Objective:To enhance the functional safety of medical electrical equipment and reduce the risk to patient when using the medical electrical equipment.Methods: Theory and rationale introduction of functional safety and provide application cases.Results: Introduce the definition and application scope of functional safety standards IEC 61508, the determination of safety integrity level of functional safety in the Medical Electrical equipment, and the design structure and development, meanwhile show some application examples.Conclusion: Provide suggestions for the manufactures for safety design that introduce functional safety standards IEC 61508 to the development process of Medical Electrical equipment will help enhance the safety level of Medical Electrical equipment and reduce the unacceptable risk’s probability to patient.

Objective To study the variations of hypothalamus pituitary-gonad axis in Tibetan male patients with hepatic diseases and to understand the serum levels of gonadal hormone in different hepatic diseases.Methods We randomly selected 93 Tibetan male hepatic patients from Tibet Autonomous Region.The types of hepatic diseases included hepatitis A,hepatitis B,alcoholic hepatitis,cirrhosis and serious hepatitis.Meanwhile we selected 19 healthy Tibetan males as controls from the same region.We detected the serum levels of testoid (T),estradiol (E 2),follicle-stimulating hormone (FSH),luteinizing hormone (LH),prolactin (PRL) and luteinizing hormone-releasing hormone (LHRH).Statistical analysis was performed by double t-test.Results The serum levels of E 2,PRL and LHRH were all significantly different in patients with hepatic disease compared with the control.(P

Objective To elucidate the relationship between polymorphisms of NRAMP1 gene and susceptibility to tuberculosis in Chinese Han nation by case control study. Methods We selected 127 patients with active pulmonary tuberculosis who were all Han people with mean age of 52.5 years and 58 ethnically matched healthy controls. We typed the polymorphisms of NRAMP1, INT4 and D543N, through polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) techniques. Results Two NRAMP1 polymorphisms were both significantly associated with smear positive pulmonary tuberculosis. Subjects who were heterozygous for polymorphisms in INT4 and D543N were related with tuberculosis. It was the cooperation of different polymorphisms of NRAMP1 that led to the susceptibility to tuberculosis. Conclusions The polymorphisms in NRAMP1 gene affect susceptibility to tuberculosis in Han people in China.

Objective To develop a new multiplex allele-specific PCR(MAS-PCR) assay to detect mutation in codon 315 of katG gene of Mycobacterium tuberculosis , mutation in this codon has been reported to be able to account for the Mycobacterium tuberculosis clinical isolates resistant to isoniazid(INH).Method Based on the sequence of katG gene of Mycobacterium tuberculosis , three specific primers are designed to carry out the MAS-PCR, 84 purified DNA preparation with known katG 315 variation detected by PCR-restriction fragment length polymorphism (PCR-RFLP) are used to optimize PCR.Results 84 Mycobacterium tuberculosis clinical stains are detected by the MAS-PCR and PCR-RFLP, respectively.The sensitivity of detection by MAS-PCR is 77.8%,and the specificity is 95.2%.katG mutation S315N(AGC→AAC), neglected in RFLP, can be detected by MAS-PCR.Conclusion MAS-PCR assay is sensitive, specific, economic and easy to carry out , can be used in clinical laboratories to detect the INH-resistant Mycobacterium tuberculosis strains.

Objective To investigate the incidence of Mycobacterium tuberculosis (TB) infection among human immunodeficiency virus (HIV)-infected individuals in Shanghai and Yunnan Province and to analyze the risk factors of TB infection.Methods Seventy HIV-infected individuals from Yunnan Province and 67 from Shanghai were enrolled.T-SPOT.TB was employed to detect TB-specific T cells in the peripheral blood mononuclear cells (PBMC).CD4+ and CD8+ T cells in PBMC from the enrolled subjects were detected by flow cytometry.Data were analyzed using Mann-Whitney test,Fisher's exact test and Logistic regression.Results The incidence of latent tuberculosis (LTB) infection among HIV-infected individuals in Yunnan Province was 64.3 ％ (45/70),which was much higher than Shanghai (20.8％ [14/ 67]).The median CD4+ T cell count of HIV-infected individuals with LTB infection in Yunnan Province was 509/μL,while that in Shanghai was 324/μL,which was significant different (U=148,P=0.003).The median CD4+ T cell count in HIV single infected individuals from Yunnan Province was 418/μL,which was not significantly different from that of H IV + LTB individuals from that area (U =378,P =0.120).Moreover,the median CD8+ T cell counts of HIV-infected individuals with latent tuberculosis infection in Yunnan Province and Shanghai were 409/μL and 781/μL,respectively (U=109,P＜0.01).Conclusions The incidence of LTB infection among HIV-infected individuals in Yunnan Province is significantly higher than Shanghai.CD4+ and CD8+ T cell counts are correlated with TB infection among HIV-infected individuals.

Objective To observe hepatitis B virus (HBV) reactivation in 12 patients with rheumatic disease undergoing immunosuppressive therapy and to evaluate whether preemptive antiviral therapy is necessary for patients receiving disease-modifying anti-rheumatic drugs (DMARDs).Methods From January 2008 to March 2012,a total of 12 HBV-infected patients with rheumatic diseases were consecutively enrolled into this long-term follow-up study.Liver function and serum levels of HBV DNA were tested during the follow-up.Results The medium duration of follow-up was 41 months (range 16-48).Four patients received steroid treatment,and among them two patients without pre-emptive antiviral therapy developed HBV reactivation.After administr-ation of LAM or ETV,HBV replication was controlled in both patients.Five patients were treated with disease-modifying anti-rheumatic drugs and the other three patients received tumor necrosis factor-alpha-blocking agents.None of these patients received pre-emptive antiviral therapy.HBV reactivation did not occur in any of them.Conclusion HBV reactivation does occur in HBV-infected patients with rheumatoid diseases after immunosuppressive therapy.Pre-emptive antiviral therapy should be administered in patients who are receiving steroid therapy for rheumatic diseases.In contrast,DMARDs and TNFBA are relatively safe for HBV-infected patients with rheumatic diseases.Close monitoring of HBV DNA and ALT levels is necessary to the mana-gement of HBV reactivation.

Objective:To investigate the clinical characteristics and prognosis of the patients with nocardiosis.Methods:From January 2013 to July 2019, 44 patients with nocardiosis in Department of Infectious Diseases, Huashan Hospital, Fudan University in Shanghai were enrolled, and their clinical data were retrospectively analyzed, including baseline characteristics, clinical manifestations, underlying diseases history of glucocorticoid therapy, laboratory data (blood routine examination, procalcitonin, C-reactive protein, lymphocytes subsets, etc.), imaging changes, bacterial strain identification, treatment regimens and outcomes. According to the locations of infection, patients were divided into pulmonary nocardiosis, extrapulmonary single-organ nocardiosis and disseminated nocardiosis. The Mann-Whitney U test was used for comparison between two groups, and the Kruskal-Wallis H test was used for comparison among multiple groups. Results:Among the 44 cases of nocardiosis, 14 cases were pulmonary nocardiosis, 17 cases were extrapulmonary single-organ nocardiosis (including nine cases with central nervous system infection, six cases with skin and soft tissue infection, one case with abdominal abscess and one case with urinary tract infection) and 13 cases were disseminated nocardiosis (including four cases with bloodstream infection, six cases with central nervous system and lung or skin and soft tissue infection, three cases of lung and skin and soft tissue infection). Thirty-four cases had underlying diseases, and 27 cases received glucocorticoid or immunosuppressant treatment. The main symptom of 11 patients in pulmonary nocardiosis group was productive cough, while that of the patients in other two groups was fever. Nocardia species were mainly Nocardia brasiliensis, Nocardia nova and Nocardia farcinicaia. The white blood cell counts and neutrophils proportion were normal or slightly increased in 42 cases, and the platelets were normal or slightly decreased in 41 cases. Erythrocyte sedimentation rate increased in 19 cases, procalcitonin increased in 21 cases, C-reactive protein increased in 34 cases, and ferritin increased in 18 cases. A total of 34 patients were tested for lymphocyte subsets, of which 15 had CD4 + T lymphocytes decreased, 14 had CD8 + T lymphocytes increased, seven had B lymphocytes increased, seven had B lymphocytes decreased, and eight had natural killer cells decreased. The hemoglobin of patients with pulmonary nocardiosis was higher than that of patients with extrapulmonary infection, and the difference was statistically significant ( U=0.095, P=0.025). The imaging manifestations were mainly abscess and inflammatory exudation. Forty cases were cured or improved, one case was still on treatment, and three cases died. Conclusions:The clinical manifestations of nocardiosis involving various organs are non-specific. Standardized treatment could reduce the mortality of nocardiosis.

Objective:To investigate the clinical characteristics and prognosis of cytomegalovirus (CMV) reactivation in patients with liver failure.Methods:A total of 75 patients diagnosed with liver failure and tested for serum CMV DNA between January 2016 and June 2019 in Huashan Hospital, Fudan University were retrospectively analyzed. According to the CMV DNA test results, the patients were divided into CMV DNA positive group and CMV DNA negative group. The classification of liver failure, the use of glucocorticoids, the proportions of T lymphocyte subsets of the two groups were compared and the prognosis was evaluated. Mann-Whitney U test and chi-square test were used to analyze the data. Results:Of the 75 patients with liver failure, 17 were CMV DNA positive and 58 were CMV DNA negative. Among the 17 CMV DNA positive patients, nine were acute (subacute) liver failure, and 13 were treated with glucocorticoids, which were all significantly higher than those in the CMV negative group (20.7%(12/58) and 20.7%(12/58), respectively). The differences were both statistically significant ( χ2=6.70 and 18.40, respectively, both P<0.05). The proportions of CD3 + T lymphocytes and CD8 + T lymphocytes in the CMV DNA positive group were both higher than those in the CMV DNA negative group, and the proportions of CD4 + T lymphocytes, the ratio of CD4 + /CD8 + T lymphocytes and the proportion of B lymphocytes were all lower than those in the CMV DNA negative group. The differences were all statistically significant ( U=274.50, 165.50, 273.00, 185.00 and 189.00, respectively, all P<0.05). Acute (subacute) liver failure (odds ratio ( OR)=4.3, 95% confidence interval ( CI) 1.3-12.6) and glucocorticoid use ( OR=12.5, 95% CI 3.4-38.3) were risk factors for CMV reactivation in patients with liver failure. The disease improvement rate in the CMV DNA negative group was 56.9% (33/58), and five out of 17 patients improved in the CMV DNA positive group, with a statistically significant difference ( χ2=1.99, P=0.04). Conclusions:The use of glucocorticoids increases the risk of CMV reactivation in patients with liver failure, and CMV reactivation in patients with liver failure presents immune disorders which seriously affect their prognosis. Therefore, it is important to pay attention to CMV DNA monitoring in patients with liver failure using glucocorticoids.

Objective To explore the role of basic leucine zipper ATF-like transcription factor (BATF) in active tuberculosis, and to provide clues for diagnosis and therapy of tuberculosis.Methods Sixteen patients with active tuberculosis (ATB), ten cases of latent tuberculosis infection (LTBI) and fourteen healthy controls (HC) were included in this study.Flow cytometry was applied to detect the expressions of BATF and programmed death-1 (PD-1) in T lymphocytes, and the changes of BATF by blockade of PD-1/PD-L pathway using specific blocking antibody antiPD-1, antiPD-L1 and antiPD-L2.The expressions of BATF were compared using Mann-Whitney U test.And the relation of BATF and PD-1 was analyzed using Pearson correlation analysis.Results The CD4+ T lymphocytes expressing BATF accounted for 5.16% (2.96%,8.71%) of CD4+ T lymphocytes in ATB group, which was higher than 1.05% (0.40%,1.27%) in LTBI group and 0.71%(0.43%,1.21%) in HC group, and the difference were statistically significant (U value were 6.5 and 9.0, respectively, both P<0.01).The CD8+ T lymphocytes expressing BATF accounted for 4.10% (2.27%,8.17%) of CD8+ T lymphocytes in ATB group, which was higher than 0.55% (0.34%,1.18%) in LTBI group and 0.84% (0.41%,1.29%) in HC group, and the difference were statistically significant (U value were 5.0 and 8.0, respectively, both P<0.01).Furthermore, the percentage of BATF+ PD-1+ CD4+ T lymphocytes in the peripheral blood of ATB was significantly higher than those in the peripheral blood of LTBI and HC, the difference were statistically significant (Uvalue were 16.0 and 14.5, respectively, both P<0.01), and the percentage of BATF+ PD-1+ CD8+ T lymphocytes in the peripheral blood of ATB was significantly higher than those in the peripheral blood of LTBI and HC, the difference were statistically significant (Uvalue were 10.0 and 16.5, respectively, both P<0.01).In addition, there was a positive correlation between the percentage of BATF+ T cells and PD-1+ T cells, both in CD4+ T cells (r=0.676,P=0.016) and CD8+ T cells (r=0.610,P=0.035).The expressions of BATF both in CD4+ T cells and CD8+ T cells were decreased followed by blockade of PD-1/PD-L pathway (P<0.05).Conclusions BATF may be involved in the regulation of immune pathogenesis of tuberculosis.In order to provide a theory for anti-tuberculosis immunotherapy fargeting BATF, further research need to be proceeded.

Objective To understand the predictors and prognostic significance of cranial nerve impairment in non-acquired immune deficiency syndrome (AIDS) patients with cryptococcal meningitis.Methods A total of 145 non-AIDS patients with cryptococcal meningitis admitted to Huashan Hospital,Fudan University from Jan 2000 to Dec 2010 were reviewed retrospectively.Clinical characteristics,initial antifungal therapies and outcome of these patients were analyzed.Continuous variables were analyzed using t test and categorical variables were compared by x2 test or Fisher's exact test.Multivariate analysis was performed by binary Logistic regressions.Results Out of 145 patients,52 (35.9％) patients had cranial nerve impairment at enrollment.Optic (25/52,48.1％) and oculomotor (22/52,42.3％) nerves were the most commonly involved,followed by auditory (12/52,23.1％),abducens (6/52,11.5％),olfactory (4/52,7.7％) and facial (3/52,5.8％) nerves.The best predictive factor of cranial nerve injury was duration of diagnosis (OR =1.056,95％ CI:1.002-1.111).The risk of cranial injury would increase by 5.6％ with one-week delay of diagnosis.Intracranial hypertension and low cerebrospinal fluid cell count were also the independent predictive factors (both P＜0.05).In the follow-up period,73.3％ patients who had cranial nerve injuries were fully recovered,with a median time of 3 (0.5-24.0) months.The independent predictors of recovery were numbers of nerve involved (OR =0.230,95 ％ CI:0.066-0.800,P=0.021) and amphotericin B (AmB) plus 5-fluorocytosine,triazole antifungal agent therapy (OR=10.317,95％CI:2.086-51.025,P=0.004).Conclusions Cranial nerve impairment occurs in one-third of non-AIDS patients with cryptococcal meningitis.Delay in diagnosis,intracranial hypertension and low cerebrospinal fluid cell count are independent predictive factors.Less cranial nerve involvement and AmB plus triazole therapy predict recovery.