Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/physiology* ; Animals ; Liver Diseases/metabolism* ; Liver/metabolism* ; Reperfusion Injury/metabolism*

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Sepsis-acquired weakness (SAW) is a common complication in critically ill patients, yet significant gaps remain in both mechanistic understanding and therapeutic interventions for this condition. SAW not only prolongs the duration of mechanical ventilation and hospitalization but is also closely associated with increased mortality. Even if these SAW patients survive, they often experience long-term physical dysfunction after hospital discharge, leading to diminished quality of life. Emerging evidence suggests that sustained mitochondrial dysfunction may constitute a pivotal pathophysiological basis for the development and progression of SAW, primarily encompassing five key aspects: dysregulated mitochondrial quality control (MtQC), impaired oxidative phosphorylation (OXPHOS), exacerbated oxidative stress, disrupted Ca²⁺; homeostasis, and their mediation of diverse myofiber injuries. This article systematically elucidates the central role of mitochondrial dysfunction in the pathogenesis of SAW. Furthermore, we explore potential therapeutic strategies targeting mitochondrial function, including mitigating mitochondrial oxidative stress, optimizing nutritional support, and supplementing with muscle-derived mesenchymal stem cells. These insights provide a critical theoretical framework for understanding SAW mechanisms and developing clinical interventions, with particular emphasis on the translational value of mitochondrial-targeted therapies in improving outcomes for septic patients.
Humans ; Sepsis/metabolism* ; Mitochondria/metabolism* ; Muscle Weakness/etiology* ; Oxidative Stress ; Oxidative Phosphorylation

Objective: To investigate the molecular mechanisms and pathways of action of total flavonoids of Dracocephalum moldavica L.(TFDM) in treating vascular cognitive impairment(VCI) based on network pharmacology and in vivo animal experiments. Methods : The swiss target prediction database, literature, and PubChem were used to screen the active components and action targets of TFDM. The online mendelian inheritance in man(OMIM) and GeneCards databases were utilized to screen for possible VCI targets. Venny software was used to obtain the intersection target of TFDM and VCI. The search tool for recurring instances of neighbouring genes(String) database and Cytoscape software was used to construct the PPI network. The database for annotation, visualization and integrated discovery(DAVID) database was utilized to screen for the kyoto encyclopedia of genes and genomes(KEGG) pathway and gene ontology(GO) enrichment analyses to explore the molecular mechanism and signaling pathway of TFDM for VCI. 24 rats were divided into Sham, Model, Donepezil, and TFDM groups. Except for the Sham group, the VCI model was created using modified bilateral common carotid artery ligation. After continuous gavage for 21 days, the Morris water maze test was used to evaluate the spatial learning and memory ability of rats. Hematoxy-lineosin(HE) staining was used to observe the pathological changes in the hippocampal CA1 and cortex region of the animals and immunohistochemistry detection of zonula occludens-1(ZO-1) content in the brains of the rats. Western blot was used to detect nuclear factor kappa-B p65(NF-κB p65) and tumor necrosis factor-α(TNF-α) in rat brains. Results : A total of 39 active ingredients of TFDM were screened, 209 corresponding targets, 10 417 gene targets of VCI, and 193 intersecting targets. According to the results of the GO enrichment of function analysis, TFDM could improve the response of reactive oxygen species and metabolic processes of reactive oxygen species, etc. KEGG pathway enrichment analysis suggested that TFDM might regulate TNF, IL-17 signing pathway, etc. The results of animal experiments showed that TFDM improved learning and memory while reduced pathological damage in the brains of VCI rats. In addition, TFDM upregulated the positive expression of ZO-1 and downregulated the protein levels of TNF-α and NF-κB p65(P<0.05). Conclusion TFDM can improve the cognitive function of VCI through multi-components and multi-targets, and its key mechanism may be related to inhibiting TNF-α/NF-κB p65 signaling pathway,reducing neuroinflammation,and improvement of blood-brain barrier permeability.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

Background Acne treatment cycle lasts long and will cause facial appearance damage.Many patients are prone to psychological problems and severe patients may even experience suicidal ideation.However,the influencing factors of psychological health problems in acne patients are still unclear.Objective To investigate the mental health status of patients with moderate-to-severe acne and to analyze the influencing factors of their psychological health problems,so as to provide references for improving their mental health.Methods A total of 120 patients with moderate-to-severe acne of grades II-IV were selected as the research subjects,who were treated in the dermatology outpatient department of the Third Hospital of Mianyang from June 2021 to June 2023.All subjects were evaluated by using the Acne-Specific Quality of Life Questionnaire(Acne-QoL),Self-rating Depression Scale(SDS),Self-rating Anxiety Scale(SAS),Rosenberg Self-Esteem Scale(RSES)and Social Phobia Inventory(SPIN).According to the evaluation results of SDS,SAS,RSES,SPIN,subjects were divided into a group with mental health problems(n=21)and a group without mental health problems(n=99).Binary Logistic regression anaylsis was adopted to explore the influencing factors of psychological health problems in acne patients.Results A total of 21 patients(17.50%)were detected to have symptoms of depression,anxiety,inferiority or social dysfunction.Statistically significant difference was observed in comparison between two groups in gender,profession,acne classification,dietary habit,age,illness course as well as the factor scores of self perception,emotional function,social function and acne symptom in Acne-QoL(χ2=7.013,23.123,9.028,11.327,t=9.913,13.022,4.081,5.383,5.361,10.203,P<0.05).The results of binary Logistic regression analysis showed that the followings were risk factors for the occurrence of psychological health problems in acne patients:female(OR=2.243,95%CI:1.136～4.429),acne of grade III(OR=3.615,95%CI:1.269～10.295)or IV(OR=1.872,95%CI:1.073～3.266),course of disease≥1.6 years(OR=2.499,95%CI:1.068～5.851),a spicy or greasy diet(OR=3.811,95%CI:1.169～12.427),Acne-QoL self perception score≤18(OR=1.802,95%CI:1.227～2.646),Acne-QoL emotional function score≤18(OR=2.252,95%CI:1.016～4.992),Acne-QoL social function score≤14(OR=3.515,95%CI:1.534～8.053)and Acne-QoL acne symptom score≤18(OR=3.586,95%CI:1.098～11.715).Protective factors for psychological health problems in acne patients included age over 30 years old(OR=0.429,95%CI:0.283～0.648),occupation as professional cadre or enterprise employee(OR=0.483,95%CI:0.249～0.939)and other occupations(OR=0.276,95%CI:0.090～0.850).Conclusion A part of patients with moderate-to-severe acne may experience psychological health problems.Patients with female gender,higher acne grades,longer disease duration,preference for greasy or spicy foods and lower scores in all Acne-QoL factors have a higher risk of experiencing psychological health problems.

Advanced gastric cancer(AGC)includes locally unresectable gastric cancer(GC),metastatic GC,and postoperative recurrent GC.Due to delayed diagnosis and lack of effective treatment for AGC,the median survival time of AGC patients is only 6-12 months.At present,the main treatment goal of AGC is to improve symptoms and prolong the survival time of patients receiving sequential chemotherapy.Although the therapeutic effect of systemic therapy on AGC is gradually becoming apparent,the patient's prognosis is far from expected.In addition,targeted therapy and novel immunotherapy have drawbacks such as high incidence of drug resistance,high toxic side effects,and heavy economic burden on patients.Therefore,finding new therapeutic targets and developing anti-tumor drugs is a key issue that urgently needs to be addressed.According to reports,abnormal activation of the hepatocyte growth factor(HGF)/cellular-mesenchymal epithelial transition factor(c-MET)pathway plays a crucial role in the progression of GC and the occurrence of multi-line resistance and may be a potential therapeutic target for GC.In recent years,some HGF/c-MET-targeting small molecule tyrosine kinase inhibitors(TKIs)have been found to show good clinical effects in the treatment of GC.Meanwhile,new HGF/c-MET inhibitors(such as monoclonal antibodies,bispecific antibodies,antibody drug conjugates,etc.)have shown good anti-tumor activity in preclinical studies,but they are all at different stages of clinical research,and their efficacy and safety still need further confirmation.This review elaborates on the latest research progress of HGF/c-MET inhibitors in the treatment of AGC and discusses the main reasons and strategies for drug resistance,aiming to provide better guidance for the treatment of AGC and provide reference for future research.

Objective:To retrieve, evaluate, and integrate evidence related to balance function management in stroke patients with hemiplegia.Methods:A systematic search was conducted on BMJ Best Practice, UpToDate, National Institute for Health and Care Excellence, Guidelines International Network, Scottish Intercollegiate Guidelines Network, Australia Joanna Briggs Institute Evidence-Based Practice Center, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, VIP, China Biology Medicine disc, PubMed, Web of Science, Medlive, and other websites or data platforms for relevant guidelines, best practices, evidence summaries, systematic reviews, and Meta-analyses on balance function management in stroke patients with hemiplegia, with a retrieval period from March 2014 to March 2024. Two researchers trained in evidence-based practices evaluated the methodological quality of the literature and extracted and summarized the relevant evidence.Results:Based on the inclusion and exclusion criteria, a total of eight guidelines and seven systematic reviews were included, yielding 29 pieces of best evidence across nine aspects: the importance of balance function training, organizational management, assessment tools, assessment timing, assessment content, assessment frequency, balance exercise programs, exercise duration, and health education.Conclusions:This study summarizes the best evidence for balance function management in stroke patients with hemiplegia, providing accurate evidence-based support for clinical practice among medical professionals. It is recommended that healthcare providers appropriately apply this evidence based on clinical scenarios to improve measures related to balance function management in stroke patients with hemiplegia.

【Objective】 To study the effects of gestational diabetes (GDM) on morphological structure of brain tissue and microribonucleotide (miRNA) expression profile in neonatal mice, and to provide a new research target for the prevention and treatment of abnormal neurodevelopment in GDM progeny. 【Methods】 The pregnant mice were divided into model group and control group,each group consisted of 10 mice. The model group mice established a GDM model by injecting streptozotocin to measure fasting blood glucose (FPG) and random blood glucose (GLU) at different times. Successful molded mice were randomly divided into model group A and model group C, and control mice were divided into control group B and control group D, with 5 mice in each group. The newborn mice in groups A and B were used for hippocampal tissue GeneChip detection and brain morphology structure observation, and group C and D newborn mice were used for qRT-PCR detection of hippocampus tissue expression differences to verify the differentially expressed genes of miRANs obtained by GeneChip screening. After giving birth, the neonatal mice were sacrificed by decapitation, and the brain tissue was dissected to observe the overall morphological structure. The structural changes of hippocampus were observed under HE chromogenic microscope. The Agilent mouse miRNA oligonucleotide gene chip was used to detect the miRNA expression profile of mouse hippocampus, screen differential miRNAs and predict their target genes, and conduct GO analysis and signal transduction pathway analysis of target genes. The relative expression levels of the screened miRNAs were verified by qRT-PCR. 【Results】 Compared with the control group, the GLU increased significantly from the 3rd day after drug administration in the model group (P<0.01). Macroscopic observation of control group B mice had normal brain morphology and structure, smooth appearance, clear gyrus, close arrangement of hippocampus cell structure, uniform staining and complete structure; in model group A, the number of hippocampus cells decreased, loose arrangement and deep staining. In the initial screen of miRNA microarray, there were 11 differentially expressed miRNAs between control and model groups, all of which were downregulated miRNAs, including let-7b-5p、miR-130b-3p、miR-181c-5p、miR-181d-5p、miR-3099-3p、miR-3470a、miR-3473a、miR-3473b、miR-500-3p、miR-532-5p、miR-7047-5p(P<0.05). Two miRNAs (miR-3473b, miR-7047-75p) and 5 target genes (MAPK3, MAPK11, MAPK14, CALM3, AKT3). The relative expression of miR-3473b and miR-7047-5p in model group C were lower than that in control group D (t=19.13 and 6.24, P<0.05), and the validation results were consistent with the microarray test results. 【Conclusion】 Compared with the offspring of normal pregnant mice, GDM offspring mice have abnormal development of brain structure and damage of hippocampal nerve cells, and there are a large number of abnormal expression of miRNAs in hippocampal tissue. Differentially expressed miRNAs can be used as research targets for prevention and treatment of GDM offspring neurodevelopmental abnormalities.