Yannan Fang

The Prevalence and Burden of Primary Headaches in China: A Population-Based Door-to-Door Survey

Objectives.— In the absence of reliable data on the prevalence and burden of primary headache disorders in the mainland of China, a population‐based survey was initiated by Lifting The Burden: the Global Campaign against Headache.

Headache yesterday in China: A new approach to estimating the burden of headache, applied in a general-population survey in China

Background In order to minimize recall bias in burden estimation, questions about headache yesterday were included in a population-based survey initiated by Lifting The Burden: The Global Campaign against Headache. Methods Throughout China, nonrelated respondents aged 18–65 years were randomly sampled from the general population by a door-to-door survey. A validated structured questionnaire included inquiry into occurrence and burden of headache on the preceding day (“headache yesterday”). Results The participation rate was 94.1%. Of 5041 participants, 286 (5.7%) (male 3.6%, female 7.9%) reported headache yesterday. Age-weighted prevalence of headache yesterday was 4.8% (male 3.0%, female 6.6%). Headache yesterday lasted all day in 36.8%, <1 hour in 14.3% and for a mean of 3.7 ± 3.3 hours in 48.9%. Headache yesterday was moderate to severe in 79.9%; disability such that they could do less than half of what they had expected was reported by 19.9% and such that they could do nothing by a further 7.5% (total 27.4%). Almost three-quarters (71.5%) with headache yesterday took medication to treat it. Conclusions Of the adult Chinese population, 1.8% have headache at any one time that is of moderate to severe intensity in 1.4%, and 1.3% lose the equivalent of a whole day to headache-attributed disability every day. In China this means 12.3 million people.

Activation of the nuclear factor E2-related factor 2/anitioxidant response element alleviates the nitroglycerin-induced hyperalgesia in rats

BackgroundAntioxidants have been proven to weaken hyperalgesia in neuropathic pain. Endogenous antioxidant defense system may have a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) pathway in regulating the activation of the trigeminovascular system (TGVS) and hypersensitivity in nitroglycerin (NTG)-induced hyperalgesia rats.MethodsThe expression levels of Nrf2, HO, HO1, and NQO1 in the trigeminal nucleus caudalis (TNC) were detected by western blot. Immunofluorescence was used to demonstrate the cell-specific localization of Nrf2 in TNC. Sulforaphane, a Nrf2 activator, was administered to NTG-induced rats. Then, the number of c-Fos- and nNOS-immunoreactive neurons in TNC was evaluated using immunofluorescence, and c-Fos and nNOS protein levels were quantified using western blot. Von Frey hair testing was used to evaluate the tactile thresholds of rats at different time points in different groups.ResultsTotal cellular and nuclear levels of the proteins Nrf2, HO1, and NQO1 were elevated in TNC after NTG injection, and Nrf2 was found to be located in the nucleus and cytoplasm of the neurons. Sulforaphane pretreatment significantly increased the nuclear Nrf2, HO1, and NQO1 levels in TNC. In addition, sulforaphane exposure effectively inhibited the expression of nNOS and c-Fos, reduced the number of nNOS and c-Fos immunoreactive neurons in TNC, and attenuated the tactile thresholds induced by NTG injection.ConclusionOxidative stress was involved in nitroglycerin-induced hyperalgesia. Activation of the Nrf2/ARE pathway inhibited the activation of TGVS and prevented the induction of hyperalgesia. Sulforaphane might therefore be an effective agent for hyperalgesia. Further studies are needed to discover the underlying mechanisms of the process.

Chronic Obstructive Pulmonary Disease as a Risk Factor for Cognitive Dysfunction: A Meta-Analysis of Current Studies

Cognitive dysfunction has been shown to be associated with many risk factors, such as smoking, diabetes, and body mass index. Chronic obstructive pulmonary disease (COPD), a common disease within the elderly population, has also been found to be related to cognitive decline. However, whether COPD is a risk factor of cognitive dysfunction is not well established. The purpose of this meta-analysis is to investigate the role COPD plays in cognitive dysfunction. PubMed, Cochrane library and Web of Science databases were searched. Three cohort studies and eleven cross-sectional studies were found to be eligible. According to our results, COPD patients had a higher risk of cognitive dysfunction than controls (OR [odds ratio]: 1.72; 95% CI, 1.12-2.65; p = 0.01). The exacerbation of COPD was strongly correlated with cognitive decline. COPD patients performed worse than controls on the Mini- Mental State Examination test, but the results were not statistically significant (OR: -0.79; 95% CI, [-1.78, 0.19]; p = 0.11). Thus, more attention should be given to the occurrence of cognitive decline in COPD patients. The prevention and control of COPD exacerbation are critical.

MFG-E8 Selectively Inhibited Aβ-Induced Microglial M1 Polarization via NF-κB and PI3K-Akt Pathways

Activated microglia are classified into two specific states: classically activated (M1) and alternatively activated (M2) subtypes. It is believed that the polarization of M1/M2 phenotype plays an important role in Alzheimer’s disease (AD). However, the mechanisms regulating this process remain unclear. Thus, we addressed this question focusing on milk fat globule epidermal growth factor 8 (MFG-E8). MFG-E8 is a unique protein which can bind to microglia and regulate its inflammatory responses. It is speculated that it might play a role in the balance of microglial polarization. In the current study, we used fibril Aβ42 in vitro to stimulate mouse primary microglial cultures and found subsequent M1 marker expression, along with retained M2 marker production. Then, we discovered that MFG-E8 pretreatment reversed the increased trend of M1 markers and the decreased expression of M2 markers, which were induced by Aβ42. Moreover, MFG-E8 effects could be effectively blocked by an MFG-E8 antibody. Further analysis on the signaling pathways showed that NF-κB upregulation and Akt downregulation in microglial cultures were observed after Aβ42 incubation. And the alteration of these pathways could also be reversed by MFG-E8. We then assessed the effects of NF-κB and PI3K-Akt on M1/M2 alteration using their specific inhibitors. Pyrrolidine dithiocarbamate, a NF-κB inhibitor, inhibited M1 marker expression; moreover, LY294002, an Akt inhibitor, enhanced M1 marker expression. Our study indicated the regulatory role of MFG-E8 on microglia M1/M2 alteration for the first time, providing a basis for understanding the potential role of microglia activation in AD.

The association between brain-derived neurotrophic factor gene polymorphism and migraine: a meta-analysis

BackgroundMigraine is a recurrent headache disease related to genetic variants. The brain-derived neurotrophic factor (BDNF) gene rs6265 (Val66Met) and rs2049046 polymorphism has been found to be associated with migraine. However, their roles in this disorder are not well established. Then we conduct this meta-analysis to address this issue.MethodsPubMed, Web of Science and Cochrane databases were systematically searched to identify all relevant studies. Odds ratio (OR) with corresponding 95% confidence interval (CI) was used to estimate the strength of association between BDNF gene rs6265 and rs2049046 polymorphism and migraine.ResultsFour studies with 1598 cases and 1585 controls, fulfilling the inclusion criteria were included in our meta-analysis. Overall data showed significant association between rs6265 polymorphism and migraine in allele model (OR = 0.86, 95%CI: 0.76–0.99, p = 0.03), recessive model (OR = 0.84, 95%CI: 0.72–0.98, p = 0.03) and additive model (GG vs GA: OR = 0.85, 95%CI: 0.72–1.00, p = 0.04), respectively. We also found significant association between rs2049046(A/T) polymorphism and migraine in allele model (OR = 0.88, 95%CI: 0.79–0.98, p = 0.02), recessive model (OR = 0.80, 95%CI: 0.67–0.96, p = 0.02) and additive model (AA vs TT: OR = 0.72, 95%CI: 0.57–0.92, p = 0.008; AA vs AT: OR = 0.81, 95%CI: 0.67–0.99, p = 0.03), respectively.ConclusionOur meta-analysis suggested that BDNF rs6265 and rs2049046 polymorphism were associated with common migraine in Caucasian population. Further studies are awaited to update this finding in Asian population and other types of migraine.

Familial occurrence of headache disorders: A population-based study in mainland China

BACKGROUND Headache disorders are highly prevalent worldwide, and familial occurrence and heredity are contributory factors attracting the interest of epidemiological researchers. Our purpose, in a large sample drawn nationwide from the Chinese general population, was to evaluate the frequency of similar headache in first-degree relatives (FDRs) of those with different headache types. METHODS This was a questionnaire-based nationwide cross-sectional door-to-door survey using cluster random-sampling, selecting one adult (18-65 years) per household. Headache was diagnosed by ICHD-II criteria. Participants with headache were asked whether or not any FDRs had similar headache to their own. Chi-squared test and multivariate logistic regression analysis were used to assess the strength and significance of associations. RESULTS Of 5041 survey participants (participation rate 94.1%), 1060 (21.0%) were diagnosed with headache (migraine 469 [9.3%], tension-type headache [TTH] 543 [10.8%], headache on ≥15 days/month 48 [0.95%]). From these, 31 were excluded because of missing data about FDRs, leaving 1029 for analysis (male 350 [mean age: 46.7±11.4years]; female 679 [mean age 46.3±11.2years]). Similar headache in one or more FDRs was reported by 22.2% (95% CI: 19.6-24.7%) overall, by 25.1% (21.1-29.1%) of those with migraine, by 19.1% (15.7-22.4%) with TTH and by 29.2% (16.3-42.0%) with headache on ≥15 days/month. The differences was significant between migraine and TTH (OR=1.4, p=0.023), but were not significant between headache on ≥15 days/month and TTH (OR=1.7, p=0.093), migraine and headache on ≥15 days/month (OR=1.2,p=0.534). In multivariate analysis: for migraine versus TTH,AOR=1.2 (p=0.015); for headache on ≥15 days/month versus TTH, AOR 2.3 (p=0.018). CONCLUSION Headache was highly prevalent in China and common among FDRs of those with any type of headache (headache on ≥15 days/month>migraine>TTH). Against the background of the general-population prevalence of each disorder, familial occurrence was a very highly influential factor in headache on ≥15 days/month. There are important implications in this for public health and education.

MFG-E8 reverses microglial-induced neurotoxic astrocyte (A1) via NF-κB and PI3K-Akt pathways: XU et al.

Recent evidence have suggested that neuroinflammation and ischemia induce the activation of two different types of reactive astrocytes, termed A1 and A2. Additionally, A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative diseases, such as Alzheimer’s disease (AD). In the current study, we constructed an Aβ42‐activated microglia‐conditioned medium to induce A1 astrocytic activation via secretion of interleukin 1α, tumor necrosis factor, and complement component 1q in vitro, and indicated the regulatory role of milk fat globule epidermal growth factor 8 (MFG‐E8) on A1/A2 astrocytic alteration through the downregulation of nuclear factor‐κB and the upregulation of PI3K‐Akt. This study showed that MFG‐E8 suppressed A1 astrocytes and holds great potential for the treatment of AD.

MFG-E8 inhibits Aβ-induced microglial production of cathelicidin-related antimicrobial peptide: A suitable target against Alzheimer’s disease

Neuroinflammation plays a pivotal role in the incidence and progression of Alzheimers disease (AD). Cathelicidin-related antimicrobial peptide (CRAMP) is critically involved in the innate neuronal responses of chronic neuroinflammation in AD and thus plays a key role in the disease. Here, we show that Aβ42 induced microglial production of CRAMP, which was effectively inhibited by milk-fat globule-epidermal growth factor 8 (MFG-E8). Production of CRAMP was associated with activation of ERK1/2, p38 and phospho-P65-NF-kB upregulation. Additionally, the phosphorylation of these signaling proteins was also reversed by MFG-E8. Pre-incubation with signaling inhibitors confirmed that MFG-E8 has a regulatory role on CRAMP through MAPK and NF-kB signaling pathways. MFG-E8 treatment may thus be a potential pharmacotherapy for chronic inflammation in AD.

Retracted: Prevalence and Burden of Headache Disorders: A Comparative Regional Study in China

Background.— Since the early 1990s, no study has been undertaken examining the prevalence and burden of headache disorders in China.