Annual review of PROTAC degraders as anticancer agents in 2022.

Following nearly two decades of development, significant advancements have been achieved in PROTAC technology. As of the end of 2022, more than 20 drugs have entered clinical trials, with ARV-471 targeting estrogen receptor (ER) showing remarkable progress by entering phase III clinical studies. In 2022, significant progress has been made on multiple targets. The first reversible covalent degrader designed to target the KRASG12C mutant protein, based on cyclopropionamide, has been reported. Additionally, the activity HDCA1 degrader surpassed submicromolar levels during the same year. A novel FEM1B covalent ligand called EN106 was also discovered, expanding the range of available ligands. Furthermore, the first PROTAC drug targeting SOS1 was reported. Additionally, the first-in-class degraders that specifically target BRD4 isoforms (BRD4 L and BRD4 S) have recently been reported, providing a valuable tool for further investigating the biological functions of these isoforms. Lastly, a breakthrough was also achieved with the first degrader targeting both CDK9 and Cyclin T1. In this review, we aimed to update the PROTAC degraders as potential anticancer agents covering articles published in 2022. The design strategies, degradation effects, and anticancer activities were highlighted, which might provide an updated sight to develop novel PROTAC degraders with great potential as anticancer agents as well as favorable drug-like properties.

Design, synthesis and biological evaluation of 1,2,3-triazole benzothiazole derivatives as tubulin polymerization inhibitors with potent anti-esophageal cancer activities.

In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18, exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC50 values were 0.042 and 0.038 µM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC50 = 0.446 µM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18, which possesses significant potential for treating esophageal cancers.

Morphological and phylogenetic analyses reveal a new species of Anthracophyllum (Omphalotaceae, Agaricales) in Zhejiang Province, China.

During the investigations of macrofungi resources in Zhejiang Province, China, an interesting wood rot fungus was collected. Based on morphological and molecular phylogenetic studies, it is described as a new species, Anthracophyllum sinense. A. sinense is characterized by its sessile, charcoal black and pleurotoid pileus, sparse lamellae occasionally branching, clavate basidia with long sterigmata [(3-)6-7(-8) µm], and non-heteromorphous cystidia. A. sinense establishes a separate lineage close to A. archeri and A. lateritium in the phylogenetic tree.

DNA-Functionalized Porphyrinic Metal-Organic Framework-Based Drug Delivery System for Targeted Bimodal Cancer Therapy.

A DNA-functionalized porphyrinic MOF (porMOF) drug delivery system was successfully constructed. porMOF as a photosensitizer and drug delivery carrier can integrate photodynamic therapy (PDT) and chemotherapy. Via the strong coordination interaction between the zirconium cluster of porMOF and the terminal phosphate group of DNA, the stable modification of the DNA layer on the porMOF surface is achieved. Meanwhile, the introduction of C/G-rich base pairs into the DNA double-stranded structure provides more binding sites of chemotherapeutic drug doxorubicin (DOX). AS1411, an aptamer of nucleolin proteins that are overexpressed by cancer cells, is introduced in the double-stranded terminal, which can endow the nanosystem with the ability to selectively recognize cancer cells. C-rich sequences in DNA double strands form an i-motif structure under acidic conditions to promote the highly efficient release of DOX in cancer cells. In vitro and in vivo experiments demonstrate that the synergistic PDT/chemotherapy modality achieves highly efficient cancer cell killing and tumor ablation without undesirable side effects.

Real-world tobacco cessation practice in China: findings from the prospective, nationwide multicenter China National Tobacco Cessation Cohort Study (CNTCCS).

Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).

Design, synthesis and biological evaluation of novel 2,4-diaminopyrimidine cinnamyl derivatives as inhibitors of FAK with potent anti-gastric cancer activities.

In this study, twenty-one novel 2,4-diaminopyrimidine cinnamyl derivatives as inhibitors targeting FAK were designed and synthesized based on the structure of TAE-226, and the inhibitory effects of these compounds on both the FAK enzyme and three cancer cell lines (MGC-803, HCT-116, and KYSE30) were investigated. Among them, compound 12s displayed potent inhibitory potency on FAK (IC50 = 47 nM), and demonstrated more significant antiproliferative activities in MGC-803, HCT-116 and KYSE30 cells (IC50 values were 0.24, 0.45 and 0.44 µM, respectively) compared to TAE-226. Furthermore, compound 12s significantly inhibited FAK activation leading to the negative regulation of FAK-related signaling pathways such as AKT/mTOR and MAPK signaling pathways. Molecular docking study suggested that compound 12s could well occupy the ATP-binding pocket site of FAK similar to TAE-226. In addition, compound 12s also efficiently inhibited the proliferation, induced apoptosis and cellular senescence in MGC-803 cells. In conclusion, compound 12s emerges a potent FAK inhibitor that could exert potent inhibitory activity against gastric cancer cells.

Visible Light-Induced Cascade Sulfonylation/Cyclization to Produce Quinoline-2,4-Diones under Metal-Free Conditions.

A general visible light-induced sulfonylation/cyclization to produce quinoline-2,4-diones was achieved under photocatalyst-free conditions. The reactions were performed at room temperature, and various substituents (halogen, alkyl, aryl) and substituted products were obtained with 29 examples within 2 h. Large-scale synthesis and derivatization study via carbonyl reduction to produce easily modified hydroxyl groups and convenient N-Ts deprotection showed the potential utility of this strategy.

Environmental determinants of childhood obesity: a meta-analysis.

BACKGROUND: The increasing prevalence of childhood obesity has contributed to the growing global burden of chronic diseases over the life course, which has been largely attributed to obesogenic environments. This giant-scale review was done to translate existing obesogenic environmental studies into evidence-based governance for fighting childhood obesity and promoting life-course health. METHODS: Following a standard strategy of literature search and inclusion, all obesogenic environmental studies, published since the inception of the electronic databases, were reviewed to identify the evidence on associations with childhood obesity of 16 obesogenic environmental factors, including 10 built environmental factors or indices (ie, land-use mix, street connectivity, residential density, speed limit, urban sprawl, and access to green space, public transport, bike lanes, sidewalks, and neighbourhood aesthetics) and six food environmental factors (ie, access to convenience stores, supermarkets, grocery stores, full-service restaurants, fast-food restaurants, and fruit and vegetable markets). A meta-analysis was conducted to quantify the influence of each factor with sufficient studies on childhood obesity. FINDINGS: A total of 24 155 search results were found and filtered, with 457 studies included in the analysis. All built environmental factors, except speed limit and urban sprawl, were negatively associated with childhood obesity by encouraging physical activity while discouraging sedentary behaviours; the access to all food venues, except convenience stores and fast-food restaurants, was negatively associated with childhood obesity by encouraging their healthy eating behaviours. There were some globally consistent associations, such as between greater access to fast-food restaurants in the neighbourhood and more fast-food consumption, between better access to bike lanes and more physical activity, between better access to sidewalks and reduced sedentary behaviours, and between greater access to green space and more physical activity and less TV or computer screen time. INTERPRETATION: Findings have formed the unprecedentedly inclusive evidence for policy making and the establishment of the future research agenda regarding the obesogenic environment. FUNDING: National Natural Science Foundation of China, Chengdu Technological Innovation R&D Project, Sichuan Provincial Key R&D Program, and Wuhan University Specific Fund for Major School-level Internationalization Initiatives.

Chaetoglobosin E inhibits tumor growth and promotes the anti-tumor efficacy of cytotoxic drugs in esophageal squamous cell carcinoma by targeting PLK1.

Background: Currently, there is no satisfactory treatment available for esophageal squamous cell carcinoma (ESCC), and thus, there is a pressing need to develop effective drugs. Chaetoglobosin E, a cytochalasan alkaloid derived from metabolites of Chaetomium madrasense 375, is a chaetoglobosin with intense anti-tumor activity. Therefore, revealing its anti-tumor mechanism for the application of cytochalasans is crucial. Methods: The cytotoxic effect of chaetoglobosin E and cisplatin on esophageal cancer KYSE-30, KYSE-150, and TE-1 cells was detected using cell viability or colony formation assays. The cell cycle, apoptosis, autophagy, invasion, and metastasis were assayed by flow cytometry or western blot. The potential target of chaetoglobosin E was assayed by RNA sequencing (RNA-seq) and large loop prediction software analysis and was assessed by western blot and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effect of its target on cell pyroptosis was assayed using overexpression and silence experiments. Results: Chaetoglobosin E significantly inhibited the proliferation of KYSE-30, KYSE-150, and TE-1 cells, especially KYSE-30 cells. Our results showed that chaetoglobosin E induced the G2/M phase arrest of KYSE-30 cells, followed by the down-regulation of cyclinB1, CDC2, and p-CDC2, and up-regulation of p21. Moreover, chaetoglobosin E also decreased the anti-apoptotic protein expression of Bcl-2, increased apoptotic expression of Bax, increased autophagy protein expressions of beclin1 and LC3, decreased invasion and metastasis protein expression of E-cadherin, and increased expression of vimentin. The RNA-seq and large loop prediction software analysis results indicated that its potential target might be polo-like kinase 1 (PLK1). Moreover, results also showed that chaetoglobosin E can reverse the PLK1 overexpression plasmid-induced up-regulation of the PLK1 protein. Furthermore, we found that chaetoglobosin E induced pyroptosis via the activation of the gasdermin E (GSDME) protein. Further studies showed that the high expression of PLK1 inactivated the GSDME protein, while the knockdown of PLK1 expression activated the GSDME protein, indicating that chaetoglobosin E induced cell pyroptosis by inhibiting PLK1. Conclusions: This study suggested that chaetoglobosin E may be a novel lead compound to the treatment of ESCC patients by targeting PLK1, and elucidated for the first time that PLK1 was involved in a new pyroptosis mechanism.

Large-Scale Preparation of Micro-Nanofibrous and Fluffy Propylene-Based Elastomer/Polyurethane@Graphene Nanoplatelet Membranes with Breathable and Flexible Characteristics for Wearable Stretchy Heaters.

Effective personal thermal management is crucial for protecting human health during cold weather. Therefore, wearable heaters based on electric-heating membranes are one of the most promising devices to become essential appliances in our daily lives. The main challenge toward this goal is the development of electric-heating membranes with adequate breathable, flexible, and stretchable characteristics. In the work presented here, micro-nanofibrous fluffy electric-heating membranes were prepared by coating polyurethane/graphene nanoplatelet (PU@GNP) films onto melt-blown propylene-based elastomer (PBE) micro-nanofibrous membranes via a facile, cheap, and large-scale method consisting of a coating-compressing cyclic process. Investigation of the resulting PBE/PU@GNP membranes showed that the PU@GNP films were uniformly deposited onto the PBE micro-nanofiber surfaces, forming fluffy interconnected conducting channels. By applying a voltage of 36 V to the prepared PBE/PU@GNP membranes, the temperature increased to 69.7 °C, confirming excellent electric-heating features. Moreover, the porosity of the fabricated membrane could be tailored readily by adjusting the coating-compressing cycles. Benefiting from the conducting channels, the PBE/PU@GNP membranes exhibited efficiently regulated air permeability ranging from 212 to 60.2 mm/s, a prominent softness score of 53.8, and an excellent elastic recovery rate of 85.5%. These findings demonstrate that PBE/PU@GNP micro-nanofibrous fluffy membranes may well be suitable for application in electric-heating clothing. The cyclic coating-compressing preparation process may be attractive in industrial manufacturing.

Multivalent Metal Ion Cross-Linked Lignocellulosic Nanopaper with Excellent Water Resistance and Optical Performance.

Cellulose nanopaper is an attractive film material exhibiting huge potential in various fields, while its terrible water stability greatly hinders practical applications. Previous efforts on addressing this issue usually sacrifice the sustainability or material performance of film. In this study, we report a high-performing lignocellulosic nanopaper with superior water resistance and excellent optical properties. The strategy involves preparing a lignin-containing cellulose nanopaper (LCNP) first, and then infiltrating metal ions into the film to build cross-linking interactions within the fiber networks. Owing to the coordination bonds formed between metal ions and lignocellulosic components, the resulting metal ions cross-linked LCNP (M+-LCNP) displays outstanding water resistance, including the highest wet mechanical strength of ∼52 MPa after immersing in water for 24 h, which retains nearly 47% of the dry mechanical strength of the film. The ultralow water uptake ratio of ∼35% also confirms it possesses a superior wet dimensional stability. Moreover, these nanopapers also showcase the desired optical performances, including both high visible transmittance (>85%) and total ultraviolet-blocking efficiency (>91%, only transmitting a little of UVA). Overall, this fully degradable film is a promising alternative to replacing conventional plastics that are applied in multiple areas.

Associations and pathways between residential greenness and metabolic syndromes in Fujian Province.

Background: Greenness exposure is beneficial to human health, but its potential mechanisms through which the risk for metabolic syndrome (MetS) could be reduced have been poorly studied. We aimed to estimate the greenness-MetS association in southeast China and investigate the independent and joint mediation effects of physical activity (PA), body mass index (BMI), and air pollutants on the association. Methods: A cross-sectional study was conducted among the 38,288 adults based on the Fujian Behavior and Disease Surveillance (FBDS), established in 2018. MetS was defined as the presence of three or more of the five components: abdominal obesity, elevated triglyceride, reduced high-density lipoprotein cholesterol (HDL-C), high blood pressure, and elevated fasting glucose. The residential greenness exposure was measured as the 3-year mean values of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) within the 250, 500, and 1,000 meters (m) buffer zones around the residential address of each participant. Logistic regression models were used to estimate the greenness-MetS association. The causal mediation analysis was used to estimate the independent and joint mediation effects of PA, BMI, particulate matter with an aerodynamic diameter of 2.5 µm (PM2.5), particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2). Results: Each interquartile range (IQR) increase in greenness was associated with a decrease of 13% (OR = 0.87 [95%CI: 0.83, 0.92] for NDVI500m and OR = 0.87 [95%CI: 0.82, 0.91] for EVI500m) in MetS risk after adjusting for covariates. This association was stronger in those aged < 60 years (e.g., OR = 0.86 [95%CI: 0.81, 0.92] for NDVI500m), males (e.g., OR = 0.73 [95%CI: 0.67, 0.80] for NDVI500m), having an educational level of primary school or above (OR = 0.81 [95%CI: 0.74, 0.89] for NDVI500m), married/cohabitation (OR = 0.86 [95%CI: 0.81, 0.91] for NDVI500m), businessman (OR = 0.82 [95%CI: 0.68, 0.99] for NDVI500m), other laborers (OR = 0.77 [95%CI: 0.68, 0.88] for NDVI500m), and non-smokers (OR = 0.77 [95%CI: 0.70, 0.85] for NDVI500m). The joint effect of all six mediators mediated about 48.1% and 44.6% of the total effect of NDVI500m and EVI500m on the MetS risk, respectively. Among them, BMI showed the strongest independent mediation effect (25.0% for NDVI500m), followed by NO2 and PM10. Conclusion: Exposure to residential greenness was associated with a decreased risk for MetS. PA, BMI, and the four air pollutants jointly interpreted nearly half of the mediation effects on the greenness-MetS association.

Awareness regarding and vaccines acceptability of human papillomavirus among parents of middle school students in Zunyi, Southwest China.

The objective of this study was to investigate the parent cognition of information regarding the human papillomavirus (HPV) and their willingness toward HPV vaccination of their middle-school-aged children in Zunyi, Guizhou Province, China.The results provide a basis for improving the awareness concerning HPV-related information as a key vaccination strategy for implementing the HPV vaccine in the local context. Methods include the random cluster sampling method and questionnaires to survey parents. General descriptive and single-factor analyses were used to assess cognition to determine factors influencing vaccine willingness. Of 1,074 parents, 28.2% (302) and 38.0% (408) had heard of HPV and its vaccine before the survey, and when given HPV-related information, 73.9% (794) parents were willing to vaccinate their children. Reasons why parents did or did not want the vaccination were surveyed, with lack of sufficient knowledge about HPV and its vaccine being the primary reason to refuse vaccination. Concerns about safety, effectiveness, and perceiving low risk are the biggest obstacle in promoting vaccination. When the price is <1000, most parents (56.1%) are willing to vaccinate their children; thus, cost is also one of the concerns. Therefore, strategies for improving public awareness regarding the risk of cervical cancer and confidence in vaccination must be considered by policymakers.If the national authority confirms that the vaccine is safe and effective, the vaccine should be included in the national immunization program to increase publicity, address safety concerns, and allow for price regulation.

Neighbourhood speed limit and childhood obesity.

As an important factor for neighbourhood walkability, the speed limit in the neighbourhood may influence children's physical activity (PA) outdoors, especially active transport, and further their weight status. This review aimed to systematically evaluate the association between neighbourhood speed limit and obesity-related behaviours and outcomes among children and adolescents. PubMed, Embase and Web of Science were systematically searched for relevant studies published from the inception of the database to 1 January 2019. Sixteen studies were included, with 13 cross-sectional studies and three longitudinal studies. Speed limit was measured as the percentage/number of high-speed roads, perception of safe driving speed, perception of speeding and use of traffic-calming tools in the neighbourhood. Eleven studies measured the use of active transport as the outcome of interest, and seven studies measured PA directly. Eleven studies revealed an association between a lower speed limit and increased PA, whereas one study showed a negative association, and three studies reported non-significant associations. Only one study associated speed limit with weight status, which reported a non-significant association. This review generally supported a negative association between speed limit and PA among children and adolescents. More studies are needed to examine their causality, as well as the association between speed limit and weight status, in order to increase the impact of this research area on public health policy making.

State-of-the-art of measures of the obesogenic environment for children.

Various measures of the obesogenic environment have been proposed and used in childhood obesity research. The variety of measures poses methodological challenges to designing new research because methodological characteristics integral to developing the measures vary across studies. A systematic review has been conducted to examine the associations between different levels of obesogenic environmental measures (objective or perceived) and childhood obesity. The review includes all articles published in the Cochrane Library, PubMed, Web of Science and Scopus by 31 December 2018. A total of 339 associations in 101 studies have been identified from 18 countries, of which 78 are cross-sectional. Overall, null associations are predominant. Among studies with non-null associations, negative relationships between healthy food outlets in residential neighbourhoods and childhood obesity is found in seven studies; positive associations between unhealthy food outlets and childhood obesity are found in eight studies, whereas negative associations are found in three studies. Measures of recreational or physical activity facilities around the participants' home are also negatively correlated to childhood obesity in nine out of 15 studies. Results differ by the types of measurement, environmental indicators and geographic units used to characterize obesogenic environments in residential and school neighbourhoods. To improve the study quality and compare reported findings, a reporting standard for spatial epidemiological research should be adopted.

Neighbourhood residential density and childhood obesity.

Residential density is considered an important attribute of the built environment that may be relevant to childhood obesity. However, findings remain inconclusive, and there are no reviews yet on the association between residential density and childhood obesity. This study aimed to systematically review the associations between residential density and weight-related behaviours and outcomes. A comprehensive literature search was conducted using the Cochrane Library, PubMed and Web of Science for articles published before 1 January 2019. A total of 35 studies conducted in 14 countries were identified, including 33 cross-sectional studies, one longitudinal study and one containing both study designs. Residential density was measured by Geographic Information Systems in 28 studies within a varied radius from 0.25 to 2 km around the individual residence. Our study found a general positive association between residential density and physical activity (PA); no significant associations were observed. This study provided evidence for a supportive role of residential density in promoting PA among children. However, it remained difficult to draw a conclusion between residential density and childhood obesity. Future longitudinal studies are warranted to confirm this association.

Urban sprawl and childhood obesity.

Urban sprawl is thought to be a risk factor for childhood obesity primarily because the physical environment it creates discourages children's physical activity while encouraging their sedentary behavior. However, there has not been any review on the association between urban sprawl and childhood obesity. This study filled this research gap by comprehensively reviewing literature focusing on associations between urban sprawl and weight-related behaviors and outcomes among children and adolescents. Only two longitudinal and three cross-sectional studies conducted in two countries were identified. Sample sizes ranged from 2324 to 129 781. Four studies used weight status, and only one study used both behaviors and weight status as outcome variables. All positive, negative, and non-significant associations were reported. This review could not identify a clear association between urban sprawl and childhood obesity. More longitudinal studies are needed for in-depth analyses on this important topic in more regions, which would be important not only for public health guidelines but also for research, practice, and policies in urban planning.

Geographic clustering and region-specific determinants of obesity in the Netherlands.

As a leading cause of morbidity and premature mortality, obesity has become a major global public health problem. It is therefore important to investigate the spatial variation of obesity prevalence and its associations with environmental and behavioral factors (e.g., food environment, physical activity), to optimize the targeting of scarce public health resources. In this study, the geographic clustering of obesity in the Netherlands was explored by analyzing the local spatial autocorrelation of municipal-level prevalence rates of adulthood obesity (aged ≥19 years) in 2016. The potential influential factors that may be associated with obesity prevalence were first selected from five categories of healthrelated factors through binary and Least Absolute Shrinkage and Selection Operator (LASSO) regressions. Geographically Weighted Regression (GWR) was then used to investigate the spatial variations of the associations between those selected factors and obesity prevalence. The results revealed marked geographic variations in obesity prevalence, with four clusters of high prevalence in the north, south, east, and west, and three clusters of low prevalence in the north and south of the Netherlands. Lack of sports participation, risk of anxiety, falling short of physical activity guidelines, and the number of restaurants around homes were found to be associated with obesity prevalence across municipalities. Our findings show that effective, region-specific strategies are needed to tackle the increasing obesity in the Netherlands.

Exercise interventions on patients with end-stage renal disease: a systematic review.

OBJECTIVE:: This study aimed to conduct an up-to-date systematic review of the literature to evaluate the effects of exercise on fatigue, anxiety, depression, physical activity, and quality of life (QOL) in patients with end-stage renal disease. DATA SOURCES:: We searched PubMed (October 2018), Embase (from 1966 to October 2018), Web of Science (from 1900 to October 2018), The Cochrane Library (October 2018), and references of papers. METHODS:: This study includes randomized controlled trials that analyzed the combined effects of exercise intervention on patients with end-stage renal disease. Two reviewers independently screened the retrieved records, extracted data, and assessed the risk of bias for inclusion in the study. The effects of exercise intervention were conducted in the meta-analysis using RevMan 5.3 software. RESULTS:: A total of 614 participants were included in 13 randomized controlled studies. The study revealed that exercise can improve fatigue, anxiety, depression, physical activity, and QOL. The effect value results were as follows: (1) fatigue, -0.97 (95% confidence interval (CI) -1.32 to -0.62, P < 0.00001); (2) anxiety, -0.78 (95% CI -1.17 to -0.39, P < 0.0001); (3) depression, -0.85 (95% CI -1.13 to -0.56, P < 0.00001) (4) physical activity, 38.15 (95% CI 21.20 to 55.10, P < 0.0001); (5) QOL, the physical component of the 36-item Short-Form Health Survey (SF-36), 4.73 (95% CI 1.92 to 7.54, P = 0.0010); and (6) the mental component of the SF-36, 3.42 (95% CI 0.27 to 6.56, P = 0.03). CONCLUSION:: Exercise intervention is more effective in fatigue, anxiety, depression, physical activity, and QOL. However, large-scale randomized controlled trials are needed to confirm the appropriate types of exercise and optimal time for patients with end-stage renal disease.