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Impact of lifestyle interventions on pathogenesis of nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2024年第20期30卷 2633-2637页

作者： Wafaa Mohamed Ezzat department of Internal Medicine Medical Research and Clinical Studies InstituteNational Research CenterGiza 12311Egypt

This editorial builds on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et al.We carried out a critical examination of nonalcoholic fatty liver disease(NAFLD)pathogenesis and how lifestyle interventions could facilitate disease resolution,particularly highlighting that non-alcoholic steatohepatitis(NASH)is a severe form of NAFLD.Our discussion details that weight loss is a pivotal factor in disease outcomes:A 3%-5%reduction is enough for resolution in 50%of non-obese individuals,while a 7%-10%reduction achieves similar benefits in obese individuals,as demonstrated by magnetic resonance spectroscopy.Additionally,the editorial underscores that such lifestyle changes are instrumental not only in resolving NAFLD but also in reversing hepatic steatosis and inflammation.These insights,derived from the research,emphasize the critical role of personalized lifestyle modifications in halting the progression of NAFLD to NASH and even reversing fibrosis,thus offering a template for effective patient management.

关键词： Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Diet Physical activity Life style

New frontiers in ectopic pancreatic tissue management

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1215-1217页

作者： Serghei Covantsev department of clinical research and Development Botkin HospitalMoscow 125284Russia

The pancreatic development variations are relatively frequent but are often overlooked in clinical practice.This is due to the fact that they do not present with a distinct clinical picture and are usually asymptomatic.It also refers to the ectopic pancreatic tissue in the stomach.This anomaly can be diagnosed in any part of the digestive system,but it is mostly seen in the upper gastrointestinal tract,especially in the stomach,duodenum and jejunum.The management of this condition has evolved due to the development of minimally invasive procedures.

关键词： Ectopic pancreatic tissue Stomach Endoscopy Laparoscopy Pancreas Anomalies

Factors Impacting Participatory Post‑Disaster Relocation and Housing Reconstruction:The Case of Tsholotsho District,Zimbabwe

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International Journal of Disaster Risk Science 2024年第1期15卷 58-72页

作者： Nombulelo Kitsepile Ngulube Hirokazu Tatano Subhajyoti Samaddar department of Social informatics Graduate School of InformaticsKyoto UniversityKyoto 606-8507Japan Disaster Prevention research Institute(DPRI) Kyoto UniversityKyoto 611-0011Japan

Relocation is not typically considered the best planning option for post-disaster reconstruction and rehabilitation,but it may be necessary if the site has suffered severe damage or is at imminent risk.There is a growing recognition that strong community participation is necessary in the post-disaster relocation decision-making process since relocation can have detrimental effects on a community’s livelihood,cultural system,and way of life,among others.However,the realization of this still needs to be improved.As of yet,few studies have examined a comprehensive account of meaningful community engagement in post-disaster relocation and reconstruction,particularly in developing countries.This study investigated what factors influenced local communities’ participation in post-disaster relocation and reconstruction works after the 2017Cyclone Dineo flood disaster in the Tsholotsho District of Zimbabwe.Qualitative research methods such as face-to-face interviews,observations,and focus groups were used to collect qualitative data from a purposive sample of 25 community members and 6 stakeholders.This empirical investigation showed that despite the fact that the relocation project was conceived as a community-centered project,there was no meaningful community engagement,due to the absence of a participatory framework or planning guidelines for stakeholder engagement,as well as the lack of political willingness among government officials.The study concluded that the lack of community involvement led to local communities abandoning the reconstruction sites because relocation projects failed to accommodate the cultural beliefs,place attachments,and livelihood concerns of local communities.This study suggested that it is imperative to enhance the awareness of government officials and other stakeholders about the importance of community participation for the effective implementation of post-disaster relocation works.Meaningful community participation can also provide avenues for incorporating local needs and concerns,cultura

关键词： Community rehabilitation Housing reconstruction-Participatory relocation Zimbabwe

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NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 153-164页

作者： Bo Shi Cheng-Jie Lyu Zhen-Kai Le Hao-Sen Ji Yi Xiao Yuan-Yuan Zhang Shou-Jiang Huang Lin-Jun Yu Qiang Shu Jin-Fa Tou Deng-Ming Lai department of Neonatal Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China department of Pulmonology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China department of Thoracic and Cardiovascular Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China

Background Macrophages are involved in various immune inflammatory disease conditions.This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western blot.Hypertonic pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3^(-/-))model of NEC.The mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments.Macrophages,intestinal epithelial cell injuries,and IL-1β release were determined.Results Compared to the gut“healthy”patients,the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3,caspase-1,and IL-1β levels.Furthermore,in vivo,the survival rate of Nlrp3^(-/-)NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC mice.NLRP3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries.Conclusions Macrophage activation may be essential for NEC development.NLRP3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.

关键词： Caspase-1 Interleukin-1β Macrophage Necrotizing enterocolitis NLRP3

Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population:a two-sample bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第1期21卷 64-80页

作者： Xiong-Bin MA Yong-Ming LIU Yan-Lin LV Lin QIAN The First clinical Medical College of Lanzhou University LanzhouGansuChina Geriatric Cardiovascular department and Gansu clinical research Center for Geriatric Diseases First Hospital of Lanzhou UniversityGansuChina

BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is uncertain.This Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction population.METHODS Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association studies.Individuals without myocardial infarction history,HF,or LV ejection fraction(LVEF)<50%(n=16,923)in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome dataset.The dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the results.RESULTS In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni adjustment.Conversely,no significant relationships were observed between other iron and LV parameters.After Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the analysis.CONCLUSIONS We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.

关键词： fraction function parameters

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Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng Luo Jijun Shi Qifei Cong clinical research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow University department of Neurology and clinical research Center of Neurological Disease The Second Affiliated Hospital of Soochow University

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived “find-me,” “eat-me,” and “don’t eat-me” molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

DNA methylation drives a new path in gastric cancer early detection:Current impact and prospects

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Genes & Diseases 2024年第2期11卷 847-860页

作者： Xinhui Wang Yaqi Dong Hong Zhang Yinghui Zhao Tianshu Miao Ghazal Mohseni Lutao Du Chuanxin Wang department of clinical Laboratory The Second Hospital of Shandong UniversityJinanShandong 250033China department of clinical Laboratory Fuling HospitalChongqing UniversityChongqing 402774China Suzhou research Institute of Shandong University SuzhouJiangsu 215123China department of Biochemistry and Molecular Biology Shandong University School of Basic Medical SciencesJinanShandong 250012China Shandong Engineering & Technology research Center for Tumor Marker Detection JinanShandong 250033China Shandong Provincial clinical Medicine research Center for clinical Laboratory JinanShandong 250033China

Gastric cancer(GC)is one of the most common and deadly cancers worldwide.Early detection offers the best chance for curative treatment and reducing its mortality.However,the optimal population-based early screening for GC remains unmet.Aberrant DNA methylation occurs in the early stage of GC,exhibiting cancer-specific genetic and epigenetic changes,and can be detected in the media such as blood,gastric juice,and feces,constituting a valuable biomarker for cancer early detection.Furthermore,DNA methylation is a stable epigenetic alteration,and many innovative methods have been developed to quantify it rapidly and accurately.Nonetheless,large-scale clinical validation of DNA methylation serving as tumor biomarkers is still lacking,precluding their implementation in clinical practice.In conclusion,after a critical analysis of the recent existing literature,we summarized the evolving roles of DNA methylation during GC occurrence,expounded the newly discovered noninvasive DNA methylation biomarkers for early detection of GC,and discussed its challenges and prospects in clinical applications.

关键词： Biomarkers DNA methylation Early detection Gastric cancer Translation

Association between body mass index and in vitro fertilization/intra-cytoplasmic sperm injection outcomes: An analysis of 15,124 normal ovarian responders in China

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中华医学杂志(英文版) 2024年第7期137卷 837-845页

作者： Zheng Danlei Wang Yuanyuan Chen Lixue Zeng Lin Li Rong department of Obstetrics and Gynecology Center for Reproductive Medicine Peking University Third Hospital Beijing 100191 China research Center of clinical Epidemiology

Background: High body mass index (BMI) results in decreased fecundity, and women with high BMI have reduced rates of clinical pregnancy and live birth inin vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI). Meanwhile, ovarian responses show great heterogeneity in patients with a high BMI. This study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian response.Methods: We performed a retrospective cohort study comprising 15,124 patients from the medical record system of the Reproductive Center of Peking University Third Hospital, with 3530 (23.3%) in the overweight group and 1380 (9.1%) in the obese group, who had a normal ovarian response (5-15 oocytes retrieved) and underwent fresh embryo transfer (ET) cycles from January 2017 to December 2018, followed by linked frozen-thawed embryo transfer (FET) cycles from January 2017 to December 2020. Cumulative live birth rate (CLBR) was used as the primary outcome. Furthermore, a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the outcomes. We used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI outcomes.Results: High BMI was associated with poor IVF/ICSI outcomes, both in cumulative cycles and in separate fresh ET or FET cycles. In cumulative cycles, compared with the normal weight group, obesity was correlated with a lower positive pregnancy test rate (adjusted odds ratio [aOR]: 0.809, 95% confidence interval [CI]: 0.682-0.960), lower clinical pregnancy rate (aOR: 0.766, 95% CI: 0.646-0.907), lower live birth rate (aOR: 0.706, 95% CI: 0.595-0.838), higher cesarean section rate (aOR: 2.066, 95% CI: 1.533-2.785), and higher rate of large for gestational age (aOR: 2.273, 95% CI: 1.547-3.341). In the generalized additive model, we found that CLBR declined with increasing BMI, with 24 kg/m2 as an inflection point. In the decision tree, BMI only made a difference in the population aged ≤34.5 yea

关键词： Obesity Body mass index In vitro fertilization Live birth Decision trees Normal ovarian response

Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

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Cancer Biology & Medicine 2024年第5期21卷 416-432页

作者： Yuexiang Liang Guannan Sheng Yu Guo Yiping Zou Hanhan Guo Zhifei Li Shaofei Chang Quan Man Song Gao Jihui Hao department of Pancreatic Cancer Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer department of Gastrointestinal Oncology The First Affiliated Hospital of Hainan Medical University department of Gastrointestinal Pancreatic Surgery Shanxi Provincial People's Hospital

Objective: Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation. Ki-67, an indicator of cellular proliferation, has been used for tumor grading and classification in breast cancer and neuroendocrine tumors. However, its prognostic significance in pancreatic ductal adenocarcinoma(PDAC) remains uncertain.Methods: Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled, and relevant prognostic factors were examined. Grade of malignancy(GOM), a novel index based on histopathological differentiation and Ki-67, is proposed, and its clinical significance was evaluated.Results: The optimal threshold for Ki-67 was determined to be 30%. Patients with a Ki-67 expression level > 30% rather than ≤ 30% had significantly shorter 5-year overall survival(OS) and recurrence-free survival(RFS). In multivariate analysis, both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS. The GOM was used to independently stratify OS and RFS into 3 tiers, regardless of TNM stage and other established prognostic factors. The tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers, and surpassed the predictive performance of TNM stage for OS and RFS.Conclusions: Ki-67 is a valuable prognostic indicator for PDAC. Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

关键词： Ki-67 Pancreatic ductal adenocarcinoma TNM stage differentiation prognosis