AIM:This study aims to investigate the mechanism by which Qingfei-Jiedu-Huatan Formula(QJHF)regulates autophagy in alveolar macrophages through mTOR in the treatment of severe pneumonia(SP)in rats.METHODS:Sixty SPF-grade male rats were randomly assigned to six groups:control,model,QJHF,moxifloxacin(MOX),rapamycin(RAPA),and QJHF+RAPA,with ten rats in each group.An SP rat model was established using Klebsiella pneumoniae.After seven days of treatment,changes in IL-33 and IFN-γ levels in bronchoalveolar lavage fluid(BALF)were measured using ELISA.Histopathological alterations in lung tissue were assessed via HE staining,and the autophagy of alveolar macrophages was detected using immunofluorescence co-localization methods.The expression levels of mTOR,beclin-1,and LC3 mRNA in lung tissue were analyzed using qPCR,while Western blot was employed to assess the protein levels of p-mTOR/mTOR,beclin-1,and LC3-II/LC3-I.RESULTS:Compared to the control group,the model group exhibited a deteriorated condition,characterized by alveolar wall rupture and thickening,significant inflammatory cell infiltration in the alveolar cavity,and extensive lung tissue damage(P<0.01).Elevated levels of IL-33 and IFN-γ in BALF were also observed(P<0.01),along with increased colocalization of CD68 and LC3 in immunofluorescence analy-sis.The mTOR mRNA expression in lung tissue decreased(P<0.01),while LC3 and beclin-1 mRNA expressions in-creased(P<0.01).Additionally,the protein expression ratio of p-mTOR/mTOR decreased(P<0.01),whereas LC3-II/LC3-I and beclin-1 protein levels increased(P<0.01).In comparison to the model group,significant improvements were noted after treatment with QJHF and MOX(P<0.01),while RAPA treatment led to a worsening of these indicators(P<0.05).A slight improvement was observed with the QJHF combined with RAPA intervention,though this was not statisti-cally significant.No significant differences were found between the MOX and QJHF groups.However,the QJHF+RAPA group displayed notable improvements in various indicators compared to the RAPA group(P<0.05).CONCLUSION:The QJHF can mitigate the inflammatory response associated with severe pneumonia,potentially by activating mTOR phos-phorylation activity,which in turn inhibits excessive autophagy in alveolar macrophages.

AIM:This study aims to investigate the therapeutic effects of Xiaozhen Fang(XZF)on epidermal growth factor receptor(EGFR)inhibitor,erlotinib-induced skin toxicity in mice,with a focus on the underlying functional mechanisms.METHODS:A mouse model of skin toxicity was established and divided into three groups(n=5 per group):blank,erlotinib(150 mg/kg),and erlotinib(150 mg/kg)combined with XZF(45 g/kg)groups.Skin toxicity se-verity and body weight were evaluated.Western blot was performed to detect protein levels of gasdermin D(GSDMD),caspase-1,and interleukin-1β(IL-1β)in skin tissue.Immunofluorescence was employed to analyze gasdermin E,IL-1β,caspase-1,and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)expression in skin tissue.In vitro,HacaT cells were cultured and treated with erlotinib followed by different concentrations of XZF-containing se-rum.Cell viability was assessed by MTT assay.Cell ultrastructure was observed by transmission electron microscopy,and p53-binding protein 1(53BP1)expression was analyzed by immunofluorescence staining.RESULTS:The XZF signifi-cantly alleviated erlotinib-induced skin toxicity in mouse model,as evidenced by reduced rash incidence,alleviated limb swelling,and increased body weight(P<0.05).Expression of Gasdermins,IL-1β,caspase-1,and NLRP3 was distinctly down-regulated in dorsal skin tissue(P<0.05 or P<0.01).In vitro,XZF-containing serum markedly suppressed pyropto-sis in HacaT cells(P<0.01),preserved cell membrane integrity,and significantly reduced 53BP1 fluorescence intensity(P<0.01).CONCLUSION:The XZF mitigates EGFR inhibitor,erlotinib-induced skin toxicity in mice,potentially by regulating pyroptosis through the NLRP3/caspase-1/GSDMD signaling pathway.This mechanism exerts a cytoprotective ef-fect and alleviates erlotinib-induced skin toxicity.

Renal cell carcinoma(RCC)is a malignant tumor that originates from the epithelial cells of the re-nal tubules,comprising 80%to 90%of all malignant renal tumors.With the dual pressures of population growth and ag-ing,both the incidence and mortality rates of RCC are on the rise.PANoptosis is a newly identified form of cell death,con-trolled by the PANoptosome complex,and exhibits characteristics of three programmed cell death pathways,pyroptosis,apoptosis,and necroptosis.Increasing research indicates that the occurrence of PANoptosis is associated with tumor devel-opment,suggesting its potential as a new therapeutic strategy for renal carcinoma.This article reviews the definition of PANoptosis,the structure of the PANoptosome protein complex,and its impact on the PANoptosis process.Additionally,it explores the interactions between PANoptosis,pyroptosis,apoptosis and necroptosis,and their effects on RCC.

Parkinson disease(PD)is one of the most prevalent neurodegenerative disorders,typically affecting the elderly.The pathogenesis of PD is intricate and involves multiple factors,with mitochondrial dysfunction recognized as a significant mechanism contributing to its development.MicroRNAs(miRNAs)play a crucial role in the onset and pro-gression of PD.This review focuses on recent research concerning miRNAs associated with PD,particularly their impact on mitochondrial dysfunction.The insights gathered here aim to support the early diagnosis and targeted treatment of PD.

Type 2 diabetes mellitus(T2DM)has emerged as a significant public health challenge and a con-siderable threat to human well-being due to its chronic nature.Consequently,it cannot be overlooked.In response to this pressing issue,scientific weight loss treatments have demonstrated their effectiveness as a coping strategy.Particularly,for patients in the early stages of the disease with preserved pancreatic islet function and obesity,weight loss treatment has been shown to significantly enhance their glucose tolerance and ameliorate metabolic disorders.Ongoing research has led to a growing body of evidence regarding the mechanisms and clinical data supporting the use of weight loss therapy in miti-gating type 2 diabetes.This paper aims to evaluate the impact of weight loss therapy on the major metabolic organs of the body,such as the liver,pancreas,skeletal muscle,and adipose tissue,and to delve into the physiological and molecular mechanisms involved in the remission of T2DM.

Maternal obesity has been shown to exert adverse transgenerational effects on offspring ovarian function,characterized by reduced ovarian follicle reserve,impaired granulosa cell function,and disrupted reproductive cycles.The underlying mechanisms involve cellular stress-induced damage characterized by mitochondrial dysfunction,oxidative stress,and apoptosis,as well as dysregulation in key regulatory pathways such as ovarian hormone secretion,gene expression,and epigenetic modifications.This review synthesizes existing evidence on how maternal obesity-induced acute stress and chronic genetic/epigenetic alterations jointly contribute to offspring ovarian impairment.The findings elu-cidate the complex relationship between maternal metabolic status and offspring reproductive health,providing a robust theoretical foundation for refining prenatal management and developing targeted intervention strategies.

Alzheimer disease(AD)is a neurodegenerative disorder characterized by the abnormal deposition of amyloid β-protein(Aβ).Inflammation plays a significant role in promoting this abnormal deposition.Toll-like receptor 4(TLR4)is recognized as a"primary regulator"of the inflammatory response,facilitating the activation of microglia and interacting with various pathways,including nuclear factor-κB and nucleotide-binding oligomerization domain-like recep-tor protein 3.This interaction can lead to an inflammatory cascade that accelerates the progression of AD.Numerous pro-spective studies have demonstrated that traditional Chinese medicine can modulate the TLR4 signaling pathway,effective-ly addressing both the onset and progression of AD.However,a comprehensive review of how Chinese medicine regulates this pathway in the treatment of AD is currently lacking.Therefore,this paper aims to detail the latest findings related to TLR4 in the prevention and treatment of AD,drawing from recent literature.It will explore the mediation of traditional Chinese medicine,preserving its essence,and provide references and a basis for clinical practices aimed at preventing and treating AD.

Ischemic stroke,which presents a heavy medical,social,and economic burden worldwide,is now the second-leading cause of high morbidity,disability,mortality,and recurrence.However,its mechanism remains un-covered.Glycine,serves as a dual-role neurotransmitter,is involved in several cellular processes.Recent studies have shown that glycine can protect against ischemic stroke by reducing cell death,attenuating glutamate excitotoxicity,inhibit-ing inflammatory responses,and inducing vascular remodeling.This review aims to provide a comprehensive overview of glycine's biological functions,receptor characteristics,signal transduction mechanisms,and highlight glycine's protec-tive role in ischemic stroke.

Joint diseases have traditionally been linked to cartilage degeneration and inflammation,often ne-glecting the vital role of the joint barrier.This review introduces the novel concept of the"joint barrier"as an essential ana-tomical and functional unit in maintaining joint homeostasis.We systematically elucidate its structural components and functional characteristics,underscoring how dysfunction of the joint barrier contributes to the pathogenesis of various joint diseases.This perspective provides fresh insights into disease mechanisms and potential therapeutic targets.We highlight cutting-edge findings on the molecular regulatory mechanisms underlying joint barrier imbalance,focusing on epigenetic modifications,metabolic reprogramming,and intercellular communication networks.These discoveries establish a new framework for understanding joint pathology and identifying innovative intervention strategies.Additionally,we propose forward-thinking research directions with significant translational potential,including exploring the association between im-mune components and synovial barrier function,developing novel drugs targeting the barrier microenvironment,and inves-tigating the regulatory mechanisms of joint barrier imbalance influenced by systemic factors.These strategies promise to revolutionize the diagnosis,treatment,and prevention of joint diseases.By integrating the latest research and proposing fu-ture directions,this review offers a comprehensive understanding of joint barrier disorders and their implications for joint diseases,paving the way for new therapeutic approaches and concepts in the field.

AIM:To construct and breed infertility model mice with ATP/GTP binding carboxypeptidase 1(Agtpbp1)gene knockout homozygote(Agtpbp1-/-)by CRISPR/Cas9 technology,so as to provide an animal model for the subsequent exploration of the pathogenesis of Agtpbp1 gene in male sterility.METHODS:The CRISPR/Cas9 technology was used to obtain Agtpbp1 gene knockout heterozygote(Agtpbp1+/-)mice according to the data of the main protein functional region of Agtpbp1 gene and combined with Cas9 nuclease.The obtained Agtpbp1+/-mice were mated,and their offspring were genotyped by PCR and agarose gel electrophoresis.The expression of Agtpbp1 at different levels was detected by RT-PCR,Western blot and immunohistochemical staining to support the identification results.The HE staining was used to observe the mouse cerebellum and eyeball structure to analyze the effect of Agtpbp1 gene knockout on Purkinje cells and photoreceptor cells.The symptoms of ataxia in mice were observed in combination with behavioral tests.The growth of mice was observed,and the changes of testicular tissue volume and weight of male mice were analyzed.The HE staining was used to observe the changes of testicular structure,and PAS staining was used to observe the changes of testicular germ cell cycle.Finally,sperm analyzer was used to analyze the sperm motility,so as to analyze the growth and develop-ment of the mice.RESULTS:The male and female Agtpbp1+/-mice could continue to mate,and three genotypes,Agtpbp1 wild-type(Agtpbp1+/+),Agtpbp1+/-and Agtpbp1-/-,were obtained.The genotypes of the offspring mice were successfully identified by PCR.The results of RT-PCR,Western blot and immunohistochemical staining verified the successful con-struction of Agtpbp1-/-mouse model at different levels(P<0.05).The results of HE staining showed that Purkinje cells were lost in the cerebellum of Agtpbp1-/-mice and the number of photoreceptor cells in the eyeball was reduced.Behavioral tests confirmed that Agtpbp1-/-mice had ataxia symptoms such as motor dysfunction and uncoordinated movements.Com-pared with control group,the testicular volume and weight of Agtpbp1-/-mice were significantly reduced.The results of HE staining showed a very small amount of sperm in the testis of Agtpbp1-/-mice.Combined with the sperm analyzer,it was ob-served that the sperm motility,vitality and movement rate of Agtpbp1-/-mice were significantly lower than those of the con-trol mice.Testicular sections with PAS staining showed cell cycle arrest of the sperm from Agtpbp1-/-mice.CONCLU-SION:In this study,Agtpbp1 knockout mice were successfully bred.The deletion of Agtpbp1 caused the arrest of sper-matogenic cell differentiation and the decrease in sperm motility in adult male mice,resulting in infertility.At the same time,it provides a new experimental tool for further exploring the molecular mechanism of Agtpbp1-induced male sterility.