Nitric oxide (NO), which is involved in the regulation of the cardiovascular system, nervous system, immune system, reproductive system, digestive system and other physiological activities, is an important biological substance with activity. Under normal physiological conditions, neuronal nitric oxide synthase (nNOS) can precisely regulate the nervous system NO production, release, diffusion and inactivation processes. But an excess of NO associates with the development of cerebral ischemia, Alzheimer's and Parkinson's psychosis nervous system diseases, while inhibition of nNOS activity can regulate the content of NO in vivo, and produce a therapeutic effect on some of the nervous system diseases. This review mainly describes the structure and regulation of nNOS and recent developments of small molecule inhibitors of nNOS.
Alzheimer Disease ; physiopathology ; Brain Ischemia ; physiopathology ; Humans ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type I ; antagonists & inhibitors ; metabolism ; Parkinson Disease ; physiopathology

OBJECTIVETuberculosis is still a public health problem. Host genetic factors, such as polymorphisms in NRAMP1 gene, may play a role in the development of tuberculosis. To clarify the effect of NRAMP1 gene polymorphisms on the development of childhood tuberculosis, the association of NRAMP1 gene polymorphisms with susceptibility to tuberculosis in the ethnic Han Chinese children was investigated.

METHODSFrom January 2005 to March 2008, 130 ethnic Han children with tuberculosis (TB group) were enrolled. Three hundred and ninety hospitalized ethnic Han children for physical examination in the surgery department were used as the control group. The controls were matched with tuberculosis children by age, sex and area. PCR-RFLP analysis was performed on DNA samples to identify allele genotypes of INT4 and D543N in NRAMP1 gene. Genotype frequency differences between tuberculosis patients and controls were analyzed using x2 test.

RESULTSNo statistical difference was found in the genotype frequency of variants G/C and C/C at the INT4 locus between the TB and the control groups. At the D543N locus, the frequency of genotype variants (G/A and A/A) was significantly higher in the TB group (34/130) than that in the control group (66/390) (x2=5.349, P<0.05; OR=1.74, 95%CI=1.08-2.79). When stratified by sex, differences in the genotype distribution were observed only in females at the D543N locus, which the variant genotypes were higher in the TB group (16/52) than in the control group (21/155) (x2=7.866, P<0.05; OR=2.84, 95%CI=1.34-5.99). For males, there was no difference between the TB and the control groups. At the INT4 locus, no difference was observed between the two groups in boys and girls.

CONCLUSIONSGenotypic variation at the D543N locus in NRAMP1 gene may be associated with susceptibility to tuberculosis in ethnic Han Chinese children. Variant genotypes in NRAMP1 gene (G/A and A/A) may be susceptible genotypes to tuberculosis in ethnic Han Chinese children. Girls with variant genotypes were more susceptible to tuberculosis.

Cation Transport Proteins ; genetics ; Child ; Child, Preschool ; China ; ethnology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Infant ; Male ; Polymorphism, Genetic ; Sex Factors ; Tuberculosis ; ethnology ; genetics

BACKGROUNDAtopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD.

METHODSA hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software.

RESULTSA total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients.

CONCLUSIONLate-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.

Adolescent ; Adult ; Dermatitis, Atopic ; diagnosis ; immunology ; Eczema ; diagnosis ; Female ; Humans ; Immunoglobulin E ; blood ; Male ; Middle Aged ; Retrospective Studies ; Surveys and Questionnaires

OBJECTIVE: To observe the clinical effect of acupuncture at sphenopalatine ganglion combined with conventional acupuncture for episodic cluster headache (CH). METHODS: One hundred and eighty patients with episodic CH were randomly divided into a combined group (60 cases, 3 cases dropped off)，an acupuncture group (60 cases, 2 cases dropped off) and a sphenopalatine ganglion group (60 cases, 2 cases dropped off and 1 case was removed). The patients in the acupuncture group were treated with conventional acupuncture at Touwei (ST 8), Yintang (GV 24⁺), Yangbai (GB 14), Hegu (LI 4), etc., once a day, 6 times a week. The patients in the sphenopalatine ganglion group were treated with acupuncture at sphenopalatine ganglion, once every other day, 3 times a week. On the basis of the conventional acupuncture, the combined group was treated with acupuncture at sphenopalatine ganglion once every other day. Two weeks were taken as a course of treatment, and 3 courses of treatment were required in the 3 groups. The score of visual analogue scale (VAS), the number of headache attacks per week, the duration of each headache attack and the score of migraine-specific quality of life questionnaire version 2.1 (MSQ) were observed before and after treatment and in follow-up of 3 months after treatment. The clinical efficacy of each group was compared. RESULTS: After treatment and in follow-up, the VAS score of headache, the number of headache attacks per week, the duration of each headache attack, and each various scores and the total score of MSQ of each group were lower than those before treatment (P<0.01). Except that the number of headache attacks per week in the combined group was lower than the sphenopalatine ganglion group (P<0.01), other indexes in the combined group were lower than the other two groups (P<0.05, P<0.01). The total effective rate in the combined group was 93.0% (53/57), which was higher than 75.9% (44/58) in the acupuncture group and 73.7% (42/57) in the sphenopalatine ganglion group（P<0.05, P<0.01). CONCLUSION Acupuncture at sphenopalatine ganglion combined with conventional acupuncture could reduce the degree of pain in patients with episodic CH, reduce the number and duration of headache attacks, and improve the quality of life of patients. It is more effective than simple conventional acupuncture or acupuncture at sphenopalatine ganglion alone.
Acupuncture Points ; Acupuncture Therapy ; Cluster Headache/therapy* ; Headache/therapy* ; Humans ; Quality of Life ; Treatment Outcome

Objective: To investigate the expression of programmed death ligand-1 (PD-L1, SP142) and PD-L1 (22C3) in triple-negative breast cancer (TNBC), and analyze their correlation with the clinicopathological factors and prognosis. Methods: The clinicopathologic data of 259 patients with TNBC treated in Cancer Hospital from August 2010 to December 2013 were collected. Whole section of surgical tissue samples were collected to conduct PD-L1 (SP142) and PD-L1 (22C3) immunohistochemical (IHC) staining. The PD-L1 expression in tumor cells and tumor infiltrating immune cells were visually assessed respectively, the relationship between PD-L1 expression and clinicopathologic characterizes were analyzed. Univariable and multivariable Cox proportional hazards regression models were used to test the correlations between PD-L1 expression and disease-free survival (DFS) and overall survival (OS). Results: The positive rates of SP142 (immune cell score, ICs≥1%) and 22C3 (combined positive score, CPS≥1) were 42.1%(109/259) and 41.3%(107/259) in TNBC tissues, respectively, with a total coincidence rate of 82.3%. The Kappa value of positive expression cases was 0.571 and the distribution difference of SP142 and 22C3 positive expression cases was statistically significant (P<0.001). The PD-L1 positive patients were less likely to have vascular invasion (P<0.05), but with higher histological grade and Ki-67 proliferation index (P<0.05). The recurrence/metastasis cases(8) of the patients with positive PD-L1 (SP142) was significantly lower than that of patients with negative PD-L1(SP142, 27, P=0.016). The positive expression of PD-L1 (SP142) patients were longer DFS (P=0.019). The OS of patients with positive PD-L1 (SP142) were longer than those with negative PD-L1 (SP142), but without significance (P=0.116). The positive expression of PD-L1 (22C3) was marginally associated with DFS and OS of patients (P>0.05). Conclusions: The expression of PD-L1 (22C3) is different from that of PD-L1 (SP142) in TNBC, and the two antibodies can't be interchangeable for each other in clinical tests. PD-L1 (SP142) status is an independent prognostic factor of DFS in TNBC. The DFS is significantly prolonged in patients with positive expression of PD-L1 (SP142).
B7-H1 Antigen/genetics* ; Humans ; Immunohistochemistry ; Prognosis ; Triple Negative Breast Neoplasms/pathology*