Objective To investigate the gait differences among patients with Alzheimer's disease (AD) and mild cognitive impairment(AD-MCI) and the person with normal cognitive function,and analyze the reasons for the abnormal gait.Methods Eighty patients were included and divided into 3 groups according to the cognitive status:noncognitive impairment (NCI group,n =30),patients with mild cognitive impairment (AD-MCI group,n =29),Alzheimer's disease (AD group,n =21).The mini-mental state examination (MMSE),the Montreal Cognitive Assessment (MoCA),Addenbrooke's Cognitive Examination (ACE-R),the connection test (TMT-A),Digit Span Test(DST),activities of daily living questionnaire(ADL) and associated gait and balance scale (5 times sit to stand test (FTSTT),3 m walking test (TUG),Berg balance scale) were used to evaluate all research objects in each group.Results There were significant differences in NCI group compared with AD-MCI group and AD group in terms of FTSTT,TUG,Berg balance Scale and leg speed((9.59±2.39) s vs.(13.71±4.65) s vs.(14.15±4.20) s,(7.70±1.58) s vs.(11.13±3.02) s vs.(11.35±4.43) s,(54.20±1.56) points vs.(48.17±4.93) points vs.(48.10±5.46) points,(82.12±22.79) cm/s vs.(57.49± 14.89) cm/s vs.(57.70±14.68) cm/s;P＜0.05).There were significant differences in NCI group compared with AD-MCI group and AD group in terms of MMSE,MoCA,ACE-R,TMT-A,DST((28.67±1.27) points vs.(26.76±2.59) points vs.(21.86±5.29) points,(26.03±2.58) points vs.(22.39±5.05) points vs.(16.90±5.05) points,(85.80±5.90) points vs.(78.03±7.58) points vs.(60.95± 13.99) points,(12.66±5.36) s vs.(18.99 ± 11.46) s vs.(30.49±26.98)s,(18.60±4.64) points vs.(15.94±4.76) points vs.(12.86±5.23) points;P ＜0.05).Conclusion Gait disorder might be an early sign for cognitive impairment.

Objective To observe the effect of electroacupuncture on urodynamic alteration in rats after complete T10 spinal cord transection.Methods Thirty-one female Sprague-Dawley rats were divided randomly into a sham operation group (n=10),a model group (n=11) and an electroacupuncture (EA) group (n=10).The spinal cords of the rats in the latter two groups were completely transected at the T10 level.Pressure was applied to the rats'lower abdomens every day while in the EA group electroacupuncture with continuous wave electricity was applied to the guanyuan (RN4) and sanyinjiao (SP6) acupoints for 15 min.The treatment was carried out daily for consecutive 7 days.Urodynamic examinations were carried out after the treatment course had finished.Results At the 9th day after the operation,average residual urine volume and bladder capacity in the EA group were both significantly lower than in the model group.Residual urine volume and bladder capacity were lowest in the sham operation group.Average voided volume and voiding rate in the EA group were significantly higher than in the model group.The average voiding rate was highest in the sham operation group.The average vesical pressure of the urine leak point and bladder compliance of the EA group rats were significantly lower than those of the model group The average vesical pressure of the urine leak point and bladder compliance of the sham operation group were lowest of all.All of these differences were statistically significant at the 1％ level of confidence.Conclusion EA can improve the lower bladder's detrusor reflex state and urinary tract function soon after complete T10 spinal cord transaction,at least in rats.

Objective To evaluate the inverse distance weighted(IDW) in revealing the characteristics of spatial distribution of water fluoride in Heze City,Shandong Province.Methods A geographic information system (GIS) database of water fluoride was established in Heze City of Shandong Province using the data of endemic fluorosis surveys collected by Endemic Disease Prevention Institute in Shandong Province during 2005-2007.IDW spatial interpolation was applied to predict the distribution of fluoride in drinking water in 139 towns of Heze City.Sensitivity and specificity were calculated.Results Mean water fluoride levels in 10 counties of Heze City were all higher than 1.0 mg,/L,and the water fluoride in Cao County,Juye,Mudan District and Juancheng were higher than 2.0 mg/L.Of all 139 townships of Heze City,129 were higher fluoride townships where fluoride was ＞ 1.0 mg/L,10 were lower fluoride townships(≤ 1.0 mg/L).IDW spatial interpolation showed that the water fluoride of most areas in Heze City were ＞ 1.0-2.0 mg/L.The areas with water fluoride of ＞ 2.0-3.0 mg/L were mainly located in eastern Juancheng,northern Mudan District,north-central Chengwu,central and southern Juye,southeastern part of Caoxian and eastern part of Shan Town.Regions of water fluoride ＞ 3.0 mg/L were mainly distributed in Xieji and Wanfeng towns of Juye County,Jishan town of Juancheng County,Sunlaojia town of Caoxian and Dusi town of Mudan County.The internal verification results showed that the sensitivity,specificity and overall accuracy rate of IDW used for predicting water fluoride content was 100.00％ (129/129),10.00％ (1/10) and 93.53％ (130/139),respectively.While the external verification results showed that the sensitivity,specificity and overall accuracy rate of IDW for predicting water fluoride content was 100.00％(31/31),11.11％(1/9) and 80.00％(32/40),respectively.Conclusion With the application of IDW interpolation,it is feasible to infer the overall spatial distribution based on the monitoring data,and to reveal the spatial characteristics of water fluoride in Heze City,Shandong Province.

Objective To investigate the application value of apparent diffusion coefficient (ADC) in monitoring the response to chemotherapy of primary bone lymphoma(PBL). Methods Sixteen consecutive patients with PBL confirmed by pathology were enrolled in this retrospective study.All patients underwent a controlled MRI including a DWI sequence before chemotherapy and after the first chemotherapy session. The ADC values of PBL lesions were measured before and after the first chemotherapy session. All patients were divided into responders and non-responders groups according to the combined response assessment criteria. The difference in ADC values between the responders and non-responders groups before and after chemotherapy and the rate of change of ADC values were compared using Wilcoxon test. The paired t test was used to compare ADC values before and after chemotherapy in each group. Results Twenty-three cases of PBL lesions were diagnosed in 16 patients before the chemotherapy. After the first chemotherapy session, 10 patients (12 lesions) and 6 patients (11 lesions) were categorized into the responder and non-responder group, respectively. The mean pre-treatment ADC value of the responder group and non-responder group were 737.1(301.7,928.4)× 10-6mm2/s and 749.2(624.4, 1186.5)× 10-6mm2/s, which had no statistically significant difference (Z=1.51,P=0.132). The mean post-treatment ADC value of the responder group and non-responder group were 1843.0(721.5,2745.8)× 10-6mm2/s and 1026.3(382.8,2100.8)× 10-6mm2/s, which had no statistically significant difference (Z=-1.75,P=0.079). The post-treatment ADC value of the responder group significantly increased [156.7(60.9,227.5)%] while the post-treatment ADC value of the non-responder group slightly increased [31.7(-44.7,147.4)%]. The difference in the percentage changes of ADC values in the responder and non-responder groups before and after the treatment was statistically significant(Z=-3.66,P<0.001). Conclusion The measurement of the percentage changes of ADC values enable a good short-term response evaluation for PBL.

This paper is aim to investigate the pharmacokinetics and absolute bioavailability of neoline in Beagle dogs, and provide a theoretical basis for further study. Ethyl acetate was used for liquid-liquid extracting after 10% ammonia alkalizing. The method of UPLC-Q-TOF-MS was established for the determination of neoline plasma concentrations. Beagle dogs were orally or intravenously administered with neoline for pharmacokinetic and absolute bioavailability study. Good linear relationship of neoline was found over the range of 0.1-4 mg x L(-1) (R2 = 0.9982) and 2-100 microg x L(-1) (R2 = 0.9945). Intra-and inter-day precision, expressed as the relativestandard (RSD) were less than 5.0%. Accuracy, expressed as the relative error (RE) was within 90.0%-115%. The recovery of neoline in dog plasma was more than 80%. After 6 mg x kg(-1) for ig and 1 mg x kg(-1) for iv administration of neoline, the main pharmacokinetic parameters were analyzed with Winnonlin software. t(1/2) were (313.88 +/- 63.18), (236.33 +/- 229.84) min, and AUC(0-infinity) were (58,027.40 +/- 14,132.69), (473,578.02 +/- 82,333.08) min x microg x L(-1) for ig and iv administration respectively. The absolute bioavail ability was (73.15 +/- 10.29) %. The method of UPLC-Q-TOF-MS described in the report was sensitive, reliable and specific, and suitable for pharmacokinetic study of neoline in Beagle dog. The high absolute bioavailability of neoline in dog suggested good absorption of neline which was worth of further investigation.
Aconitine ; analogs & derivatives ; chemistry ; pharmacokinetics ; Animals ; Biological Availability ; Dogs ; Drug Stability ; Female ; Male

A high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method was developed for determining degradation dynamics and final residues of myclobutanil 25% WG in ginseng root, stem, leaf and soil. The samples were extracted with acetonitrile, cleaned-up with primary secondary amine (PSA) solid phase extraction cartridge, separated by Kromasil Eternity-5-C18 (2.1 mm x 150 mm, 5 microm) column with a gradient of acetonitrile and 0.1% formate in water as mobile phases, and analyzed with the multiple reaction monitoring (MRM) in positive ion mode by employing the external standard method. The average recoveries and the relative standard derivations (RSDs) of myclobutanil at the spiked level of 0.01-0.20 mg x kg(-1) were 80.9%-90.7% and 5.54%-9.29%, respectively, and the limit of quantification (LOQ) was 0.005 mg x kg(-1). The method with good reproducible, high precision and low detection limit could meet the requirements of residual analysis on ginseng production. The half-lives of myclobutanil were from 6.25 days to 9.94 days in ginseng root, stem, leaf and soil at spraying dosage of 1 152 g x hm(-2) The final residues were below 0.060 1 mg x kg(-1) in root, below 0.081 7 mg x kg(-1) in stem, 0.006 0-0.102 2 mg x kg(-1) in leaf and below 0.037 6 mg x kg(-1) in soil at spraying dosage range from 576 to 1 152 g x hm(-2). It is recommended that the MRLs of myclobutanil in dried ginseng may be suggested to be 0.10 mg x kg(-1) temporarily, and the preharvest interval was set at 35 days.
Chromatography, High Pressure Liquid ; methods ; Drug Contamination ; Fungicides, Industrial ; chemistry ; Nitriles ; chemistry ; Panax ; chemistry ; Plant Leaves ; chemistry ; Plant Roots ; chemistry ; Plant Stems ; chemistry ; Soil Pollutants ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; methods ; Tandem Mass Spectrometry ; methods ; Triazoles ; chemistry

Objective To investigate the respiratory burst function of neutrophils in very low birth weight infants (VLBWI).Methods Twenty two VLBWI was divided into two groups:neonatal respiratory distress syndrome (NRDS) and non NRDS (11 in each).The respiratory burst function of neutrophils in the peripheral blood of VLBWI within 48 hours after birth was determined using the flow cytometrydihydrorhodamine 1,2,3 method before and after the chemical stimulation of phorbol-12-myrismte 14 acetate (PMA),and the gp91Phox was also measured in resting neutrophils by flow cytometry.Twenty healthy term neonates served as controls.Mann-Whitney U test was used for statistical analysis.Results Before the stimulation of PMA,the percentage of activated neutrophils of VLBWI [(49.10±20.19) ％] producing a respiratory burst was higher than that of term neonates [(18.73 ±6.81) ％] (Z--4.911,P=0.000),however,after the stimulation of PMA,the percentage of activated neutrophils of VLBWI [(96.58 ± 3.44) ％] was lower than that of term neonates [(99.20±0.62) ％] (Z--3.186,P=0.001),and the stimulation index (SI) of VLBWI (171.40 ± 103.35) was lower than that of term neonates (306.30 ± 138.47),with significant difference (Z=-3.413,P=0.001).The geometric mean of gp91Phox in VLBWI (21.66± 19.87) was higher compared with term neonates (19.60±8.03),however,the difference was not significant (P=0.350).The percentage of neutrophils that expressed gp91Phox [(56.11 ± 29.40) ％] was lower in VLBWI than that in term neonates [(80.14± 14.87) ％],with significant difference (Z=-2.374,P=0.018).Before the stimulation of PMA,the percentage of activated neutrophils of VLBWI with NRDS (63.40± 16.45) ％] was higher than that of VLBWI without NRDS [(34.80± 11.65) ％],with significant difference (Z=-3.382,P=0.001),the SI of VLBWI with NRDS (129.46 ± 75.36) was significantly lower than that of VLBWI without NRDS (213.35 ± 113.49) (Z=-2.331,P=0.020).Conclusions Neutrophils producing a respiratory burst in both VLBWI and term neonates are active without stimulation of PMA,while the phenomenon is more obvious in VLBWI.Neutrophils in VLBWI and term infants can be activated by the stimulation of PMA,and express gp91Phox.The activation and gp91Phox expression of neutrophils in VLBWI with NRDS tend to be lower than those in VLBWI without NRDS.

Xuefu Zhuyu decoction (XFZYD) is a famous traditional Chinese medicine (TCM) formula, is widely used in the treatment of cardiovascular and cerebrovascular diseases in China over one hundred years. But its effect on antioxidant and drug-metabolizing enzymes are unknown. This study was to observe the effects of Xuefu Zhuyu decoction (XFZYD) on the activities of antioxidant and drug metabolism enzymes (DMEs) in liver of rats. Male SD rats, treated with XFZYD at the dosage of 3.51, 7.02 and 14.04 g x kg(-1) per day for 15 days, serum were collected, tissue fluid, cytosols and microsomes isolated from liver tissues were prepared by centrifugation according to the standard procedure, the activities of antioxidant enzymes and drug-Metabolizing Enzymes were determined by UV-V is spectrophotometer. In serum, the activities of AST was not significantly affected by the treatment with XFZYD, at the high- est dose, the levels of ALT, Cr and BUN were significantly decreased (P < 0.05). GPX were significantly increased at the dose of 7.02, 14.04 g x kg(-1) (P < 0.05), CAT were significantly increased at the highest dose (P < 0.05). T-SOD was not significantly af- fected by this treatment. In the liver tissue, GPX was significantly increased at the dose of 3.51, 7.02 g x kg(-1) (P < 0.05), GST, CAT and T-SOD were not significantly affected following this treatment. In cytosols, GST was significantly increased at the dose of 3.51 g x kg(-1) (P < 0.05), T-SOD was remarkable induced at the dose of 3.51 and 7.02 g x kg(-1) (P < 0.05). In microsomes, XFZYD had no significant effect on Cytochromeb5, NADPH-Cytochrome P450 reductase, CYP3A, CYP2E1 and UGT, XFZYD significantly in- duced GST at the dose of 3.51 and 7.02 g x kg(-1) (P < 0.05), and the level of GSH were significantly increased by XFZYD at the dose of 3.51, 7.02 and 14.04 g kg(-1) (P < 0.05). These findings suggest XFZYD can induce the activities of GPX, CAT, SOD, GST and increase GSH level in liver of rats, which indicate XFZYD may have detoxification and antioxidant functions.
Animals ; Antioxidants ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Inactivation, Metabolic ; drug effects ; Liver ; drug effects ; enzymology ; Male ; Rats ; Rats, Sprague-Dawley

Objective To analyze the efficacy and tolerance of methotrexate(MTX)in remission maintenance of Crohn′s disease (CD).Methods From June 2012 to August 2015 ,49 CD patients who received MTX as mainly treatment medication to maintain remission were enrolled.The pre-medication history,efficacy,dosage and side effects of MTX were analyzed.The effects of inducing strategy on disease recurrence were analyzed.Chi-square test and t test were used for statistical analysis.Results Among the 49 patients,34 (69.4%)received steroids for remission inducing,nine (18.4%)received infliximab for remission inducing and six (12.2%)achieved remission after operation.In the 44 patients treated with azathioprine (AZA)before,the median treatment time was one month and the dosage for withdrawal of AZA was (42.0 ± 14.8)mg/d.The most common reason was leucopenia (81 .8%, 36/44).Till the time point of follow-up,46 of the 49 CD patients still took MTX orally with a median treatment time of 16 months,and the weekly dosage was (12.7 ±2.0)mg.Thirty-one cases (67.4%) achieved clinical stability,while 15 cases (32.6%)underwent clinical recurrence.The median Crohn′s disease activity index (CDAI)was 123.5 ± 66.6.The weekly dosage of clinical stability group was (12.5 ±2.1)mg,and that of clinical recurrence group was (13.0 ±1 .7 )mg,there was no statistically significant difference between the two groups (t =0.802,P =0.426 ).The recurrence rate of steroids-induced remission group was 41 .2% (14/34 ),which was higher than that of infliximab and surgery-induced remission group (1/15),and the differnce was statistically significant (χ2 =5 .177,P =0.023 ). The common side effects were gastrointestinal reaction (26.5 %, 13/49 ), impaired liver function (20.4%,10/49)and leukopenia (12.2%,6/49).Only three cases could not tolerate the side effects and underwent medication withdrawal.Conclusions As a second-line immunosuppressant for maintanence remission in CD,MTX is effective and well-tolerated in patients.So it can be an important option during the long course of CD.

OBJECTIVETo construct a recombinant lentiviral vector for manganese superoxide dismutase (MnSOD) gene expression, and observe its effect on the proliferation of esophageal cancer cells in vitro.

METHODSChemical methods were employed for synthesis of the MnSOD cDNA sequence sections, along with the attB sites. Target gene fragment was constructed on the pMD-18T vector, and the recombinant plasmid pDONR221 was obtained after BP recombination reaction. Sequencing was followed by LR recombination reaction between the plasmid and DEST to obtain the lentiviral vector, which worked with helper plasmid for co-transfection of human embryonic kidney epithelial cells (293T cells). Amplification was done to determine its titer, and both transfection and selection procedures were made to get two stable transfected esophageal cancer TE-1 cell lines with medium MnSOD expression (TE-1Mm cells) and high MnSOD expression (TE-1Mh cell), and empty vector cell (TE-1Mn cells). Reverse transcription polymerase chine reaction (RT-PCR), immunofluorescence, immunocytochemistry and Western blot were used to detect the target gene with respect to its expression in the TE-1 cells. Additionally, colorimetric 3-[4,5-dimethy thiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, agar colony formation assay, annexin V-FITC/PI staining and flow cytometry experiments were also conducted as to observe the influence of the medium and high MnSOD overexpressions on the proliferation of esophageal cancer cells.

RESULTSRT-PCR indicated that the transfected TE-1 cells showed positive MnSOD expression at different levels. Immunofluorescence, immunocytochemistry and Western blot suggested that TE-1Mm cells and TE-1Mh cells had MnSOD protein expression at different levels. MTT assay indicated that TE-1Mm cells had a significantly decreased survival rate compared with that of the two control cells (TE-1 cells and TE-1Mn cells), and TE-1 Mh cells had an significantly increased survival rate (P<0.05). The colony formation ability of TE-1Mm cells was (23.0 +/- 2.7)%, and that of TE-1Mh cells was (45.3 +/- 4.5)%, significantly different form the (34.7 +/- 4.2)% in TE-1 cells and (33.7 +/- 4.7)% in TE-1Mn cells (P<0.05). Annexin V-FITC/PI double staining experiment of the stably transfected cells cultured for 48 h showed that the early apoptosis rate in TE-1Mm cells was (10.6 +/- 1.0)%, significantly higher than (2.6 +/- 0.2)% in the TE-1 cells, (2.5 +/- 0.6)% in the empty vector cells and (1.0 +/- 0.1)% in the TE-1Mh cels (P<0.05). The fluorescence index (FI) of mitochondrial apoptosis of TE-1Mm cells was 0.948 +/- 0.019, significantly lower than that of TE-1 cell (1.000 +/- 0.022) and empty vector The fluorescence index of TE-1Mn cells (0.997 +/- 0.023) and TE-1 cells (1.000 +/- 0.022) were significant different from that of 0.948 +/- 0.019 in TE-1Mm cells and 1.076 +/- 0.022 in TE-1Mh cells, indicating a significant difference of mitochondrial apoptosis between the cell groups. FCM results indicated that the ROS fluorescence index of TE-1Mm cells was 0.859 +/- 0.040, that of TE-1Mh cells was 0.763 +/- 0.039, significantly lower than that of TE-1 cells (1.000 +/- 0. 042) and empty vector cells (1.002 +/- 0.047) (P<0.05).

CONCLUSIONSStably transfected cell lines with MnSOD expression have been successfully established. MnSOD overexpression shows bidirectional effect on the proliferation of esophageal cancer cells.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Esophageal Neoplasms ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Genetic Vectors ; HEK293 Cells ; Humans ; Lentivirus ; genetics ; Mitochondria ; pathology ; Plasmids ; RNA, Messenger ; metabolism ; Reactive Oxygen Species ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; Superoxide Dismutase ; genetics ; metabolism ; Transfection