Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

Aim To investigate the effects of sodium lactate(NALA)on right heart failure induced by monocrotaline(MCT)-induced pulmonary arterial hy-pertension in rats and to reveal the underlying mecha-nisms.Methods Forty male Sprague-Dawley(SD)rats were randomly allocated into four groups,with ten rats in each group,namely,MCT group,NALA group,and NALA+MCT group;the MCT and NALA+MCT groups were administered a single intraperito-neal injection of MCT at 60 mg·kg-1 to induce pul-monary hypertension,and one week later,the NALA and NALA+MCT groups received intraperitoneal in-jections of NALA at 0.1 g·kg-1(once a day,for 5 weeks),while the CON and MCT groups received e-qual volumes of physiological saline(once a day,for 5 weeks);right heart function was assessed using echo-cardiography,right ventricular and pulmonary artery remodeling were evaluated via histopathological sec-tions,and the expression levels of ANP,BNP,and in-flammatory factors were measured by ELISA,along with assessments of oxidative stress levels,Western blot detection of the expression levels of proteins in the TLR4/NF-κB signaling pathway.Results Compared to the CON group,the MCT group exhibited increased RVSP and RVHI,decreased right heart function,in-creased collagen fiber deposition,and elevated oxida-tive stress and inflammatory factor expression,and the expression levels of proteins in the TLR4/NF-κB signa-ling pathway increased(P＜0.05);compared to the MCT group,the NALA+MCT group showed reduced RVSP and RVHI,improved right heart function,atten-uated pulmonary vascular remodeling,decreased ex-pression of ANP,BNP,inflammatory factors,and H2O2,along with increased antioxidant enzyme expres-sion,and the expression levels of proteins in the TLR4/NF-κB signaling pathway decreased(P＜0.05).Conclusion NALA can inhibit right ventric-ular remodeling in rats with pulmonary hypertension,and the underlying mechanism may involve the allevia-tion of inflammatory responses and oxidative stress through the inhibition of the TLR4/NF-κB signaling pathway.

Objective:To explore the relationship between suicide attempts,school bullying,and psychological resilience in children and adolescents with major depressive disorder(MDD)and school bullying and psychological resilience.Methods:A total of 784 patients with MDD aged 10 to 18 years were included.The Chinese version of the Olweus Bullying Victimization Questionnaire,Adolescent Psychological Resilience Scale,and a suicide attempt assessment were utilized to evaluate school bullying,psychological resilience,and suicide attempt.Stepwise logistic regression was applied to identify the associated factors of suicide attempts.Results:The occurrence of suicide at-tempts in children and adolescents with MDD was positively associated with physical bullying(OR=1.85,95％CI:1.14-3.02)and indirect bullying(OR=1.48,95％CI:1.06-2.04),and negatively associated with higher levels of goal focus(OR=0.62,95％CI:0.45-0.85)and positive cognition(OR=0.62,95％CI:0.45-0.85)at higher levels.Conclusion:Bullying significantly increases the risk of suicide attempts in children and adolescents with MDD,while higher psychological resilience could mitigate this risk.

Objective To evaluate the efficacy and safety of Qixian Tongluo Formula in the treatment of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome,and to preliminarily explore the molecular mechanism of Qixian Tongluo Formula in improving impaired motor function from the perspective of cross-kingdom regulation of Chinese medicine microRNA(miRNA).Methods A pragmatic randomized controlled trial was conducted with 102 patients in the recovery period of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome in our hospital.Patients were randomly divided into trial group and control group,with 51 cases in each group.The control group received standard Western medicine standard treatment,while the trial group received Qixian Tongluo Formula in addition to the standard treatment,with one dose per day,boiled in water,and taken warm after breakfast and dinner for a course of 2 months.The disability rate was used as the main efficacy indicator,and the incidence of adverse reactions was used as a safety indicator.miRNA from patient serum and Qixian Tongluo decoction were extracted respectively,and high-throughput sequencing was performed.The two sequences were compared to screen out the cross-kingdom gene transfer of Chinese medicine miRNA.Finally,its target genes of miRNA were predicted,and GO function and KEGG pathway enrichment analysis were carried out.Results A total of 67 patients completed the clinical trial,including 36 cases in the trial group and 31 cases in the control group;The disability rate in the trial group(13.9%)was lower than that in the control group(35.5%)(P<0.05);The incidence of adverse reactions was similar between the trial group(7.69%)and the control group(6.06%)(P>0.05);A total of 9530 Qixian Tongluo decoction miRNA sequences were screened,with 150 potentially involved in cross-kingdom gene transfer,including families such as miR-15 and miR-17;According to the target gene prediction of the top 10 miRNAs in cross-kingdom gene transfer of Chinese medicine,345 overlapping target genes were obtained;GO functional enrichment analysis revealed 16 biological processes,7 cellular components,and 2 molecular functions among the top 25 enriched functions,while KEGG pathway analysis mainly focused on the transforming growth factor-βsignaling pathway,neurotrophin signaling pathway,which are closely related to neural repair and functional recovery processes such as glial scar formation and synaptic plasticity after cerebral ischemia.Conclusion Qixian Tongluo Formula can significantly improve the functional independence level of patients with kidney deficiency and blood stasis syndrome in the recovery period of paralysis after cerebral infarction,offering a safe and effective treatment option for these patients;There were a large number of miRNAs in Qixian Tongluo decoction,some of which could cross-kingdom transferred into the human blood circulation,and promote the recovery of motor function in patients with cerebral infarction through multi-target,multi link and multi pathway gene network regulation.This study provides a new idea for subsequent clinical and basic research.

Objective To study the characteristics of animal models of pulmonary fibrosis so as to provide a reference for the standardization of such models,and to guide research on the pathogenesis,diagnosis,and treatment of pulmonary fibrosis.Methods Studies using experimental pulmonary fibrosis in animals published in the past 10 years were retrieved from the CNKI,Wanfang,VIP,SinoMed,and PubMed databases.Factors including animal species,sex,modeling method,and detection index were summarized,and the data were analyzed using Excel.Results A total of 292 eligible studies were included.The animals mainly included SD rats,Wistar rats,and C57BL/6 mice,and most were male.The most common modeling drugs were bleomycin,paraquat,and silica suspension,mainly administered by intratracheal injection,with a typical modeling cycle of 28 d.The detection indexes mainly comprised lung tissue pathology and measurements of protein expression,cytokine levels,and biochemical indexes.Conclusions SD rats and C57BL/6 mice were the most commonly used animals for experimental pulmonary fibrosis,and intratracheal injection of bleomycin(5 mg/kg)was the most frequently used modeling method.This approach allows for the straightforward and effective replication of pathological features resembling human pulmonary fibrosis,and may serve as a reference for future experimental studies using animal models of pulmonary fibrosis.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

BACKGROUND:Unlike non-inflammatory cell apoptosis,pyroptosis is a form of inflammatory cell death,characterized by membrane integrity disruption and release of pro-inflammatory intracellular substances.Thus,it is associated with various diseases.The sirtuin family is a group of histone deacetylases dependent on nicotinamide adenine dinucleotide.In addition to deacetylation,it also possesses other enzymatic activities such as desuccinylation,demalonylation,adenosine diphosphate-ribosylation and playing crucial roles in the regulation of pyroptosis.OBJECTIVE:To review the role of the sirtuins in pyroptosis.METHODS:The first author conducted a search on PubMed,Web of Science,CNKI,and WanFang Data from inception to March 2024,using the Chinese and English search terms"Sirtuins,Sirtuin1,Sirtuin2,Sirtuin3,Sirtuin4,Sirtuin5,Sirtuin6,Sirtuin7,pyroptosis",resulting in the inclusion of 71 articles.RESULTS AND CONCLUSION:(1)The sirtuin family all participates in the regulation of pyroptosis.(2)Overexpression of sirtuin1 and sirtuin4 can inhibit pyroptosis through various pathways,thus alleviating the damage caused by pyroptosis to the organism.(3)In addition to affecting the classical pathway of pyroptosis,sirtuin3 can also inhibit pyroptosis by enhancing mitochondrial reactive oxygen species scavenging capacity and mitosis.(4)Sirtuin5 is involved in the regulation of intracellular metabolism and energy balance,including energy intake,storage,and consumption.(5)Sirtuin6 can influence pyroptosis through various pathways and also affect macrophage M1 polarization,generation of reactive oxygen species,and cleavage of pyroptosis-related factor sclerotin D to inhibit pyroptosis.(6)Overexpression of sirtuin7 can suppress pyroptosis.(7)Sirtuin2,unlike other family members,can restrain pyroptosis only after knockdown,but there are fewer reports,requiring more in-depth and comprehensive research.

Ferroptosis is a programmed cell death depends on iron and lipid peroxidation,which has been recognized as the key pathogenic factor for the occurrence of various diseases in recent years,especially playing a significant role in neurodegenerative diseases.Ferroptosis triggers lipid peroxidation and oxidative stress in neuronal cells,leading to neuronal damage and death,thereby accelerating disease progression.Hydrogen sulfide,as an endogenous gaseous signaling molecule,exhibits multiple protective effects,including anti-inflammatory,antioxidant,and anti-ferroptosis properties.Hydrogen sulfide can effectively inhibit the occurrence of ferroptosis through various mechanisms,such as regulating iron metabolism,inhibiting lipid peroxidation,and enhancing the activity of antioxidant enzymes,thereby slowing down the progression of neurodegenerative diseases.This article reviews the related research progress on hydrogen sulfide and ferroptosis and ferroptosis-mediated neurodegenerative diseases,and analyzes the underlying mechanisms,aims to provide new insights and theoretical foundations for the treatment of neurodegenerative diseases.

Aim To investigate the effects of sodium lactate(NALA)on right heart failure induced by monocrotaline(MCT)-induced pulmonary arterial hy-pertension in rats and to reveal the underlying mecha-nisms.Methods Forty male Sprague-Dawley(SD)rats were randomly allocated into four groups,with ten rats in each group,namely,MCT group,NALA group,and NALA+MCT group;the MCT and NALA+MCT groups were administered a single intraperito-neal injection of MCT at 60 mg·kg-1 to induce pul-monary hypertension,and one week later,the NALA and NALA+MCT groups received intraperitoneal in-jections of NALA at 0.1 g·kg-1(once a day,for 5 weeks),while the CON and MCT groups received e-qual volumes of physiological saline(once a day,for 5 weeks);right heart function was assessed using echo-cardiography,right ventricular and pulmonary artery remodeling were evaluated via histopathological sec-tions,and the expression levels of ANP,BNP,and in-flammatory factors were measured by ELISA,along with assessments of oxidative stress levels,Western blot detection of the expression levels of proteins in the TLR4/NF-κB signaling pathway.Results Compared to the CON group,the MCT group exhibited increased RVSP and RVHI,decreased right heart function,in-creased collagen fiber deposition,and elevated oxida-tive stress and inflammatory factor expression,and the expression levels of proteins in the TLR4/NF-κB signa-ling pathway increased(P＜0.05);compared to the MCT group,the NALA+MCT group showed reduced RVSP and RVHI,improved right heart function,atten-uated pulmonary vascular remodeling,decreased ex-pression of ANP,BNP,inflammatory factors,and H2O2,along with increased antioxidant enzyme expres-sion,and the expression levels of proteins in the TLR4/NF-κB signaling pathway decreased(P＜0.05).Conclusion NALA can inhibit right ventric-ular remodeling in rats with pulmonary hypertension,and the underlying mechanism may involve the allevia-tion of inflammatory responses and oxidative stress through the inhibition of the TLR4/NF-κB signaling pathway.

Objective To evaluate the clinical efficacy of Jiannao Kaiqiao Acupuncture combined with sensory integration training(SIT)in children with autism spectrum disorder(ASD)based on the brain-gut interaction theory.Methods A total of 135 children diagnosed with ASD at the Shenzhen Longgang Maternal and Child Health Hospital from March 2021 to March 2024 were enrolled.The patients were randomly divided into an observation group and a control group,with 68 patients in each group.The control group was given SIT treatment,while the observation group was treated with Jiannao Kaiqiao Acupuncture plus SIT,both groups were treated for 3 months.The changes in Childhood Autism Rating Scale(CARS)scores,Autism Behavior Checklist(ABC)scores,developmental quotient(DQ),serum neurofilament light chain(NFL),S100 calcium-binding protein β(S100β),and gut microbiota(Lactobacillus,Enterococcus,Bifidobacterium,Escherichia coli)were observed.Results(1)Both groups showed significant improvements in CARS,ABC,and DQ scores(P＜0.05),the observation group showed superior improvements compared to the control group,the difference being statistically significant(P＜0.05).(2)Serum NFL and S100β levels improved in both groups(P＜0.05),the observation group showed superior improvements compared to the control group,the difference being statistically significant(P＜0.05).(3)Gut microbiota composition(Lactobacillus,Enterococcus,Bifidobacterium,Escherichia coli)significantly normalized in both groups(P＜0.05),the observation group showed superior improvements compared to the control group,the difference being statistically significant(P＜0.05).(4)The total efficacy rate was 94.06％(66/68)in the observation group versus 85.07％(57/67)in the control group,the observation group showed superior improvements compared to the control group,the difference being statistically significant(P＜0.05).Conclusion Jiannao Kaiqiao Acupuncture combined with SIT effectively enhances cognitive function,alleviates clinical symptoms,modulates serum NFL/S100β levels,and restores gut microbiota balance in children with ASD.