Objective To investigate the relationship between cerebrospinal fluid(CSF)colony stimulating factor 1 receptor(CSF1R)and CSF biomarkers of Alzheimer disease(AD),and to analyze whether CSF1R is associated with mild cognitive impairment patients'cognition.Methods Data from non-demented adults were collected from the Alzheimer Disease Neuroimaging Initiative database,and participants were divided into four groups(A-/TN-,A+/TN-,A+/TN+and A-/TN+),according to the NIA-AA criteria,and the dynamic changes of CSF1R in CSF at different pathological stages of AD were tracked.Multiple linear regression models were used to analyze the relationship between CSF1R and AD biomarkers and cognition,and mediation models were used to investigate the potential association between CSF1R and AD pathology.Results A total of 451 non-demented adults were enrolled in this study,and we found that CSF CSF1R levels were increased in the A-/TN+group(P<0.05)and the A+/TN+group(P<0.05)compared with the A+/TN-group.CSF CSF1R levels were significantly and positively correlated with CSF tau protein(P<0.001)and phosphorylated tau protein(P<0.001)levels but not with amyloid β-protein(P=0.123),and similar results were obtained in the cognitively normal and mild cognitive impairment groups.In the mild cognitive impairment group,higher CSF CSF1R levels were associated with lower cognitive(P<0.05)levels.Furthermore,the relationship between CSF1R and AD pathology was mediated in part by soluble triggering receptor expressed on myeloid cells 2(sTREM2)(percentage:19.3%to 31.4%).Conclusions This study is the first study to discover the association of CSFIR with AD biomarkers and cognition,and CSF1R may influence AD pathology through soluble TREM2(sTREM2).

Objective:Exploring the safety and efficacy of intermittent theta rhythm stimulation on cortical excitability and upper limb motor function in patients with stroke at recovery stage.Method:From January,2022 to April 2023,30 patients with stroke at recovery stage who received rehabilita-tion treatment were randomly divided into the experimental group(n=15)and the control group(n=15)using the random number method.Both groups were subjected to routine rehabilitation training.The experimental group was given additional intermittent theta rhythm stimulation on the basis of routine rehabilitation,and the control group added intermittent theta rhythm sham stimulation,5 times a week for 4 weeks.Neurophysiologic indexes were tested on both the healthy and affected sides of the patients in the 2 groups before and after the intervention,as well as the assessment of upper limb motor function.Result:After 4 weeks of intervention,there were no statistical differences in MEP maximum wave ampli-tude,MEP latency,CMCT value,CSP value and RMT value of the healthy side between before and after in-tervention and between the groups(P>0.05);MEP maximum wave amplitude of the affected side of the experi-mental group was higher than before intervention(P<0.05);the affected side of the experimental group had a low-er MEP latency,CSP value,and RMT value than before intervention and the control group(P<0.01,P<0.05).Fugl-Meyer upper limb function scores,MBI scores,grip strength on the affected side,and nine-hole post time spent in the experimental group improved after the intervention compared to before the intervention(P<0.01,P<0.05).Fugl-Meyer upper extremity function scores,MBI scores,and time spent on the affected side of the nine-hole column improved in the experimental group after the intervention compared to the control group(P<0.01,P<0.05).Conclusion:Intermittent theta rhythm stimulation combined with conventional rehabilitation training did not show significant effects on the cortical excitability of the healthy side of patients with stroke at recovery stage.However,it could improve the cortical excitability of the affected side of patients with stroke at recovery stage and improve the motor function of the upper limbs.

Objective:Exploring the safety and efficacy of intermittent theta rhythm stimulation on cortical excitability and upper limb motor function in patients with stroke at recovery stage.Method:From January,2022 to April 2023,30 patients with stroke at recovery stage who received rehabilita-tion treatment were randomly divided into the experimental group(n=15)and the control group(n=15)using the random number method.Both groups were subjected to routine rehabilitation training.The experimental group was given additional intermittent theta rhythm stimulation on the basis of routine rehabilitation,and the control group added intermittent theta rhythm sham stimulation,5 times a week for 4 weeks.Neurophysiologic indexes were tested on both the healthy and affected sides of the patients in the 2 groups before and after the intervention,as well as the assessment of upper limb motor function.Result:After 4 weeks of intervention,there were no statistical differences in MEP maximum wave ampli-tude,MEP latency,CMCT value,CSP value and RMT value of the healthy side between before and after in-tervention and between the groups(P>0.05);MEP maximum wave amplitude of the affected side of the experi-mental group was higher than before intervention(P<0.05);the affected side of the experimental group had a low-er MEP latency,CSP value,and RMT value than before intervention and the control group(P<0.01,P<0.05).Fugl-Meyer upper limb function scores,MBI scores,grip strength on the affected side,and nine-hole post time spent in the experimental group improved after the intervention compared to before the intervention(P<0.01,P<0.05).Fugl-Meyer upper extremity function scores,MBI scores,and time spent on the affected side of the nine-hole column improved in the experimental group after the intervention compared to the control group(P<0.01,P<0.05).Conclusion:Intermittent theta rhythm stimulation combined with conventional rehabilitation training did not show significant effects on the cortical excitability of the healthy side of patients with stroke at recovery stage.However,it could improve the cortical excitability of the affected side of patients with stroke at recovery stage and improve the motor function of the upper limbs.

Objective:To investigate the correlation between triglyceride-glucose-body mass index (TyG-BMI index) and the outcome of young patients with acute ischemic stroke (AIS).Methods:Consecutive young patients with first-ever AIS (aged 18-45 years) admitted to Pingyi County People's Hospital and Qingdao Municipal Hospital from January 2020 to December 2023 were included retrospectively. The demographic data, vascular risk factors, baseline blood pressure, baseline laboratory tests, classification of stroke etiology, baseline National Institutes of Health Stroke Scale (NIHSS) scores, and main treatment methods were collected. At 3 months after the onset of stroke, the modified Rankin Scale was used for outcome evaluation. A score of 0-2 was defined as good outcome and >2 were defined as poor outcome. Multivariate logistic regression analysis was used to identify independent factors associated with poor outcome in young patients with AIS. Results:A total of 253 young patients with AIS were enrolled, including 196 males (77.5%), aged 38.65±5.34 years; baseline NIHSS score 3.03±2.88. At 90 days after onset, 206 patients (81.4%) had good outcome, while 47 (18.6%) had poor outcome. The poor outcome group had significantly higher systolic blood pressure, triglycerides, fasting blood glucose, triglyceride glucose (TyG) index, body mass index (BMI), TyG-BMI index, and baseline NIHSS score than those of the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for gender, systolic blood pressure, baseline NIHSS score, and antiplatelet drug use, the TyG-BMI index was significantly independently associated with the poor outcome in young patients with AIS (odds ratio 1.039, 95% confidence interval 1.021-1.057; P<0.001). Conclusion:A higher baseline TyG-BMI index is independently associated with the poor outcome in young patients with AIS.

Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2-3 fold increased risk of developing colorectal cancer(CRC).Unfortunately,there is currently no effective intervention available.Huangqin decoction(HQD),a well-known traditional Chinese medicine(TCM)formula,is frequently clinically prescribed for treating patients with colitis,and its active ingredients have effective antitumour efficacy.Nonetheless,the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear.A strategy integrating metagenomic,lipidomic,and messenger RNA(mRNA)sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome,metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation.Our study revealed that HQD suppressed colorectal inflammatory cancer transformation,which was associated with enhanced in-testinal barrier function,decreased the inflammatory response,and regulation of the gut microbiome.Notably,cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis.Moreover,gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism,especially the remodeling of arachidonic acid metabolism,which was associated with the amelioration of pathological transformation.Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase(ALOX12)were affected by HQD treatment,and no obvious protective effect of HQD was observed in Alox12-/-mice,which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation.In summary,multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

Colorectal inflammatory cancer transformation poses a major risk to patients with colitis. Patients with chronic intestinal inflammation have an approximately 2-3 folds increased risk of developing colorectal cancer (CRC). Unfortunately, there is currently no effective intervention available. Huangqin decoction (HQD), a well-known traditional Chinese medicine (TCM) formula, is frequently clinically prescribed for treating patients with colitis, and its active ingredients have effective antitumour efficacy. Nonetheless, the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear. A strategy integrating metagenomic, lipidomic, and messenger RNA (mRNA) sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome, metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation. Our study revealed that HQD suppressed colorectal inflammatory cancer transformation, which was associated with enhanced intestinal barrier function, decreased the inflammatory response, and regulation of the gut microbiome. Notably, cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis. Moreover, gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism, especially the remodeling of arachidonic acid metabolism, which was associated with the amelioration of pathological transformation. Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase (ALOX12) were affected by HQD treatment, and no obvious protective effect of HQD was observed in Alox 12 ^-/- mice, which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation. In summary, multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

Objective To investigate the relationship between cerebrospinal fluid(CSF)colony stimulating factor 1 receptor(CSF1R)and CSF biomarkers of Alzheimer disease(AD),and to analyze whether CSF1R is associated with mild cognitive impairment patients'cognition.Methods Data from non-demented adults were collected from the Alzheimer Disease Neuroimaging Initiative database,and participants were divided into four groups(A-/TN-,A+/TN-,A+/TN+and A-/TN+),according to the NIA-AA criteria,and the dynamic changes of CSF1R in CSF at different pathological stages of AD were tracked.Multiple linear regression models were used to analyze the relationship between CSF1R and AD biomarkers and cognition,and mediation models were used to investigate the potential association between CSF1R and AD pathology.Results A total of 451 non-demented adults were enrolled in this study,and we found that CSF CSF1R levels were increased in the A-/TN+group(P<0.05)and the A+/TN+group(P<0.05)compared with the A+/TN-group.CSF CSF1R levels were significantly and positively correlated with CSF tau protein(P<0.001)and phosphorylated tau protein(P<0.001)levels but not with amyloid β-protein(P=0.123),and similar results were obtained in the cognitively normal and mild cognitive impairment groups.In the mild cognitive impairment group,higher CSF CSF1R levels were associated with lower cognitive(P<0.05)levels.Furthermore,the relationship between CSF1R and AD pathology was mediated in part by soluble triggering receptor expressed on myeloid cells 2(sTREM2)(percentage:19.3%to 31.4%).Conclusions This study is the first study to discover the association of CSFIR with AD biomarkers and cognition,and CSF1R may influence AD pathology through soluble TREM2(sTREM2).

Objective This study aims to extract medical events from the ancient Chinese medical book"Treatise on Febrile Diseases"and explore their internal connections.By constructing an event evolution graph,this study visualizes the progression of diseases related to the three Yang and three Yin,provides new ideas for the digitization of ancient Chinese medical literature,and offers more intuitive learning and reference material for modern clinical practice and education in Traditional Chinese Medicine(TCM).Methods Taking the classic TCM literature"Treatise on Febrile Diseases"as the research subject,we initially used a combination of the BERT model and LSTM-CRF model to identify medical events and their argument constituents in the ancient text.Then,an improved SpERT model was employed to identify multi-event relationships.Finally,we constructed an event evolution graph of"Treatise on Febrile Diseases"with medical events as nodes and event relationships as edges,which represents the internal connections among medical events.Results The models mentioned above achieved a precision rate of 0.768,a recall rate of 0.761,and an F1 score of 0.772 for identifying medical events and their argument constituents.Additionally,achieving a precision rate of 0.736,a recall rate of 0.682,and an F1 score of 0.687 for recognizing complex event relationships.Through the above model,the text of Treatises of Febrile Diseases was extracted,and finally the theory graph was constructed by Neo4j,which contained 3518 medical events and 5294 event relationships.Conclusion The event evolution graph organizes medical events in a cohesive manner,facilitating understanding of the relationships among diseases,patterns,treatments,prescriptions,and outcomes.Therefore,it provides a multidimensional approach for learning and guiding clinical practice in TCM.

Objective To analyze the potential mechanism of action of Portulaca oleracea L.in the treatment of colorectal cancer(CRC)using network pharmacology and experimental verification.Methods With reference to TCMSP and ETCM databases,the effective ingredients and targets of Chinese medicine P.oleracea were obtained,and targets related to CRC were retrieved from Genecards,Drugbank and OMIM databases,which were imported into Venny database,String database and Cytoscape platform to construct the PPI proteins.The common core targets were analyzed for GO function and KEGG pathway enrichment using Metascape database and Microbiology Letter platform,and the active ingredients and key targets were molecularly docked using Autodock and Pymol software.To construct a CRC mouse model and give P.oleracea treatment,observe the histopathological changes of its colon,and validate the key targets using qRT-PCR experiments and Western blot experiments.In addition,quercetin,luteolin,and kaempferol were used to act on HCT116 cells to observe the effects on cell proliferation and calculate the IC50,which was further verified using qRT-PCR assay and Western blot assay.Results Network pharmacological yielded 11 active ingredients and 209 targets corresponding to the target of P.oleracea.Disease targets were 2667.By analyzing the results,it was predicted that the active ingredients such as quercetin,luteolin,and kaempferol were involved in biological processes such as cellular response to lipids through key targets such as IL6,TP53,and IL1β,which were closely related to pathways in cance.Molecular docking showed that quercetin,luteolin,and kaempferol had good affinity for IL6,TP53 and IL1β.In vivo experiments confirmed that P.oleracea significantly inhibited colon tumorigenesis in mice,and inhibited the levels of IL6,IL1β inflammatory factors and increased the expression level of P53 protein.In vitro experiments showed that quercetin,luteolin and kaempferol could inhibit the proliferation of HCT116 cells to different degrees,and luteolin could inhibit the expression of IL6 and IL1β and up-regulate the expression of P53.Conclusion Through network pharmacology,in vivo and in vitro experiments,the"multi-component-multi-target-multi-pathway"effect of P.oleracea in the treatment of CRC has been confirmed,which reveals that inhibition of inflammation and delay of inflammation-cancer transformation may be one of the potential therapeutic pathways,and provides a theoretical basis and research direction for further exploration of the mechanism and clinical application of P.oleracea.

Objective This study aims to extract medical events from the ancient Chinese medical book"Treatise on Febrile Diseases"and explore their internal connections.By constructing an event evolution graph,this study visualizes the progression of diseases related to the three Yang and three Yin,provides new ideas for the digitization of ancient Chinese medical literature,and offers more intuitive learning and reference material for modern clinical practice and education in Traditional Chinese Medicine(TCM).Methods Taking the classic TCM literature"Treatise on Febrile Diseases"as the research subject,we initially used a combination of the BERT model and LSTM-CRF model to identify medical events and their argument constituents in the ancient text.Then,an improved SpERT model was employed to identify multi-event relationships.Finally,we constructed an event evolution graph of"Treatise on Febrile Diseases"with medical events as nodes and event relationships as edges,which represents the internal connections among medical events.Results The models mentioned above achieved a precision rate of 0.768,a recall rate of 0.761,and an F1 score of 0.772 for identifying medical events and their argument constituents.Additionally,achieving a precision rate of 0.736,a recall rate of 0.682,and an F1 score of 0.687 for recognizing complex event relationships.Through the above model,the text of Treatises of Febrile Diseases was extracted,and finally the theory graph was constructed by Neo4j,which contained 3518 medical events and 5294 event relationships.Conclusion The event evolution graph organizes medical events in a cohesive manner,facilitating understanding of the relationships among diseases,patterns,treatments,prescriptions,and outcomes.Therefore,it provides a multidimensional approach for learning and guiding clinical practice in TCM.