Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Epidemiological investigation of tinnitus in Sichuan and Chongqing / 中华耳鼻咽喉头颈外科杂志

Objectives: To investigate the prevalence and associated risk factors of tinnitus in Sichuan and Chongqing. Methods: We designed a tinnitus epidemiological questionnaire. The multi-stage stratified cluster random sampling methods was applied to obtain study subjects in six areas (Nanchong, Jiangjin, Fengdu, Yunyang, Suining and Ya'an), which were selected for epidemiological investigation. Home visit completion of epidemiological questionnaires was conducted. The trained investigators guided the respondents to fill in the tinnitus epidemiological questionnaires, and the epidemiological status of six areas on prevalence and risk factor was investigated. SPSS 22.0 software was used for statistical analysis. Results: Sampling population were 10 289, in which 9 273 were valid questionnaires. There were 4 281 males and 4 992 females, with an average age of 47.3 years, among which 34.83% (3 230/9 273) had tinnitus. 3.99% (370/9 273) were diagnosed with bothersome tinnitus. In a multivariable logistic regression mod, the following factors were associated with onsetting of tinnitus: sleep disorder [Odds Ratio(OR)=3.74] and noise exposure(OR=1.99). The risk of disease was lowest in the age of 30-40 years old, while the risk of disease was higher for people under 30 and over 40. In another multivariable logistic regression mode, the following factors were associated with having bothersome tinnitus: older people were more likely to suffer from tinnitus, sleep disorders (OR=4.68) and noise exposure (OR=1.56). Conclusions: The prevalence of tinnitus in Sichuan and Chongqing is about 34.83%, but most of the tinnitus is short-lived and has low loudness, which will not affect the patients. Only a small number of patients with tinnitus (3.99%) persist and affect their health and need treatment. The occurrence and exacerbation of tinnitus may be related to sleep, age, and noise exposure.

The HLA-B*4601-DRB1*0901 haplotype is positively correlated with juvenile ocular myasthenia gravis in a southern Chinese Han population.

Myasthenia gravis (MG) is a sporadic disorder that has been increasingly linked to inherited genetic factors. Previous studies have demonstrated that human leukocyte antigen (HLA) plays an important role in the pathogenesis of MG. We determined the genotypes of the HLA-A, B, and DRB1 alleles in 257 southern Chinese Han MG patients using polymerase chain reaction sequence-based typing (PCR-SBT). The allele frequencies in the MG patients were compared to 292 healthy controls using the case-control method. HLA-A*0207, HLA-B*4601, HLA-DRB1*0403, HLA-DRB1*0901, and HLA-DRB1*1602 were more frequent in juvenile ocular MG patients than controls. HLA-DRB1*0701 was significantly reduced in the juvenile ocular MG group compared with controls. HLA-A*0207-B*4601, HLA-B*4601-DRB1*0403, HLA-B*4601-DRB1*0901, and HLA-B*4601-DRB1*1602 were found to be in strong linkage disequilibrium in juvenile ocular MG patients. Within the MG patients, there was a strong positive association between HLA-B*4601-DRB1*0901 and juvenile ocular MG patients, and the value of odds ratios (OR) decreased as the disease became more severe and the age of onset increased. We believe this could be the main heredity phenotype in juvenile ocular MG patients from southern China and may be a clinical marker to predict the severity of the disease.

The high frequency and clinical feature of seronegative myasthenia gravis in Southern China.

Anti-acetylcholine receptor antibodies (anti-AChR-Ab) are responsible for the failure of neuromuscular junction in myasthenia gravis (MG). Some anti-AChR-Ab-seronegative MG patients have anti-muscle-specific tyrosine kinase antibodies (anti-MuSk-Ab). Here, the anti-AChR-Ab was tested in 250 MG outpatients from Southern China. While anti-MuSk-Ab was tested in 66 patients who had no anti-AChR-Ab in blood serum, but none of them was positive. The antibodies were measured by a radioimmunoprecipitation assay. The frequency of anti-AChR-Ab was 51.2 %. The percentage of anti-AChR-Ab in ocular type was lower than generalized type (44.9 vs. 66.2 %, P = 0.002). Seronegative MG was characterized by a lower percentage of thymoma than seropositive patients (P = 0.013). It seemed to be less severe in seronegative MG than seropositive MG in these 250 patients. In ocular type, seronegative MG mainly manifesting blepharoptosis but seldom diplopia or eyeball fixation related to ocular movement disability (P = 0.016). While in generalized type, seronegative MG was characterized by a lower percentage of bulbar muscle involvements than seropositive patients (P = 0.005). Logistic regression analysis revealed that bulbar weakness was affected by the existence of anti-AChR antibodies (OR = 3.524, P = 0.015). Besides, seronegative MG tended to be characterized by a lower percentage of neck extensor involvement, but this did not reach significance. The percentage of anti-AChR antibodies was much lower than other countries. Seronegative MG has characteristic clinical features that are different from features of the remaining seropositive MG. This emphasises the predictive value of anti-AChR antibodies analysis in MG patients.

[Efficacy and safety of low-dose cyclophosphamide plus corticosteroids for type I/II myasthenia gravis].

OBJECTIVE: To evaluate the efficacy and safety of low-dose cyclophosphamide plus corticosteroids for type I/II myasthenia gravis (MG). METHODS: This trial was prospective, non-random and open-labeled. We selected 160 patients with steroid-insensitive MG from January 1999 to October 2011. Each patient received an oral dose of prednisone 0.5 mg×kg(-1)×d(-1), cyclophosphamide 8 mg×kg(-1)×time(-1) once weekly intravenously and oral pyridostigmine 36 mg×kg(-1)×d(-1). The efficacies were assessed by absolute and relative MG scores. The clinical treatment cycle was 30 weeks. RESULTS: (1) Among them, 74/106 type I MG patients (69.9%) reached clinical relative scores ≥ 95% in 30 weeks. The total dose of cyclophosphamide was 12 g. And 35/54 type II MG patients (64.8%) reached clinical relative scores ≥ 95% in 30 weeks. No statistically significant difference existed between two groups (P = 0.521). (2) All patients had various degrees of improvement in 30 weeks. The difference was statistically significant by Mann-Whitney U test (P ≤ 0.05). (3) There were minor side effects in these all patients. (4) When the total dose of cyclophosphamide reached 4 g, the cure rate in type I patients was higher than that of in type II patients (P = 0.000). When the total dose of cyclophosphamide reached 12 g, the cure rate in type II patients was higher than that of in type I patients (P = 0.001). (5) The cure dose of cyclophosphamide was 4-8 g in 58.4% of type I patients versus 8 - 12 g in 61.1% of type II patients. CONCLUSION: The combined treatment of low-dose cyclophosphamide and corticosteroids in glucocorticoid-insensitive type MG (type I/II) is both effective and safe. And the sensitivity to cyclophosphamide varies for different clinical types. It is higher in type I than type II patients.

[Randomized controlled clinical trial of middle-dose cyclophosphamide plus methylprednisolone for myasthenia gravis patients in crisis].

OBJECTIVE: To evaluate the efficacy and safety of middle-dose cyclophosphamide plus methylprednisolone for myasthenia gravis (MG) patients in crisis. METHODS: For this prospective, open, parallel, randomized controlled trial, we recruited a total of 156 MG patients in crisis from January 1999 to October 2011 at Department of Neurology, First Affiliated Hospital, Sun Yat-sen University. They were divided into two groups of cyclophosphamide and control (n = 78 each). In the cyclophosphamide group, each received methylprednisolone 500 mg/d for 3 days, then tapered to 250 mg/d and tapered half every 3 days until 62.5 mg/d. Afterward an oral dose of prednisone was prescribed at 30 mg/d until the end of the trial. At the same time, an intravenous injection of cyclophosphamide was offered at 0.4 g/d for 3 days and then 0.4 g/d every 3 days. In the control group, each received methylprednisolone alone. And the efficacies were assessed by absolute and relative MG scores. RESULTS: (1) There were 54 (69.2%) patients off-ventilation in 3 days in the cyclophosphamide group versus 36 (46.2%) patients in 8 - 14 days in the control group. Notable statistical significance existed between two groups (P = 0.000). (2) More than half of the patients in cyclophosphamide group with extremity weakness (n = 44, 56%) and dysphagia (n = 47, 60.3%) significantly improved in 10 - 14 days versus 28 days in the control group. Notable statistical significance existed between two groups (P = 0.000). (3) In the cyclophosphamide group, dyspnea disappeared in 54 (69.2%) patients when the dose reached 1.2 g. The recovery of dysphagia (n = 47, 60.3%) and extremity weakness (n = 44, 56.4%) occurred in more than half of the patients when the dose reached 2.8 g. Notable statistical significance existed among three groups (P = 0.000). (4) During the treatment period, there were 17 cases (21.8%) with pulmonary infection in the cyclophosphamide group versus 53 cases (67.9%) in the control group. Notable statistical significance existed between two groups (P = 0.000). (5) Brief and minor side effects appeared in the patients of the cyclophosphamide group. CONCLUSION: (1) The combined treatment of middle-dose cyclophosphamide and methylprednisolone for MG patients in crisis is both effective and safe. (2) When combined with methylprednisolone, 90% of patients with MG crisis are successfully off-ventilation when the dose of cyclophosphamide reaches 1.6 g.

[Response to thymectomy and analysis of influencing factors in the treatment of children with myasthenia gravis].

OBJECTIVE: To evaluate the efficacy of thymectomy and relevant influencing factors in the treatment of children with myasthenia gravis through a long-term follow-up. METHODS: The clinical records of 59 patients undergoing expanded thymectomy for the treatment of myasthenia gravis (MG) between January 2003 and August 2009 were reviewed retrospectively. Their postoperative outcomes were categorized into complete stable remission (CSR), pharmacological remission (PR), improvement, no change and deterioration (including mortality). RESULTS: During a median follow-up period of 35 months, none of them died or deteriorated clinically among 53 patients with a postoperative follow-up. The overall remission rate was 69.8% and the effective rate 90.6%. No symptomatic relapse occurred among 16 patients in CSR. None of the ocular patients progressed to generalized MG while 16 thymectomized generalized MG developed from ocular MG. Both univariate and logistic regression analyses revealed that the preoperative duration of illness influenced the surgical curative effect (P < 0.05). Survival analysis indicated that the rates of overall remission were 56% or 88% at 24 months and 42% or 75% at 48 months among ocular MG and generalized MG respectively. According to Log-rank analysis, no difference in remission existed between two types of MG. CONCLUSION: Thymectomy is an effective and safe treatment in selected MG children, especially in those with a shorter illness duration.

A retrospective review of 15 patients with familial myasthenia gravis over a period of 25 years.

We observed, during a 25-year period, 15 patients from 6 families with autoimmune myasthenia gravis (all Chinese Han from Guangdong Province) referred to our department. Their mean onset age was 13.4 years (range 2-25 years) with 10 patients with juvenile onset. The female:male ratio was 3:2. Acetylcholine receptors antibody titers were increased in 11 patients (range 1.62-19.8 nmol/L). Thymectomy was performed in six patients, who received corticosteroids /immune inhibitor plus pyridostigmine treatments after surgery. The other patients were placed on therapy with azathioprine, cyclophosphamide, corticosteroids and acetylcholinesterase inhibitors. All patients responded well to immunosuppressants, and psychiatric symptoms were observed only in one patient who received a high dose of corticosteroids. Patients with generalized type in the same family had different presentations with variable prognosis. HLA-A 0207 was found in 9 patients (9/15), HLA-B 4601 in 11 patients (11/15), and HLA-DRB1 0901 in 12 patients (12/15). When compared to familial autoimmune myasthenia gravis in other countries, we observed peculiar characteristics of Chinese populations, such as the within-family consistency was only found in families with ocular MG type (50% of all MG families), while the pathogenetic conditions and the prognoses of the generalized MG patients may differ greatly within the same family. These findings may shed new light on the genetic predisposition and the origin of immune abnormalities of MG patients.

[Clinical study and case follow-up of 61 cases of familial myasthenia gravis in 28 families].

OBJECTIVE: To explore the clinical features and prognosis of familial myasthenia gravis (FMG). METHODS: The clinical data were collected and analyzed for 61 FMG patients from 28 families from February 1998 to March 2009 at the department of neurology, First Affiliated Hospital, Sun Yat-sen University. And they were compared with 257 cases of sporadic myasthenia gravis (MG) by case-control method. Age at onset, gender, Osserman clinical classification, diagnosis, treatment, thymus imaging examination, prognosis and other family members were measured retrospectively. RESULTS: (1) The proportion of FMG in Southern China was 2.03% and it was lower than the other countries. (2) Onset age was younger in FMG than in sporadic MG. Juvenile MG was more common in FMG than in sporadic MG (70.5% vs 52.1%, P = 0.009). (3) Ocular MG was more common in FMG than in sporadic MG (83.6% vs 62.7%, P = 0.002). (4) There was a higher proportion in FMG with thymic hyperplasia than in sporadic MG (98.3% vs 83.7%, P = 0.014). (5) Better prognosis was found in FMG than in sporadic MG. FMG patients had a higher proportion of completely stable remission than sporadic MG (24.5% vs 11.7%, P = 0.009). (6) The so-called "consistency of the same disease" could only be found in families with pure ocular diseases. If the patients with general type MG were present in the family, their pathogenetic conditions and prognosis might vary greatly. CONCLUSION: There characteristics of FMG in south China are different from those of other countries. Their exact inheritance patterns await further explorations.

[Correlation study between Chinese myasthenia gravis patients from Guangdong province and the polymorphism of HLA immunogene].

OBJECTIVE: To explore the correlation between Chinese myasthenia gravis (MG) patients from Guangdong province and the polymorphism of HLA immunogene. METHODS: The genotypes of HLA-A, B and DRB1 alleles in 104 MG patients and 121 healthy blood donors were detected by PCR-SBT (polymerase chain reaction-sequencing-based typing). RESULTS: (1) There were 15 alleles at A locus, 32 at B locus and 23 at DRB1 locus in MG group. (2) The frequency of HLA-A*02:07(P = 0.000, RR = 3.715), -B*46:01(P = 0.000, RR = 5.698), -DRB1*04:03(P = 0.033, RR = 6.312), -DRB1*09:01(P = 0.000, RR = 5.884) in MG patients was higher than that in healthy controls. (3) There were positive associations of HLA-DRB1*09:01(P = 0.000, RR = 1.349) with juvenile-onset ocular MG. CONCLUSION: There is susceptibility association of HLA-A*02:07, -B*46:01, -DRB1*04:03, -DRB1*09:01 with Chinese MG patients from Guangdong province. There is a close genetic and immunological correlation between HLA alleles and the pathogenesis of MG. It has directional significance in the race and region incidence study, clinical classification, differential diagnosis, treatment and prognosis of MG.

[Therapeutic efficacy and safety of tacrolimus for intractable myasthenia gravis: a report of 36 patients].

OBJECTIVE: To examine the efficacies and adverse events of low-dose tacrolimus in intractable myasthenia gravis (MG) patients during a long-term follow-up. METHODS: Tacrolimus was administered at 0.1 mg×kg(-1)×d(-1) to 36 generalized or ocular MG patients at our department from November 2008 to December 2010. The efficacies of tacrolimus were assessed by the myasthenia gravis activities of daily living (MG-ADL) profile and the classification of Myasthenia Gravis Foundation of America (MGFA). And the adverse events of tacrolimus were monitored in each patient. RESULTS: (1) All patients were followed up for 7 - 23 months. Adverse events occurred in 6 patients (16.67%). (2) The myasthenic symptoms improved up to the levels of MG-ADL and MGFA in 24 patients (66.67%). There was notable statistical significance in the comparison of clinical status at pre- and post-treatment (P = 0.000). (3) The efficacies in patients with generalized MG were better than those with ocular MG (P = 0.032). (4) The average blood trough levels of tacrolimus were lower than the recommended maintenance range from other countries in 24 effective patients. CONCLUSION: The administration of tacrolimus induces symptomatic improvements in MG patients especially in generalized type. And the adverse events should be closely monitored.

[Roles of Bacillus Calmette-Guérin with immunological memory in the pathogenesis of myasthenia gravis].

OBJECTIVE: To explore the roles of immunological memory in the pathogenesis of myasthenia gravis (MG) by Bacillus Calmette-Guérin (BCG). METHODS: For this randomized comparative clinical trial, 58 newly diagnosed MG patients and 32 age-and-gender-matched healthy controls were analyzed by purified protein derivative (PPD) test. The results were observed after 72 hours. peripheral blood mononuclear cell (PBMC) was collected from the MG patients before and after extended thymectomy and cultured with BCG. After a 72-hour incubation, the level of interferon gamma (IFN-γ) was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: In PPD test, the MG patients did not show a markedly higher positive percentage [48.3% (28/58) vs 65.6% (21/32), P = 0.114]. The pre-thymectomy PBMC had a higher level of IFN-γ than the control group: (650 ± 312) pg/ml vs (346 ± 153) pg/ml. After extended thymectomy, the level of IFN-γ returned to normal: (219 ± 113) pg/ml. The P value is 0.003, 0.001. CONCLUSION: The impairment of immunological memory, may be an important pathogenic cause of relapse in the MG patients.

[Analysis of prognostic factors and efficacy of plasmapheresis in the treatment of myasthenia crisis].

OBJECTIVE: To examine the prognostic factors and efficacy of myasthenia gravis (MG) in crisis on plasmapheresis and detect the reasons for ineffective plasmapheresis. METHODS: The investigators analyzed a total of 69 MG patients in crisis on plasmapheresis by case control study. Gender, age at onset of myasthenic symptoms, duration between the onset of crisis and plasmapheresis, pre-therapeutic use of glucocorticoids, pulmonary infections, other complications, nutritional status, history of thymectomy in 48 hours before crisis, thymic pathology, combined intravenous immunoglobulin (IVIG) and total sessions of plasmapheresis were measured retrospectively. RESULTS: Univariate analysis showed that pulmonary infections (P = 0.000, OR = 29.250), history of thymectomy in 48 hours before crisis (P = 0.046, OR = 0.267), combined intravenous immunoglobulin (P = 0.003, OR = 0.136) and total sessions of plasmapheresis (P = 0.022, OR = 0.498) were all influencing factors of plasmapheresis. However the analysis of multivariate logistic regression revealed that pulmonary infections (P = 0.000, OR = 23.600) was an independent risk factor and combined intravenous immunoglobulin (P = 0.047, OR = 0.192) was an independent protection factor of plasmapheresis. CONCLUSION: Plasmapheresis is ineffective in MG crisis with pulmonary infections. Control of pulmonary infections and combined intravenous immunoglobulin can improve the response to plasmapheresis in patients with MG crisis.

[Study of incidence and correlation factors of depression, anxiety and insomnia in patients with myasthenia gravis].

OBJECTIVE: To investigate the incidence rate and correlation factors of depression, anxiety and insomnia in patients with myasthenia gravis (MG). METHODS: A total of 161 MG patients were assessed and graded with HAMD, HAMA, PSQI, QMG, ADL and a self-made scale chart. And the correlation factors were analyzed by Logistic stepwise regression. RESULTS: The prevalence of depression, anxiety and insomnia was 58.3%, 45.3% and 39.1% respectively. The correlation factors with significant influences on MG were as follows: depression with age, physical weakness, score of QMG, life scale grading; anxiety with experience-sharing; insomnia age, dyspnea, thymoma, physical status at 1 month post-operation, prednisone dose and score of QMG. CONCLUSION: Nearly one half of the MG patients suffer from affective disorders to different degrees. And an analysis of its correlation factors provides references to prevent and treat the affective disorders concurrently with MG.

[The role of CD4+ CD25+ T cells in the mechanism of myasthenia gravis in children and adults].

OBJECTIVE: To investigate the role of CD4+CD25+ regulatory T cells in the mechanism of myasthenia gravis (MG) in children and adults. METHODS: Peripheral blood samples were collected from 13 MG patients, 5 being aged > 14 and 8 being aged

[Correlation between pathogenesis of myasthenia gravis and thymus mature dendritic cells].

OBJECTIVE: To investigate the correlation between onset of myasthenia gravis (MG) and the changes of the number and distribution of thymus mature dendritic cells (mDC). METHODS: The specimens of thymus were obtained during operation from 39 MG patients who hadn't received immunosuppressive therapy before thymectomy and 19 sex- and age-matched patients who underwent cardiosurgery as controls. Immunohistochemistry with antibody against DC-LAMP, specific surface marker of DC, was used to examine the number and distribution of thymus mDCs. RESULTS: (1) mDCs were restricted in the medulla and cortex-medulla junctional zone of thymus in the control group; while were irregularly distributed in the cortex, medulla, and stroma in the MG group. (2) mDCs presented a roughly uniform distribution in the medulla of thymus in the control group, while clustering distribution was more often in the MG group, especially dense around the germinal center. (3) The relative ratio and numbers of mDCs per average field of vision in the positive areas of the MG group were (10.9% +/- 2.2%) and (50 +/- 9), both significantly higher than those of the control group [(8.5% +/- 1.5%) and (41 +/- 7) respectively, both P < 0.05]. CONCLUSION: The number and ratio of the thymus mDCs in MG are high, high, and the distribution abnormal. mDC actively may be actively involved in the pathogenesis of MG.

[Association between angiotensin-converting enzyme and polymorphisms of N5, N10-methylenetetrahydrofolic acid reductase gene in patients with ischemic stroke].

OBJECTIVE: To explore the association between angiotensin-converting enzyme (ACE) and the polymorphisms of N5, N10-methylenetetrahydrofolic acid reductase (MTHFR) gene in patients with ischemic stroke (IS). METHODS: Totally 454 patients with IS (IS group) and 334 controls (control group) were recruited in our study. Their I/D polymorphisms of ACE gene and C677T polymorphisms of MTHFR gene were detected by PCR and denaturing high performance liquid chromatography. RESULTS: The frequencies of DD, ID, II and CC, CT, TT genotype in IS group were 22.5%, 43.4%, 34.1%, and 51.8%, 40.5%, 7.7%, respectively, and were 17.4%, 45.5%, 37.1% and 56.9%, 38.3%, 4.8% in the control group, respectively. DD genotype was associated with large-artery atherosclerosis (LAA), and TT genotype and T allele were associated with LAA and cardioembolism. Synergistic effects were found between TT and DD/ID DD genotypes in the pathogenesis of ischemic stroke. CONCLUSION: DD, TT genotype and T allele are risk factors of IS, and ACE gene and MTHFR gene have synergistic effects in the pathogenesis of IS.

[Relationship between angiotensin converting enzyme gene and ischemic stroke].

OBJECTIVE: To study relationship between angiotensin converting enzyme (ACE) gene and ischemic stroke (IS). METHODS: (1)Four hundred and fifty-four patients and 334 controls were recruited in our study, their I/D polymorphisms of ACE gene were detected by polymerase chain reaction (PCR) and denaturing high performance liquid chromatogram, and their risk factors of IS were recorded at the same time. (2)In addition, 29 stroke-prone spontaneously hypertensive rats (SHR-SP) and 40 Sprague-Dawley (SD) rats were enrolled, and hypoxia- apnoea animal models and simple apnoea animal models were used at the same time. Their plasma angiotensin II (Ang II) levels were determined. RESULTS: The frequencies of DD, ID and II genotype in IS patients were 22.5%, 43.4% and 34.1%, respectively, and 17.4%, 45.5% and 37.1%, respectively in controls. DD genotype was associated with large artery arteriosclerosis (LAA). Plasma Ang II level in SHR-SP group was (164.49+/-34.58) ng/L, and it was higher than that in control group [(150.92+/-24.92)ng/L] with no significant difference (P>0.05). Ang II levels in apnoea and hypoxia-apnoea group were (382.84+/-62.75) ng/L and (295.90+/-55.07) ng/L, respectively, and they were significantly higher than that in control group (all P<0.01). The relative risks of DD genotype and D alleles in IS patients with smoking, alcohol abuse, or with diabetes mellitus were higher than those in controls, but II genotype and I alleles were lower than those in controls. CONCLUSION: DD genotype is a risk factor for IS, Ang II takes part in the course of hypoxia-stress, and it is correlated with smoking, alcohol abuse and diabetes mellitus in the pathogenesis of IS.