Objective:To elucidate the mechanism of acute lung injury (ALI) by investigating the relationship of sirtuin 6 (SIRT6) with lactylation of mitochondrial fission 1 protein (FIS1) and mitophagy in mice.Methods:Twenty-four SPF-grade healthy wild-type C57BL/6 mice of either sex, aged 6-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=6 each) using a table of random numbers: sham operation group (group S), ALI group, ALI + agonist group (group AA), and ALI+ agonist+ lactate group (group AAL). The mouse ALI model was established by intratracheal instillation of lipopolysaccharide 5 mg/kg in anesthetized animals. Immediately after developing the model, UBCS039 30 mg/kg was injected via the tail vein in group AA, UBCS039 30 mg/kg was injected via the tail vein and L-lactic acid sodium 1 mg/g was intraperitoneally injected in group AAL, and vehicle 0.5 ml was given instead in group S. Another 6 Prkn-/- mice were selected and assigned to Prkn-/-+ ALI+ agonist group (group PAA), and UBCS039 30 mg/kg was injected via the tail vein immediately after developing the ALI model. The mice were anesthetized and sacrificed at 12 h after lipopolysaccharide instillation, and the lung tissue was obtained for determination of the FIS1 lactylation and ubiquitination levels, the binding levels of FIS1 to SIRT6 and Parkin (using co-immunoprecipitation), expression of PTEN-induced kinase 1 (PINK1), microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), and mitochondrial Parkin (by Western blot) and for microscopic examination of the pathological changes (after haematoxylin and eosin staining) which were scored. The wet/dry lung weight (W/D) ratio was calculated, and the apoptosis rate of cells in lung tissues was calculated by TUNEL assay. Results:Compared with group S, the FIS1 lactylation level, W/D ratio, apoptosis rate of cells, and lung injury score were significantly increased in group ALI ( P<0.05). Compared with group ALI, the FIS1 lactylation level, W/D ratio, apoptosis rate of cells, and lung injury score were significantly decreased, the binding level of FIS1 to Parkin and FIS1 ubiquitination level were increased, and the expression of PINK1, LC3Ⅱ and mitochondrial Parkin was up-regulated in group AA ( P<0.05). Compared with group AA, the FIS1 lactylation level was significantly increased, and the binding level of FIS1 to Parkin was decreased in group AAL, and the W/D ratio, apoptosis rate of cells, and lung injury score were significantly increased, the FIS1 ubiquitination level was decreased, and the expression of PINK1, LC3Ⅱ and mitochondrial Parkin was down-regulated in group AAL and group PAA ( P<0.05). Conclusions:SIRT6 inhibits FIS1 lactylation, increases the binding of FIS1 to Parkin, and thus promotes mitophagy, which is involved in the process of ALI in mice.

Objective:To elucidate the mechanism of acute lung injury (ALI) by investigating the relationship of sirtuin 6 (SIRT6) with lactylation of mitochondrial fission 1 protein (FIS1) and mitophagy in mice.Methods:Twenty-four SPF-grade healthy wild-type C57BL/6 mice of either sex, aged 6-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=6 each) using a table of random numbers: sham operation group (group S), ALI group, ALI + agonist group (group AA), and ALI+ agonist+ lactate group (group AAL). The mouse ALI model was established by intratracheal instillation of lipopolysaccharide 5 mg/kg in anesthetized animals. Immediately after developing the model, UBCS039 30 mg/kg was injected via the tail vein in group AA, UBCS039 30 mg/kg was injected via the tail vein and L-lactic acid sodium 1 mg/g was intraperitoneally injected in group AAL, and vehicle 0.5 ml was given instead in group S. Another 6 Prkn-/- mice were selected and assigned to Prkn-/-+ ALI+ agonist group (group PAA), and UBCS039 30 mg/kg was injected via the tail vein immediately after developing the ALI model. The mice were anesthetized and sacrificed at 12 h after lipopolysaccharide instillation, and the lung tissue was obtained for determination of the FIS1 lactylation and ubiquitination levels, the binding levels of FIS1 to SIRT6 and Parkin (using co-immunoprecipitation), expression of PTEN-induced kinase 1 (PINK1), microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), and mitochondrial Parkin (by Western blot) and for microscopic examination of the pathological changes (after haematoxylin and eosin staining) which were scored. The wet/dry lung weight (W/D) ratio was calculated, and the apoptosis rate of cells in lung tissues was calculated by TUNEL assay. Results:Compared with group S, the FIS1 lactylation level, W/D ratio, apoptosis rate of cells, and lung injury score were significantly increased in group ALI ( P<0.05). Compared with group ALI, the FIS1 lactylation level, W/D ratio, apoptosis rate of cells, and lung injury score were significantly decreased, the binding level of FIS1 to Parkin and FIS1 ubiquitination level were increased, and the expression of PINK1, LC3Ⅱ and mitochondrial Parkin was up-regulated in group AA ( P<0.05). Compared with group AA, the FIS1 lactylation level was significantly increased, and the binding level of FIS1 to Parkin was decreased in group AAL, and the W/D ratio, apoptosis rate of cells, and lung injury score were significantly increased, the FIS1 ubiquitination level was decreased, and the expression of PINK1, LC3Ⅱ and mitochondrial Parkin was down-regulated in group AAL and group PAA ( P<0.05). Conclusions:SIRT6 inhibits FIS1 lactylation, increases the binding of FIS1 to Parkin, and thus promotes mitophagy, which is involved in the process of ALI in mice.

Objective To analyze changes in intestinal microbiota composition and metabolites in mice with nitrous oxide poisoning using 16S rDNA sequencing and metabolomics,and to examine correlations between gut microbes and metabolites in order to explore the mechanisms of nitrous oxide poisoning.Methods C57BL/6 mice were randomly divided into a control group and a nitrous oxide poisoning group(n=6).The poisoning group was exposed to 90,000 ppm nitrous oxide twice daily for 1 h over 28 days,while the control group was exposed to air.Fecal samples were collected 24 h after the last exposure.16S rDNA sequencing was used to analyze structural differences in microbial communities and identify significantly different taxa.Metabolomics analysis was performed to detect changes in fecal metabolites and identify differential metabolites.Correlation analysis was conducted between differential microbiota and metabolites.Results 16S rDNA sequencing showed that the poisoning group had increased microbial abundance compared with controls,while species diversity remained unchanged.Significant differences were observed in gut microbiota structure between groups.Metabolomics identified 112 differential metabolites related to nitrous oxide poisoning,mainly involving the cAMP signaling pathway and sphingolipid metabolism.Spearman correlation analysis revealed a strong association between differential microbiota and differential metabolites.Conclusion Nitrous oxide poisoning alters the structure and metabolic profiles of intestinal microbiota.Changes in microbial abundance affect multiple metabolic pathways,which may be related to damage to the nervous and hematological systems.These findings provide a basis for further research on the mechanisms of nitrous oxide poisoning and for clinical treatment.

Objective:To explore the psychological vulnerability characteristics of patients after percutaneous coronary intervention (PCI) based on symptom network analysis, and to provide evidence for maintining their psychological health.Methods:Using a cross-sectional survey method, from October 2023 to March 2024, a convenience sampling approach was employed to conduct a questionnaire survey among patients who underwent percutaneous coronary intervention (PCI) in the general ward of the Cardiology Department at Peking University Third Hospital. The survey involved a general information questionnaire and Mental Vulnerability Questionnaire. The R language was used to construct a symptom network to describe the relationship between each symptom of patients′psychological vulnerability, and its centrality index was calculated.Results:A total of 260 post-PCI patients were enrolled, including191 males and 69 females, with a mean age of (62.38 ± 12.91) years and a total psychological vulnerability score of (47.25 ± 13.18). Multiple linear regression analysis showed that the level of mental vulnerability was higher in patients with female gender ( β = 0.207, P = 0.001) and higher number of comorbidities/past history ( β = 0.126, P = 0.039). In the symptom network analysis, the symptoms with the highest node strength, tight centrality, and mediator centrality were "You often feeling unwell" ( rs = 1.25, rc = 0.003 45, rb = 2.61), "You always in a bad mood" ( rs = 1.15) and "You often have anxiety attacks" ( rs = 1.13) were second only to "You often feeling unwell" in the center of intensity. Conclusions:The core symptom of psychological vulnerability in post-PCI patients is "You often feeling unwell", and mental symptoms are in a more central position. Nursing staff should take mental symptoms as the target of intervention, and strengthen the holistic care for patients′physical-psychological-mental symptoms, so as to effectively reduce the level of psychological vulnerability of the patients, and to maintain their psychological health.

A bladder cancer patient underwent intravesical Bacillus Calmette-Guérin (BCG) instillation in Xiamen Branch, Zhongshan Hospital, Fudan University in April 2023. Following 8 instillations the patient presented with fever, cough and dyspnea, and was diagnosed as interstitial pneumonia (IP). Symptoms resolved after anti-tuberculosis and methylprednisolone treatment, with subsequent successful discharge. Using the keywords ′Bacillus Calmette-Guérin, ′ ′intravesical instillation, ′ ′pneumonia, ′ Wanfang Data, China National Knowledge Infrastructure(CNKI), Weipu(VIP), and PubMed databases were searched for relevant literature published between January 2014 and June 2024, and 20 cases of BCG instillation-induced pneumonia were retrieved, including 10 IP cases and 10 miliary pneumonia cases. Among 10 IP cases, 7 received corticosteroids combined with anti-tuberculosis therapy. Two cases unresponsive to combination therapy resulted in mortality, while others showed therapeutic efficacy. Miliary pneumonia demonstrated better prognosis, with 6 cases achieving complete remission through anti-tuberculosis monotherapy. The results indicate that severe BCG-related pneumonia generally necessitates combined anti-tuberculosis and corticosteroid therapy.

Objective To analyze changes in intestinal microbiota composition and metabolites in mice with nitrous oxide poisoning using 16S rDNA sequencing and metabolomics,and to examine correlations between gut microbes and metabolites in order to explore the mechanisms of nitrous oxide poisoning.Methods C57BL/6 mice were randomly divided into a control group and a nitrous oxide poisoning group(n=6).The poisoning group was exposed to 90,000 ppm nitrous oxide twice daily for 1 h over 28 days,while the control group was exposed to air.Fecal samples were collected 24 h after the last exposure.16S rDNA sequencing was used to analyze structural differences in microbial communities and identify significantly different taxa.Metabolomics analysis was performed to detect changes in fecal metabolites and identify differential metabolites.Correlation analysis was conducted between differential microbiota and metabolites.Results 16S rDNA sequencing showed that the poisoning group had increased microbial abundance compared with controls,while species diversity remained unchanged.Significant differences were observed in gut microbiota structure between groups.Metabolomics identified 112 differential metabolites related to nitrous oxide poisoning,mainly involving the cAMP signaling pathway and sphingolipid metabolism.Spearman correlation analysis revealed a strong association between differential microbiota and differential metabolites.Conclusion Nitrous oxide poisoning alters the structure and metabolic profiles of intestinal microbiota.Changes in microbial abundance affect multiple metabolic pathways,which may be related to damage to the nervous and hematological systems.These findings provide a basis for further research on the mechanisms of nitrous oxide poisoning and for clinical treatment.

Objective:To explore the psychological vulnerability characteristics of patients after percutaneous coronary intervention (PCI) based on symptom network analysis, and to provide evidence for maintining their psychological health.Methods:Using a cross-sectional survey method, from October 2023 to March 2024, a convenience sampling approach was employed to conduct a questionnaire survey among patients who underwent percutaneous coronary intervention (PCI) in the general ward of the Cardiology Department at Peking University Third Hospital. The survey involved a general information questionnaire and Mental Vulnerability Questionnaire. The R language was used to construct a symptom network to describe the relationship between each symptom of patients′psychological vulnerability, and its centrality index was calculated.Results:A total of 260 post-PCI patients were enrolled, including191 males and 69 females, with a mean age of (62.38 ± 12.91) years and a total psychological vulnerability score of (47.25 ± 13.18). Multiple linear regression analysis showed that the level of mental vulnerability was higher in patients with female gender ( β = 0.207, P = 0.001) and higher number of comorbidities/past history ( β = 0.126, P = 0.039). In the symptom network analysis, the symptoms with the highest node strength, tight centrality, and mediator centrality were "You often feeling unwell" ( rs = 1.25, rc = 0.003 45, rb = 2.61), "You always in a bad mood" ( rs = 1.15) and "You often have anxiety attacks" ( rs = 1.13) were second only to "You often feeling unwell" in the center of intensity. Conclusions:The core symptom of psychological vulnerability in post-PCI patients is "You often feeling unwell", and mental symptoms are in a more central position. Nursing staff should take mental symptoms as the target of intervention, and strengthen the holistic care for patients′physical-psychological-mental symptoms, so as to effectively reduce the level of psychological vulnerability of the patients, and to maintain their psychological health.

A bladder cancer patient underwent intravesical Bacillus Calmette-Guérin (BCG) instillation in Xiamen Branch, Zhongshan Hospital, Fudan University in April 2023. Following 8 instillations the patient presented with fever, cough and dyspnea, and was diagnosed as interstitial pneumonia (IP). Symptoms resolved after anti-tuberculosis and methylprednisolone treatment, with subsequent successful discharge. Using the keywords ′Bacillus Calmette-Guérin, ′ ′intravesical instillation, ′ ′pneumonia, ′ Wanfang Data, China National Knowledge Infrastructure(CNKI), Weipu(VIP), and PubMed databases were searched for relevant literature published between January 2014 and June 2024, and 20 cases of BCG instillation-induced pneumonia were retrieved, including 10 IP cases and 10 miliary pneumonia cases. Among 10 IP cases, 7 received corticosteroids combined with anti-tuberculosis therapy. Two cases unresponsive to combination therapy resulted in mortality, while others showed therapeutic efficacy. Miliary pneumonia demonstrated better prognosis, with 6 cases achieving complete remission through anti-tuberculosis monotherapy. The results indicate that severe BCG-related pneumonia generally necessitates combined anti-tuberculosis and corticosteroid therapy.

A retrospective analysis was made on the clinical data and gene mutation characteristics of 2 children admitted to the Children′s Hospital of Zhejiang University School of Medicine for epilepsy without periventricular nodules caused by the ARF1 gene mutation from August 2023 to February 2024, and relevant literature was reviewed.Both patients presented with seizures and psychomotor retardation, and 1 of them was diagnosed with West syndrome.Whole exome sequencing confirmed that the 2 patients carried a missense mutation in the ARF1 gene (c.55C>A, p.R19S).Brain magnetic resonance imaging (MRI) of 2 patients revealed no obvious abnormalities.A summary analysis of 5 cases of ARF1 gene mutations reported in three foreign literatures showed that patients with ARF1 gene mutations usually presented with seizures, developmental delay, hypotonia, mental retardation, and motor stereotypies.MRI showed periventricular nodular heterotopia, corpus callosum dysplasia, subcortical white matter abnormalities, and delayed myelination.This study found for the first time that ARF1-related disorders can occur without significant brain structural malformations, indicating that there are inconsistencies in neuroimaging findings, adding valuable phenotypic information to this gene.The differences in imaging findings may be the result of genetic background or variation in ARF1-interacting proteins, or may be caused by altered regulatory mechanisms of protein activity.

Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis(PF).It is considered as a promising ther-apeutic target anti-PF.The well-documented against PF properties of Tanshinone ⅡA(Tan ⅡA)have been primarily attributed to its antioxidant and anti-inflammatory potency.Emerging evidence suggests that TanⅡA may target energy metabolism pathways,including glycolysis and tricarboxylic acid(TCA)cycle.However,the detailed and advanced mechanisms underlying the anti-PF activities remain obscure.In this study,we applied[U-13C]-glucose metabolic flux analysis(MFA)to examine metabolism flux disruption and modulation nodes of Tan ⅡA in PF.We identified that Tan ⅡA inhibited the glycolysis and TCA flux,thereby suppressing the production of transforming growth factor-β1(TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro.We further revealed that Tan ⅡA inhibited the expression of key metabolic enzyme hexokinase 2(HK2)by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)pathway activities,which decreased the accumulation of abnormal metabolites.Notably,we demonstrated that Tan ⅡA inhibited ATP citrate lyase(ACLY)activity,which reduced the collagen synthesis pathway caused by cytosol citrate consumption.Further,these results were validated in a mouse model of bleomycin-induced PF.This study was novel in exploring the mechanism of the occurrence and develop-ment of Tan ⅡA in treating PF using 13C-MFA technology.It provided a novel understanding of the mechanism of Tan ⅡA against PF from the perspective of metabolic reprogramming.