AIM: To investigate the mutation type in the IDUA gene of Liaoning district mucopolysaccharidosis I (MPS-I) patients. METHODS: The mutation type and polymorphism site in the IDUA gene of Liaoning district MPS-I patients were detected by PCR-RFLP, SSCP and DNA sequencing. RESULTS: ① There is a new mutation (1278-g-a) in the IDUA gene of Liaoning district MPS-I patients. ② There is no the common mutation (W402X and Q70X) of European patients and the common mutation (R89Q) of Japanese patients in the 10 families we studied. CONCLUSION: The mutation type in the IDUA gene of Liaoning district MPS-I patients is different from that of other countries and districts.

AIM: To investigate the mutatation type and polymorphism site in the ?-L-iduronidase (IDUA) gene of Liaoning district MPS-I patients. METHODS: The mutation type and polymorphism site in the IDUA gene of Liaoning district mucopolysaccharidosis type I (MPS-I) patients were detected by PCR-SSCP and DNA sequencing. RESULTS: ① 2 new mutations: R363H, 880+g-c in the IDUA gene of Liaoning district MPS-I patients were found. ② There were 3 polymorphism sites: R105Q、L118 and A361T in the IDUA gene of Liaoning district MPS-I patients. CONCLUSIONS: The mutation type in the IDUA gene of Liaoning district MPS-I patients is different from that of other countries and districts, while the polymorphism site in the IDUA gene of Liaoning district MPS-I patients is the same as that of other countries. [

Objective To evaluate the roles of positron emission tomography (PET) with N-methyl [11C]2-(4' -methylaminophenyi-6-hydroxybenzathiazole) (11C-PIB) in the early diagnosis of Alzheimer's disease (AD).Methods Six AD patients,7 mild cognitive impairment (MCI) patients and 6 normal controls (NC) were diagnosed and assessed with brain PET with 11C-PIB.The emission images obtained at 5,25 and 45 min after 11C-PIB administration were analysed.Results Using visual analysis to summarize the characteristics of the imagings of each group: comparing to NC,the AD patients show high 11C -PIB up take,and low clearance rate of 11C-PIB at 45 min.The imagings of MCI group show heterogeneous,overlapping with AD and NC group.The statistical analysis shows: in AD group,the standard uptake value (SUV) ratio of parietal lobe,frontal lobe,temporal lobe,occipital lobe and hippocampal at 45 min was 1.91±0.21,2.09±0.41,1.92±0.35,1.66±0.41,1.55±0.28 respectively,and were higher than that of NC group (value being 1.48±0.53,1.57±0.64,1.36±0.53,1.27±0.40,1.17±0.33) with statistical significance,t=8.114,5.620,5.705,3.650 and 2.866,P=0.0001,0.0002,0.0002,0.0045 and 0.0170 respectively.In MCI group,the SUV ratio of parietal lobe,frontal lobe,temporal lobe,occipital lobe and hippocampal at 45 min was 1.48 ± 0.53,1.57 ± 0.64,1.36±0.53,1.27 ± 0.40,1.17±0.33 respectively,and were higher than that of NC group,but there was no statistical significance.Conclusion 11C-PIB PET imaging can differentiate AD patients from normal and anticipate the transformation of MCI patients.

BACKGROUND:At present, some neurological imaging methods, including MRI, fMRI, 2-(1-(6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyi) ethylidene) malononitrile (18F-FDDNP) positron emission tomography (PET), are helpful but not specific for the diagnosis of Alzheimer disease (AD). 18F-FDG is a special marker of beta-amyloid (Aβ), thus AD can be diagnosed by 18F-FDDNP PET at early period.OBJECTIVE: To evaluate the role of 18F-FDDNP PET in the diagnosis of AD, and establish reliable clinical biological indexes for the diagnosis of AD patients.DESIGN: A controlled analysis.SETTINGS : Department of Geriatric Neurology and Department of Nuclear Medicine, the General Hospital of Chinese PLA. PARTICIPANTS: Patients visiting the General Hospital of Chinese PLA from May 2004 to March 2005 were selected. Informed consents were obtained from all the participants. ① AD group (n =7): (74.88±12.03) years old; Accorded with the criteria related to diagnosis of AD in NINCDS/ADRDA (National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer Disease and Related Disease Association) and revision of Diagnostic and statistical Manual (DSM-Ⅳ, 4th ed.); brain CT or magnetic resonance imaging (MRI) examination displayed that inter-uncus distance of temporal lobes was ≥ 30 mm. ② Vascular dementia group (n =6): (73.83±4.75) years old; Accorded with the diagnostic criteria of NINDS-AIREN (National Institute of Neurological Diseases and Stroke, USA) and DSM-Ⅳ for vascular dementia; Inter-uncus distance of temporal lobes ＜ 30 mm. ③ Control group (n =6): (71.17±3.71) years old; Without rarefaction of white matter; Intelligence examination was normal.METHODS: PET was performed in all the subjects. PET scanner type was SEIMENS ECAT EXACT HR. The tracer selected was 18F-FDDNP which had radiochemical purity higher than 95% and error of radioactivity measurement lower than 10%. The images were collected at 5, 25 and 45 minutes after injection of 18F-FDDNP. Horizontal and coronary tomograms of brain were obtained after reconstruction.MAIN OUTCOME MEASURES: Characteristics of 18F-FDDNP brain PET images.RESULTS: ① In the control group, signs of obvious atrophy of brain were not seen. At about 45 minutes, the radioactivity in cortex and subcortical nucleus groups was essentially cleared and the structures of brain could not be differentiated clearly. ② In the vascular dementia group, brain atrophy and enlargement of ventricular system to various degrees could be seen. The clearance of radioactivity at three time points was similar to that in the control images. ③ In the AD group, the brain was obviously atrophied and the ventricular system was enlarged. The clearance of radioactivity at the three time points was significantly different from the images of other two groups. The radioactivity in cortex and hippocampus was cleared slower. At 45 minutes, the gray matter could still be clearly differentiated from the white matter, but the radioactivity in corpus striatum and thalamus was not higher than that in cortex and much radioactivity retention could be seen in cortex and hippocampus.CONCLUSION: 18F-FDDNP PET brain images can differentiate AD and vascular dementia, and it is an effective imaging index for the diagnosis of AD.

Objective To explore the positive affect of dementia caregivers.Methods Questionnaire method was used to investigate seventy-six dementia caregivers (the dementia group)and seventy-six non-dementia caregivers(the control group).Results The total score and the score of each dimension in the dementia group was significantly lower than those got from the control group.Conclusions Dementia caregivers can feel the positive affect from dementia patients.Compared with non-dementia caregivers,dementia caregivers feel lower positive affect,especially positive feedback from dementia patients.

A simple and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was de-veloped and validated for simultaneous determination of acetaminophen and oxycodone in human plasma. Acetaminophen-d4 and oxycodone-d3 were used as internal standards. The challenge en-countered in the method development that the high plasma concentration level of acetaminophen made the MS response saturated while the desired lower limit of quantification (LLOQ) for oxycodone was hard to reach was well solved. The analytes were extracted by protein precipitation using acetonitrile. The matrix effect of the analytes was avoided by chromatographic separation using a hydrophilic C18 column coupled with gradient elution. Multiple reaction monitoring in positive ion mode was performed on tandem mass spectrometer employing electrospray ion source. The calibration curves were linear over the concentration ranges of 40.0–8000 ng/mL and 0.200–40.0 ng/mL for acetaminophen and oxycodone, respectively. This method, which could contribute to high throughput analysis and better clinical drug monitoring, was successfully applied to a pharmacokinetic study in healthy Chinese volunteers.

Objective To construct a recombinant adenovirus vector expressing mouse SPINK5 gene,and observe its curative effect on the skin lesions in atopic dermatitis mice model. Methods By recombining DNA technology,the sequence of mouse SPINK5 gene was cloned into adeno?virus shuttle plasmid. Then it was transformed into HEK 293 cells with the adenoviral backbone plasmid to obtain the recombinant adenovirus. A mouse model of atopic dermatitis was established by system and local sensitization of Balb/c mice with ovalbumin . The effect of recombinant adeno?virus on the lesions of atopic dermatitis mice model was observed. Results The SPINK5 over?expressing adenovirus vector and atopic dermatitis mice model were successfully constructed. After 2 weeks of adenovirus?mediated SPINK5 gene intracutaneous injection,the redness and edema of lesions of AD model mice were obvious relieved. The pathological detection indicated that epidermal thickness and prickle cell layer ,inflammatory cell infiltration significant decreased accompanied with the model blank control. Conclusion The adenovirus?mediated SPINK5 gene had signifi?cant therapeutic effect to the atopic dermatitis mice model ,which provided a laboratory basis of application of SPINK5 gene product to therapy atopic dermatitis.

Objective A simple,specific and rapid LC-MS/MS method was established to determine flumatinib and its two major metabolites in human plasma for clinical therapeutic drug monitoring.Methods The determination was performed on an ACQUITY UPLC HSS T3 column(2.1 mm×50 mm,1.8 μm)with mobile phases consisting of acetonitrile and 10 mmol·L-1 ammonium formate(containing 0.1%formic acid)with gradient elution at the flow rate of 0.5 mL·min-1.The elution time was 6 min.The temperature of the column was 38℃.The ion source was electrospray ion source and the scanning mode was multiple reaction monitoring scanning in positive ion mode.Results The mass concentrations of flumatinib and its metabolites(flumatinib M1 and flumatinib M3)have a good linear relationship within the concentration range investigated.The precision and stability of the method are good.The precision is less than 15%,and the relative deviation is within±15%.The extraction recoveries of flumatinib and its metabolites approach nearly 100%.Conclusion The method is simple and sensitive,and can accurately determine the plasma concentration of flumatinib and its metabolites,providing a basis for clinical rational drug use.

Objective To investigate the prevalence of cognitive and motor disorders as well as emotional and sleep abnormality in the veterans from military communities in Beijing. Methods The participants underwent a comprehensive in-person evaluation including detailed neuropsychological testing,Hospital Anxiety and Depression Scale and special questionnaires for movement and sleep disorders. Results The overall prevalence of cognitive impairment, extrapyramidal diseases was 32.7%, 8.8% . The prevalence of mild cognitive impairment, dementia, Parkinson disease, essential tremor, anxiety and depression was 26.2% , 6.5% , 2.0% , 6.1 % , 1.4% and 4.1% respectively. Prevalence of all kinds of sleep disorders ranged from 10. 3% to 53. 9%. The prevalence of cognitive impairment had no significant difference of sex, but were correlated to age and education, the correlation coefficient was 0. 326 and -0.221 ( P<0.01) . Conclusion Veterans from military communities had higher prevalence of cognitive impairment, extrapyramidal diseases and sleep disorders and lower that of anxiety and depression relatively.

Objective:To investigate the risk factors and their warning effectiveness for meniscus tear secondary to delayed anterior cruciate ligament (ACL) reconstruction.Methods:A retrospective cohort study was conducted to analyze the clinical data of 114 patients (114 knees) with ACL injury, who were admitted to Affiliated Hospital of Nanjing University of Chinese Medicine from December 2018 to December 2023, including 78 males and 36 females, aged 11-50 years [29(21, 35)years]. The patients were divided into tear group ( n=46) and non-tear group ( n=68) according to whether combined with meniscus tear or not during the surgery. Gender, age, duration of disease, smoking history, Body Mass Index (BMI), cause of injury, mechanism of injury, side of the injury, Beighton score, difference of KT-2000 examination, Tegner activity scale of the knee joint, anterior tibial translation sign, medial posterior tibial slope angle, lateral posterior tibial slope angle, and pivot shift grading of the patients in the two groups were recorded. Correlations between the above-mentioned indicators and occurrence of meniscus tear secondary to delayed ACL reconstruction were assessed. In the meantime, the independent risk factors were determined by univariate and multivariate binary logistic regression analysis. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to evaluate the warning effectiveness of each risk factor for meniscal tear secondary to delayed ACL reconstruction. Results:Univariate analysis showed correlation of duration of disease, BMI, Tegner activity scale of the knee joint, medial posterior tibial slope angle, lateral posterior tibial slope angle and high-grade pivot shift with occurrence of meniscus tear secondary to delayed ACL reconstruction ( P<0.01). The results of multivariate binary logistic regression analysis showed that the duration of disease ≥14.5 weeks ( OR=1.20, 95% CI 1.05, 1.38, P<0.01), BMI≥26.9 kg/m 2 ( OR=1.36, 95% CI 1.03, 1.81, P<0.05), Tegner activity scale of the knee joint ≥4 points ( OR=2.29, 95% CI 1.18, 4.46, P<0.05), medial posterior tibial slope angle ≥11.2° ( OR=2.27, 95% CI 1.06, 4.89, P<0.05) and high-grade pivot shift ( OR=0.03, 95% CI 0.01, 0.03, P<0.05) were significantly correlated with occurrence of meniscus tear secondary to delayed ACL reconstruction. Results of ROC curve analysis showed that the medial posterior tibial slope angle (AUC=0.86, 95% CI 0.80, 0.93) and duration of disease (AUC=0.85, 95% CI 0.77, 0.92) had good warning value, BMI (AUC=0.78, 95% CI 0.69, 0.87) and Tegner activity scale of the knee joint (AUC=0.73, 95% CI 0.64, 0.83) had ordinary warning value, and the warning value of high-grade pivot shift (AUC=0.60, 95% CI 0.49, 0.71) was the lowest. The combination of the risk factors revealed superior warning effectiveness for meniscus tear second to delayed ACL reconstruction (AUC=0.97, 95% CI 0.96, 1.00). Conclusions:The duration of disease ≥14.5 weeks, BMI ≥26.9 kg/m 2, Tegner score ≥4 points, medial posterior tibial slope angle ≥11.2°and high-grade pivot shift are independent risk factors for meniscus tear secondary to delayed ACL reconstruction. The medial posterior tibial slope angle and duration of disease have good warning value, BMI and Tegner scores have ordinary warning value and high-grade pivot shift has the lowest warning value. The combination of the above risk factors has better warning effectiveness for meniscus tear secondary to delayed ACL reconstruction.