XinHua Hospital

BACKGROUND: Preterm birth is the leading cause of death in children younger than 5 years worldwide. Although preterm survival rates have increased in high-income countries, preterm newborns still die because of a lack of adequate newborn care in many low-income and middle-income countries. We estimated global, regional, and national rates of preterm birth in 2014, with trends over time for some selected countries. METHODS: We systematically searched for data on preterm birth for 194 WHO Member States from 1990 to 2014 in databases of national civil registration and vital statistics (CRVS). We also searched for population-representative surveys and research studies for countries with no or limited CRVS data. For 38 countries with high-quality data for preterm births in 2014, data are reported directly. For countries with at least three data points between 1990 and 2014, we used a linear mixed regression model to estimate preterm birth rates. We also calculated regional and global estimates of preterm birth for 2014. FINDINGS: We identified 1241 data points across 107 countries. The estimated global preterm birth rate for 2014 was 10·6% (uncertainty interval 9·0-12·0), equating to an estimated 14·84 million (12·65 million-16·73 million) live preterm births in 2014. 12· 0 million (81·1%) of these preterm births occurred in Asia and sub-Saharan Africa. Regional preterm birth rates for 2014 ranged from 13·4% (6·3-30·9) in North Africa to 8·7% (6·3-13·3) in Europe. India, China, Nigeria, Bangladesh, and Indonesia accounted for 57·9 million (41×4%) of 139·9 million livebirths and 6·6 million (44×6%) of preterm births globally in 2014. Of the 38 countries with high-quality data, preterm birth rates have increased since 2000 in 26 countries and decreased in 12 countries. Globally, we estimated that the preterm birth rate was 9×8% (8×3-10×9) in 2000, and 10×6% (9×0-12×0) in 2014. INTERPRETATION: Preterm birth remains a crucial issue in child mortality and improving quality of maternal and newborn care. To better understand the epidemiology of preterm birth, the quality and volume of data needs to be improved, including standardisation of definitions, measurement, and reporting. FUNDING: WHO and the March of Dimes.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmatising, and can improve awareness and patient identification.

BACKGROUND: Caesarean section (CS) rates continue to evoke worldwide concern because of their steady increase, lack of consensus on the appropriate CS rate and the associated additional short- and long-term risks and costs. We present the latest CS rates and trends over the last 24 years. METHODS: We collected nationally-representative data on CS rates between 1990 to 2014 and calculated regional and subregional weighted averages. We conducted a longitudinal analysis calculating differences in CS rates as absolute change and as the average annual rate of increase (AARI). RESULTS: According to the latest data from 150 countries, currently 18.6% of all births occur by CS, ranging from 6% to 27.2% in the least and most developed regions, respectively. Latin America and the Caribbean region has the highest CS rates (40.5%), followed by Northern America (32.3%), Oceania (31.1%), Europe (25%), Asia (19.2%) and Africa (7.3%). Based on the data from 121 countries, the trend analysis showed that between 1990 and 2014, the global average CS rate increased 12.4% (from 6.7% to 19.1%) with an average annual rate of increase of 4.4%. The largest absolute increases occurred in Latin America and the Caribbean (19.4%, from 22.8% to 42.2%), followed by Asia (15.1%, from 4.4% to 19.5%), Oceania (14.1%, from 18.5% to 32.6%), Europe (13.8%, from 11.2% to 25%), Northern America (10%, from 22.3% to 32.3%) and Africa (4.5%, from 2.9% to 7.4%). Asia and Northern America were the regions with the highest and lowest average annual rate of increase (6.4% and 1.6%, respectively). CONCLUSION: The use of CS worldwide has increased to unprecedented levels although the gap between higher- and lower-resource settings remains. The information presented is essential to inform policy and global and regional strategies aimed at optimizing the use of CS.

The Lancet Commission on pollution and health reported that pollution was responsible for 9 million premature deaths in 2015, making it the world's largest environmental risk factor for disease and premature death. We have now updated this estimate using data from the Global Burden of Diseases, Injuriaes, and Risk Factors Study 2019. We find that pollution remains responsible for approximately 9 million deaths per year, corresponding to one in six deaths worldwide. Reductions have occurred in the number of deaths attributable to the types of pollution associated with extreme poverty. However, these reductions in deaths from household air pollution and water pollution are offset by increased deaths attributable to ambient air pollution and toxic chemical pollution (ie, lead). Deaths from these modern pollution risk factors, which are the unintended consequence of industrialisation and urbanisation, have risen by 7% since 2015 and by over 66% since 2000. Despite ongoing efforts by UN agencies, committed groups, committed individuals, and some national governments (mostly in high-income countries), little real progress against pollution can be identified overall, particularly in the low-income and middle-income countries, where pollution is most severe. Urgent attention is needed to control pollution and prevent pollution-related disease, with an emphasis on air pollution and lead poisoning, and a stronger focus on hazardous chemical pollution. Pollution, climate change, and biodiversity loss are closely linked. Successful control of these conjoined threats requires a globally supported, formal science-policy interface to inform intervention, influence research, and guide funding. Pollution has typically been viewed as a local issue to be addressed through subnational and national regulation or, occasionally, using regional policy in higher-income countries. Now, however, it is increasingly clear that pollution is a planetary threat, and that its drivers, its dispersion, and its effects on health transcend local boundaries and demand a global response. Global action on all major modern pollutants is needed. Global efforts can synergise with other global environmental policy programmes, especially as a large-scale, rapid transition away from all fossil fuels to clean, renewable energy is an effective strategy for preventing pollution while also slowing down climate change, and thus achieves a double benefit for planetary health.

Over the past 2 decades, nonalcoholic fatty liver disease (NAFLD) has grown from a relatively unknown disease to the most common cause of chronic liver disease in the world. In fact, 25% of the world's population is currently thought to have NAFLD. Nonalcoholic steatohepatitis (NASH) is the subtype of NAFLD that can progress to cirrhosis, hepatocellular carcinoma (HCC), and death. NAFLD and NASH are not only found in adults-there is also a high prevalence of these diseases in children and adolescents. Because of the close association of NAFLD with type 2 diabetes (T2DM) and obesity, the latest models predict that the prevalence of NAFLD and NASH will increase, causing a tremendous clinical and economic burden and poor patient-reported outcomes. Nonetheless, there is no accurate noninvasive method to detect NASH, and treatment of this disease is limited to lifestyle modifications. To examine the state of NAFLD among different regions and understand the global trajectory of this disease, an international group of experts came together during the 2017 American Association for the Study of Liver Diseases Global NAFLD Forum. We provide a summary of this forum and an assessment of the current state of NAFLD and NASH worldwide.

BACKGROUND: The caesarean section (CS) rate continues to increase across high-income, middle-income and low-income countries. We present current global and regional CS rates, trends since 1990 and projections for 2030. METHODS: We obtained nationally representative data on the CS rate from countries worldwide from 1990 to 2018. We used routine health information systems reports and population-based household surveys. Using the latest available data, we calculated current regional and subregional weighted averages. We estimated trends by a piecewise analysis of CS rates at the national, regional and global levels from 1990 to 2018. We projected the CS rate and the number of CS expected in 2030 using autoregressive integrated moving-average models. RESULTS: Latest available data (2010-2018) from 154 countries covering 94.5% of world live births shows that 21.1% of women gave birth by caesarean worldwide, averages ranging from 5% in sub-Saharan Africa to 42.8% in Latin America and the Caribbean. CS has risen in all regions since 1990. Subregions with the greatest increases were Eastern Asia, Western Asia and Northern Africa (44.9, 34.7 and 31.5 percentage point increase, respectively) while sub-Saharan Africa and Northern America (3.6 and 9.5 percentage point increase, respectively) had the lowest rise. Projections showed that by 2030, 28.5% of women worldwide will give birth by CS (38 million caesareans of which 33.5 million in LMIC annually) ranging from 7.1% in sub-Saharan Africa to 63.4% in Eastern Asia . CONCLUSION: The use of CS has steadily increased worldwide and will continue increasing over the current decade where both unmet need and overuse are expected to coexist. In the absence of global effective interventions to revert the trend, Southern Asia and sub-Saharan Africa will face a complex scenario with morbidity and mortality associated with the unmet need, the unsafe provision of CS and with the concomitant overuse of the surgical procedure which drains resources and adds avoidable morbidity and mortality. If the Sustainable Development Goals are to be achieved, comprehensively addressing the CS issue is a global priority.

Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]), nonalcoholic fatty liver disease, and alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second-most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its "leader in liver diseases" title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China.

In recent decades, with the continuous development of high-throughput sequencing technology, data volume in medical research has increased, at the same time, almost all clinical researchers have their own independent omics data, which provided a better condition for data mining and a deeper understanding of gene functions. However, for these large amounts of data, many common and cutting-edge effective bioinformatics research methods still cannot be widely used. This has encouraged the establishment of many analytical platforms, a portion of databases or platforms were designed to solve the special analysis needs of users, for instance, MG RAST, IMG/M, Qiita, BIGSdb, and TRAPR were developed for specific omics research, and some databases or servers provide solutions for special problems solutions. Metascape was designed to only provide functional annotations of genes as well as function enrichment analysis; BioNumerics and RidomSeqSphere+ perform multilocus sequence typing; CARD provides only antimicrobial resistance annotations. Additionally, some web services are outdated, and inefficient interaction often fails to meet the needs of researchers, such as our previous versions of the platform. Therefore, the demand to complete massive data processing tasks urgently requires a comprehensive bioinformatics analysis platform. Hence, we have developed a website platform, Sangerbox 3.0 (http://vip.sangerbox.com/), a web-based tool platform. On a user-friendly interface that also supports differential analysis, the platform provides interactive customizable analysis tools, including various kinds of correlation analyses, pathway enrichment analysis, weighted correlation network analysis, and other common tools and functions, users only need to upload their own corresponding data into Sangerbox 3.0, select required parameters, submit, and wait for the results after the task has been completed. We have also established a new interactive plotting system that allows users to adjust the parameters in the image; moreover, optimized plotting performance enables users to adjust large-capacity vector maps on the web site. At the same time, we have integrated GEO, TCGA, ICGC, and other databases and processed data in batches, greatly reducing the difficulty to obtain data and improving the efficiency of bioimformatics study for users. Finally, we also provide users with rich sources of bioinformatics analysis courses, offering a platform for researchers to share and exchange knowledge.

In 1985 when a group of experts convened by the World Health Organization in Fortaleza, Brazil, met to discuss the appropriate technology for birth, they echoed what at that moment was considered an unjustified and remarkable increase of caesarean section (CS) rates worldwide.1 Based on the evidence available at that time, the experts in Fortaleza concluded: ‘there is no justification for any region to have a caesarean section rate higher than 10–15%’.1 Over the years, this quote has become ubiquitous in scientific literature, being interpreted as the ideal CS rate. Although this reference range was intended for ‘populations’, which are defined by geopolitical boundaries, in many instances it has been mistakenly used as the measurement for healthcare facilities regardless of their complexity or other characteristics. In addition to the case mix of the obstetric population served, the use of CS at healthcare facilities is also affected by factors such as their capacity to handle cases, availability of resource and the clinical management protocols used locally. Since its publication and for the last 30 years, this reference rate for CS has received intense criticism and has led to controversy, concern, polarised opinions and heated debates, while in parallel, the use of CS as a mode of delivery has continued its worrying rise worldwide. The need to revisit the recommended CS rate has been considered more and more necessary in view of the significant improvements in clinical obstetric care and in the methodology to assess evidence and issue recommendations in the last three decades. The global concern around CS rates is understandable. When medically justified, a CS can prevent maternal and perinatal mortality and morbidity. There is no evidence, however, showing the benefits of the procedure for women or infants where it is not required. CS is associated with short- and long-term risk, which can extend beyond the current delivery and affect future pregnancies. In addition, the increase in CS rates seems uncontrollable, with no signs that it is slowing down. The situation is aggravated by the fact that the causes of the rise are not fully understood but emerge as a complex multifactorial labyrinth involving health systems, health care providers, women, societies, and even fashion and media.2-6 Lastly, non-clinical interventions to reduce unnecessary CS have shown limited effectiveness to date.7 In light of these issues, WHO convened a meeting in Geneva, Switzerland, on 8–9 October 2014 with the objective of (1) establishing the current WHO position on the CS rate or range for optimal maternal and perinatal outcomes at population level, and (2) agreeing on a proposal for a tool to monitor CS rates at facility level. The Statement on Caesarean Section Rates recently released by WHO summarises the results of the systematic reviews and analyses conducted for this purpose and conveys the thinking emerging from the discussions of the meeting.8 A systematic review and an ecological analysis were performed and concluded that at population level, CS rates higher than 10% were not associated with reductions in maternal and newborn mortality rates.9, 10 The Statement notes, however, that the association between CS rates and other relevant outcomes such as stillbirths, maternal and perinatal morbidity, paediatric outcomes and psychological or social well-being could not be determined due to the lack of data on these other outcomes at the population level. This lack of data represents a limitation of these analyses that needs to be borne in mind. Beyond numbers and rates, the Statement emphasises that the critical role played by the quality of care in this equation cannot be overstated. As with any surgery, CS is associated with short- and long-term risks, particularly in settings that lack the facilities or capacity to conduct safe surgery or treat surgical complications properly, or where access to labour care or repeat CS in subsequent pregnancies cannot be taken for granted. On the other hand, inadequate access to timely CS may result in perinatal asphyxia, stillbirth, uterine rupture or obstetric fistula, a marker for exceptionally prolonged, obstructed labour.11 Thus, CS should be undertaken when medically necessary, and rather than striving to achieve a specific rate, efforts should focus on providing caesarean section to all women in need. How to define the woman ‘in need’ can only be ascertained by the health care providers caring for the woman on a case-by-case basis. Most importantly, at the healthcare facility level, clinicians and administrators struggle to monitor CS rates in a meaningful, reliable and action-oriented manner. Historically, caesarean sections have often been categorised using its indications as the unit being classified. Using indications to classify CS has always been problematic due to the lack of uniform definitions for most common indications and has resulted in poor reproducibility and unsatisfactory comparisons.12 In 2001, Dr Michael Robson proposed a system of 10 groups that classifies all women admitted for delivery (and not indications) according to five obstetric characteristics that are generally routinely collected in most maternities.13 Two systematic reviews conducted at WHO identified this classification as the most appropriate system to fulfil current international and local needs.12, 14 The WHO Statement proposes the use of the Robson classification as the global standard for assessing, monitoring and comparing CS rates within healthcare facilities over time, and between facilities. In the last decade, this classification has witnessed an extraordinary expansion in its use worldwide, particularly in healthcare facilities, due to its intrinsic appealing characteristics: simplicity of design, validity of purpose, ease of implementation and directness of initial interpretation.14 WHO envisions that the information stemming from the classification can be a powerful tool to inform practice. The classification will allow not only for stratification of CS rates in more uniform groups of women but also the assessment of CS rates in relation to other perinatal outcomes and processes (e.g. rates of oxytocin usage, postpartum haemorrhage, newborn outcomes, length of labour). WHO will guide and support countries in the use, implementation and interpretation of the classification so that we can start comparing CS rates in a meaningful, targeted, transparent and useful manner. By endorsing the Robson classification, this Statement should become a catalyst for action. The time has come to put the debate about the preferable rate of CS on hold. Let's start to collect data uniformly so that in the near future we will be able to move our focus from CS rates at population level to monitoring and discussing CS rates and outcomes in each group of the Robson classification. Only then will we have the data and evidence that will lead us more clearly to actions to improve care.15 Ultimately, we hope the debate can recommence with more valuable, solid and informative data to support our discussions. None declared. Completed disclosure of interests form available to view online as supporting information. All authors contributed to the writing of the commentary. This commentary has been written without any external funding. No ethical approval was sought for the writing of this commentary. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of the World Health Organization or other organizations. WHO Working Group on Caesarean Section: HA Aleem (Department of Obstetrics and Gynecology, Women's Health Center, Assiut University Hospital, Assiut, Egypt), F Althabe (Institute for Clinical Effectiveness and Health Policy, Buenos Aires, Argentina), T Bergholt (Department of Obstetrics, University of Copenhagen, Copenhagen, Denmark), L de Bernis (United Nations Population Fund, Geneva, Switzerland), G Carroli (Centro Rosarino de Estudios Perinatales, Rosario, Argentina), C Deneux-Tharaux (INSERM U1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Epidemiology and Statistics Sorbonne Paris Cité, Paris Descartes University, Paris, France), R Devlieger (UZLeuven, Campus Gasthuisberg, Department of Obstetrics and Gynecology, Leuven, Belgium), S Debonnet (International Confederation of Midwives, 2517 AN The Hague, the Netherlands), T Duan (Shanghai No.1 Maternal & Infant Health Hospital, Shanghai, China), C Hanson [International Federation of Gynecology & Obstetrics (FIGO), London, UK], J Hofmeyr (Department of Health, Effective Care Research Unit, University of Fort Hare, East London, Eastern Cape, South Africa), R Gonzalez Pérez (Department of Maternal and Gynaecological Health, Pontificia Universidad Catolica de Chile, Santiago de Chile, Chile), A de Jonge (Midwifery Science, AVAG and the EMGO Institute of Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands), K Khan (Women's Health Research Unit, Multi-disciplinary Evidence Synthesis Hub, The Blizard Institute, London, UK), S Lansky (Ministry of Health, Belo Horizonte Minas Gerais, Brazil), G Lazdane (WHO Regional Office for Europe, Copenhagen, Denmark), P Lumbiganon (Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand), D Mackeen (Department of Obstetrics and Gynecology, Division of Maternal–Fetal Medicine, Geisimger Health System, Danville, PA, USA), R Mahaini (WHO Office for the Eastern Mediterranean Region, Cairo, Egypt), S Manyame (Department of Obstetrics & Gynaecology, Harare Hospital & University of Zimbabwe, Harare, Zimbabwe), M Mathai (Department of Maternal and Child Health, World Health Organization, Geneva, Switzerland), R Mikolajczyk (ESME – Epidemiological and Statistical Methods Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany), R Mori (Department of Health Policy, National Center for Child Health and Development, Tokyo, Japan), B De Mucio (Latin American Center for Perinatology, Women and Reproductive Health (CLAP/WR), WHO Regional Office for the Americas, Montevideo, Uruguay), OT Oladapo (UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO, Geneva, Switzerland), E Ortiz-Panozo (Center for Population Health Research, National Institute of Public Health, Cuernavaca, Mexico), L Ouedraogo (WHO Regional Office for Africa, Brazzaville, Congo), C Parker (Obstetrics and Gyneacology Department, Baragwanath Maternity Hospital, Johannesburg, South Africa), M Robson (National Maternity Hospital, Dublin, Ireland), S Serruya (Latin American Center for Perinatology, Women and Reproductive Health (CLAP/WR), WHO Regional Office for the Americas, Montevideo, Uruguay), JP Souza [Department of Social Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto (SP), Brazil], CY Spong (Deputy Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda, MD, USA), C Stanton (Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA), ME Stanton (USAID, Washington DC, USA), EA Sullivan (Faculty of Health, University of Technology, Sydney, Australia), M Temmerman (UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO, Geneva, Switzerland), A Tita (Department of Obstetrics and Gynecology, Division of Maternal–Fetal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA), Ӧ Tunçalp (UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO, Geneva, Switzerland), P Velebil (Perinatal Center of the Institute for the Care of Mother and Child, Prague, Czech Republic), JP Vogel (UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO, Geneva, Switzerland), M Weber (WHO Regional Office for Europe, Copenhagen, Denmark), D Wojdyla (Duke Clinical Research Institute, Durham, NC, USA), J Ye (Ministry of Education–Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China), K Yunis (Department of Pediatrics & Adolescent, Medicine and Department of Pediatrics, American University of Beirut, Beirut, Lebanon), J Zamora (Clinical Biostatistics Unit, Hospital Ramón y Cajal, Madrid, Spain), A Zongo (Research Institute for Development, Université Paris Descartes, Sorbonne Paris Cité, UMR 216, Paris, France and Direction de la santé de la famille, Ministère de la Santé, Ouagadougou, Burkina Faso) Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

BACKGROUND: Rates of caesarean section surgery are rising worldwide, but the determinants of this increase, especially in low-income and middle-income countries, are controversial. In this study, we aimed to analyse the contribution of specific obstetric populations to changes in caesarean section rates, by using the Robson classification in two WHO multicountry surveys of deliveries in health-care facilities. The Robson system classifies all deliveries into one of ten groups on the basis of five parameters: obstetric history, onset of labour, fetal lie, number of neonates, and gestational age. METHODS: We studied deliveries in 287 facilities in 21 countries that were included in both the WHO Global Survey of Maternal and Perinatal Health (WHOGS; 2004-08) and the WHO Multi-Country Survey of Maternal and Newborn Health (WHOMCS; 2010-11). We used the data from these surveys to establish the average annual percentage change (AAPC) in caesarean section rates per country. Countries were stratified according to Human Development Index (HDI) group (very high/high, medium, or low) and the Robson criteria were applied to both datasets. We report the relative size of each Robson group, the caesarean section rate in each Robson group, and the absolute and relative contributions made by each to the overall caesarean section rate. FINDINGS: The caesarean section rate increased overall between the two surveys (from 26.4% in the WHOGS to 31.2% in the WHOMCS, p=0.003) and in all countries except Japan. Use of obstetric interventions (induction, prelabour caesarean section, and overall caesarean section) increased over time. Caesarean section rates increased across most Robson groups in all HDI categories. Use of induction and prelabour caesarean section increased in very high/high and low HDI countries, and the caesarean section rate after induction in multiparous women increased significantly across all HDI groups. The proportion of women who had previously had a caesarean section increased in moderate and low HDI countries, as did the caesarean section rate in these women. INTERPRETATION: Use of the Robson criteria allows standardised comparisons of data across countries and timepoints and identifies the subpopulations driving changes in caesarean section rates. Women who have previously had a caesarean section are an increasingly important determinant of overall caesarean section rates in countries with a moderate or low HDI. Strategies to reduce the frequency of the procedure should include avoidance of medically unnecessary primary caesarean section. Improved case selection for induction and prelabour caesarean section could also reduce caesarean section rates. FUNDING: None.

OBJECTIVE: To investigate the risk of adverse pregnancy outcomes among adolescents in 29 countries. DESIGN: Secondary analysis using facility-based cross-sectional data of the World Health Organization Multicountry Survey on Maternal and Newborn Health. SETTING: Twenty-nine countries in Africa, Latin America, Asia and the Middle East. POPULATION: Women admitted for delivery in 359 health facilities during 2-4 months between 2010 and 2011. METHODS: Multilevel logistic regression models were used to estimate the association between young maternal age and adverse pregnancy outcomes. MAIN OUTCOME MEASURES: Risk of adverse pregnancy outcomes among adolescent mothers. RESULTS: A total of 124 446 mothers aged ≤24 years and their infants were analysed. Compared with mothers aged 20-24 years, adolescent mothers aged 10-19 years had higher risks of eclampsia, puerperal endometritis, systemic infections, low birthweight, preterm delivery and severe neonatal conditions. The increased risk of intra-hospital early neonatal death among infants born to adolescent mothers was reduced and statistically insignificant after adjustment for gestational age and birthweight, in addition to maternal characteristics, mode of delivery and congenital malformation. The coverage of prophylactic uterotonics, prophylactic antibiotics for caesarean section and antenatal corticosteroids for preterm delivery at 26-34 weeks was significantly lower among adolescent mothers. CONCLUSIONS: Adolescent pregnancy was associated with higher risks of adverse pregnancy outcomes. Pregnancy prevention strategies and the improvement of healthcare interventions are crucial to reduce adverse pregnancy outcomes among adolescent women in low- and middle-income countries.

BACKGROUND: Salidroside (SDS) is the main effective ingredient of Rhodiola rosea L with a variety of pharmacologic properties. We aim to investigate the effects of SDS on ventilation induced lung injury (VILI) and explore the possible underlying molecular mechanism. METHODS: Lung injury was induced in male ICR mice via mechanical ventilation (30 ml/kg) for 4h. The mice were divided in four groups:(1) Control group; (2) Ventilation group; (3) SDS group; (4) Ventilation with SDS group. SDS (50 mg/kg) was injected intraperitoneally 1h before operation. Mouse lung vascular endothelial cells (MLVECs) were subjected to cyclic stretch for 4h. RESULTS: It was found that SDS attenuated VILI as shown in HE staining, cell count and protein content levels in BAL fluid, W/D and Evans blue dye leakage into the lung tissue. SDS treatment inhibited the activation of NLRP3 inflammasome and subsequent caspase-1 cleavage as well as interleukin (IL)-1β secretion both in vivo and in vitro. Moreover, SDS administration up-regulated SIRT1 expression. Importantly, knockdown of SIRT1 reversed the inhibitory effect of SDS on NLRP3 inflammasome activation. CONCLUSIONS: Taken together, these findings indicate that SDS may confer protection against ventilation induced lung injury via SIRT1-de-pendent inhibition of NLRP3 inflammasome activation.

Microglia-mediated neuroinflammation is a common feature of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Microglia can be categorized into two opposite types: classical (M1) or alternative (M2), though there's a continuum of different intermediate phenotypes between M1 and M2, and microglia can transit from one phenotype to another. M1 microglia release inflammatory mediators and induce inflammation and neurotoxicity, while M2 microglia release anti-inflammatory mediators and induce anti-inflammatory and neuroprotectivity. Microglia-mediated neuroinflammation is considered as a double-edged sword, performing both harmful and helpful effects in neurodegenerative diseases. Previous studies showed that balancing microglia M1/M2 polarization had a promising therapeutic prospect in neurodegenerative diseases. We suggest that shifting microglia from M1 to M2 may be significant and we focus on the modulation of microglia polarization from M1 to M2, especially by important signal pathways, in neurodegenerative diseases.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

INTRODUCTION Parkinson’s disease (PD) is the second most common neurodegenerative disorder and leads to slowness of movement, tremor, rigidity, and, in the later stages of PD, cognitive impairment. Pathologically, PD is characterized by the accumulation of α-synuclein in Lewy bodies and neurites. There is degeneration of neurons throughout the nervous system, with the degeneration of dopamine neurons in the substantia nigra pars compacta leading to the major symptoms of PD. RATIONALE In the brains of PD patients, pathologic α-synuclein seems to spread from cell to cell via self-amplification, propagation, and transmission in a stereotypical and topographical pattern among neighboring cells and/or anatomically connected brain regions. The spread or transmission of pathologic α-synuclein is emerging as a potentially important driver of PD pathogenesis. The underlying mechanisms and molecular entities responsible for the transmission of pathologic α-synuclein from cell to cell are not known, but the entry of pathologic α-synuclein into neurons is thought to occur, in part, through an active clathrin-dependent endocytic process. RESULTS Using recombinant α-synuclein preformed fibrils (PFF) as a model system with which to study the transmission of misfolded α-synuclein from neuron to neuron, we screened a library encoding transmembrane proteins for α-synuclein-biotin PFF–binding candidates via detection with streptavidin-AP (alkaline phosphatase) staining. Three positive clones were identified that bind α-synuclein PFF and include lymphocyte-activation gene 3 (LAG3), neurexin 1β, and amyloid β precursor-like protein 1 (APLP1). Of these three transmembrane proteins, LAG3 demonstrated the highest ratio of selectivity for α-synuclein PFF over the α-synuclein monomer. α-Synuclein PFF bind to LAG3 in a saturable manner (dissociation constant = 77 nM), whereas the α-synuclein monomer does not bind to LAG3. Co-immunoprecipitation also suggests that pathological α-synuclein PFF specifically bind to LAG3. Tau PFF, β-amyloid oligomer, and β-amyloid PFF do not bind to LAG3, indicating that LAG3 is specific for α-synuclein PFF. The internalization of α-synuclein PFF involves LAG3 because deletion of LAG3 reduces the endocytosis of α-synuclein PFF. LAG3 colocalizes with the endosomal guanosine triphosphatases Rab5 and Rab7 and coendocytoses with pathologic α-synuclein. Neuron-to-neuron transmission of pathologic α-synuclein and the accompanying pathology and neurotoxicity is substantially attenuated by deletion of LAG3 or by antibodies to LAG3. The lack of LAG3 also substantially delayed α-synuclein PFF–induced loss of dopamine neurons, as well as biochemical and behavioral deficits in vivo. CONCLUSION We discovered that pathologic α-synuclein transmission and toxicity is initiated by binding to LAG3 and that neuron-to-neuron transmission of pathological α-synuclein involves the endocytosis of exogenous α-synuclein PFF by the engagement of LAG3 on neurons. Depletion of LAG3 or antibodies to LAG3 substantially reduces the pathology set in motion by the transmission of pathologic α-synuclein. The identification of LAG3 as an α-synuclein PFF–binding protein provides a new target for developing therapeutics designed to slow the progression of PD and related α-synucleinopathies. LAG3 deletion or antibodies to LAG3 delay α-synuclein PFF transmission. Compared with wild-type neurons, binding and endocytosis of α-synuclein PFF is dramatically reduced with antibodies to LAG3 or when LAG3 is deleted, resulting in delayed pathologic α-synuclein transmission and toxicity. Illustration credit: I-Hsun Wu

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.

Pickering emulsion, a kind of emulsion stabilized only by solid particles locating at oil-water interface, has been discovered a century ago, while being extensively studied in recent decades. Substituting solid particles for traditional surfactants, Pickering emulsions are more stable against coalescence and can obtain many useful properties. Besides, they are more biocompatible when solid particles employed are relatively safe in vivo. Pickering emulsions can be applied in a wide range of fields, such as biomedicine, food, fine chemical synthesis, cosmetics and so on, by properly tuning types and properties of solid emulsifiers. In this article, we give an overview of Pickering emulsions, focusing on some kinds of solid particles commonly serving as emulsifiers, three main types of products from Pickering emulsions, morphology of solid particles and as-prepared materials, as well as applications in different fields.

BACKGROUND: Cisplatin-based chemotherapy is frequently used to treat advanced gastric cancer (GC). However, the resistance often occurs with the mechanisms being not well understood. Recently, emerging evidence indicates that tumor-associated macrophages (TAMs) play an important role in chemoresistance of cancer. As the important mediators in intercellular communications, exosomes secreted by host cells mediate the exchange of genetic materials and proteins to be involved in tumor aggressiveness. The aim of the study was to investigate whether exosomes derived from TAMs mediate cisplatin resistance in gastric cancer. METHODS: M2 polarized macrophages were obtained from mouse bone marrow or human PBMCs stimulated with IL-4 and IL-13. Exosomes isolated from M2 macrophages culture medium were characterized, and miRNA expression profiles of M2 derived exosomes (M2-exos) were analyzed using miRNA microarray. In vitro cell coculture was further conducted to investigate M2-exos mediated crosstalk between TAMs and tumor cells. Moreover, the in vivo experiments were performed using a subcutaneous transplantation tumor model in athymic nude mice. RESULTS: In this study, we showed that M2 polarized macrophages promoted cisplatin (DDP) resistance in gastric cancer cells and exosomes derived from M2 macrophages (M2-exos) are involved in mediating the resistance to DDP. Using miRNA profiles assay, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and cell lysate isolated from M2 polarized macrophage. Functional studies revealed that exosomal miR-21 can be directly transferred from macrophages to the gastric cancer cells, where it suppresses cell apoptosis and enhances activation of PI3K/AKT signaling pathway by down-regulation of PTEN. CONCLUSIONS: Our findings suggest that exosomal transfer of tumor-associated macrophages derived miR-21 confer DDP resistance in gastric cancer, and targeting exosome communication may be a promising new therapeutic strategy for gastric cancer patients.

Fifty-eight acute promyelocytic leukemia (APL) patients (11 newly diagnosed and 47 relapsed) were studied for arsenic trioxide (As2O3) treatment. Clinical complete remission (CR) was obtained in 8 of 11 (72.7%) newly diagnosed cases. However, As2O3 treatment resulted in hepatic toxicity in 7 cases including 2 deaths, in contrast to the mild liver dysfunction in one third of the relapsed patients. Forty of forty-seven (85.1%) relapsed patients achieved CR. Two of three nonresponders showed clonal evolution at relapse, with disappearance of t(15;17) and PML-RARalpha fusion gene in 1 and shift to a dominant AML-1-ETO population in another, suggesting a correlation between PML-RARalpha expression and therapeutic response. In a follow-up of 33 relapsed cases over 7 to 48 months, the estimated disease-free survival (DFS) rates for 1 and 2 years were 63.6% and 41.6%, respectively, and the actual median DFS was 17 months. Patients with white blood cell (WBC) count below 10 x 10(9)/L at relapse had better survival than those with WBC count over 10 x 10(9)/L (P =.038). The duration of As2O3-induced CR was related to postremission therapy, because there was only 2 of 11 relapses in patients treated with As2O3 combined with chemotherapy, compared with 12 of 18 relapses with As2O3 alone (P =.01). Reverse transcription polymerase chain reaction (RT-PCR) analysis in both newly diagnosed and relapsed groups showed long-term use of As2O3 could lead to a molecular remission in some patients. We thus recommend that ATRA be used as first choice for remission induction in newly diagnosed APL cases, whereas As2O3 can be either used as a rescue for relapsed cases or included into multidrug consolidation/maintenance clinical trials.