Targeting Janus Kinase (JAK) for Fighting Diseases: The Research of JAK Inhibitor Drugs.

Janus Kinase (JAK), a nonreceptor protein tyrosine kinase, has emerged as an excellent target through research and development since its discovery in the 1990s. As novel small-molecule targeted drugs, JAK inhibitor drugs have been successfully used in the treatment of rheumatoid arthritis (RA), myelofibrosis (MF), and ulcerative colitis (UC). With the gradual development of JAK targets in the market, JAK inhibitors have also received considerable feedback in the treatment of autoimmune diseases, such as atopic dermatitis (AD), Crohn's disease (CD), and graft-versus-host disease (GVHD). This article reviews the research progress of JAK inhibitor drugs, focusing on the existing JAK inhibitors in the market and some JAK inhibitors in clinical trials currently. In addition, the synthesis of various types of JAK inhibitors and the effects of different drug structures on drug inhibition and selectivity are summarized.

Neurocognitive impairment in Chinese patients with obstructive sleep apnoea hypopnoea syndrome.

BACKGROUND AND OBJECTIVE: Sleep-disordered breathing is known to be associated with impairment in cognitive function. The aim of this study was to characterize neurocognitive impairment in a cohort of Chinese patients with varying severities of obstructive sleep apnoea hypopnoea syndrome (OSAHS), and to develop a sensitive instrument for routine screening of cognitive impairment. METHODS: Eligible patients (n = 394) were categorized into a primary snoring group, and mild, moderate and severe OSAHS groups, based on assessment of AHI. The Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) questionnaires were administered to assess cognitive function, and the correlations between questionnaire scores and clinical and polysomnographic parameters were further evaluated by stepwise multivariate regression. RESULTS: MoCA scores decreased progressively across the spectrum from primary snoring to severe OSAHS. Importantly, mild neurocognitive impairment as defined by a MoCA score <26 was more common in the moderate (38.6%) and severe (41.4%) OSAHS groups than in the mild OSAHS (25.0%) and primary snoring (15.2%) groups. In contrast, MMSE scores were largely normal and comparable among all four groups. Evaluation of MoCA subdomains further revealed selective reduction in memory/delayed recall, visuospatial and executive function, and attention span in the severe OSAHS group compared with the other groups. Stepwise multivariate regression analysis demonstrated that MoCA scores correlated significantly with lowest oxygen saturation (L-SaO(2) ) and years of education. CONCLUSIONS: Neurocognitive impairment is common in patients with OSAHS. The MoCA is a brief and sensitive tool for the assessment of cognitive impairment in OSAHS patients, whose performance on the MMSE is in the normal range.

Daytime sleepiness and its determining factors in Chinese obstructive sleep apnea patients.

OBJECTIVE: The aim of this study was to characterize excessive daytime sleepiness (EDS) in a large cohort of Chinese patients with various severity of obstructive sleep apnea-hypopnea syndrome (OSAHS), and investigate its correlations with clinical/polysomnographic variables. MATERIALS AND METHODS: A total of 1,035 consecutive Chinese patients with snoring (mean age ± SD 45 ± 15 years, BMI 26.6 ± 4.3 kg/m(2)) were examined by overnight polysomnography, and subjective EDS was assessed using the Epworth Sleepiness Scale (ESS). RESULTS: The 1,035 patients were compared according to severity of sleep-disordered breathing: AHI <5 (primary snoring group or normal overall AHI) (24.1%), AHI 5-20 (mild OSAHS, 21.7%), AHI >20-40 (moderate OSAHS 16.5%), and AHI >40 (severe OSAHS 37.7%). ESS score progressively increased as the severity of OSAHS aggravated among these patients. More severe OSAHS patients were characterized by EDS, nocturnal hypoxemia, and disruption of sleep structure. Progressive worsening of nocturnal hypoxemia was observed from mild to severe OSAHS patients with a strong correlation with ESS score. The stepwise multiple regression analysis performed to evaluate the correlations of individual clinical and polysomnographic variables with the ESS score revealed that the ESS score significantly correlated with the oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and body mass index (BMI), and ODI was the strongest determinant of ESS score. CONCLUSION: EDS is correlated with the severity of OSAHS. More severe patients are characterized by higher ESS score, higher BMI, and progressive worsening of nocturnal hypoxemia. Nocturnal hypoxemia is a major determinant of EDS in Chinese OSAHS patients.