Volume 87  ·   Issue 39  ·  2007

According to the traditional view, we defined multiple sclerosis (MS) with more than two sites of inflammatory demyelinating sclerosis and more than two episodes in the central nervous system, which was considered to be glial hyperplasia and sclerotic scar formation plaque.

Multiple sclerosis (MS) has various clinical manifestations, which are related to the central nervous system sites involved. The diagnosis of MS is mainly based on the multiple incidence of inflammatory demyelinating lesions in the central nervous system in the site and time, which is difficult to diagnose and misdiagnosed. With the widespread application of MRI technology, the accuracy of diagnosis is greatly improved, but there are still many patients who are difficult to diagnose early.

Objective to determine the level of memory T cell subsets in patients with multiple sclerosis (MS) and to explore the possible mechanisms leading to the changes of memory T cell subsets. Methods Flow cytometry and enzyme-linked immunosorbent assay (ELISA) were used to detect the phenotype of memory T cell subsets in peripheral blood and the plasma interleukin-15 (IL-15) concentration in untreated MS, cerebral infarction and normal controls, respectively. Results The CD8+ central memory T cells (TCM) in MS patients were significantly higher than those in normal controls (20%±11% and 13%±6%, P<0.05), and the CD8+ terminal effector memory T cells were significantly lower than those in normal controls (24%±15% and 39%±19%, P<0.05). The plasma levels of IL-15 in MS patients were significantly higher than those in normal controls (36.01 pg/ml and 9.53 pg/ml, P<0.05). Conclusion The upregulation of CD8+ TCM in peripheral blood of MS patients may reflect a sustained chronic inflammatory response induced in the early stage of MS, while IL-15 may be involved in the regulation of TCM differentiation.

Objective to investigate the significance of detecting neurofilament protein light chain (NF-L) and its antibody in the diagnosis and prognosis of multiple sclerosis (MS), and to further reveal the pathogenesis of MS. Methods The levels of NF-L and its antibody, anti-myelin basic protein (MBP) and anti-myelin oligodendrocyte glycoprotein (MOG) antibody in serum and cerebrospinal fluid were detected by enzyme-linked immunosorbent assay (ELISA) in 63 patients with MS, 15 patients with neuromyelitis optica (ONM) and other controls [31 patients with other inflammatory neurological diseases (OIND), 18 patients with other non-inflammatory neurological diseases (NIND) and 46 normal neurological controls (NC)]. The normal distribution data were expressed by (-x) ±, and the non-normal distribution data were expressed by M (QR). Results the concentration of NF-L in cerebrospinal fluid was 26 (33) ng/L in MS group, 20 (92) ng/L in ONM group, 19 (82) ng/L in OIND group, 30 (194) ng/L in NIND group and 10 (7) ng/L in NC group The level of NF-L antibody in MS group was lower than that in OIND group and higher than that in NIND group and NC group (both P<0.05). The level of NF-L antibody in cerebrospinal fluid of MS patients was significantly correlated with the level of MBP antibody (r =0.784, P<0.01) and IgG (r =0.675, P<0.01); But there is no correlation with MOG antibody levels. Conclusion NF-L or its antibody can not be used as an ideal marker for differentiating various neurological diseases; There were axonal injuries in MS, ONM, OIND and NIND groups; Inflammation may not be the main cause of NF-L antibody production leading to axonal damage.

Objective to investigate the relationship between human leukocyte antigen (HLA) -DRB1 and HLA-DPB1 gene polymorphisms and multiple sclerosis (MS) in southern Chinese Han nationality. Methods Sequencing-based typing (SBT) was used to perform HLA-DRB1 and HLA-DPB1 allele typing in 26 patients with common MS (C-MS), 13 patients with optic nerve-spinal MS (OS-MS) and 50 normal controls in southern Han nationality. Results A total of 27 HLA-DRB1 and 13 HLA-DPB1 allele fragments were detected, among which the genotype frequencies of DRB1*0406 and DRB1*1302 were higher in OS-MS patients than in normal people (P values were 0.014 and 0.007, OR values were 2.09 and 2.84, respectively); The frequency of DRB1*120201 was higher in C-MS patients than in the normal population (P =0.021, OR =3.89) and OS-MS patients (P =0.07, OR =6.87); The frequency of HLA-DPB1*2101 in OS-MS patients was higher than that in the normal population (P =0.04). However, the above differences were not statistically significant after adjustment (all Pc>0.1). The genotype frequencies of HLA-DRB1*1501 and DPB1*0501 were not statistically significant between C-MS and OS-MS patients in this group and between them and the normal controls (all P>0.1). Conclusion The correlation between MS and HLA-DRB1 and DPB1 gene polymorphisms in southern Han population is different from that in western, Japanese and northern China.

Objective to investigate the distribution and significance of abnormal glucose metabolism in brain white matter in patients with Alzheimer's disease (AD). Methods Thirteen patients with AD who met the diagnostic criteria of DSM-Ⅳ were collected, including 6 patients with dementia psychiatric behavioral symptoms (BPSD), 7 patients without BPSD, and 10 healthy controls. Results (1) The glucose metabolism of white matter in AD patients was widely lower than that in healthy controls, and the more obvious areas were right frontal subcortical white matter and left frontal superior middle gyrus subcortical white matter (P =0.001); (2) Glucose metabolism in subcortical white matter of left frontal medial gyrus and left occipital cuneus gyrus in AD patients was higher than that in healthy controls (P =0.001); (3) Subcortical white matter glucose metabolism in left and right middle occipital gyrus, left occipital wedge gyrus, right inferior parietal lobule, left temporal fusiform gyrus and left medial frontal gyrus was higher in AD patients with BPSD than in AD patients without BPSD (P =0.001); The glucose metabolism of subcortical white matter in left and right frontal paracentral gyrus, right superior and middle frontal gyrus, left superior temporal gyrus and other brain regions was lower than that in AD patients without BPSD (P =0.001). Conclusion There are extensive white matter metabolism abnormalities in AD brain, mainly manifested as lower white matter metabolism in frontal, parietal and temporal subcortical contact area, stronger subcortical white matter metabolism in medial frontal gyrus and occipital cuneus gyrus, and BPSD symptoms are related to metabolism abnormalities in some brain regions.

Objective to analyze the clinical characteristics of patients with hereditary angioedema (HAE) and summarize the pathogenesis and clinical manifestation patterns of HAE. Methods the clinical and laboratory data of 133 patients in 40 HAE families were retrospectively analyzed by clinical consultation, medical record review, telephone follow-up and family survey. Results (1) Clinical manifestations: All patients had a history of limb and/or facial and genital edema. 89 patients (66.9%) had laryngeal edema during the course of the disease, 4 patients had undergone tracheotomy due to asphyxia caused by laryngeal edema. 102 patients (76.7%) had abdominal symptoms including mild abdominal discomfort and even intolerable abdominal cramps. Abdominal B-ultrasound examination of 6 patients who were in the stage of abdominal pain at the time of consultation showed ascites. (2) Frequency of disease: Without diagnosis and treatment, 100 patients (75.2%) had the frequency of disease ≤ once a month, 31 patients (23.3%) had the frequency of disease 1~3 times a month, and only 2 patients had the frequency of disease ≥4 times a month, that is, 1~2 times a week. (3) Family history: Only 3 patients in 1 family with C1-INH content slightly higher than normal and C1-INH function 2% of normal were diagnosed as type Ⅱ HAE (HAE-Ⅱ). (5) Long-term prophylactic therapy: In this study, 58 patients (43.6%) were treated with oral danazol for long-term prophylactic therapy, which could prevent the attack of all patients, and most patients tolerated danazol well. Conclusion (1) Hereditary angioedema is a rare autosomal dominant genetic disease. (2) HAE-Ⅱ is rare in China, which seems to be different from those reported abroad. (3) Long-term application of danazol can effectively prevent the attack of hereditary angioedema, and patients tolerated it well.

Objective to preliminarily analyze the related factors affecting the occurrence of depression in stroke patients, and predict the main intervention ways to reduce the occurrence of depression in stroke patients, so as to guide stroke patients to adopt correct treatment measures and good lifestyle. Methods 180 hospitalized patients 3 months after the onset of primary stroke were selected, and the general conditions of patients such as gender, age, occupation and disease characteristics were recorded. Stepwise multiple regression analysis was used to analyze and screen the meaningful related factors. Results Factors such as whether or not to undergo rehabilitation treatment, pre-stroke personality, family relationship, age, presence or absence of comorbidities and economic status can enter the regression equation. Conclusion Factors such as whether or not to undergo rehabilitation treatment, pre-stroke personality, family relationship, age, presence or absence of comorbidities and economic status can better predict the score of post-stroke depression scale in stroke patients, and have a great influence on the occurrence of post-stroke depression.

Objective to investigate the difference of tumor biological characteristics of estrogen receptor (ER) + /progesterone receptor (PR) -and ER + /PR + breast cancer patients. Methods 3124 breast cancer patients with ER + /PR-or ER + /PR + were retrospectively studied, and the molecular biological indexes determined by clinical pathology and immunohistochemistry were compared.Results The peak age of ER + /PR + and ER + /PR-breast cancer patients was 50 years old, which was significantly higher than that of ER- /PR-patients (48 years old) (P<0.05). Moreover, the tumor diameter of ER + /PR-breast cancer was larger than that of ER + /PR +, the number of lymph node metastases was higher, the histological grade was lower, the expression level of ER was lower, the expression of c-erbB-2 was high (P<0.05), and the expression of Cathepsin D was low (P<0.05); However, there was no significant difference in mean age between the two groups (P>0.05). Multivariate analysis showed that the factors affecting the different phenotypes of the two groups were: ER expression level (OR =1.792, 95% CI =1.484-2.164, P =0.000), Cathepsin D status (OR =1.380, 95% CI =1.023-1.862, P =0.035) and cerbB-2 expression status (OR =0.639, 95% CI =0.463-0.883, P =0.007). Conclusion ER + /PR + Breast cancer may have the same cause of onset as ER + /PR-, but the expression of PR in ER + state may have many factors, which may lead to the difference of biological behavior of the two breast cancers. Finding new therapeutic targets according to these differences may be more helpful to improve the endocrine therapy effect and prognosis of ER + /PR-patients.

Objective to compare the differential expression patterns of genes in Down syndrome (DS) and normal fetal cerebral cortex, and to identify the human chromosome 21 gene (HC21) which is closely related to the abnormal development of DS cerebral cortex and even the occurrence of mental retardation, so as to lay the foundation for building the molecular network of mental retardation in trisomy 21 (T21). Methods The differential expression patterns of HC21 gene in 20-week DS and normal fetal cerebral cortex were analyzed by Affymetrix U133A gene microarray, and the selected HC21 genes were identified by semi-quantitative RT-PCR and reverse Northern blot hybridization. Results Affymetrix U133A gene microarray contained 127 known HC21 genes, of which 56 were not expressed in both types of cerebral cortex. Among the 71 HC21 genes expressed in both types of tissues, the expression of HC21 genes was up-regulated by more than 1.4 times. Conclusion the differential expression of HC21 genes in DS and normal fetal brain tissues may be the root cause of abnormal development of brain tissue structure and function in DS, and it is also an important candidate gene that causes mental retardation. In-depth research on the molecular pathways of these genes is the basis for comprehensively revealing the molecular mechanism of abnormal development of cerebral cortex and even mental retardation in DS fetuses.

Objective to monitor the drug resistance of Gram-negative pathogens obtained in 15 teaching hospitals in different regions of China in 2005.Methods 1927 strains of Gram-negative pathogens obtained in hospital were collected according to the design scheme.After the strains were reviewed by the central laboratory, the minimum inhibitory concentration (MIC) of 18 kinds of antimicrobial drugs in 6 kinds was determined by agar dilution method, and the data were entered into WHONET5.4 software for drug resistance analysis.Results Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis, which do not produce extended spectrum β-lactamase (ESBL), have high susceptibility to the tested β-lactam drugs. For Escherichia coli and Klebsiella pneumoniae, the only drugs with susceptibility rate of more than 80% were meropenem, imipenem and piperacillin-trizobactam. The susceptibility of Escherichia coli, which does not produce ESBL, to fluoroquinolones is very low (34.8% ~36.1%), The susceptibility of ESBL-producing Escherichia coli was lower (13.4% ~17.1%). For cephalosporinase (AmpC) -producing strains (including Enterobacter cloacae, Enterobacter aerogenes, Citrobacter, Serratia and Proteus vulgaris), the susceptibility rate of antibiotics was greater than 80%: meropenem, imipenem and piperacillin-triazobactam. In addition, the susceptibility rate of fluoroquinolones was 52.5% ~86.2% for antibacteria with higher susceptibility was cefepime (67.3% ~100%), amikacin (67.3% ~95.2%), ceftazidime (52.9% ~100%) and cefoperazone-sulbactam (51.9% ~100%). Pseudomonas aeruginosa had the highest susceptibility to polymyxin B (95.6%), and the susceptibility rate was 70% ~80%: meropenem, imipenem, amikacin and piperacillin-triazobactam. The susceptibility rate of Acinetobacter baumannii was 98.3%, followed by imipenem (80.8%), meropenem (76.2%) and minoxide Minocycline (85.0%), levofloxacin (82.5%) and trimethoprim-sulfamethoxazole (77.5%) were the antimicrobial drugs with higher susceptibility to Burkholderia cepacia. Minocycline (77.2%) and meropenem (61.4%) were the antimicrobial drugs with higher susceptibility to Burkholderia cepacia. Conclusion Carbapenenes, piperacillin-triazobactam, amikacin and cefepime maintained high antibacterial activity against Enterobacteriaceae isolated from hospitals, while the susceptibility of non-fermenting Gram-negative bacilli to clinical drugs was reduced compared with previous monitoring.

Objective to observe the effects of citalopram on the proliferation and differentiation of fetal rat hippocampal neural precursor cells (NPC). Methods the hippocampus of fetal rats was isolated and cultured in vitro by limited dilution method. The monoclonal cells were divided into groups with different concentrations of citalopram and control groups. The proliferation and differentiation of NPC were promoted by serum-free NPC medium and fetal bovine serum respectively. The effects of different concentrations of citalopram on the proliferation and differentiation of NPC were observed by tetramethylazole blue (MTT) assay and immunofluorescence assay respectively. After 7 days of intervention with citalopram (0.5 μ mol/L, 1.0 μ mol/L), the rates of NeuN positive cells reached 59.5%±2.8% and 57.8%±2.1%, respectively, which were higher than those in the control group (47.3%±4.3%) (all P<0.05). Conclusion Citalopram promotes the proliferation and differentiation of fetal rat NPC into neurons.

Objective to investigate the expression and activity of cAMP response element binding protein (CREB) in lung of rabbits with hemorrhagic shock complicated with endotoxemia-induced acute lung injury (ALI). Methods Thirty-six rabbits were randomly divided into two groups: 2 hours after modeling, 12 hours after modeling and control group.The pathological changes of arterial blood oxygen partial pressure (PaO2), lung wet/dry weight (W/D) and lung tissue were analyzed.The content of tumor necrosis factor (TNF) -α in lung tissue homogenate was detected by enzyme-linked immunosorbent assay (ELISA), the expression of CREB protein in lung tissue was detected by Western blot, and the binding activity of CREB/DNA was detected by gel electrophoresis mobility (EMSA) assay.Results The pathological changes showed that the alveolar structure was destroyed in the group 12 hours after modeling, and there were a large number of neutrophils infiltrated and more red blood cells exudated in the alveolar wall and lung interstitium, while the lesions were mild in the group 2 hours after modeling. The PaO2 in the group 12 hours after modeling was significantly lower than that in the control group (55.0 ± 11.0 mm Hg vs 92.9 ± 14.6 mm Hg; P The content of TNF-α in lung tissue homogenate was significantly higher in the group at 12 h after modeling than in the control group (491.6±59.2pg/ml vs 159.3±44.9pg/ml; P<0.01), but the expression of CREB protein in lung tissue was significantly higher in the group at 2 h and 12 h after modeling than in the control group (0.874±0.182, 0.775±0.258 vs 0.483±0.199; P<0.01), and the binding activity of CREB/DNA in the group at 2 h and 12 h after modeling was also significantly higher than that in the control group (355±79, 330±108 vs 185±68; P<0.01). Conclusion Hemorrhagic shock combined with endotoxemia promoted the expression and activation of CREB in lung tissue, and CREB may participate in the inflammatory response process of acute lung injury by promoting the expression of inflammatory factors.

Objective to investigate the anti-tumor immune effects of allogeneic dendritic cells (DC) impacted by heat shock tumor cell lysates. Methods the dendritic cells (DC) derived from mouse bone marrow cells impacted by heat shock mouse Lewis lung cancer cell (LLC) lysates (LhTCL) were used as tumor vaccine (DC/LhTCL). FITC-labeled LhTCL and CFSE-labeled allogeneic DCs were used for in vitro phagocytosis and in vivo tracing experiments, respectively. The effects of LhTCL uptake by immature allogeneic DCs on their phenotype and IL-12 production and the uptake of allogeneic DCs by mice inoculated with local drainage lymph node DC (LD-DC) were observed by enzyme-linked immunosorbent (ELISA), flow cytometry (FCM) and confocal fluorescence microscopy. Immunoprophylaxis of LLC transplanted tumors and treatment of early tumor-bearing mice were studied to evaluate the anti-tumor immune effect of C57BL mice vaccinated with allogeneic or syngeneic DC/LhTCL tumor vaccine.Results (1) Heat shock increased the expression of HSP70 in LLC cytoplasm. (2) Immature allogeneic DC of mice could fully uptake LhTCL and promote DC maturation (increasing the expression of costimulatory molecules on DC surface and IL-12 secretion). (3) Subcutaneous injection of allogeneic DC impinged with LhTCL could promote the uptake of allogeneic DC by murine DC. (4) Splenocytes of C57BL mice immunized with LhTCL impinged allogeneic DC could specifically kill live LLC and secrete Th-1-related cytokines (high level of IFN-γ and low level of IL-4 and IL-10). (5) Immunoprotection and treatment experiments of LLC transplanted tumors in C57BL mice confirmed that immunization with allogeneic DC/LhTCL tumor vaccine could prevent or delay the growth of LLC tumors, and the immune

Objective to clone the promoter sequence of human Mucin 1 (MUC1) Mucin and study its function in driving the targeted expression of human sodium/iodine co-transporter (hNIS) gene in pancreatic cancer cells. Methods MUC1 promoter was amplified from human pancreatic cancer cell line CAPAN-Ⅱ by nested PCR method. pDC316-MUC1/hNIS was introduced into MUC1-positive human pancreatic cancer cell lines CAPAN-Ⅱ, PANC-1 and MUC1-negative human cervical cancer cell line HeLa by liposome transfection. The mRNA level and protein expression of hNIS in the transfected cells were detected by RT-PCR and immunohistochemistry 48 h after transfection. After transfection 48 h, the iodine absorption function of NIS to 125 iodine in tumor cells was detected. Results The sequence of the amplified MUC1 promoter core regulatory region was consistent with the reference sequence. 48 h after transfection of recombinant pDC316-MUC1/hNIS, hNIS protein was positively expressed in CAPAN-Ⅱ and PANC-1 cells, but not in HeLa cells. After transfection of pDC316-MUC1/hNIS, high iodine absorption was detected only in CAPAN-Ⅱ and PANC-1 cells, which was 7 and 12 times that of pDC316-MUC1 transfected group, respectively. Conclusion MUC1 promoter can drive the targeted expression of NIS gene in MUC1-positive tumor cells, which provides a basis for further application of radioiodine targeted therapy for pancreatic cancer in vivo

A 44-year-old male complained of low back pain for 2 years, accompanied by limb weakness for 1 year. Two years ago, he had pain in the waist, groin area and chest without inducement. The chest pain was aggravated during deep breathing and postural change, but did not alleviate after rest.

Multiple sclerosis (MS) is an inflammatory demyelinating disease that occurs in the white matter of the central nervous system (CNS). According to the clinical course of the disease, it can be divided into relapsing-remitting MS (RRMS), primary progressive MS (PPMS) and secondary progressive MS (SPMS).

85% of patients with multiple sclerosis (MS) have the form of acute or subacute neurological dysfunction with single white matter damage, which often manifests as single optic neuritis, an isolated brainstem symptom, or a simple partial spinal cord symptom. This is the so-called clinical isolated syndrome (CIS). Because CIS is often the early clinical manifestation of MS, the study of CIS will provide useful help to prevent the progression of MS.

A 22-year-old male was admitted to the hospital on June 28, 2006 due to nasal congestion, earache accompanied by fever for more than 1 month, epistaxis, blood in sputum for half a month, melena and rash for 3 days. The patient developed sore throat, nasal congestion and watery discharge after catching cold a month ago. A few days later, he felt pain in both ears and tinnitus, and fever appeared at the same time. The body temperature was 37.5~38℃, and the fever pattern was irregular.