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Background Multiple sclerosis is a rare neurological disease which is addressed by few epidemiological studies in China. This population-based study aimed to estimate the prevalence of multiple sclerosis in China by using national medical insurance databases. Methods Data from the Urban Employee Basic Medical Insurance database and the Urban Residence Basic Medical Insurance database, which were collected during 2012-2016 and included approximately 0.20 billion residents in six provinces, were used in this population-based study. The prevalent patients with multiple sclerosis were identified via diagnostic text or disease codes. Results The crude prevalence in 2016 was 2.44 per 100 000 population (95% confidence interval (CI): 2.18 to 2.72), with the prevalence of females being higher than that of males. The standardized prevalence (based on 2010 Chinese census data) was 2.29 (95% CI: 2.21 to 2.38). The prevalence in both sexes in 2016 increased up to the age range of 30-34-years-old. Subsequently, the female prevalence declined with increasing age, but the male prevalence stabilized with increasing age. During the five-year time period, the prevalence ranged from 2.32 (95% CI: 2.06 to 2.60) in 2015 to 2.91 (95% CI: 2.39 to 3.47) in 2012. Conclusions The prevalence of multiple sclerosis in China was lower than that in Europe and North America. The temporal trend of prevalence in China was also observed to be stable. As the first prevalence study of multiple sclerosis in mainland China, this population-based study can provide useful information for worldwide health care services and prevention of multiple sclerosis.

Background Information on incidence of gastrointestinal stromal tumor (GIST), the most common type of mesenchymal tumor in gastrointestinal tract, was limited in China. This study aimed to estimate the incidence of GIST in urban population from mainland China in 2016. Methods Urban Employee Basic Medical Insurance (UEBMI) and Urban Residence Basic Medical Insurance (URBMI) in China were used. The denominator of incidence was the total person‐years of insured individuals in 2016 in the database, covering approximately 0.43 billion individuals. The numerator was the number of incident GIST cases in 2016. Results The crude incidence in 2016 was 0.40 per 100,000 person‐years (95% CI, 0.06–1.03). Male incidence was higher than female incidence (0.44 vs. 0.36, rate ratio: 1.22, p, This is the first study using national data in mainland China, covering 0.43 billion population, to estimate the incidence of gastrointestinal stromal tumor. The incidence in 2016 was 0.40 per 100,000 person‐years, with the age trend of incidence becoming obviously steep after 50 years old and male incidence higher than female incidence.

BACKGROUND Community-acquired pneumonia (CAP) is one of the major global health problems worldwide. However, the epidemiological information of CAP is limited in China. This study aimed to estimate the incidence rate of CAP and describe the epidemiologic characteristics among the Chinese population. METHODS We conducted a retrospective analysis of CAP incidence using the Chinese Urban Basic Medical Insurance database of 23 provinces in 2016, which covered 427.52 million urban beneficiaries of all age groups in Mainland China. CAP episodes were identified using a diagnosis-term-derived algorithm, and multiple CAP records of one single person within 90 continuous days were considered as one single episode. The incidence rates were calculated and described by sex, age, region, and season. RESULTS A total of 1.42 million patients were identified as having one or more CAP episodes, and finally a sum of 1.48 million CAP episodes were counted. The overall incidence of CAP was 7.13 (95% CI: 6.11-8.15) per 1000 person-years, in males 7.32 (95% CI: 6.28-8.35) and females 6.93 (95% CI: 5.92-7.94) per 1000 person-years, respectively. The incidence varied by age with a U-shaped curve peaking in children aged

Background While the prevalence and disease burden of bronchiectasis are increasing, data in the world’s largest population are lacking. We aimed to investigate the prevalence and disease burden of bronchiectasis in Chinese adults. Methods We conducted a population-based study using data between 2013 and 2017 from the national databases of Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance in China. Data from over 380 million patients aged 18 years and older during the study period were analyzed, and a total of 383,926 bronchiectasis patients were identified. Primary outcomes included the age- and sex-specific prevalence of bronchiectasis. Annual visits and hospitalizations, as well as annual costs were also calculated. Results The prevalence of bronchiectasis in Chinese adults increased 2.31-fold, from 75.48 (62.26, 88.69) per 100,000 in 2013 to 174.45 (137.02, 211.88) per 100,000 in 2017. The increase was more remarkable for patients aged over 50 years in both genders. The per-capita total cost and hospitalization cost of patients with bronchiectasis increased 2.18-fold and 1.83-fold from 2013 to 2017, respectively, mostly driven by non-bronchiectasis costs. The average annual hospitalization ranged from 1.20 to 1.24 times during the 5 years. Conclusion The prevalence and disease burden of bronchiectasis in Chinese urban adults ≥ 18 years had increased significantly between 2013 and 2017.

Background Extramammary Paget’s disease (EMPD) is an intraepithelial adenocarcinoma. The chronic relapsing clinical course and unbearable clinical symptoms of extramammary Paget’s disease usually result in a markedly diminished quality of life. No national data are available on descriptive epidemiology of EMPD in China, the most populous country over the world. This population-based study aimed to estimate the prevalence and associated sex and age patterns of EMPD in China. Methods This study was conducted using data from China’s Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance, covering approximately 0.43 billion Chinese urban residents in 2016. Patients with EMPD were identified based on the diagnostic names and codes in claim data. Results A total of 53 males and 31 females with EMPD were found. The crude prevalence in 2016 was 0.04 per 100,000 population [95% confidence interval (CI) 0.02–0.06], ranging from 0.01 (95% CI 0.00–0.02) in North or Northeast China to 0.08 (95% CI 0.03–0.16) in Southwest China. The rate was higher in males (0.05, 95% CI 0.03–0.08) compared with females (0.03, 95% CI 0.02–0.05). The mean age of patients was 65.87 (standard deviation: 14.21) years, with the peak prevalence appeared in patients aged 70–79 (0.28, 95% CI 0.16–0.42). Conclusions The prevalence of EMPD was markedly lower than those in the United States and Europe, and varied across regions in China. Chinese patients were much younger, with significant male predominance. Further studies are warranted to examine potential pathophysiologic mechanism.

Background: HUS is a severe syndrome that imposes a substantial burden on patients and their families, furthermore, it’s the leading cause of acute kidney failure in children. However, data on the epidemiology and disease burden of HUS are limited in Asia, including in China. We aimed to estimate the incidence and cost of HUS in China.Methods: Data on HUS from 2012 to 2016 were extracted from the databases of the Urban Employee Basic Medical Insurance (UEBMI) and the Urban Resident Basic Medical Insurance (URBMI). All cases were identified by the ICD code and Chinese diagnostic terms. The national incidence rates in 2016 were estimated and stratified by sex, age and season; the associated medical costs were also calculated. Results: The crude incidence was 0.66 per 100,000 person-years (95% CI: 0.57 to 1.06), and the standardized incidence was 0.57 (0.19 to 1.18). The highest incidence was observed in patients younger than 1 year old (5.08,95% CI: 0.23 to24.87). Meanwhile, the incidence was 0.38 per 100,000 person-years (95% CI: 0.13 to 0.75) in patients younger than 5 years old, and 0.29 per 100,000 person-years (95% CI: 0.09 to 0.57) in patients younger than 18 years old. The season with the highest incidence was autumn, followed by winter. The average cost was 1.75 thousand US dollars per patient, which was higher than the national average cost for all inpatients in the same period. Conclusions: The incidence of HUS in our study was lower than those in the most developed countries, and with different age and season distribution in incidence, which may suggest that the cause of HUS in China may be different from that elsewhere. Due to insufficient knowledge of physicians and lacking laboratory facilities required for an accurate diagnosis, the incidence rate of HUS may be underestimated. In view of the healthcare economic burden of HUS, further analyses and supports are needed in the future.

Compared with traditional lead-acid batteries, nickel–cadmium batteries and nickel-hydrogen batteries, lithium-ion batteries (LIBs) are much more environmentally friendly and much higher energy density. Besides, LIBs own the characteristics of no memory effect, high charging and discharging rate, long cycle life and high energy conversion rate. Therefore, LIBs have been widely considered as the most promising power source for mobile devices. Commonly used LIBs contain carbonate based liquid electrolytes. Such electrolytes own high ionic conductivity and excellent wetting ability. However, the use of highly flammable and volatile organic solvents in them may lead to problems like leakage, thermo runaway and parasitic interface reactions, which limit their application. Solid polymer electrolytes (SPEs) can solve these problems, while they also bring new challenges such as poor interfacial contact with electrodes and low ionic conductivity at room temperature. Many approaches have been tried to solve these problems. This article is divided into three parts to introduce polyethylene oxide (PEO) based polymer-ceramic hybrid solid electrolyte, which is one of the most efficient way to improve the performance of SPEs. The first part focuses on polymer-lithium salt (LiX) matrices, including their ionic conduction mechanism and impact factors for their ionic conductivity. In the second part, the influence of both active and passive ceramic fillers on SPEs are reviewed. In the third part, composite SPEs’ preparation methods, including solvent casting and thermocompression, are introduced and compared. Finally, we propose five key points on how to make composite SPEs with high ionic conductivity for reference.

Background Extramammary Paget’s disease (EMPD) is an intraepithelial adenocarcinoma. The chronic relapsing clinical course and unbearable clinical symptoms of EMPD usually result in a markedly diminished quality of life. No national data are available on descriptive epidemiology of EMPD in China, the most populous country over the world. This population-based study aimed to estimate the prevalence and associated sex and age patterns of EMPD in China. Methods This study was conducted using data from China’s Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance, covering approximately 0.43 billion Chinese urban residents in 2016. Patients with EMPD were identified based on the diagnostic names and codes in claim data. Results A total of 53 males and 31 females with EMPD were found. The crude prevalence in 2016 was 0.04 per 100 000 population [95% confidence interval (CI): 0.02 to 0.06], ranging from 0.01 (95% CI: 0.00 to 0.02) in North or Northeast China to 0.08 (95% CI: 0.03 to 0.16) in Southwest China. The rates were higher in males (0.05, 95% CI: 0.03 to 0.08) compared with females (0.03, 95% CI: 0.02 to 0.05). The mean age of patients was 65.87 (standard deviation: 14.21) years, with the peak prevalence appeared in patients aged 70–79 (0.28, 95% CI: 0.16 to 0.42). Conclusions The prevalence of EMPD was markedly lower than those in the United States and Europe, and varied across regions in China. Chinese patients were much younger, with significant male predominance. Further study is warranted to examine potential pathophysiologic mechanism.

Background Studies regarding the lipid-cognition relationship have increasingly gained popularity but have generated much mixed results. To date, few studies have focused on the difference between sexes. Methods This study included 6792 Chinese adults aged over 45 years (women, 48.56%; mean age, 57.28 years), who were free of severe conditions known to affect cognitive function at the baseline (2011). Blood concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) were assessed at baseline, and both continuous and categorical values were used in final analyses. Global cognitive functions were assessed by the word recall test and the mental status test in 2011, 2013, and 2015, respectively. We graded participants into three groups according to the cognitive change slopes: no decline (≥ 0), moderate decline (median to 0), and severe decline (< median). Sex-specific associations between blood lipids and cognitive decline were analyzed using ordinal logistic models, adjusting for sociodemographic information, lifestyle behaviors, and health status. Results Higher baseline TC and LDL-C concentrations exhibited no significant association with 5-year cognitive decline in men but were significantly associated with greater 5-year cognitive decline in women [odds ratio (OR) 1.026, 95% confidence interval (CI) 1.003, 1.050; OR 1.026, CI 1.002, 1.051, respectively]. For higher serum HDL-c levels, a significantly protective effect on cognition was observed in men, but a slightly adverse effect was found in women (not significant after Bonferroni correction). TG presented almost no effect on later cognition in either sex. Conclusion Different associations between sexes were observed for the lipid-cognition relationship, and maintaining serum cholesterol levels at an appropriate range may have a positive effect on cognitive health.

No national data have been available on descriptive epidemiology of mammary Paget’s disease (MPD) in China. This population-based study aimed to estimate the prevalence of MPD and its pattens by sex, age and area in China. We conducted a population-based study using data in 2016 from China’s Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance, covering approximately 0.43 billion residents. MPD cases were identified based on the diagnostic names and codes in claim data. A total of 825 patients of confirmed diagnosis of MPD were found during the study period. The prevalence of MPD in 2016 was 0.42 per 100,000 population (95% CI 0.19 to 0.73), with marked female predominance. The prevalence rates peaked at 40–59 years and ≥ 80 years in females and males, respectively. The prevalence rates varied among different regions, ranging from 0.06 (95% CI 0.00 to 0.23) in Northeast China to 1.21 (95% CI 0.07 to 3.72) in Northwest China. MPD showed marked female predominance in China. Chinese female patients were much younger, with lower prevalence than that in the United States. Obvious sex difference in the age pattern of MPD prevalence was also observed in China.

BACKGROUND WeChat official account is one of the most commonly used social media platform for patients with rare neurological diseases to obtain knowledge on their treatment options. Yet, there still lacks a comprehensive assessment on the WeChat posts. OBJECTIVE To assess the quality, readability and endorsement of online information about rare neurological diseases released by WeChat official accounts. METHODS A four-stage methodological sampling technique was used in this cross-sectional study to identify articles related to the top-seven rare neurological diseases (with the largest hospitalized patients) in China during May to August 2019. The quality was independently scored by two researchers using DISCERN, while the readability and the endorsement were calculated through a Chinese readability formula and the like ratio respectively. All the three indices were then compared among different affiliation categories and different treatment types. RESULTS A total of 173 eligible articles were selected from 28 WeChat official accounts. For all articles, the mean (SD) DISCERN score was 30.27 (7.20; 95% CI, 29.19-31.35), only three of 173 articles (1.73%) achieved the good level. The mean (SD) score of readability was 10.07 (1.35; 95% CI, 9.88-10.27), which geared to the level 4 (undergraduate). The mean (SD) like ratio was 0.010 (0.015; 95% CI, 0.007-0.012), statistically different among affiliation categories (H = 31.915, P < .001) and treatment types (H = 14.829, P = .01). Articles on psychological intervention had the highest endorsement but the lowest quality. Articles related to traditional Chinese medicine got the lowest like ratio and the most difficult readability. CONCLUSIONS Our findings indicate that the accessible online information about rare neurological diseases released on WeChat official accounts varies by sources and is generally of poor quality. The information presented is obscure and might exceed the average education level of the public, which therefore limits it to be further diffused. Future efforts to improve the quality, readability and endorsement of online information on rare neurological diseases are needed. CLINICALTRIAL

Additional file 1: Supplementary Table 1. TC, LDL-c levels in different HDL-c grades. Supplementary Table 2. Adjusted odds ratio in 5-year cognitive change in different plasma lipid levels across education levels, OR (95%CI. Abbreviations: OR, odds ratio; CI, confidence interval; LDL-c, low-density lipoprotein cholesterol; HDL-c, high-density lipoprotein cholesterol. † Adjusted for baseline age, marital status, registered residence, body mass index, alcohol use, smoking status, diabetes, hypertension, social activity, health insurance status and lipid-lowering medication use. * P

ObjectiveAmyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease and information on disease burden of ALS in mainland China was limited. We aimed to estimate the prevalence and incidence of ALS in China.MethodsWe used 2012–2016 data from China’s Urban Employee Basic Medical Insurance and Urban Residence Basic Medical Insurance, covering approximately 0.43 billion individuals. ALS cases were identified by the primary diagnosis (International Classification of Diseases code or text of diagnosis) in the insurance database.ResultsThe crude prevalence and incidence in 2016 were 2.91 per 100 000 person-years (95% CI 2.31 to 3.58) and 1.65 (95% CI 1.33 to 2.01), respectively. The standardised prevalence and incidence based on 2010 Chinese census data were 2.97 (95% CI 2.91 to 3.03) and 1.62 (95% CI 1.58 to 1.67), respectively. The annual prevalence between 2013 and 2016 remained relatively constant, ranging from 2.91 (95% CI 2.31 to 3.58) in 2016 to 3.29 (95% CI 2.51 to 4.17) in 2014 (linear regression: β=−0.129, p=0.104). Both rates peaked in the group aged 75–79 years.ConclusionsThe prevalence and incidence of ALS in mainland China were lower than those in developed countries, and maintained a relatively stable trend. The age at onset and age at diagnosis for ALS patients were younger than those in developed countries. Further research is expected to clarify the potential pathophysiological mechanism of ALS.

This systematic review assesses the accuracy of molecular diagnostic methods for the detection of pulmonary tuberculosis in studies performed in China, published in Chinese and English. We searched for studies that assessed the accuracy of molecular diagnostics for pulmonary TB in China in the China National Knowledge Infrastructure, the Wanfang Database, SinoMed, VIP Information, Pubmed, Embase, and the Cochrane Library. For each index test, a summary estimation for sensitivity and specificity was calculated using the bivariate random-effects model. A total of 59 studies were included in our analysis. Loop-mediated isothermal amplifcation (LAMP) assay (six studies; pooled sensitivity 90%, 95% CI 78–95%; specificity 93%, 85–97%), line probe assay (LPA) (one study; 87%, 84–90%; 94%, 92–95%) and polymerase chain reaction (PCR) (FQ-PCR and RT-PCR) (four studies; 90%, 55–99%; 93%, 71–99%) showed good diagnostic performance in the meta-analysis. The highest pooled sensitivity was from Xpert MTB/RIF (20 studies; pooled sensitivity 91%, 95% CI 87–94%). The highest pooled specificity was from cross-priming amplification (CPA) (six studies; pooled specificity 97%, 95–99%). The lowest pooled sensitivity and specificity were from simultaneous amplification and testing (SAT)-TB (three studies; 79%, 66–88%; 72%, 48–88%). In subgroup analysis, molecular diagnostics demonstrated higher sensitivity for pulmonary TB detection in smear-positive specimens. Xpert MTB/RIF, LAMP, LPA, CPA and PCR demonstrated high accuracy overall for pulmonary tuberculosis detection, while SAT-TB had poor performance.

Histone deacetylase inhibitor (HDACi) has been shown to demethylate the mammalian genome, which further strengthens the concept that DNA methylation and histone modifications interact in regulation of gene expression. Here, we report that an HDAC inhibitor, depsipeptide, exhibited significant demethylating activity on the promoters of several genes, including p16, SALL3, and GATA4 in human lung cancer cell lines H719 and H23, colon cancer cell line HT-29, and pancreatic cancer cell line PANC1. Although expression of DNA methyltransferase 1 (DNMT1) was not affected by depsipeptide, a decrease in binding of DNMT1 to the promoter of these genes played a dominant role in depsipeptide-induced demethylation and reactivation. Depsipeptide also suppressed expression of histone methyltransferases G9A and SUV39H1, which in turn resulted in a decrease of di- and trimethylated H3K9 around these genes’ promoter. Furthermore, both loading of heterochromatin-associated protein 1 (HP1 and HP1) to methylated H3K9 and binding of DNMT1 to these genes’ promoter were significantly reduced in depsipeptide-treated cells. Similar DNA demethylation was induced by another HDAC inhibitor, apicidin, but not by trichostatin A. Our data describe a novel mechanism of HDACi-mediated DNA demethylation via suppression of histone methyltransferases and reduced recruitment of HP1 and DNMT1 to the genes’ promoter. DNA methylation and histone modifications are critical epigenetic processes that help control chromatin structure and gene regulation (4, 6, 26, 28, 50). Although there are many kinds of histone modifications in mammalian cells (5, 33, 40, 41), up to this point it seems that it is histone acetylation and histone methylation which are associated with DNA methylation status in regulating gene expression. For example, chromatin with unmethylated CpG islands is always enriched in hyperacetylated histone, while methylated DNA has been shown to be associated with repressed chromatin (6, 26). Early evidence showed that DNA methylation might be a dominant factor in the suppression of gene expression, because the demethylating agent 5-aza-2-deoxycytidine (5-aza-CdR) alone

Most agents that damage DNA act through posttranslational modifications of p53 and activate its downstream targets. However, whether cellular responses to nucleoside analogue-induced DNA damage also operate through p53 posttranslational modification has not been reported. In this study, the relationship between p53 activation and its posttranslational modifications was investigated in the human cancer cell lines A549 and HCT116 in response to 5-aza-2'-deoxycytidine (5-aza-CdR) or cytarabine treatment. 5-Aza-CdR induces p53 posttranslational modifications through activation of an ATM- and Rad3-related (ATR) signaling pathway, and 5-aza-CdR-induced association of replication protein A with chromatin is required for the binding of ATR to chromatin. Upon treatment with 5-aza-CdR, ATR activation is clearly associated with p53 phosphorylation at Ser(15), but not at Thr(18), Ser(20), or Ser(37). This specific p53 phosphorylation at Ser(15) in turn results in acetylation of p53 at Lys(320) and Lys(373)/Lys(382) through transcriptional cofactors p300/CBP-associated factor and p300, respectively. These p53 posttranslational modifications are directly responsible for 5-aza-CdR induced p21(Waf1/Cip1) expression because the binding activity of acetylated p53 at Lys(320)/Lys(373)/Lys(382) to the p21(Waf1/Cip1) promoter, as well as p21(Waf1/Cip1) expression itself are significantly increased after 5-aza-CdR treatment. It is of interest that p53 phosphorylation at Ser(15) and acetylations at Lys(320)/Lys(373)/Lys(382) mutually interact in the 5-aza-CdR induced p21(Waf1/Cip1) expression shown by transfection of artificially mutated p53 expression vectors including S15A, K320R, and K373R/K382R into p53-null H1299 cells. These data taken together show for the first time that 5-aza-CdR activates the ATR signaling pathway, which elicits a specific p53 phosphorylation-acetylation cascade to induce p21(Waf1/Cip1) expression.

Autophagy is characterized by the sequestration of bulk cytoplasm, including damaged proteins and organelles, and delivery of the cargo to lysosomes for degradation. Although the autophagic pathway is also linked to tumour suppression activity, the mechanism is not yet clear. Here we report that cytosolic FoxO1, a forkhead O family protein, is a mediator of autophagy. Endogenous FoxO1 was required for autophagy in human cancer cell lines in response to oxidative stress or serum starvation, but this process was independent of the transcriptional activity of FoxO1. In response to stress, FoxO1 was acetylated by dissociation from sirtuin-2 (SIRT2), a NAD(+)-dependent histone deacetylase, and the acetylated FoxO1 bound to Atg7, an E1-like protein, to influence the autophagic process leading to cell death. This FoxO1-modulated cell death is associated with tumour suppressor activity in human colon tumours and a xenograft mouse model. Our finding links the anti-neoplastic activity of FoxO1 and the process of autophagy.

Proliferating cell nuclear antigen (PCNA) has been demonstrated to interact with multiple proteins involved in several metabolic pathways such as DNA replication and repair. However, there have been fewer reports about whether these PCNA-binding proteins influence stability of PCNA. Here, we observed a physical interaction between PCNA and MutT homolog2 (MTH2), a new member of the MutT-related proteins that hydrolyzes 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP). In several unstressed human cancer cell lines and in normal human fibroblast cells, PCNA and MTH2 formed a complex and their mutual binding fragments were confirmed. It was intriguing that PCNA and MTH2 were dissociated dependent on acetylation of PCNA, which in turn induced degradation of PCNA in response to UV irradiation, but not in response to other forms of DNA-damaging stress. To further explore the link between dissociation of PCNA-MTH2 and degradation of PCNA, RNAi against MTH2 was performed to mimic the dissociated status of PCNA to evaluate changes in the half-life of PCNA. Knockdown of MTH2 significantly promoted degradation of PCNA, suggesting that the physiological interaction of PCNA-MTH2 may confer protection from degradation for PCNA, whereas UV irradiation accelerates PCNA degradation by inducing dissociation of PCNA-MTH2. Moreover, secondary to degradation of PCNA, UV-induced inhibition of DNA synthesis or cell cycle progression was enhanced. Collectively, our data demonstrate for the first time that PCNA is protected by this newly identified partner molecule MTH2, which is related to DNA synthesis and cell cycle progression.

Background and objectiveMoyamoya disease (MMD) is an increasingly recognised cause of stroke, mainly described in East Asia. China is the largest nation in Asia, but few studies reported the epidemiology of MMD, especially at a national level. We aimed to estimate the incidence and prevalence of MMD in China.MethodsWe performed a population-based study using data from the national databases of Urban Basic Medical Insurance between 2013 and 2016, covering approximately 0.50 billion individuals. MMD cases were identified by diagnostic code (International Classification of Diseases, 10th Revision I67.5) or related diagnostic text.ResultsA total of 1987 MMD patients (mean age 44.45±14.30 years, female-to-male ratio 1.12) were identified, representing a national crude incidence of 0.59 (95% CI: 0.49 to 0.68) and a prevalence of 1.01 (95% CI: 0.81 to 1.21) per 100 000 person-years in 2016. Rates were higher in females than in males for the incidence (0.66 vs 0.52) and prevalence (1.05 vs 0.90). And the age-specific rates showed a bimodal distribution, with the highest peak in middle-aged group and the second peak in child group.ConclusionsOur results confirm that MMD is relatively common in East Asians, but the rates in China were lower than those in other East Asian countries such as Japan and Korea. The unique epidemiological features, including a relatively weak female predominance and a shift in the highest peak of incidence from children to adults, revealed new sight into MMD. Further research is expected to explore the potential pathogenesis of MMD.

Histone deacetylase (HDAC) inhibitors have been shown to induce cell cycle arrest and apoptosis in cancer cells. However, the mechanisms of HDAC inhibitor induced apoptosis are incompletely understood. In this study, depsipeptide, a novel HDAC inhibitor, was shown to be able to induce significant apoptotic cell death in human lung cancer cells. Further study showed that Bim, a BH3-only proapoptotic protein, was significantly upregulated by depsipeptide in cancer cells, and Bim's function in depsipeptide-induced apoptosis was confirmed by knockdown of Bim with RNAi. In addition, we found that depsipeptide-induced expression of Bim was directly dependent on acetylation of forkhead box class O1 (FoxO1) that is catalyzed by cyclic adenosine monophosphate-responsive element-binding protein-binding protein, and indirectly induced by a decreased four-and-a-half LIM-domain protein 2. Moreover, our results demonstrated that FoxO1 acetylation is required for the depsipeptide-induced activation of Bim and apoptosis, using transfection with a plasmid containing FoxO1 mutated at lysine sites and a luciferase reporter assay. These data show for the first time that an HDAC inhibitor induces apoptosis through the FoxO1 acetylation-Bim pathway.