Volume 88  ·   Issue 07  ·  2008

190 years ago, James Parkinson, a British physician, opened up the nearly two centuries of human research on Parkinson's disease (PD) with a book entitled "Tremor Paralysis" [1].

Parkinson's disease is a chronic progressive neurodegenerative disease with tremor, stiffness, bradykinesia and abnormal posture and gait as main manifestations. It mostly occurs in the elderly. With the aging of the population, the number of patients is increasing.

Objective To investigate the changes of predictive ocular motor function in the patients with Parkinson's disease(PD),and to discuss its clinical value.Methods Videonystagmography(VNG)Was used to examine 24 patients with idiopathic Parkinson's disease,15 males and 9 females,aged 61 ±6(50-69),and 24 sex and age-matched healthy control subjects on random ocular saccade(with the target moving at random intervals to random positions)and predictive ocular saccade(with the 1.25-second light target moving 10 degrees right or left from the center).Result In the random ocular saccade program,the latency of saccade of the PD patients was 284 ms ±58 ms,significantly longer-than that of the healthy controls(236 ms ±37 ms,P=0.003).In the predictive ocular saccade pattern,the latency of saccades the PD patients was 150 ms±138 ms,significantly longer than that of the healthy controls(59 ms ±102 ms,P=0.002).The appearance rate ofpredictive saeeades(with the latency of saccade＜80 ms)in the PD group was 21%,significantly lower than that in the control group(31%,P=0.003).Conclusion There is dysfunction of predictive ocular motor control in the PD patients,and the cognitive function may be impaired at the early stage of PD.

Objective To investigate the characteristics of Chinese characters morphological and phonetic working memory in early Parkinson disease(PD)patients and the underlying neuropsychological and patho-physiological mechanisms.Methods The Smith working memory software was modified and further developed to be used to investigate the Chinese characters morphological and phonetic working memory in early PD patients and healthy controls.Results Twenty early PD patients,10 males and 10 females,aged(62.2±2.3),with(13.6±0.6)years of full-time study and the MMSE score of (28.2±0.5),and 25 sex,age,schooling time,and MMSE score-matched healthy controls underwent Chinese characters morphological working memory test.The correct rate of Chinese characters morphological working memory of the PD patients was 91.8%±1.9%.not significantly different from that of the healthy controls(91.3%±1.4%,P=0.823).Twenty-five early PD patients,13 males and 12 females,aged (64±11),with(14.4±2.2)years of full-time study and the MMSE score of(28.9±0.4),and 25 sex,age,schooling time,and MMSE score-matched healthy controls underwent Chinese characters phonetic working memory test.The correct rate of Chinese characters phonetic working memory of the PD patients was 89.3%±6.3%,significantly lower than that of the healthy controls(94.1%±5.1%,P=0.007).Further more the Chinese characters in the test were classified into four groups according to the syllable and intonation:with same syllable and same intonation,with same syllable and different intonation,with different syllable and same intonation,and with both different syllable and intonation.The correct rates to these groups were recorded separately.The correct rate to Chinese character group of the same syllable with different intonation of the PD patients was 80.2%±2.5%.significantly lower than that of the healthy controls(86.3%±1.8%,P=0.01),and there were not significant differences in the correct rate to other Chinese character groups.The correct rate of phonetic working memory of the PD patients with left extremity onset was 88.0%±6.5%,significantly lower than that of the healthy controls(94.1%±5.1%,P=0.003).Conclusion Phonetic verbal working memory impairment exists in early PD patients.Intonation may play a role in the phonetic verbal working memory impairment in the early PD patients.Different verbal working memory subsystems may use different neurocircuits.

Objective To investigate whether FoxP3+regulatory T cells(Treg)are present in the acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and the correlation between Treg and COPD.Methods Peripheral blood samples were collected from 21 patients of AECOPD,20 males and 1 female,aged(70±9)(52-85).Lymphocytes were isolated by three-color labeled three colors monoclonal antibodies flow cytometry to examine the quantities and percentages of CD4+CD25+,CD4+CD25+FoxP3+(CD4+Treg),CD8+CD25+,and CD8+CD25+FoxP3+(CD8+ Treg).ELISA was used to detect the expression of transforming growth factor β1(TGF-β1),interleukin-10(IL-10),and tumor necrosis factor α(TNF-α).Middle correlation coemcient r≥0.3 was analysed and discussed.Resnits The percentages of CD4+CD25+,CD4+Treg,CD8+ CD25+,and CD8+Treg in AECOPD were(18±6)%,(19 ±13)%,(5±4)%,and(12±10)%respectively.Linear correlation analysis indicated that the quantity and percentage of Treg were significantly correlated with age,course of disease,smoking index,quantity of white cells,and blood pH,and there were complex causal relations between the immunity of patients and these factors.However,TGF-β1 and IL-10 showed no correlation with Treg.Conclusion CD4+Treg and CD8+Treg are expressed in the peripheral blood of AECOPD patients and contribute to the immune suppression of these patients,so they can be used as new markers of immunity of these patients.

Objective To assess the presentation,imaging features,and prognostic factors of primary soft tissue sarcoma of mediastinum.Methods The clinical data of 22 patients with primary soft tissue sarcoma of mediastinum,12 males and 10 females,aged 46(28-69),hospitalized over 27 years were retrospectively reviewed,focusing on the clinical presentations,preoperative diagnosis,imaging features,immunohistochemical studies,treatment,and survival.Results Chest pain,dyspnea,cough,and shoulder pain were the most common complaints.Imaging findings showed large lobulated mass.The overall 5-year survival rate was 62.8%.The 5-year survival rate of the patients with tumors larger than 10 cm was 65.6%.significantly higher than that of the patients with tumors smaller than 10 cm(38.8%,P=0.019).The long-term survival rate of the patients who received complete resection was 84 months,longer,though not significantly,than that of the patients who received incomplete resection(8 months,P=0.059).The 5-year survival rate of the patients with lesions at high grade and stage Ⅲ were 38.2% and 38.2% respectively,both lower,though not significantly,than those of lesions at low grade and stage Ⅰ(60% and 60% respectively,both P=0.3 17).The 5-year survival rate of the patients who received surgery only was 8 months,shorter,though not significantly,than that of the patients who received surgery plus adjuvant therapy(12 months,P=0.204).Conclusion Tumor size and character of resection are important prognostic factors for primary soft tissue sarcoma of mediastinum.

Objective To study the relationship of coping behavior and mental health of military medical researchers and technicians.Methods A cross-sectional survey was conducted,using the selfrating anxiety scale(SAS),self-rating depression scale(SDS),and self-rating scale of coping behavior,among 325 military medical laboratory scientists and technicians with different professional titles.Results The anxiety and depression scores of the military medical researchers and technicians were 30±6 and 37±8respectively,both significantly lower than those of the national norm(34±6 and 42±11 respectively,both P＜0.01).The depression score of the associate chief technicians was 42±7,significantly higher than those of the medical researchers and technicians with any other professional titles(all P＜0.05),and the anxiety score of the associate chief technicians was 32±7.significantly higher than that of the research fellows(28±4,P＜0.05).The seeking help score of the associate chief technicians was 2.8±0.5,not significantly different from that of the associate research fellows(2.8±0.5),but significantly lower than those of the military medical researchers and technicians with any other titles(all P＜0.01).The self-blame score of the associate chief technicians was 1.9±0.6,significantly higher than that of the assistant research fellows (1.0±0.6,P＜0.01)and that of the research fellows(1.6±0.6,P＜0.05).Correlation and regression analysis showed that active coping behaviors were significantly positively correlated with depression(rl=-0.519)and anxiety(r3=-0.348);and negative coping behaviors were significantly negatively correlated with depression(r2=0.314)and anxiety(r4=0.407).Conclusion Coping behavior has significant influence on the medical researchers and technician.Increasing seeking help and decreasing self-blame and imagination help release the anxiety and depression among the medical researchers and technicians.

Objective To investigate the correlation between histological grade (HG) of vertebral growth plates and Risser grade in the female idiopathic scoliosis(IS)patients;and to identify whether Risser grading is a reliable indicator for accurate evaluation of the spinal residual growth potential.Methods Thirtynine samples of vertebral growth plates obtained during operation from 15 females IS patients,all female,aged 15.1(12.4-18.0),underwent HE staining and light microscopy to determine the values of HG.Xray photography of pelvis was conducted before operation to identify the Risser sign.The correlation of Risser grade with pubertal status was analyzed.Results All the vertebral growth plates of the IS patients with the Risser grade of 0 showed growth activity.The vertebral growth plates showed HG Ⅱ activity in 6 of the 16 IS patients with the Risser grade of 4.All the vertebral growth plates showed no growth activity in the 3 IS patients with the Risser grade of 5.There was a negative correlation between the HG and Risser grade in all 39 patients(r=-0.645,P=0.000).The HG of the patients with the Risser grade of 4 was negatively correlated with the menarchal status(time between menarche and operation)(r=-0.710,P=0.002).The residual growth potential of spinal growth plates of the patients with the Risser grades of 2-5 was significantly lower than of the patients with the Risser grades of 0-1(P=0.020).Conclusion Risser sign may be a reliable indicator for predicting the spinal residual growth potential in IS patients,but it should be correlated with menarchal status and chronological ages.

Objective To investigate the spinal segment instant and fatigue stability of anterior lumbar interbody fusion with stand-alone cage.Methods The vertebrae L4 and S1 of 6 human lumbar specimens(L3-S1)were embedded with dental base acrylic resin powder and fixed on mechanical machine,and the L4/Ls and L5/S1 disk spaces were left active.The 6 specimens underwent mechanical test as control group first,and then used as experimental group with a cage implanted in L5/S1.Instant instability Was tested in three directions:flexion,extension,and lateral bend.The relative movement of L4/L5 and L5/S1 was recorded.Fatigue instability was tested after 50 000 times of flexion-extension movement,and the relative displacement between the cage and S1 Was recorded.Result In the three directions of flexion,extension,and lateral bend,the relative movements of L5/S1 in the experimental group were 0.83±0.26°,1.60±0.19°,and 0.72±0.20°respectively,all significantly decreased than those of the control group (3.60±0.30°,4.82±0.34°,and 3.80±0.28°respectively,all P＜0.01).The relative movement of L4/L5 of the experimental group were 5.82±0.36°,5.38±0.30°,and 4.96±0.29°in the three directions respectively.all significantly higher than those of the control group(4.16±0.33°,4.02±0.30°,and 3.48±0.34°respectively,all P＜0.01).After 50 000 times of flexion-extension fatigue movement,the relative displacement between the cage and S1 was zero.Conclusion Anterior lumbar interbody fusion with a stand-alone cage has excellent instant and fatigue stability,which can provide enough stability for clinical bone fusion without other internal fixation.

Objective To detect the new and old surface markers of regulatory T cells(Treg cells)in the CD4+T cells of the patients with systemic lupus erythematosus(SLE)in order to reveal the role of Treg cells in the pathogenesis of SLE.Methods Peripheral blood samples were collected from 29 newly diagnosed and treatment-na(i)ve SLE patients,3 males and 26 females,aged(34±13),and 24 sex and aged-matched healthy controls.Three-color flow cytometry was used to detect the CD4+ CD25+ CD127low/-T cells,CD4+ CD25high T cells,and CD4+ CD25+ FOXP3+ T cells.The serum anti-nuclear antibody(ANA),anti-ds-DNA antibody,anti-smooth muscle antibody,anti-nucleosome antibody,anti-Clq,C3,and C4 were detected.Blood and urine routine examinations were conducted.Results The proportion of blood CD4+ CD25+ CD127low/-T cells of the SLE patients was not significantly different from that of the controls (P＞0.05),however,the proportions of CD4+ CD25+ FOXP3+T cells and CD4+ CD25highT cells ofthe SLE patients were 2.1±1.2 and 0.8 ±0.4 respectively,both significantly lower than those of the controls (4.0 ±1.4 and 1.8 ±0.8 respectively,both P＜0.01).The ratios of the CD4+ CD25+ CD127low/-T cells,CD4+ CD25highT cells.and CD4+ CD25+ FOXP3+T cells to the CD4+ CD25+T cells of the SLE patients were 0.5±0.1,0.1 ±0,and 0.3 ±0.1 respectively,all significantly lower than those of the controls(0.6±0.1,0.2 ±0.1,and 0.5±0.respectivelv,all P＜0.01).The level of CD4+ CD25+ CD127low/-T cell was positively correlated with the levels of CD4+ CD25+ FOXP3+T cells and CD4+ CD25highT cell (both P＜0.01 ).The levels of these 3 kinds of cells and their ratios to CD4+ CD25+ T cells had no correlation with age,sex,course,IgG,IgA,IgM,urine protein,TIPU,anti-dsDNA,anti-C1q,anti-nuclear body antibody (all P＞0.05),however,were significantly associated negatively with SLE disease activity index,P＜0.05).Only the CD4+ CD25+ CD127low/-T cells/CD4+ CD25+T cells was negatively correlated with C4(P＜0.01).Conclusion The relative ratio of Treg cells to the activated CD4+ T cells may play an important role in the pathogenesis of SLE.

Objective To investigate the effects of glutamine(Gln)on the cytokine expression of the peripheral blood mononuclear cells(PBMCs)stimulated by lipopolysaceharide(LPS).Methods PBMCs were extracted from healthy volunteer by density gradient centrifugation.Suspension of PBMCs was pretreated with Gln of the concentrations of 1 mmol/L,8 mmol/L,10 mmol/L,and 15 mmol/L for 0.5 h and 2 h respectively.Suspension of PBMCs without Gln pretreatment but stimulated by LPS was used as positive control group,and suspension without LPS stimulation was used as negative control group.Then LPS was added ELISA was used to examine the levels of the mediators of inflammation,TNF-α,IL-1β,IL-4,IL-6,IL-8,and IL-10,in the supernatant,and Gene Array Protocol was used to examine the mRNA expression of these cytokines.Result After LPS stimulation,the expression levels of all the cytokines were obviously enhanced.The expression levels of the proinflammatory mediator,except for IL-6,of the Gln 8 mmol/L 0.5h group were significantly lower than those of the positive control group;and the expression levels of all the cytokines of the Gln 15 mmol/L 0.5 h group were significantly lower than those of the positive control group,however,all still significantly higher than those of the negative control group(P＜0.01 or P＜0.05).Theexpression levels of the proinflammatory mediator except for IL-8 of the Gln 1 mmol/L 0.5 h group did not significantly changed in comparison with the positive control group;and the level of IL-8 was significantly decreased(P＜0.01).The expression levels of all the cytokines of the high concentrations Gln groups were all significantly lower than those of the positive control group.The levels of TNF-α,IL-6,and IL-8 of thehigh concentration Gln 2 h groups were all significantly higher then those of the concentration Gln 0.5 h groups(all P＜0.01),however,there was not significant difference in the level of IL-1β between the high concentration 0.5 h and 2 h Gln groups.The level of the anti-inflammatory mediator IL-10 of the high concentration Gln 0.5 h and 2 h groups,especially that of the latter group,were significantly lower than that of the positive control group(both P＜0.01),however,the IL-10 level of the high concentration Gln 0.5 h group was still significantly higher than that of the negative control group(P＜0.05).Gene chip analysis confirmed the above results.Conclusion Glutamine dose-and time-dependently downregnlates the expression of the mediators of inflammation,and lessen the excessive expression of those cytokines in cells stimulated bv LPS.

Objecfive To investigate the probable relationship between the genetic polymorphisms of Ⅲ collagen α1(COL3A1)gene and sporadic intracranial aneurysm patients in China of Han nationality.Methods Peripheral blood samples were collected from 56 randomly selected sporadic intracranial aneurysm patients and 57 control cases without intracranial aneurysm,related risk factors,subarachnoid hemorrhage,and stroke history.Genomic DNA was extracted.PCR and sequencing were performed to evaluate the frequency discrepancy of the single nucleotide polymorphisms(SNPs).After statistical analysis the polymorphism site correlated with intracranial aneurysm was further investigated with bioinformatics methods to explore the influence of the mutations of polymorphie sites on the stability of type Ⅲ collagen.Results Both the genotype and allele frequencies of rs1800255 between the intracranial aneurysm and control group were statistically significant.There were no significant differences in the genotype and allele frequencies of thee SNPs rs2271683,rs151446,and nt2346.Data showed that the amino acid change induced by the polymorphism site could sabotage the stability of type Ⅲ collagen.Conclusion There is significant correlation between rs1800255 of COL3A1 gene and Chinese sporadic intracranial aneurysm patients of Han nationality,which confirms the COL3A1 gene is one of the susceptible genes of Chinese sporadic intracranial aneurysm patients of Han nationality.

Objective To evaluate the effects of transplantation of human hepatocyte growth factor (hHGF)gene-modified osteoblasts combined with core decompression in treatment of avascular necrosis of femoral head(ANFH).Methods The plasmid pcDNA3.1(+)-hHGF containing hHGF gene was constructed.Osteoblasts were isolated from fetal rabbits,cultured,and transfect3d with the plasmid pcDNA3.1(+)-hHGF or blank plasmid pcDNA3.1(+),or used as controls.Thirty-six adult New Zealand rabbits were made into ANFH models,underwent core decompression,and were randomly divided into 3 groups.Group A,transplanted with osteoblasts transfected with pcDNA3.1(+)-hHGF plasmid,Group B,transplanted with osteoblasts not transfected with pcDNA3.1(+)-hHGF plasmid,and Group C,injected with PBS medium.2,4,and 8 weeks later samples of femoral head were obtained to undergo CT,histological examination,and capillary ink infusion so as to observe the angiogenesis and osteogenesis.Results The pcDNA3.1(+)-hHGF transfected osteoblasts showed stable expression of hHGF.The numbers of newly formed vessels of the femoral heads of the group transfected with pcDNA3.1(+)-hHGF-transfected osteoblasts 2 and 4 weeks later were(29.47±1.64)and(34.02±1.72)/cm2 respectively,both significantly higher than those of the group transfected with blank plasmid-trsansfected osteoblasts[(20.61±1.91)and(25.57±2.20)/cm2 respectively,both P＜0.01].Eight weeks later the numbers of mature trabeeular bone and bone marrow of Groups A and B were significantly higher than those of Group C.Conclusion Core decompresson combined with transplantation of HGF gene-modified osteoblasts promotes angiogenesis,enhances bone formation,and improves the restoration of avascular necrosis of femoral head.

Objective To investigate the role of N-[N-(3,5-Difluorophenacetyl-L-alanyt)-S-phenylglycine t-butyl ester(DAPT),a gamma-secretases inhibitor,on the proliferation and differentiation of neural stem cells(NSCs).Methods NSCs were isolated from Sprague-Dawley rat brain,cuhured,and treated with DAPT for 6 weeks.Cell counting was conducted every 24 h.CCK8 assay was used to draw the growth curve.Immunonuoresence staining was performed to observe the proportions of β-tubulin Ⅲ positive cells(neurons),glial fibrillary acidic protein (GFAP) positive cells (astrocytes),and 2',3'-cyclic nucleotide3' phosphohydrolase (CNPase) positive cells (oligodentrocytes).RT-PCR was employed to assay the mRNA expression of RBP-Jk and Hesl genes,downstream genes of the Notch pathway.Results Cell counting and CCK-8 assay showed that DAPT reduced the rate of NSC proliferation.Addition of DAPT altered NSC differentiation in vitro,percentage of The proportions neurons of the DAPT group was(13.84±1.22)%,significantly higher than that ofthe control group[(3.7±1.04)%,P＜0.01],the proportion of the oligodendrocytes of the DAPT group was(14.75±1.58)%,significantly higher than that pf the control group[(4.8±1.22)%,P＜0.01].However,the proportion of astrocytes of the DAPT group was (63.41±1.20)%,significantly lower than that of the control group[(82.84±3.68)%,P＜0.01].The expression levels of RBP-Jk and Hes1 mRNA(RBP-Jk/GAPDH and Hes1/GAPDH)in the NSC treated with DAPT were 0.52±0.13 and 0.66±0.18 respectively.both significantly lower than those of the control group(0.28±0.06 and 0.16±0.08 respectively,both P＜0.05).Conclusion DAPT inhibits the NSC proliferation and alters the NSC committed differentiation.These effects are mediated via Notch signaling down regulation as a result of the inhibition of gamma-secretase.

Objective To investigate the effects of human telomerase reverse transcriptase(hTERT)promoter and survivin promoter in tumor-specific gene therapy.Methods hTERT promoter and survivin promoter were obtained by PCR using Jurkat genomic DNA.Recombinant adeno-associated virus(AAV)vectors containing exogenous TRAIL gene and hTERT promoter or survivin promoter were constructed and designated as rAAV-hTERT-TRAIL(h/TRAIL)or rAAV-survivin-TRAIL(s/TRAIL).rAAV particles were obtained after packing and purification and the virus titer was calculated by real-time PCR.Human hepatocellular carcinoma(HCC)cells of the lines SMMC-7721,BEL-7402,HepG2,and Hep3B.and primary human hepatocytes(PHHs)were transfected with h/TRAIL or s/TRAIL.Flow cytometry was used to detect the expression of the reporter gene enhanced green fluorescent protein(EGFP),so as to examine the activitV of the two promoters.MTT method was used to detect the activity of the cells.Fifteen BalB/C mice underwent subcutaneous injection of SMMC-7721 cells so as to establish tumor models and then were randomly divided into 3 groups to undergo intra-tumor injection of h/TRAIL,s/TRAIL,or PBS.The growth of tumor was observed for 5 weeks,and then peripheral blood samples were collected to examine the serum AST and ALT levels.TUNEL was used to detect the apoptosis if the tumor cells.Results All the SMMC-7721,BEL-7402,HepG2,and Hep3B cells driven by both h/TRAIL and s/TRAIL showed EGFP expression,however,no fluorescence could be seen in the PHHs transfected with h/TRAIL and s/TRAIL.MTT method showed that 72 hours after the transfection of h/TRAIL and s/TRAIL the survival rates of the SMMC-7721,BEL-7402,and HepG2 cells all decreased,however,the survival rate of the Hep3B cells and PHHs did not changed significantly.The size of the subcutaneous tumor of the mice of the h/TRAIL group was 625 mm3,significantly smaller than that of the PBS group(1500 mm3,P＜0.05),however.the tumor size of the s/TRAIL group was 1117 mm3,not significantly different from that of the PBS group(P＞0.05).The AST and ALT levels of all mice did not change significantly 5 weeks after the intratumor injection.Conclusion Tumor-specific promoters are promising candidates in targeted tumor gene therapy.

A 33-year-old female was admitted to hospital due to 24+ weeks of menopause, 3 d of dazzle, headache and 1 d of elevated blood pressure. She had a history of hypokalemia for 3 years, and the serum potassium fluctuated from 2.4 to 2.6 mmol/L. She took 10 to 20 ml of potassium chloride by herself, under 37/d, without regular diagnosis and treatment.

Professor Strup, head of urology at the University of Kentucky, USA, has recently gained a new perspective on the treatment of small kidney cancer.

In 1986, Sen et al. [1] first reported that NF-κ B is located in B lymphocytes and binds to the B site of the enhancer of the kappa light chain gene of immunoglobulin to regulate the transcription of the kappa light chain of immunoglobulin, so it was named nuclear factor-κ B (NF-κ B).

Parkinson's disease (PD) is a common senile neurodegenerative disease, which occurs more than 60 years old. Clinically, PD is mainly characterized by quiescent tremor, bradykinesia and increased muscle tone. Pathologically, PD is characterized by progressive degeneration and loss of dopamine neurons in the midbrain, accompanied by intracellular Lewy body formation.

Parkinson's disease is a chronic degenerative motor system disease. Its main pathological changes are the degeneration of dopaminergic neurons in the dense part of substantia nigra and the large reduction of dopamine in the striatum.

Addison's disease, namely hypoadrenal cortex, is a clinical syndrome caused by the destruction of bilateral adrenal cortex and the decrease of corticosteroid secretion. Autoimmunity is one of the main causes of Addison's disease. In the past 20 years, 7 cases of diffuse connective tissue disease complicated with Addison's disease have been treated in Peking Union Medical College Hospital, which are reported as follows.