30,60,and 120 rain after glucose loading were significantly lower than those in HG group[(0.554± 0.18 vs 0.95±0.28.0.43±0.17 vs 0.85±0.21,0.47±0.11 vs 0.76±0.16,0.58±0.13 vs 1.08±0.26)ng/ml,P<0.05],along with decreased AUCi/AUCg and Δ115'/ΔG15'[(9.56±2.53 vs 21.36±4.16)×10~(-7);(3.95±3.45 vs 27.02±8.62)×10~(-7),both P<0.05].(2)Image analysis of pancreatic islet immunocytoehemistry showed that the insulin staining positive area,area ratio and total density of insulin positive cells per islet were significantly lower in FG group than those in HG group(P<0.05).(3)The percentage of β-cell apoptosis in the FG group was statistically higher than that in the HG group[(24.17±7.25 vs 16.55±5.11)%,P<0.01].Conclusion Compared with the consistent high blood glucose,intermittent high glucose could lead to further impairment of β-cell function and increased β-cell apoptosis may partially contribute to this process.

Objective To characterize the mutation of phenylalanine hydroxylase (PAH) gene in patients with phenylketonuria(PKU) in Ningxia area,China.Methods Seventy-three children diagnosed with PKU at the Child and Maternal Healthcare Hospital of Ningxia Hui Autonomous Region between January 2010 and June 2013,and 100 non-PKU children randomly chosen from children with normal results in PKU screening were enrolled in the study.Venous blood was collected and the PAH gene sequence was determined by direct DNA sequencing after amplification with the polymerase chain reaction technique.The new gene mutations were defined based on the national and international literature search and databases.The source of the newly discovered mutations was also measured by examining and sequencing the blood samples of their parents.The Chi-square test was used for statistical analysis.Results Among 146 alleles of the 73 PKU children,the detection rate of mutation of PAH gene was 79.5％ (116/146),including 37 types of mutations occurring in 11 exons other than exon 2 and exon 13.The 37 different mutations included 22 missense mutations (59.5％,22/37),six nonsense mutations(16.2％,6/37),six splice site mutations(16.2％,6/37) and three deletion mutations(8.1％,3/37).p.R243Q(17.1％,25/146),EX6-96A ＞ G (6.8％,10/146),p.R241C(6.2％,9/146),p.R413P (5.5％,8/146),p.Rl11X(4.8％,7/146) and IVS4-1G ＞ A(4.8％,7/146) were found to have a higher mutation frequency.Meanwhile,p.R243Q was the most common mutation among Han and Hui ethnic groups with a frequency of 18.8％(12/64) and 15.9％ (13/82),respectively.In contrast,p.R241C showed a significant higher frequency in the Hui group [9.8％(8/82) vs 1.6％(1/64),x2=4.17,P=0.04].Four new mutations of PAH genes,including p.Q304K,p.H107R,p.F392I and p.N223I,were discovered after literature search and comparative studies.Conclusions PAH gene mutations in children with PKU in Ningxia area are unique and are characterized by the diversity and complexity of mutation occurrence in this ethnic region.

Objective To investigate the effect of metformin on the growth of human anaplastic thyroid cancer cell HTh74Rdox which is doxorubicin resistant. Methods The HTh74Rdox was treated with different concentrations of metformin for 48 h. Cell morphology was observed by microscope, cell viability was tested by methylthiazoletetrazolium (MTT), cell apoptosis by annexin Ⅴ and propidium iodide double staining, the anti-oncogenic miRNA was assayed by realtime fluorescence quantitative PCR (RT-PCR), and the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway tested by western blot. Furthermore, the anti-oncogenic miRNAs were knockdown by miRNA inhibitors (miR-34a, miR-101, miR-125b, and miR-138 inhibitors) and the cells were treated by metformin for 48 h, after that, cell apoptosis was detected by annexin Ⅴ and propidium iodide double staining, the expression of protein related to AMPK/mTOR signaling pathway was detected by western blot. Results Metformin inhibited the growth of human anaplastic thyroid cancer cell HTh74Rdox in a concentration-dependent manner, the cell apoptosis was induced by metformin, and there was a significantly lower expression of miR-34a, miR-101, miR-125b, and miR-138 in the HTh74Rdox. However, the four above miRNAs were upregulated by metformin, and AMPK/mTOR pathway was also activated by metformin. When these miRNAs were suppressed by miR-inhibitors (miR-34a, miR-101, miR-125b, miR-138 inhibitors), the stimulating effect of apoptosis and AMPK/mTOR pathway by metformin were reversed. Conclusion Metformin significantly suppresses cell viability of human anaplastic thyroid cancer cell HTh74Rdox, and stimulates AMPK/mTOR pathway and apoptosis by upregulating the expressions of miR-34a, miR-101, miR-125b, miR-138 in HTh74Rdox cell.

Objective To evaluate the effect of rehabilitation training on dysphagia and trismus in patients with nasopharyngeal carcinoma after radiotherapy.Methods Fony-three post-radiotherapy nasopharyngeal carcino-ma patients were divided into a rehabilitation group and a control group.Both groups were subjected to routine treat-ment,while the rehabilitation group received rehabilitation training in addition.The patients were assessed with a wa-ter-swallowing test of swallowing.Late effects of normal tissues/subjective and objective medical analysis(LENT/SOMA)scored and inter-incisor distance were measured to assess trismus before and after treatment.Results The rehabilitation group displayed significant improvement in swallowing as well as increased inter-incisor distance.Con-clusions Rehabilitation training can improve swallowing,prevent or delay trismus and improve the quality of life of patients.

Objective To explore the specific role of autophagy and ubiquitin-proteasome pathway in apoptosis, specific protease inhibitor and (or) macroautophagy inhibitors.Methods The stimulators were selected to work on the pheochromocytoma (PC12) cell lines transfected with human mutant α-synuclein (A53T).Cell activity and apeptosis rate were detected by MTT law and flow cytometry.NO energy, heat shock protein 70 (Hsp70) and Caspase-3 expression were determined in cell culture.Results A53T cell survival rate significantly decreased 24 hours after handling with the protease inhibitor (100 nmol/L) and (or) autophagy inhibitors 3-MA (10 mmol/L, A =0.23±0.01,0.19±0.01 and 0.17±0.01 respectively; P <0.05) compared with the control group (A =0.32±0.06).Cell survival rate was significantly higher than the other drug group after 24 hours handling with autophagy stimulators (A =0.44±0.08).Compared with the control group or autophagy stimulator of rapamycin (0.2 μg/ml) group (1.55%±1.15%), A53T cells apeptosis percentage rate was significantly higher after treated with proteasome inhibitor and macroautophagy inhibitors 24 hours (4.74%±0.91%, 4.59%±1.18% and 5.40%±1.75%respectively, P <0.05); and a slight decrease with stimulators.Protein Hsp70 and NO were significantly higher in proteasome inhibitor groups than the control group.But in antophagy inhibitor and stimulator group, NO and Hsp70 protein was similar to the control group.Conclusion The inhibition of macroautophagy and proteasome can promote apoptosis.Inhibiting or stimulating autophagy has less impact on Hsp70 and NO than proteasome pathway.

Objective To investigate the processing characteristics of locative prepositions in patients with Chinese aphasia,and to provide the theoretical evidence for the rehabilitation of aphasia.Methods Twenty aphasic patients caused by left-hemisphere stroke and twenty matched normal controls were studied.Using the locative prepo- sition repeating task(single words,locative preposition phrases and words in sentences),the comprehension task, filling-gap task,the visual-spatial function task and the short-term memory task,we compared the performance be- tween these two groups.Results The aphasic patients had more difficulty in repeating locative prepositions in sen- tences,in comprehension task and filling-gap task,their short term memory was impaired.Both groups did well in re- peating single words and phrases.Conclusion The processing of locative prepositions was impaired in Chinese aphasics.The repetition of locative prepositions was more difficult than that of phrases and single words.The preposi- tions were often omitted.It might be due to the impairment of their short-term memory,or it might have something to do with role they played in the syntactic structure.The latter might also impact the comprehension and filling-gap score.We should make plans before rehabilitation therapy.

In the process of conducting implementation research on health service issues, stakeholders' preference for contents related to evidence-based practice (EBP) and implementation strategies is closely related to whether EBP can be effectively implemented.However, multiple preference assessment methods exist, each with their own strengths, weaknesses, and application scenarios, which makes it challenging for researchers to select appropriate and effective preference assessment methods. This paper aims to review the origins, characteristics, and application scenarios of commonly used preference assessment methods, with the hope of providing valuable reference and lessons for domestic scholars to select and apply appropriate preference assessment methods in implementation research.

Heat shock protein(HSP) is a family of high expressed proteins under the different stimulus.This family is highly conserved in structure and can protect cells in function.In recent years,there are some researches illustrate that HSP 27 and HSP 70 have protective effect on retinal cells and optical nerve cells,while the HSP-27 Ab and HSP-70 Ab can promote the apoptosis of these cells.In the cell culture and animal experiment,we have observed that it is beneficial to protect retinal cells and optical cells through blocking the express of HSP-27 Ab and HSP-70 Ab.This article reviews the relationship between HSP 27 and HSP 70 with retinal diseases and optical nerve diseases.

Objective To investigate the clinical significance of flow cytometry (FCM) assay in following up of the minimal residual disease (MRD) used for predicting relapse and guiding chemotherapy. Methods The clinical data of 43 acute leukemia patients diagnosed by MIC were collected in our hospital from 2005 July to 2008 June.Bone marrow aspirates were collected from 43 patients with newly diagnosed acute leukemia after induction therapy and during constimulation therapy. The cells with leukemia associated with immunophenotype were investigated using FCM, as immunologic target of MRD. Results MRD were detected earlier in predicting the relapse than those of the traditional bone marrow cells morphology assay by an average of 4-6 months. The results of the MRD following up: MRD was negative at CR in 26 cases, 6 cases relapse, 20 cases of them were kept negative during following up. MRD was positive in 17 cases at CR, 9 cases of them were relapse. 4 cases after intensified chemotherapy the MRD became negative and kept egative for more than one year. The MRD of the 43 cases at CR were divided into 3 groups, MRD less than 1×10-4 group (A group) MRD between 5×10-3 and 1×10-4 group (B group) and MRD above 5×10-3 group(C group). By chi square test. There was no statistical significance between A group and B group, but there was tatistical significance between B group and C group (P=0.02). Conclusion The application of FCM in detecting MRD has important clinical significance in predicting relapse and guiding chemotherapy.

OBJECTIVETo observe the effect of Bushen Yizhi Recipe (BSYZR) on neurotransmitter release in A beta segment neurotoxin induced NG108-15 cellular model of Alzheimer disease (AD).

METHODSThe levels of choline acetyltransferase (ChAT) activity, synapsin and functional synapse formation rate in the cellular model treated with BSYZR containing serum were determined by Western blot analysis, immunoradiometric assay and electrophysiologic technique.

RESULTSBSYZR containing serum treatment could cause increase of ChAT activity and synapsin level in model cells, as compared with those in normal control model cells treated with non-drug containing serum, it also could regulate the release capacity of transmitter and raise the functional synapse formation.

CONCLUSIONBSYZR could reduce the reaction of cell to A beta neurotoxin, indicating that it could be antagonistic to the pathological development of AD by means of raising the neurotransmitter release capacity.

Alzheimer Disease ; metabolism ; pathology ; Amyloid beta-Peptides ; metabolism ; Animals ; Cell Line ; Choline O-Acetyltransferase ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Neurotoxins ; pharmacology ; Neurotransmitter Agents ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Synapsins ; metabolism