Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies.

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease. Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes. With the development of immunological technology, many studies have shown that diabetic nephropathy is an immune complex disease, and that most patients have immune dysfunction. However, the immune response associated with diabetic nephropathy and autoimmune kidney disease, or caused by ischemia or infection with acute renal injury, is different, and has a com-plicated pathological mechanism. In this review, we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism, to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Hydrogen therapy promotes macrophage polarization to the M2 subtype in radiation lung injury by inhibiting the NF-κB signalling pathway.

Background: Radiotherapy has become a standard treatment for chest tumors, but a common complication of radiotherapy is radiation lung injury. Currently, there is still a lack of effective treatment for radiation lung injury. Methods: A mouse model of radioactive lung injury (RILI) was constructed and then treated with different cycles of hydrogen inhalation. Lung function tests were performed to detect changes in lung function.HE staining was used to detect pathological changes in lung tissue. Immunofluorescence staining was used to detect the polarization of macrophages in lung tissue. Immunohistochemistry was used to detect changes in cytokine expression in lung tissues. Western Blot was used to detect the expression of proteins related to the NF-κB signalling pathway. Results: Lung function test results showed that lung function decreased in the model group and improved in the treatment group.HE staining showed that inflammatory response was evident in the model group and decreased in the treatment group. Immunohistochemistry results showed that the expression of pro-inflammatory factors was significantly higher in the model group, and the expression of pro-inflammatory factors was significantly higher in the treatment group. The expression of pro-inflammatory factors in the treatment group was significantly lower than that in the model group, and the expression of anti-inflammatory factors in the treatment group was higher than that in the model group. Immunofluorescence showed that the expression of M1 subtype macrophages was up-regulated in the model group and down-regulated in the treatment group. The expression of M2 subtype macrophages was up-regulated in the treatment group relative to the model group. Western Blot showed that P-NF-κB p65/NF-κB p65 was significantly increased in the model group, and P-NF-κB p65/NF-κB p65 was decreased in the treatment group. Conclusion: Hydrogen therapy promotes macrophage polarization from M1 to M2 subtypes by inhibiting the NF-κB signalling pathway, thereby attenuating the inflammatory response to radiation lung injury.

Glucose metabolism reprogramming in gynecologic malignant tumors.

The incidence and mortality of gynecological tumors are progressively increasing due to factors such as obesity, viral infection, unhealthy habits, as well as social and economic pressures. Consequently, it has emerged as a significant threat to women's health. Numerous studies have revealed the remarkable metabolic activity of tumor cells in glycolysis and its ability to influence malignant biological behavior through specific mechanisms. Therefore, it is crucial for patients and gynecologists to comprehend the role of glycolytic proteins, regulatory molecules, and signaling pathways in tumorigenesis, progression, and treatment. This article aims to review the correlation between abnormal glucose metabolism and gynecologic tumors including cervical cancer (CC), endometrial carcinoma (EC), and ovarian cancer (OC). The findings from this research will provide valuable scientific insights for early screening, timely diagnosis and treatment interventions while also aiding in the prevention of recurrence among individuals with gynecological tumors.

The pathological mechanisms and potential therapeutic drugs for myocardial ischemia reperfusion injury.

BACKGROUND: Cardiovascular disease is the main cause of death and disability, with myocardial ischemia being the predominant type that poses a significant threat to humans. Reperfusion, an essential therapeutic approach, promptly reinstates blood circulation to the ischemic myocardium and stands as the most efficacious clinical method for myocardial preservation. Nevertheless, the restoration of blood flow associated with this process can potentially induce myocardial ischemia-reperfusion injury (MIRI), thereby diminishing the effectiveness of reperfusion and impacting patient prognosis. Therefore, it is of great significance to prevent and treat MIRI. PURPOSE: MIRI is an important factor affecting the prognosis of patients, and there is no specific in-clinic treatment plan. In this review, we have endeavored to summarize its pathological mechanisms and therapeutic drugs to provide more powerful evidence for clinical application. METHODS: A comprehensive literature review was conducted using PubMed, Web of Science, Embase, Medline and Google Scholar with a core focus on the pathological mechanisms and potential therapeutic drugs of MIRI. RESULTS: Accumulated evidence revealed that oxidative stress, calcium overload, mitochondrial dysfunction, energy metabolism disorder, ferroptosis, inflammatory reaction, endoplasmic reticulum stress, pyroptosis and autophagy regulation have been shown to participate in the process, and that the occurrence and development of MIRI are related to plenty of signaling pathways. Currently, a range of chemical drugs, natural products, and traditional Chinese medicine (TCM) preparations have demonstrated the ability to mitigate MIRI by targeting various mechanisms. CONCLUSIONS: At present, most of the research focuses on animal and cell experiments, and the regulatory mechanisms of each signaling pathway are still unclear. The translation of experimental findings into clinical practice remains incomplete, necessitating further exploration through large-scale, multi-center randomized controlled trials. Given the absence of a specific drug for MIRI, the identification of therapeutic agents to reduce myocardial ischemia is of utmost significance. For the future, it is imperative to enhance our understanding of the pathological mechanism underlying MIRI, continuously investigate and develop novel pharmaceutical agents, expedite the clinical translation of these drugs, and foster innovative approaches that integrate TCM with Western medicine. These efforts will facilitate the emergence of fresh perspectives for the clinical management of MIRI.

Stem Cell-Based Approaches in Parkinson's Disease Research.

Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of midbrain dopaminergic neurons, leading to motor symptoms. While current treatments provide limited relief, they don't alter disease progression. Stem cell technology, involving patient-specific stem cell-derived neurons, offers a promising avenue for research and personalized regenerative therapies. This article reviews the potential of stem cell-based research in PD, summarizing ongoing efforts, their limitations, and introducing innovative research models. The integration of stem cell technology and advanced models promises to enhance our understanding and treatment strategies for PD.

[Research progress on pathological mechanism and clinical correlation between medial meniscus posterior root tear and tibial rotation].

Objective: To summarize the current research progress on the concept, clinical presentation, diagnosis, biomechanical changes, and pathological mechanisms of the medial meniscus posterior root tear (MMPRT), and its clinical correlations with tibial rotation. Methods: The research literature on MMPRT and its relationship with tibial rotation at home and abroad in recent years was extensively consulted and summarized. Results: MMPRT is a specific and common type of medial meniscus injury of the knee joint. The occurrence of posterior medial pumping pain events following low-energy trauma in patients provides important clues for the diagnosis of this injury, with MRI being the preferred imaging modality. The biomechanical effects generated by MMPRT are similar to those caused by total removal of the medial meniscus. And this injury is usually associated with tibial rotation. MMPRT induces pathological external rotation of the tibia, which can be restored by timely medial meniscus posterior root repair. Furthermore, changes in tibial rotation are related to the healing status after medial meniscus posterior root repair. Conclusion: MMPRT is closely related to tibial rotation. Understanding the biomechanics, pathological mechanisms, and clinical correlations between the two is of great significance for improving the diagnosis and treatment strategies.

Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases.

Globally, millions of individuals are impacted by neurodegenerative disorders including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Although a great deal of energy and financial resources have been invested in disease-related research, breakthroughs in therapeutic approaches remain elusive. The breakdown of cells usually happens together with the onset of neurodegenerative diseases. However, the mechanism that triggers neuronal loss is unknown. Lipid peroxidation, which is iron-dependent, causes a specific type of cell death called ferroptosis, and there is evidence its involvement in the pathogenic cascade of neurodegenerative diseases. However, the specific mechanisms are still not well known. The present article highlights the basic processes that underlie ferroptosis and the corresponding signaling networks. Furthermore, it provides an overview and discussion of current research on the role of ferroptosis across a variety of neurodegenerative conditions.

Monoclonal antibody therapy for Alzheimer's disease focusing on intracerebral targets.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Due to the complexity of the disorder and the presence of the blood-brain barrier (BBB), its drug discovery and development are facing enormous challenges, especially after several failures of monoclonal antibody (mAb) trials. Nevertheless, the Food and Drug Administration's approval of the mAb aducanumab has ushered in a new day. As we better understand the disease's pathogenesis and identify novel intracerebral therapeutic targets, antibody-based therapies have advanced over the past few years. The mAb drugs targeting ß-amyloid or hyperphosphorylated tau protein are the focus of the current research. Massive neuronal loss and glial cell-mediated inflammation are also the vital pathological hallmarks of AD, signaling a new direction for research on mAb drugs. We have elucidated the mechanisms by which AD-specific mAbs cross the BBB to bind to targets. In order to investigate therapeutic approaches to treat AD, this review focuses on the promising mAbs targeting intracerebral dysfunction and related strategies to cross the BBB.

The Impact of Microglia on Neurodevelopment and Brain Function in Autism.

Microglia, as one of the main types of glial cells in the central nervous system (CNS), are widely distributed throughout the brain and spinal cord. The normal number and function of microglia are very important for maintaining homeostasis in the CNS. In recent years, scientists have paid widespread attention to the role of microglia in the CNS. Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder, and patients with ASD have severe deficits in behavior, social skills, and communication. Most previous studies on ASD have focused on neuronal pathological changes, such as increased cell proliferation, accelerated neuronal differentiation, impaired synaptic development, and reduced neuronal spontaneous and synchronous activity. Currently, more and more research has found that microglia, as immune cells, can promote neurogenesis and synaptic pruning to maintain CNS homeostasis. They can usually reduce unnecessary synaptic connections early in life. Some researchers have proposed that many pathological phenotypes of ASD may be caused by microglial abnormalities. Based on this, we summarize recent research on microglia in ASD, focusing on the function of microglia and neurodevelopmental abnormalities. We aim to clarify the essential factors influenced by microglia in ASD and explore the possibility of microglia-related pathways as potential research targets for ASD.

Single-cell sequencing reveals lung cell fate evolution initiated by smoking to explore gene predictions of correlative diseases.

Continuous smoking leads to adaptive regulation and physiological changes in lung tissue and cells, and is an inductive factor for many diseases, making smokers face the risk of malignant and nonmalignant diseases. The impact of research in this area is getting more and more in-depth, but the stimulant effect, mechanism of action and response mechanism of the main cells in the lungs caused by smoke components have not yet been fully elucidated, and the early diagnosis and identification of various diseases induced by smoke toxins have not yet formed a systematic relationship method. In this study, single-cell transcriptome data were generated from three lung samples of smokers and nonsmokers through scRNA-seq technology, revealing the influence of smoking on lung tissue and cells and the changes in immune response. The results show that: through UMAP cell clustering, 16 intermediate cell states of 23 cell clusters of the four main cell types in the lung are revealed, the differences of the main cell groups between smokers and nonsmokers are explained, and the human lung cells are clarified. Components and their marker genes, screen for new marker genes that can be used in the evolution of intermediate-state cells, and at the same time, the analysis of lung cell subgroups reveals the changes in the intermediate state of cells under smoke stimulation, forming a subtype intermediate state cell map. Pseudo-time ordering analysis, to determine the pattern of dynamic processes experienced by cells, differential expression analysis of different branch cells, to clarify the expression rules of cells at different positions, to clarify the evolution process of the intermediate state of cells, and to clarify the response of lung tissue and cells to smoke components mechanism. The development of this study provides new diagnosis and treatment ideas for early disease detection, identification, disease prevention and treatment of patients with smoking-related diseases, and lays a theoretical foundation based on cell and molecular regulation.

Hydrogen therapy promotes macrophage polarization to the M2 subtype by inhibiting the NF-κB signaling pathway / 中国辐射卫生

Objective To investigate the role of hydrogen therapy in reducing radiation-induced lung injury and the specific mechanism. Methods Forty C57BL/6 mice were randomly divided into four groups: normal control group, model group, hydrogen therapy group I, and hydrogen therapy group II. A mouse model of radiation-induced lung injury was established. The pathological changes in the lung tissue of the mice were examined with HE staining. Immunofluorescence staining was used to detect the expression of surface markers of M1 and M2 macrophages to observe macrophage polarization. The expression of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 in the lung tissue was measured by immunohistochemistry. The expression of nuclear factor-kappa B (NF-κB) p65 and phosphorylated NF-κB (P-NF-κB) p65 was measured by Western blot. Results HE staining showed that compared with the control group, the model group exhibited alveolar septal swelling and thickening, vascular dilatation and congestion, and inflammatory cell infiltration in the lung tissue; the hydrogen groups had significantly reduced pathological damage and inflammatory response than the model group, with more improvements in hydrogen group II than in hydrogen group I. Immunohistochemical results showed that compared with those in the control group, the levels of the inflammatory cytokines IL-6 and TNF-α were significantly increased in the model group; the hydrogen groups showed significantly decreased IL-6 and TNF-α levels and a significantly increased level of the anti-inflammatory factor IL-10 than the model group, which were more marked in hydrogen group II than in hydrogen group I. Immunofluorescence results showed that compared with the control group, the expression of the surface marker of M1 macrophages in the model group was significantly upregulated; the hydrogen groups showed significantly downregulated M1 marker and significantly upregulated M2 marker, and hydrogen group II showed significantly increased M2 marker compared with hydrogen group I. Western blot results showed that compared with that in the control group, the ratio of P-NF-κB p65/NF-κB p65 in the model group was significantly increased; the P-NF-κB p65/NF-κB p65 ratio was significantly reduced in the hydrogen groups than in the model group, and was significantly lower in hydrogen group II than in hydrogen group I. Conclusion Hydrogen inhalation therapy may reduce the inflammatory response of radiation-induced lung injury by inhibiting the NF-κB signaling pathway to promote the polarization of the macrophage M1 subtype to the M2 subtype.

Treatment of Liver Failure by Chinese Medicine Mediating Related Signaling Pathways： A Review / 中国实验方剂学杂志

Liver failure （LF） is a great trouble to the majority of patients due to its severe onset， many complications， difficult treatment， poor prognosis and other characteristics. This disease is liver injury caused by infection， hepatotoxic substances， autoimmunity， circulation disorders and other factors. It is a group of common clinical symptoms mainly manifested by coagulation disorders， jaundice， hepatic encephalopathy， ascites， and so on. In traditional Chinese medicine， it falls under the categories of "tympanites"， "jaundice" and other diseases. At present， the research progress of Western medicine in the treatment of LF is slow， and its clinical application effect is still not ideal. In contrast， traditional Chinese medicine has a long history in the treatment of this disease， with over thousands of years of clinical practice and verification. It is characterized by exact efficacy and fewer side effects. The pathological mechanism of LF is extremely complex， involves a variety of signaling pathways， and is mainly related to inflammation， oxidative stress， liver fibrosis， cell apoptosis and other processes. In recent years， many studies have shown that traditional Chinese medicine can intervene in the occurrence and development of LF by mediating relevant signaling pathways in vivo， but there is still a lack of relevant summary. Therefore， this review summarized several signaling pathways related to the intervention of traditional Chinese medicine in LF by referring to and sorting out relevant literature worldwide， including nuclear factor kappa B （NF-κB）， mitogen-activated protein kinase （MAPK）， phosphatidylin-ositol-3-kinase/protein kinase B （PI3K/Akt）， transforming growth factor-β/ drosophila mothers against decapentaplegic proteins （TGF-β/Smads）， and nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， and elaborated the specific mechanism of their intervention in LF. This paper aims to provide practical and effective pathways and corresponding mechanisms for the treatment of LF by traditional Chinese medicine， and to provide new ideas and a theoretical basis for the clinical treatment of LF and further scientific research.

Exercise-mediated macrophage polarization modulates the targeted therapeutic effect of NAFLD: a review.

PURPOSE: This review aims to explore the exercise-mediated hepatic macrophage polarization mechanism and its effect on improving and regulating non-alcoholic fatty liver disease (NAFLD) by analyzing the pathogenesis of NAFLD and the cause of the influence of hepatic macrophage polarization. In addition to exploring the varied effects of different exercise types on macrophage polarization regulation in NAFLD, to provide a direction and basis for the treatment of NAFLD. METHODS: The research methodology involved a comprehensive search of the PubMed database using specific keywords such as "NAFLD", "macrophage polarization", and "exercise", to retrieve relevant literature published. RESULTS: (1) The main factors inducing NAFLD were high-fat diet, obesity, insulin resistance (IR), changes in gut microbiota, and genetic variation in susceptibility. (2) Drug treatment, nutrient induction, microfactor induction, physiological environment induction, and other factors can induce the polarization of hepatic macrophages and affect NAFLD. (3) Different intensities, types, and frequencies of exercise have different effects on polarization macrophages, and may also differently effects improving liver inflammation, fibrosis, and NAFLD. Curently, regular moderate-intensity aerobic exercise is the most effective therapy for treating NAFLD. CONCLUSION: Approaches to ameliorate NAFLD with exercise involve strategies to alter macrophage polarization by inhibiting M1 or driving M2 activation. However, research on the different types of exercise-mediated macrophage polarization mechanisms and differences in therapeutic effects is not yet sufficient. Future research is necessary to explore the exact mechanisms and differences in the effects of different exercises on the treatment of NAFLD.

Integrating bioinformatic resources to identify characteristics of rheumatoid arthritis-related usual interstitial pneumonia.

BACKGROUND: Rheumatoid arthritis (RA) is often accompanied by a common extra-articular manifestation known as RA-related usual interstitial pneumonia (RA-UIP), which is associated with a poor prognosis. However, the mechanism remains unclear. To identify potential mechanisms, we conducted bioinformatics analysis based on high-throughput sequencing of the Gene Expression Omnibus (GEO) database. RESULTS: Weighted gene co-expression network analysis (WGCNA) analysis identified 2 RA-positive related modules and 4 idiopathic pulmonary fibrosis (IPF)-positive related modules. A total of 553 overlapped differentially expressed genes (DEG) were obtained, of which 144 in the above modules were further analyzed. The biological process of "oxidative phosphorylation" was found to be the most relevant with both RA and IPF. Additionally, 498 up-regulated genes in lung tissues of RA-UIP were screened out and enriched by 7 clusters, of which 3 were closely related to immune regulation. The analysis of immune infiltration showed a characteristic distribution of peripheral immune cells in RA-UIP, compared with IPF-UIP in lung tissues. CONCLUSIONS: These results describe the complex molecular and functional landscape of RA-UIP, which will help illustrate the molecular pathological mechanism of RA-UIP and identify new biomarkers and therapeutic targets for RA-UIP in the future.

Primary biliary cholangitis: molecular pathogenesis perspectives and therapeutic potential of natural products.

Primary biliary cirrhosis (PBC) is a chronic cholestatic immune liver disease characterized by persistent cholestasis, interlobular bile duct damage, portal inflammation, liver fibrosis, eventual cirrhosis, and death. Existing clinical and animal studies have made a good progress in bile acid metabolism, intestinal flora disorder inflammatory response, bile duct cell damage, and autoimmune response mechanisms. However, the pathogenesis of PBC has not been clearly elucidated. We focus on the pathological mechanism and new drug research and development of PBC in clinical and laboratory in the recent 20 years, to discuss the latest understanding of the pathological mechanism, treatment options, and drug discovery of PBC. Current clinical treatment mode and symptomatic drug support obviously cannot meet the urgent demand of patients with PBC, especially for the patients who do not respond to the current treatment drugs. New treatment methods are urgently needed. Drug candidates targeting reported targets or signals of PBC are emerging, albeit with some success and some failure. Single-target drugs cannot achieve ideal clinical efficacy. Multitarget drugs are the trend of future research and development of PBC drugs.

A Study on Autophagy Related Biomarkers in Alzheimer's Disease Based on Bioinformatics.

Alzheimer's disease (AD) is a neurodegenerative disease with an annual incidence increase that poses significant health risks to people. However, the pathogenesis of AD is still unclear. Autophagy, as an intracellular mechanism can degrade damaged cellular components and abnormal proteins, which is closely related to AD pathology. The goal of this work is to uncover the intimate association between autophagy and AD, and to mine potential autophagy-related AD biomarkers by identifying key differentially expressed autophagy genes (DEAGs) and exploring the potential functions of these genes. GSE63061 and GSE140831 gene expression profiles of AD were downloaded from the Gene Expression Omnibus (GEO) database. R language was used to standardize and differentially expressed genes (DEGs) of AD expression profiles. A total of 259 autophagy-related genes were discovered through the autophagy gene databases ATD and HADb. The differential genes of AD and autophagy genes were integrated and analyzed to screen out DEAGs. Then the potential biological functions of DEAGs were predicted, and Cytoscape software was used to detect the key DEAGs. There were ten DEAGs associated with the AD development, including nine up-regulated genes (CAPNS1, GAPDH, IKBKB, LAMP1, LAMP2, MAPK1, PRKCD, RAB24, RAF1) and one down-regulated gene (CASP1). The correlation analysis reveals the potential correlation among 10 core DEAGs. Finally, the significance of the detected DEAGs expression was verified, and the value of DEAGs in AD pathology was detected by the receiver operating characteristic curve. The area under the curve values indicated that ten DEAGs are potentially valuable for the study of the pathological mechanism and may become biomarkers of AD. This pathway analysis and DEAG screening in this study found a strong association between autophagy-related genes and AD, providing new insights into the pathological progression of AD. Exploring the relationship between autophagy and AD: analysis of genes associated with autophagy in pathological mechanisms of AD using bioinformatics. 10 autophagy-related genes play an important role in the pathological mechanisms of AD.

Preclinical study of diabetic foot ulcers: From pathogenesis to vivo/vitro models and clinical therapeutic transformation.

Diabetic foot ulcer (DFU), a common intractable chronic complication of diabetes mellitus (DM), has a prevalence of up to 25%, with more than 17% of the affected patients at risk of amputation or even death. Vascular risk factors, including vascular stenosis or occlusion, dyslipidemia, impaired neurosensory and motor function, and skin infection caused by trauma, all increase the risk of DFU in patients with diabetes. Therefore, diabetic foot is not a single pathogenesis. Preclinical studies have contributed greatly to the pathogenesis determination and efficacy evaluation of DFU. Many therapeutic tools are currently being investigated using DFU animal models for effective clinical translation. However, preclinical animal models that completely mimic the pathogenesis of DFU remain unexplored. Therefore, in this review, the preparation methods and evaluation criteria of DFU animal models with three major pathological mechanisms: neuropathy, angiopathy and DFU infection were discussed in detail. And the advantages and disadvantages of various DFU animal models for clinical sign simulation. Furthermore, the current status of vitro models of DFU and some preclinical studies have been transformed into clinical treatment programs, such as medical dressings, growth factor therapy, 3D bioprinting and pre-vascularization, Traditional Chinese Medicine treatment. However, because of the complexity of the pathological mechanism of DFU, the clinical transformation of DFU model still faces many challenges. We need to further optimize the existing preclinical studies of DFU to provide an effective animal platform for the future study of pathophysiology and clinical treatment of DFU.

Pneumatosis cystoides intestinalis in dermatomyositis: a case series report and literature review.

Pneumatosis cystoides intestinalis (PCI) in adult dermatomyositis (DM) is rarely described. This report aimed to describe the clinical features and prognosis of PCI in six adult patients with DM (four with anti-MDA5 antibodies, one with anti-SAE antibodies, and one with anti-TIF-1γ antibodies). Except for one patient with transient abdominal pain, the remaining five patients were asymptomatic. PCI occurred in the ascending colon in all patients, of whom five had free gas in the abdominal cavity. No patients received excessive treatment, and PCI disappeared in four patients during the follow-up. Additionally, we reviewed previous studies on this complication.

[Molecular pathological mechanism of liver metabolic disorder in mice with severe spinal muscular atrophy].

OBJECTIVE: To explore the molecular pathological mechanism of liver metabolic disorder in severe spinal muscular atrophy (SMA). METHODS: The transgenic mice with type Ⅰ SMA (Smn-/- SMN20tg/2tg) and littermate control mice (Smn+/- SMN20tg/2tg) were observed for milk suckling behavior and body weight changes after birth. The mice with type Ⅰ SMA mice were given an intraperitoneal injection of 20% glucose solution or saline (15 µL/12 h), and their survival time was recorded. GO enrichment analysis was performed using the RNA-Seq data of the liver of type Ⅰ SMA and littermate control mice, and the results were verified using quantitative real-time PCR. Bisulfite sequencing was performed to examine CpG island methylation level in Fasn gene promoter region in the liver of the neonatal mice. RESULTS: The neonatal mice with type Ⅰ SMA showed normal milk suckling behavior but had lower body weight than the littermate control mice on the second day after birth. Intraperitoneal injection of glucose solution every 12 h significantly improved the median survival time of type Ⅰ SMA mice from 9±1.3 to 11± 1.5 days (P < 0.05). Analysis of the RNA-Seq data of the liver showed that the expression of the target genes of PPARα related to lipid metabolism and mitochondrial ß oxidation were down-regulated in the liver of type Ⅰ SMA mice. Type Ⅰ SMA mice had higher methylation level of the Fasn promoter region in the liver than the littermate control mice (76.44% vs 58.67%). In primary cultures of hepatocytes from type Ⅰ SMA mice, treatment with 5-AzaC significantly up-regulated the expressions of the genes related to lipid metabolism by over 1 fold (P < 0.01). CONCLUSION: Type Ⅰ SMA mice have liver metabolic disorder, and the down-regulation of the target genes of PPARα related to lipid and glucose metabolism due to persistent DNA methylation contributes to the progression of SMA.