No Overlap among Serum GAD65, NMDAR and AQP4 Antibodies in Patients with Neuromyelitis Optica Spectrum Disorders.

OBJECTIVE: To evaluate whether serum glutamic acid decarboxylase (GAD), N-methyl-D-aspartate-receptor (NMDAR), and aquaporin-4 (AQP4) autoantibodies coexist in patients with neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD). METHODS: Serum samples were collected from 98 patients with NMO/NMOSD. Serum GAD65, NMDAR and AQP4 antibodies were measured using a cell-based assay. RESULTS: A total of 63 patients (64.3%) had myelitis and optic neuritis and satisfied the revised diagnostic criteria for NMO. Longitudinally extensive transverse myelitis was seen on spinal cord magnetic resonance imaging, showing continuous T2-weighted signal abnormalities in at least three vertebral segments in 26 patients (26.5%); 5 patients (5.1%) had recurrent optic neuritis, and 4 patients (4.1%) had brain syndromes with optic neuritis and myelitis. None of the 98 patients had diabetes, stiff-man syndrome, or epilepsy. All 98 patients tested positive for AQP4 antibody. No patients tested positive for GAD65 and NMDAR antibodies. CONCLUSIONS: In the present study, we found no simultaneous presence of serum GAD65, NMDAR and AQP4 antibodies in patients with NMO/NMOSD.

Fast fixing and comprehensive identification to help improve real-time ligands discovery based on formaldehyde crosslinking, immunoprecipitation and SDS-PAGE separation.

BACKGROUND: Fast Fixation is necessary to study real-time protein-protein interactions under physiological conditions. Fast formaldehyde cross-linking can fix transient and weak protein interactions, thereby reducing the number of false negatives but producing great complexity. To reduce this complexity, immunoaffinity purification can Fish out complexes that include particular target proteins, but affinity-based co-purification has a limited capacity to eliminate nonspecific binding to beads and/or antibodies. To Filter out these complexes, SDS-PAGE is used to disrupt non-covalent bonds, thereby eliminating uncross-linked complexes and simultaneously providing molecular weight information for identification. RESULTS: We described a 4 F strategy to help improve real-time ligands discovery based on formaldehyde crosslinking, immunoprecipitation and SDS-PAGE separation: Fast Fix, Fish, and Filter, using albumin interactome as an example. The use of gel excision without staining makes this strategy comprehensive and sensitive. The target protein must be identified in the same slice as its ligands. The ligands must be identified in slices for the experimental group but not in the corresponding control slices. Only proteins that appear in the range of molecular weights equal to or greater than the sum of the proteins' theoretical molecular weights, together with the target, are considered ligands. In this study, 5 s of cross-linking with 10% formaldehyde was achieved in human blood. The use of this strategy identified 35 ligands for albumin. Comparison with four major previous studies of the albuminome revealed that 68.57% of the 35 ligands identified in our study were identified in these other studies. CONCLUSIONS: Fast cross-linking was achieved. The 4 F strategy can be used to identify real-time in situ interactions without prior intervention and to comprehensively identify ligands of particular target proteins with fewer false positives.

Dynamic changes of urinary proteins in a focal segmental glomerulosclerosis rat model.

BACKGROUND: In contrast to blood, which has mechanisms to maintain a homeostatic internal environment, urine is more likely to reflect changes in the body. As urine accumulates all types of changes, identifying the precise cause of changes in the urine proteome is challenging and crucial in biomarker discovery. To reduce the effects of both genetic and environmental factors on the urinary proteome, this study used a rat model of adriamycin-induced nephropathy resembling human focal segmental glomerulosclerosis (FSGS) development. RESULTS: Urine samples were collected at before adriamycin administration and day3, 7, 11, 15 and 23 after. Urinary proteins were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Of 23 changed proteins with disease development, 20 have human orthologs, and 13 proteins were identified as stable in normal human urine, meaning that changes in these proteins are more likely to reflect disease. Fifteen of the identified proteins have not been established to function in FSGS development. Seven proteins were selected for verification in ten more rats as markers closely associated with disease severity by western blot. CONCLUSION: We identified proteins changed in different stages of FSGS in rat models, which may aid in biomarker development and the understanding of FSGS pathogenesis.

Comparison at the peptide level with post-translational modification consideration reveals more differences between two unenriched samples.

RATIONALE: In shotgun strategies, peptide sequences are first identified from tandem mass (MS/MS) spectra, and the existence and abundance of the proteins are then inferred from the peptide information. However, the protein inference step can produce errors and a loss of information. To identify the information that is lost using the traditional approaches, this study compared the proteomic data of two leukemia cell lines (Jurkat and K562) at the peptide level with consideration of post-translational modifications (PTMs). METHODS: The raw files from the two cell lines were searched against the decoy IPI-human database version 3.68, which contains forward and reverse sequences. Then the observed modification name in the results was matched with the modification classification on the Unimod website by a manual search. Only the peptides with 'post-translational' modifications were compared between the two cell lines. RESULTS: After searching the database with consideration of PTMs, a total of 44046 non-redundant peptides were identified in both the Jurkat and K562 cell lines. Of these peptides, even without specific PTM enrichment, 11.43% of them (with at least two spectra in one cell line) existed in different PTM forms between the two cell lines, and 1.73% of the peptides were modified in both cell lines, but with different modifications or possibly on different sites. CONCLUSIONS: Comparing proteomic data at the peptide level with consideration of PTMs can reveal more differences between two unenriched samples.

Antineutrophil cytoplasmic antibodies in patients with idiopathic inflammatory-demyelinating diseases.

OBJECTIVE: We assessed the clinical significance of antineutrophil cytoplasm antibodies (ANCA) in patients with idiopathic inflammatory-demyelinating disease (IIDD). METHODS: A consecutive cohort of 269 subjects with IIDD and 595 controls was analyzed retrospectively. RESULTS: Among all subjects, ANCA positivity rates were low [9.5% in a perinuclear pattern (pANCA) and 2.3% in a cytoplasmic pattern (cANCA)]. One of the 117 patients with multiple sclerosis (MS) had cANCA and 2 had pANCA. Ten patients with neuromyelitis optica (NMO; 13.9%) had pANCA and 3 (4.2%) had cANCA. Four patients with recurrent longitudinal extensive transverse myelitis (RLETM; 19.0%) had pANCA and 1 (4.8%) had cANCA. In monophasic TM, 22.9% were pANCA seropositive. Among patients with brainstem syndromes, 14.3% were pANCA seropositive. Patients with NMO, RLETM or monophasic TM had higher pANCA levels than patients with MS. There was a positive association between spinal cord (SC) lesions and ANCA, and especially between longitudinal extensive transverse myelitis and ANCA. Among anti-aquaporin 4 antibody-positive patients, ANCA-positive patients (n = 16) were older and had higher Expanded Disability Status Scale scores, more antinuclear antibodies, longer SC lesions and fewer brain abnormalities than the ANCA-negative patients (n = 68). In the NMO subgroup, ANCA-positive patients were older and had more antinuclear antibodies and longer SC lesions than ANCA-negative patients. CONCLUSION: Among the IIDDs, we found a higher occurrence of ANCA in patients with NMO spectrum disorders than in patients with MS. Therefore, ANCA is another interesting marker of autoimmunity in IIDD patients, especially those with anti-aquaporin 4 antibody.

A tool for biomarker discovery in the urinary proteome: a manually curated human and animal urine protein biomarker database.

Urine is an important source of biomarkers. A single proteomics assay can identify hundreds of differentially expressed proteins between disease and control samples; however, the ability to select biomarker candidates with the most promise for further validation study remains difficult. A bioinformatics tool that allows accurate and convenient comparison of all of the existing related studies can markedly aid the development of this area. In this study, we constructed the Urinary Protein Biomarker (UPB) database to collect existing studies of urinary protein biomarkers from published literature. To ensure the quality of data collection, all literature was manually curated. The website (http://122.70.220.102/biomarker) allows users to browse the database by disease categories and search by protein IDs in bulk. Researchers can easily determine whether a biomarker candidate has already been identified by another group for the same disease or for other diseases, which allows for the confidence and disease specificity of their biomarker candidate to be evaluated. Additionally, the pathophysiological processes of the diseases can be studied using our database with the hypothesis that diseases that share biomarkers may have the same pathophysiological processes. Because of the natural relationship between urinary proteins and the urinary system, this database may be especially suitable for studying the pathogenesis of urological diseases. Currently, the database contains 553 and 275 records compiled from 174 and 31 publications of human and animal studies, respectively. We found that biomarkers identified by different proteomic methods had a poor overlap with each other. The differences between sample preparation and separation methods, mass spectrometers, and data analysis algorithms may be influencing factors. Biomarkers identified from animal models also overlapped poorly with those from human samples, but the overlap rate was not lower than that of human proteomics studies. Therefore, it is not clear how well the animal models mimic human diseases.

Reevaluating the transcranial Doppler criteria for estimation of anterior circulation artery stenosis: transcranial Doppler sonography versus digital subtraction angiography.

OBJECTIVES: The criteria for evaluating cerebral artery stenosis by transcranial Doppler sonography are inconsistent. We aimed to identify the accuracy of transcranial Doppler criteria compared with digital subtraction angiography for diagnosis of anterior circulation artery stenosis. METHODS: A total of 170 patients who underwent transcranial Doppler sonography and digital subtraction angiography were recruited. The anterior circulation arteries were evaluated by transcranial Doppler sonography and digital subtraction angiography. We defined the best cutoff value for substantial anterior circulation artery stenosis by receiver operating characteristic curve analyses and calculated the sensitivity, specificity, and positive and negative predictive values. RESULTS: An anterior circulation artery peak systolic velocity (PSV) of 120 cm/s had the largest area under the receiver operating characteristic curve compared with PSVs of 110, 130, and 140 cm/s and mean flow velocities of 60, 70, and 80 cm/s. The sensitivity, specificity, false-positive rate, false-negative rate, accuracy, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and Youden index for transcranial Doppler sonography were 90.6%, 85.0%, 15.0%, 9.4%, 87.9%, 87.2%, 88.9%, 6.04, 0.11, and 0.756, respectively. The reliability index included the agreement rate and κ value, which were 87.9% and 0.757. CONCLUSIONS: A PSV of 120 cm/s combined with additional parameters was an accurate criterion for diagnosing anterior circulation artery stenosis. Transcranial Doppler sonography could be considered a valuable method for screening diagnosis of cerebral artery stenosis.

Is elevated SUA associated with a worse outcome in young Chinese patients with acute cerebral ischemic stroke?

BACKGROUND: Elevated serum uric acid (SUA) levels can enhance its antioxidant prosperities and reduce the occurrence of cerebral infarction. Significantly elevated SUA levels have been associated with a better prognosis in patients with cerebral infarction; however, the results from some studies on the relationship between SUA and the prognosis of patients with cerebral infarction remain controversial. METHODS: We analyzed the relationship between SUA and clinical prognosis of 585 young Chinese adults with acute ischemic stroke as determined by the modified Rankin Scale at discharge. Using multivariate logistic regression modeling, we explore the relationship between SUA levels and patient's clinical prognosis. RESULTS: Lower SUA levels at time of admission were observed more frequently in the lowest quintile for patients with severe stroke (P = 0.02). Patients with cerebral infarction patients caused by small-vessel blockage had higher SUA concentrations (P = 0.01) and the lower mRS scores (P < 0.01) were observed in, while the lowest SUA concentrations and the highest mRS scores were seen in patients with cardiogenic cerebral infarction patients. Logistic regression analysis adjusted for confounders confirmed the following independent predictors for young cerebral infarction: uric acid (-0.003: 95%CI 0.994 to 0.999) and platelet (0.004, 95%CI 0.993 to 0.996). CONCLUSION: Elevated SUA is an independent predictor for good clinical outcome of acute cerebral infarction among young adults.

Cerebral venous sinus thrombosis may be associated with hepatitis B virus infection: a preliminary finding.

OBJECTIVE: To assess the clinical significance of hepatitis B virus (HBV) infection in patients with cerebral venous sinus thrombosis (CVST). METHODS: Twenty-two patients with CVST confirmed by magnetic resonance venography (MRV) or digital subtraction angiography (DSA) and 743 controls with ischemic stroke confirmed by magnetic resonance imaging (MRI) were analyzed retrospectively. RESULTS: Among all researches, HBV surface antigen (HBsAg)-positive rate was high. Six of the 22 (27.3%) confirmed cases had HBsAg. However, HBsAg-positive rate in patients with ischemic stroke was only 45 of the 743 cases (6.1%), closed to the average prevalence in China (∼ 8.6%), but much lower than the positive rate in CVST patients (27.3 vs 6.1%, P  =  0.002). Odd ratio (OR) value between HBsAg-positive CVST patients (27.3%) and HBsAg-positive ischemic stroke patients (6.1%) was 5.78. The OR value between HBsAg-positive CVST patients (27.3%) and average prevalence of HBV infection in China (8.6%) was nearly 3.99. It meant that HBV infection might be a risk factor for CVST. However, there existed no statistically significant difference in HBV surface antibody (HBsAb), HBV e antigen (HBeAg), HBV e antibody (HBeAb), and HBV central antibody (HBcAb)-positive rate. The HBV surface antigen (HBsAg)-positive CVST patients did not show worse liver function. Most of them were inactive HBV carriers. CONCLUSION: Hepatitis B virus infection may be a risk factor for CVST.

Syndrome of inappropriate antidiuretic hormone secretion in patients with aquaporin-4 antibody.

The objective of this study was to analyze the frequency of syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with positive aquaporin-4 (AQP4) antibodies and evaluate the relationship between SIADH and hypothalamic lesions in patients with NMO and NMO spectrum disorder (NMOSD). AQP4 antibodies were tested by an indirect immunofluorescence assay employing HEK-293 cells transfected with recombinant human AQP4. Clinical data of patients were analyzed retrospectively. In total, 192 patients with AQP4 antibodies were certified, of which 41 patients (21.4 %) were included in the present study. Six patients (14.6 %, 6/41) met the criteria of SIADH, of which hyponatremia was mild in one patient, and severe in five. Five patients experienced confusion or decreased consciousness. Four patients were diagnosed with NMO and two were diagnosed with recurrent optic neuritis. Magnetic resonance imaging showed 11 of 41 patients (26.8 %) had hypothalamic lesions. All patients with SIADH had hypothalamic abnormalities. Hyponatremia resolved in all patients after intravenous methylprednisolone and intravenous immunoglobulin therapy. SIADH is not rare in patients with NMO/NMOSD, especially in patients with lesions close to the hypothalamus.

Clinical manifestations of neuromyelitis optica in male and female patients.

Neuromyelitis optica (NMO) is a severe, idiopathic, immuno-mediated, inflammatory demyelinating disease of the central nervous system. We examined the clinical features between male and female NMO patients, for which not much data exist. One hundred and eight Chinese Han patients with NMO were analysed retrospectively, all had been detected for the aquaporin-4 (AQP4) antibody using a cell-based assay. Of 108 NMO patients, 92 were female and 16 were male (female/male = 5.75). Ninety-four (87%) were positive for the AQP4 antibody in their serum and/or cerebral spinal fluid. Aquaporin-4 antibody-positive NMO patients had a higher female/male ratio than the negative group (P = 0.001). Female NMO patients had a higher positive rate of the AQP4 antibody than male NMO patients (92.4 vs 56.3%, P = 0.001). All NMO male patients were divided according to their AQP4 antibody status. 77.8% (7/9) of patients in the seropositive group had initial optic neuritis, while only one patient (14.3%, 1/7) in the negative group had optic neuritis (P = 0.041). Limb paraesthesia was reported in only one patient in the negative group (11.1%), but it was reported in all patients in the positive group (100%) (P = 0.001). The mean length of vertebral segments of the spinal cord lesions was 3.6 ± 1.3 in the positive group, while it was 6.6 ± 2.6 in the negative group (P < 0.0001). The involvement of the cervical spinal cord was found in 88.9% (8/9) of the positive members, but only 11.1% in the negative group (P = 0.009). However, the involvement of the thoracic spinal cord was found in 22.2% of patients in the positive group and 85.7% of patients in the negative members (P = 0.041). In conclusion, male NMO is rare and has a low positive rate of AQP4 antibody.

Brain gadolinium enhancement along the ventricular and leptomeningeal regions in patients with aquaporin-4 antibodies in cerebral spinal fluid.

BACKGROUND: Aquaporin-4 (AQP4) is densely expressed in the ependymal region and leptomeninges, and it is susceptible to pathological responses triggered by antibodies from blood and cerebral spinal fluid (CSF). Therefore, enhancement of these regions may be related to neuromyelitis optica spectrum disorder (NMOSD). METHODS: MRI from a consecutive cohort of 84 subjects (NMOSD=47, multiple sclerosis [MS]=37) with AQP4 antibodies in serum and CSF were analyzed retrospectively. RESULTS: The brain was normal in five of the 47 patients with NMOSD and none of the MS patients showed a normal brain. Twelve patients in each group had parenchymal enhancing lesions. Of these, white matter enhancement was more frequently found in MS patients than in NMOSD patients (12/12 vs 4/12, p=0.001). "Cloud-like" enhancement was found in three NMOSD patients (3/12) and in one MS patient. Nine of the 12 NMOSD patients showed "pencil-thin" ependymal enhancement, whereas one of the 12 MS patients showed ependymal enhancement (p=0.003). Enhancement along the lateral ventricle was more frequently found in NMOSD patients than in MS patients (p=0.027), whereas enhancing lesions around the fourth ventricle tended to be more frequent in NMOSD patients than MS patients (p=0.097). Leptomeningeal enhancement around the brainstem was found in six (12.8%) NMOSD patients and in no MS patients (p=0.032). CONCLUSION: Enhancement of the leptomeninges and ventricular ependymal region more frequently occurs in NMOSD patients than in MS patients. This may be considered as characteristic clue in the diagnosis of NMOSD.

The association baseline NIH Stroke Scale score with ABO blood-subtypes in young patients with acute ischemic stroke.

OBJECTIVES: The presence of the A and B blood group antigens has been associated with risk of arterial thrombosis. The aim of the current study was to design a new simpler form of National Institutes of Health Stroke Scale (NIHSS) for use on admission, and assess the association of blood groups with NIHSS score in young stroke patients. METHODS: We conducted this study in 1311 young Chinese adults with acute ischemic cerebral stroke. The outcome measures included a composite favorable outcome (defined as a modified Rankin Scale (mRS) of 0 or 2) and poor outcome (defined as a modified Rankin Scale score of 3 or 6) at discharge; a minor strokes (NIHSS scores 0-5) and severe strokes (NIHSS scores ≥6). Logistic regression analyses were used to determine the association between ABO blood groups and stroke severity. RESULTS: Regression analysis confirmed in relative to patients with AB subtype, Oxfordshire community stroke project classification (OCSP) subtype and serum white blood cell (WBC) were the major predictors for stroke severity. Meanwhile, diabetes, serum triglyceride and uric acid levels were determined as independent indicators of stroke severity in A, B and O blood subtype respectively. The optimal cutoff score of the baseline NIHSS was ≤5 for patients with non-O subtype, the optimal cutoff score of the baseline NIHSS was ≤7 for patients with blood O subtype. CONCLUSIONS: Our analysis provide compelling information regarding the ABO blood groups differences in predictors of stroke severity and the different validity of NIHSS scores in predicting prognosis at discharge between O subtype and non-O subtype.

The potent different risk factors for cerebral infarction in young patients with and without type 2 diabetes: subanalysis of the Young Cerebral Infarction Study (YCIS).

BACKGROUND: To compare risk factors, stroke characteristics, and short-term prognosis between diabetic and nondiabetic young ischemic stroke patients to provide information for patient management, counseling, and future research in these patient groups. METHODS: All consecutive patients between the ages of 18 and 45 years with first-ever cerebral infarction during 2001-2010 were recruited to participate in the study. Using multivariate logistic regression modeling, demographic characteristics, cerebrovascular risk factors, clinical events, stroke subtypes, and outcome in ischemic stroke patients with and without diabetes were compared. RESULTS: Logistic regression analysis adjusted for confounders confirmed the following independent susceptibility markers: in a substudy of young patients with and without diabetes, the predictors of short-term outcome were more likely to be TOAST subtype, initial stroke severity and serum uric acid, and age at onset, dyslipidemia, initial stroke severity and serum fibron levels correlate with a higher risk for incident stroke in young with diabetes. CONCLUSION: Our findings suggest that diabetic and nondiabetic ischemic stroke patients exhibit a distinct risk-factor and etiologic profile and may help clinicians to assess prognosis more accurately.

Different independent susceptibility markers for first-ever cerebral infarction and myocardial infarction in young patients.

Cerebral infarction (CI) and myocardial infarction (MI) share some common features, but there are other differences in risk factors. The aim of our study is to determine whether there are some significantly independent susceptibility markers for them. All consecutive patients between the ages of 18 and 45 years with first-ever CI and MI during 2001-2010 were recruited to participate in the study. Using multivariate logistic regression modeling, we explore many different data, such as age at onset, sex ratio, numbers of patients with history of hypertension, smoking, drinking, and serum lipid, uric acid, prealbumin (PA), and white blood cell (WBC) count levels. Logistic regression analysis adjusted for confounders confirmed the following independent susceptibility markers for young CI patients: hypertension, admission serum PA levels, daily alcohol [odds ratio (OR), 0.251; 95% confidence interval (CI), 0.097-0.648, p = 0.004; OR, 0.994; 95% CI, 0.988-0.999, p = 0.031; OR, 0.150; 95% CI, 0.047-0.473, p = 0.001], and for MI patients: age at onset, current smoking, serum WBC, and glucose levels (OR, 1.293; 95% CI, 1.146-1.457, p = 0.000; OR, 8.914; 95% CI, 3.575-22.231, p = 0.000; OR, 1.344; 95% CI, 1.169-1.544, p = 0.000; OR, 1.149; 95% CI, 1.022-1.291, p = 0.020). We conclude that there are some significantly different independent susceptibility markers for young CI and MI patients.

Serum prealbumin (transthyretin) predict good outcome in young patients with cerebral infarction.

Low serum protein and albumin are considered to significantly associate with malnutrition, impaired functional status, poor outcome, and mortality. We hypothesized that serum prealbumin (transthyretin, PA) was a reliable and robust survival marker in young cerebral infarction patients and attempted to test the foregoing hypothesis. We analyzed the relationship between serum PA and stroke severity as determined by the modified Rankin Scale at discharge in 585 young cerebral infarction patients. By multivariate logistic regression modeling, we determined the influence of prealbumin on stroke severity, and the analyses were adjusted for the effects of potential confounders. Patients with a severe stroke had significantly more often prealbumin on admission in the lowest quintile (P = 0.031). Those cardiogenic cerebral infarction patients had significantly lower serum prealbumin concentrations and higher mRS scores. A logistic regression adjusted for confounders confirmed the following independent (odds ratio, 95% CI) good outcome predictors: uric acid (-0.002, 0.996-1.000) and prealbumin (-0.003, 0.995-1.000). Prealbumin is an independent predictor of the good clinical outcome of young cerebral infarction patients. The serum prealbumin may be a useful prognostic indicator for judging the prognosis of cerebral infarction.

Sex differences in risk factors, etiology, and short-term outcome of cerebral infarction in young patients.

Investigations to date have demonstrated that the underlying etiology, causes and burden of stroke may be different for women and men. However, data regarding sex differences among young cerebral ischemic stroke patients remains scarce. We conducted this study in 669 young Chinese adults with acute ischemic stroke as determined by the modified Rankin Scale at discharge. Stepwise multiple logistic regression analysis confirmed that NIHSS score (OR 1.277; 95% CI 1.179-1.383, p=0.000), diabetes mellitus (OR 0.121; 95% CI 0.0209-0.718, p=0.020) and serum glucose levels on admission (OR 1.135; 95% CI 0.997-1.293, p=0.046) independently predict short-term outcomes at discharge in young female patients with acute stroke, but the significant variables related to male patients appeared to be Apo A1 (OR 0.165; 95% CI 0.035-0.776, p=0.023) and NIHSS score on admission (OR 1.458; 95% CI 1.325-1.605, p=0.000). In our series, our data suggest that there are several sex differences for risk of cerebral infarction in young patients, which have important implications for the diagnosis, management and prognosis of stroke in young adults.

Admission markers predict lacunar and non-lacunar stroke in young patients.

Stroke in young adults is an important cause of lifelong morbidity. The aim of this study was to explore some possible admission indicator of subsequent lacunar or non-lacunar strokes. We enrolled 626 patients with the first young cerebral strokes and divided them into lacunar and non-lacunar stroke based on clinical presentation and neuroradiological findings; and the analyses were adjusted for the effects of potential confounders. Hypertension, hyperlipidemia, atrial fibrillation, cerebral vascular moyamoya malformation were significantly more frequent in non-lacunar patients than lacunar patients (respectively P=0.005, 0.048, 0.000, 0.015, 0.030). Serum BUN, Triglyceride, Cholesterol, HDL, UA, White cell count, Fibrinogen, INR and bilirubin (including Total bilirubin, Direct bilirubin, Indirect bilirubin) levels on admission were higher in non-lacunar strokes than in lacunar strokes. Serum white blood cell count (Odds Ratio 1.097; 95% Confidence Interval 1.006-1.195, P=0.035), lower high-density lipoprotein levels (defined as HDL<0.9 mmol/L) (Odds Ratio 1.884; 95% Confidence Interval 1.035-3.285, P=0.038) and serum total bilirubin (Odds Ratio 1.054; 95% Confidence Interval 1.019-1.091, P=0.003) were associated with increased risk for non-lacunar stroke, whereas lacunar stroke was related to age at onset (Odds Ratio 0.929; 95% Confidence Interval 0.888-0.972, P=0.001) and SUA (Odds Ratio 0.997; 95% Confidence Interval 0.995-0.999, P=0.015). The excess risks were blood WBC, lower HDL and total bilirubin levels for non-lacunar strokes, and serum UA and age at onset for lacunar strokes in young Chinese patients.