This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Object:To explore the feasibility of using artificial intelligence for quality control of echocardiographic images.Methods:Retrospectively，5 000 two-dimensional echocardiographic video images within the period from 2021 to 2023 were randomly retrieved from the echocardiography database of Nanjing Drum Tower Hospital，Affiliated Hospital of Medical School，Nanjing University. Among these selected images，1 559 of them were apical views. The physician team formulated the scoring rules，which specifically included four scoring criteria：gain，scaling ratio，cardiac axis angle，and structure. Subsequently，the data were labeled with view classification and image quality scores. The labeled data were further partitioned into the training set（ n = 643），the validation set（ n = 276），and the test set（ n = 640）. The training and validation sets were utilized for constructing the models for view classification and quality assessment，while the test set was employed to verify the models' effectiveness. The view classification module was implemented using the SlowFast model，and the quality assessment module involved algorithms such as ResNet，Video Swin Transformer，SSD，and U-Net. Results:The average accuracy，precision，recall rate and F1 score of the classification model in identifying each apical view were 0.987 1，0.983 0，0.987 1 and 0.984 9 respectively，and the inference time was（333.4 ± 105.4）ms. The average accuracies of the quality assessment module in terms of gain，scaling ratio，cardiac axis angle and display of main structures were 0.915 1，0.928 2，0.938 7 and 0.965 6 respectively，and the overall scoring accuracy was 0.912 7.Conclusions:The echocardiogram quality control system developed in this research can effectively classify and evaluate the quality of two-dimensional images of the apical views in echocardiograms. Moreover，it guarantees the objectivity，timeliness and high-efficiency of quality control，which has reference value for the establishment of the echocardiogram quality control system.

AIM:To investigate the effects of the neutrophil elastase(NE)inhibitor sivelestat on the pathologi-cal changes of cardiac tissues in mice with heart failure with preserved ejection fraction(HFpEF).METHODS:Eight-week-old C57BL/6J mice were randomly divided into 3 groups:control group(n=5),model group(n=6),and treatment group(n=18).The HFpEF mouse model was established using a combined approach of high-fat diet and NG-nitro-L-argi-nine methyl ester(L-NAME).The mice in treatment group received intraperitoneal injection of sivelestat at doses of 12.5,25 and 50 mg·kg-1·d-1(n=6),while those in control and model groups were injected with the same volume of nor-mal saline.After 12 weeks,small animal ultrasound was employed to assess changes in cardiac function,and the lung weight-to-tibia length(LW/TL)ratio was calculated to evaluate pulmonary edema.An exercise fatigue test was conducted to assess exercise intolerance.Histological evaluations were performed using HE,wheat germ agglutinin,dihydroethidium and Sirius red staining to examine overall heart morphology,cross-sectional area of cardiomyocytes,levels of oxidative stress,and the extent of cardiac fibrosis.The expression of fibrosis-related proteins was analyzed using Western blot.RE-SULTS:Compared with model group,sivelestat at various concentrations significantly improved cardiac diastolic function in HFpEF mice,indicated by an increased E/A ratio and a decreased E/e'ratio(P＜0.05).The LW/TL ratio decreased,alleviating lung congestion and exercise intolerance(P＜0.05).The heart weight-to-tibia length(HW/TL)ratio,overall heart cross-sectional area,and cardiomyocyte cross-sectional area all decreased,indicating attenuation in cardiac hypertro-phy(P＜0.05).Additionally,cardiac fibrosis and reactive oxygen species levels were significantly reduced(P＜0.05).CONCLUSION:Inhibition of NE exerts a protective effect against diastolic dysfunction and cardiac fibrosis induced by HFpEF in mice.

To observe the effect of penthorum chinense pursh(PCP)on diarrhea in weaned pig-lets,and to explore its mechanism through network pharmacology and in vivo animal experiments.Animal experiment 1 A total of 160 1-day-old piglets were randomly divided into control group,low-dose prevention group(0.25％),medium-dose prevention group(0.50％)and high-dose pre-vention group(1.00％).Starting from the 14 th day,0.25％,0.50％and 1.00％PCP were added to the basal diet of the three prevention groups and weaned.PCP was stopped on the 29th day,and the diarrhea rate of piglets was recorded for 35 d.In animal experiment 2,35 4-week-old male Kunming mice were randomly divided into 5 groups(control group,LPS group,low-dose group,medium-dose group and high-dose group)for 8 d.The low-dose group,the medium-dose group and the high-dose group were intragastrically administered with 200,400 and 800 mg/kg PCP for 7 consecutive days,respectively.The control group and the LPS group were intragastrically administered with the same amount of sterile saline.On the 8th day of the experiment,except that the Control group was intraperitoneally injected with sterile normal saline,the other groups were intraperitoneally injec-ted with the same amount of LPS(15 mg/kg)to establish an intestinal injury model.HE staining was used for ileal histopathological observation,and fluorescence quantitative PCR was used to de-tect the expression levels of inflammatory factors and tight junction protein mRNA.The TCMSP database was used to screen the active components and targets of PCP,and the GeneCards database was used to obtain the targets of diarrhea.The targets of PCP and diarrhea were imported into Li-anchuan biological cloud platform,and the Venn diagram was obtained after intersection.The pro-tein-protein interaction(PPI)network was constructed by combining Cytoscape 3.7.1 and STRING database,and GO and KEGG enrichment analysis was performed by KOBAS-i platform.The results showed that compared with the control group,the diarrhea rate of weaned piglets in the low-dose prevention group(0.25％),the medium-dose prevention group(0.50％),and the high-dose prevention group(1.00％)was significantly reduced at 28-62 d(P＜0.05).According to the prediction of network pharmacology,there were 32 corresponding targets of 145 potential com-ponents of PCP,6 332 targets of diarrhea,and 118 intersection targets.The protective mechanism of PCP in the treatment of diarrhea may be related to NF-κB and PI3k-Akt signaling pathways.Further experiments confirmed that compared with the LPS group,PCP can significantly improve the pathological state of ileum in mice,the mRNA expression level of intestinal tight junction pro-tein Occludin(P＜0.05)was reversed.At the same time,PCP also significantly down-regulated the mRNA level of NF-κB.The results showed that PCP may alleviate diarrhea in piglets through multiple targets and multiple pathways.The main mechanism may be related to the inhibition of Akt-NF-κB signaling pathway.This study is conducive to providing a theoretical basis for the clini-cal application of PCP.

To observe the effect of penthorum chinense pursh(PCP)on diarrhea in weaned pig-lets,and to explore its mechanism through network pharmacology and in vivo animal experiments.Animal experiment 1 A total of 160 1-day-old piglets were randomly divided into control group,low-dose prevention group(0.25％),medium-dose prevention group(0.50％)and high-dose pre-vention group(1.00％).Starting from the 14 th day,0.25％,0.50％and 1.00％PCP were added to the basal diet of the three prevention groups and weaned.PCP was stopped on the 29th day,and the diarrhea rate of piglets was recorded for 35 d.In animal experiment 2,35 4-week-old male Kunming mice were randomly divided into 5 groups(control group,LPS group,low-dose group,medium-dose group and high-dose group)for 8 d.The low-dose group,the medium-dose group and the high-dose group were intragastrically administered with 200,400 and 800 mg/kg PCP for 7 consecutive days,respectively.The control group and the LPS group were intragastrically administered with the same amount of sterile saline.On the 8th day of the experiment,except that the Control group was intraperitoneally injected with sterile normal saline,the other groups were intraperitoneally injec-ted with the same amount of LPS(15 mg/kg)to establish an intestinal injury model.HE staining was used for ileal histopathological observation,and fluorescence quantitative PCR was used to de-tect the expression levels of inflammatory factors and tight junction protein mRNA.The TCMSP database was used to screen the active components and targets of PCP,and the GeneCards database was used to obtain the targets of diarrhea.The targets of PCP and diarrhea were imported into Li-anchuan biological cloud platform,and the Venn diagram was obtained after intersection.The pro-tein-protein interaction(PPI)network was constructed by combining Cytoscape 3.7.1 and STRING database,and GO and KEGG enrichment analysis was performed by KOBAS-i platform.The results showed that compared with the control group,the diarrhea rate of weaned piglets in the low-dose prevention group(0.25％),the medium-dose prevention group(0.50％),and the high-dose prevention group(1.00％)was significantly reduced at 28-62 d(P＜0.05).According to the prediction of network pharmacology,there were 32 corresponding targets of 145 potential com-ponents of PCP,6 332 targets of diarrhea,and 118 intersection targets.The protective mechanism of PCP in the treatment of diarrhea may be related to NF-κB and PI3k-Akt signaling pathways.Further experiments confirmed that compared with the LPS group,PCP can significantly improve the pathological state of ileum in mice,the mRNA expression level of intestinal tight junction pro-tein Occludin(P＜0.05)was reversed.At the same time,PCP also significantly down-regulated the mRNA level of NF-κB.The results showed that PCP may alleviate diarrhea in piglets through multiple targets and multiple pathways.The main mechanism may be related to the inhibition of Akt-NF-κB signaling pathway.This study is conducive to providing a theoretical basis for the clini-cal application of PCP.

This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.

AIM:To investigate the effects of the neutrophil elastase(NE)inhibitor sivelestat on the pathologi-cal changes of cardiac tissues in mice with heart failure with preserved ejection fraction(HFpEF).METHODS:Eight-week-old C57BL/6J mice were randomly divided into 3 groups:control group(n=5),model group(n=6),and treatment group(n=18).The HFpEF mouse model was established using a combined approach of high-fat diet and NG-nitro-L-argi-nine methyl ester(L-NAME).The mice in treatment group received intraperitoneal injection of sivelestat at doses of 12.5,25 and 50 mg·kg-1·d-1(n=6),while those in control and model groups were injected with the same volume of nor-mal saline.After 12 weeks,small animal ultrasound was employed to assess changes in cardiac function,and the lung weight-to-tibia length(LW/TL)ratio was calculated to evaluate pulmonary edema.An exercise fatigue test was conducted to assess exercise intolerance.Histological evaluations were performed using HE,wheat germ agglutinin,dihydroethidium and Sirius red staining to examine overall heart morphology,cross-sectional area of cardiomyocytes,levels of oxidative stress,and the extent of cardiac fibrosis.The expression of fibrosis-related proteins was analyzed using Western blot.RE-SULTS:Compared with model group,sivelestat at various concentrations significantly improved cardiac diastolic function in HFpEF mice,indicated by an increased E/A ratio and a decreased E/e'ratio(P＜0.05).The LW/TL ratio decreased,alleviating lung congestion and exercise intolerance(P＜0.05).The heart weight-to-tibia length(HW/TL)ratio,overall heart cross-sectional area,and cardiomyocyte cross-sectional area all decreased,indicating attenuation in cardiac hypertro-phy(P＜0.05).Additionally,cardiac fibrosis and reactive oxygen species levels were significantly reduced(P＜0.05).CONCLUSION:Inhibition of NE exerts a protective effect against diastolic dysfunction and cardiac fibrosis induced by HFpEF in mice.

Object:To explore the feasibility of using artificial intelligence for quality control of echocardiographic images.Methods:Retrospectively，5 000 two-dimensional echocardiographic video images within the period from 2021 to 2023 were randomly retrieved from the echocardiography database of Nanjing Drum Tower Hospital，Affiliated Hospital of Medical School，Nanjing University. Among these selected images，1 559 of them were apical views. The physician team formulated the scoring rules，which specifically included four scoring criteria：gain，scaling ratio，cardiac axis angle，and structure. Subsequently，the data were labeled with view classification and image quality scores. The labeled data were further partitioned into the training set（ n = 643），the validation set（ n = 276），and the test set（ n = 640）. The training and validation sets were utilized for constructing the models for view classification and quality assessment，while the test set was employed to verify the models' effectiveness. The view classification module was implemented using the SlowFast model，and the quality assessment module involved algorithms such as ResNet，Video Swin Transformer，SSD，and U-Net. Results:The average accuracy，precision，recall rate and F1 score of the classification model in identifying each apical view were 0.987 1，0.983 0，0.987 1 and 0.984 9 respectively，and the inference time was（333.4 ± 105.4）ms. The average accuracies of the quality assessment module in terms of gain，scaling ratio，cardiac axis angle and display of main structures were 0.915 1，0.928 2，0.938 7 and 0.965 6 respectively，and the overall scoring accuracy was 0.912 7.Conclusions:The echocardiogram quality control system developed in this research can effectively classify and evaluate the quality of two-dimensional images of the apical views in echocardiograms. Moreover，it guarantees the objectivity，timeliness and high-efficiency of quality control，which has reference value for the establishment of the echocardiogram quality control system.

This study aims to observe the effect of Panax notoginseng extracts on inflammatory re-sponse in immunosuppressed broilers and to investigate the mechanism through network pharma-cology and molecular docking combined with in vivo animal tests.Based on the TCMSP database and GeneCard and other disease databases,we searched for targets related to Panax notoginseng and broiler inflammation,screened key compounds and targets by applying Cytoscape 3.7.1 and String databases,respectively,and constructed a network relationship diagram of traditional Chi-nese medicine(TCM)-key components-targets,and carried out GO functional enrichment and KEGG pathway enrichment analyses by using the DAVID platform.The GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out by the DAVID platform,visual-ized by the Chiplot online website,and finally,the core clustered proteins were analyzed by Pymol software to obtain the core targets,and molecular docking technology was used to predict the de-gree of matching between the active ingredients and the core targets as well as the animal experi-ments to further explore the pharmacological mechanism of Panax notoginseng extracts.Sixty 1-day-old red-feathered broilers were randomly divided into three groups(LPS group,CON group,and PN group),and the test period was 35 days.The LPS and PN groups were injected intraperito-neally with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline on the 12,14,33,and 35 d.The LPS and PN groups were injected with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline.The effect of Panax notoginseng extract on inflammatory cytokines in serum was detected by ELISA,and the hormone content in serum was also detected in each group,and fluorescence quantitative PCR was used to detect the effect of each group on the mRNA ex-pression levels of STAT3,IL-6,and CASP3.The results showed that the serum levels of IFN-γ,IL-6,iNOS,TNF-α,and TNF-β were significantly increased(P＜0.05),while the level of IL-10 was significantly decreased(P＜0.05)after LPS tapping at weeks 2 and 5.The serum levels of IFN-y,IL-6,iNOS,TNF-α,and TNF-β were significantly decreased(P＜0.05)and IL-10 was sig-nificantly increased(P＜0.05)by the addition of Panax ginseng extracts to the basal diet com-pared with the LPS group.Panax notoginseng extracts significantly decreased the serum levels of adrenocorticotropic hormone(ACTH)and corticosterone(CORT)(P＜0.05)and increased the levels of growth hormone(GH)(P＜0.05).A total of 8 active ingredients and 123 potential tar-gets for broiler inflammation were predicted by network pharmacology.The protective mechanism of Panax notoginseng against broiler inflammation may be related to the C-type lectin receptor(CLR)signaling pathway,Toll-like receptor(TLR)signaling pathway,MAPK signaling pathway,NOD-like receptor(NLR)signaling pathway,and FoxO signaling pathway.According to the pre-diction,the alleviation of inflammatory response in broiler chickens by Panax notoginseng may be related to the action on 12 key targets.Fluorescence quantitative PCR showed that Panax notogin-seng extract down-regulated the mRNA expression of IL-6 and CASP3(P＜0.05)and up-regula-ted that of STAT3(P＜0.05),and molecular docking results also showed that the active ingredi-ents in Panax notoginseng extracts could exert anti-inflammatory effects through IL-6 and CASP3.The results suggested that Panax quinquefolium extracts might alleviate the inflammatory response of immune-stressed broilers through multi-components,multi-targets,and multi-path-ways,and this study helps propose new therapeutic strategies and provides a theoretical basis for the development of feed additives based on Penthorum chinense Pursh extract.