Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that severely affects the health of the elderly, marked by its incurability, high prevalence, and extended latency period. The current approach to AD prevention and treatment emphasizes early detection and intervention, particularly during the pre-AD stage of mild cognitive impairment (MCI), which provides an optimal “window of opportunity” for intervention. Clinical detection methods for MCI, such as cerebrospinal fluid monitoring, genetic testing, and imaging diagnostics, are invasive and costly, limiting their broad clinical application. Speech, as a vital cognitive output, offers a new perspective and tool for computer-assisted analysis and screening of cognitive decline. This is because elderly individuals with cognitive decline exhibit distinct characteristics in semantic and audio information, such as reduced lexical richness, decreased speech coherence and conciseness, and declines in speech rate, voice rhythm, and hesitation rates. The objective presence of these semantic and audio characteristics lays the groundwork for computer-based screening of cognitive decline. Speech information is primarily sourced from databases or collected through tasks involving spontaneous speech, semantic fluency, and reading, followed by analysis using computer models. Spontaneous language tasks include dialogues/interviews, event descriptions, narrative recall, and picture descriptions. Semantic fluency tasks assess controlled retrieval of vocabulary items, requiring participants to extract information at the word level during lexical search. Reading tasks involve participants reading a passage aloud. Summarizing past research, the speech characteristics of the elderly can be divided into two major categories: semantic information and audio information. Semantic information focuses on the meaning of speech across different tasks, highlighting differences in vocabulary and text content in cognitive impairment. Overall, discourse pragmatic disorders in AD can be studied along three dimensions: cohesion, coherence, and conciseness. Cohesion mainly examines the use of vocabulary by participants, with a reduction in the use of nouns, pronouns, verbs, and adjectives in AD patients. Coherence assesses the ability of participants to maintain topics, with a decrease in the number of subordinate clauses in AD patients. Conciseness evaluates the information density of participants, with AD patients producing shorter texts with less information compared to normal elderly individuals. Audio information focuses on acoustic features that are difficult for the human ear to detect. There is a significant degradation in temporal parameters in the later stages of cognitive impairment; AD patients require more time to read the same paragraph, have longer vocalization times, and produce more pauses or silent parts in their spontaneous speech signals compared to normal individuals. Researchers have extracted audio and speech features, developing independent systems for each set of features, achieving an accuracy rate of 82% for both, which increases to 86% when both types of features are combined, demonstrating the advantage of integrating audio and speech information. Currently, deep learning and machine learning are the main methods used for information analysis. The overall diagnostic accuracy rate for AD exceeds 80%, and the diagnostic accuracy rate for MCI also exceeds 80%, indicating significant potential. Deep learning techniques require substantial data support, necessitating future expansion of database scale and continuous algorithm upgrades to transition from laboratory research to practical product implementation.

ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

Objective:To conduct a scoping review of research on the self-advocacy of adult cancer patients to identify their self-advocacy needs, behaviors, strengths and weaknesses, so as to provide guidance for future research in this field.Methods:Using the scoping review guidelines of Joanna Briggs Institute in Australia as a methodological framework, relevant literatures were searched in PubMed, Web of Science, Cochrane Library, Embase, Science Direct, CINAHL, Scopus, China National Knowledge Infrastructure, Wanfang, VIP and China Biology Medicine disc. The search period was from establishment of the databases to December 2023, and the results were summarized and analyzed.Results:A total of 14 articles were included, and self-advocacy needs included six types of needs, such as symptom management, communication, interpersonal support, disease information, decision-making and emotional management. Self-advocacy included four aspects, including seeking information, self-decision-making, strengthening contact with the outside world and effective communication.Conclusions:Adult cancer patients have diverse types of self-advocacy needs and certain self-advocacy behaviors. Future research should pay attention to self-advocacy needs assessment, develop corresponding tools, focus on self-advocacy behaviors, leverage the advantages of self-advocacy and explore strategies to achieve effective self-advocacy support.

Objective:To conduct a scoping review of the application of mobile health applications (MHA) in the care of patients with colorectal cancer, summarizing the development process, the functions achieved, as well as the evaluation metrics, to provide references for MHA practice and related research.Methods:Following the scoping review framework, a comprehensive search was conducted across both domestic and international databases, including the China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure (CNKI), VIP Database, Cochrane Library, PubMed, Embase, CINAHL, Web of Science, and Scopus. The search period was from the database inception to February, 2024.Results:A total of 16 studies were included. The development of MHA involved multiple methods including literature reviews, qualitative interviews, consultations with multidisciplinary teams, and guidance from theoretical models. The functions of MHA include health education, peer support, guided feedback, monitoring, and reminder features. Evaluation metrics for MHA comprise usability, adherence, and effectiveness.Conclusions:MHA has demonstrated positive effects in enhancing patients' knowledge and alleviating symptoms such as fatigue and vomiting in colorectal cancer patients. However, it is still in its early stages, and further high-quality studies are needed to scientifically develop MHA that meets patients' needs.

AIM To study the chemical constituents from the branches and leaves of Toona ciliata Roem.var.pubescens(Franch.)Hand-Mazz.and their antitumor activities.METHODS The compounds were isolated and purified by silica gel,RP-18 reverse phase silica gel and semi-preparative HPLC,the structures of compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT method.RESULTS Fifteen compounds were isolated and identified as toonaolide D(1),toonaciliatin E(2),bourjotinolone A(3),(21R,23R)-epoxy-21α-ethoxy-24S,25-dihydroxyapotirucalla-7-en-3-one(4),(Z)-toonasterone C(5),(E)-toonasterone(6),3-epi-dyscusin C(7),(Z)-aglawone(8),(E)-volkendousin(9),8(14),15-isopimaradiene-2α,3α,19-triol(10),(-)-loliolide(11),cyclohexenone(12),pubinernoid A(13),quercetin-3-O-(4″-methoxy)-α-L-rahmnopyranosyl(14),5-hydroxymethyl-2-furancarboxaldehyde(15).The IC50 values of compounds 3 and 4 on K562 cells were 54.2 and 47.3 μmol/L,respectively,and the IC50 values on HEL cells were 47.3 and 61.1 μmol/L,respectively.CONCLUTION Compounds 4,7,10 and 11 are isolated from Toona genus for the first time,and compounds 2,15 are first isolated from this plant.Compounds 3 and 4 show weak antitumor activities.

Objective:To explore the diagnostic value of laboratory examination in bronchoalveolar lavage fluid(BALF) for interstitial lung disease (ILD) and its application value in assessing the degree of fibrosis in the disease.Methods:Retrospective analysis. The clinical data of ILD patients treated in Shanghai First People′s Hospital from January 1, 2021 to December 31, 2023[104 cases, male︰female=48︰56, (62.79±1.24) years] were collected. According to the imaging scores, they were divided into a mild fibrosis ILD group [53 cases, male︰female=26︰27, (61.32±1.71) years] and a moderate to severe ILD fibrosis group [51 cases, male︰female=22︰29, (64.31±1.88) years]. Patients with community-acquired pneumonia without fibrotic lesions by HRCTduring the same period were selected as the control group [49 cases, male︰female=25︰24, (65.37±1.65)years]. The clinical information of all study subjects, as well as BALF lymphocyte subset analysis, cytokine and cytology count detection results were collected. Furthermore, the Kruskal-Wallis H test was used to screen the differential indexes, and the receiver operating characteristic (ROC) curve was used to evaluate the differential indexes to assess the degree of ILD pulmonary fibrosis.Results:Compared with the non-fibrotic pneumonia group, IL-6, IL-8, CD4+CD45RO+cells and macrophages (M%) were significantly upregulated in the mild fibrosis ILD group (P<0.05), and significantly higher in the moderate to severe fibrosis ILD group ( P<0.05). Compared with the non-fibrotic pneumonia group, IL-1β and white blood cell (WBC) count were significantly upregulated only in the moderate to severe fibrotic ILD group ( P<0.05). The correction model was constructed by stepwise logistic regression analysis, and the differential indexes were combined, and the proportion of IL-1β+IL-6+IL-8+CD4+CD45RO+cells+macrophages was finally screened as the optimal combined diagnostic mode, with an area under the curve of 0.925, sensitivity of 92.3%, and specificity of 80.0%. Conclusion:Compared with the non-fibrotic pneumonia group, BALF-derived IL-1β, IL-6, IL-8, CD4+CD45RO+cells, WBC count and M% can be used as potential biomarkers to assess the degree of fibrosis, and the combination of IL-1β+IL-6+IL-8+CD4+CD45RO+cells+macrophages has a better diagnostic efficacy for moderate to severe fibrotic ILD.

Objective:To investigate the tissue methylation features of adenocarcinoma patients presenting as pulmonary nodules on CT scans.Methods:A retrospective analysis was conducted on 70 adenocarcinoma patients with pulmonary nodules diagnosed at the Shanghai General Hospital from June 1, 2022 to January 20, 2024. Participants were assigned to two groups using the random number table, with 40 in the discovery group and 30 in the validation group. In the discovery group, tissue samples were analyzed using reduced representation bisulfite sequencing (RRBS) technology to compare the average methylation levels between cancer tissues and paired adjacent non-cancerous tissues. Differentially methylated regions (DMRs) were screened for analysis of their distribution across various genomic functional elements, and hierarchical clustering was plotted. GO and KEGG pathway enrichment analyses were further conducted on the DMRs. Subsequently, candidate DMRs associated with lung adenocarcinoma were validated using TCGA lung adenocarcinoma cohort and targeted bisulfite sequencing technology in the validation group. The comparison of methylation levels between groups was conducted using t-tests or non-parametric tests, while rates and composition ratios were analyzed using chi-square tests or Fisher′s exact test.Results:In discovery cohort, the average methylation level in cancer tissues was lower compared to adjacent normal tissues [(42.369±4.627) vs (44.370±4.046), t=?2.059, P=0.043]. A total of 37 995 DMRs were identified, including 16 889 upregulated regions and 21 106 downregulated regions, predominantly locating in promoter regions (48.917%), introns (36.457%), and exons (10.812%). The DMR clustering heatmap revealed two distinct clusters corresponding to cancer tissues and adjacent non-cancerous tissues. GO analysis showed that DMRs associated genes were mainly located in the cell membrane and nuclear chromatin, and were primarily involved in RNA polymerase Ⅱ-related transcription and regulation. KEGG pathway enrichment analysis indicated that DMRs associated genes were mainly involved in neuroactive ligand-receptor interaction, cancer pathways, calcium signaling pathway, cAMP signaling pathway, and MAPK signaling pathway. Validation in the TCGA cohort confirmed 11 potential characteristic DMRs. In the validation group, TBS confirmed that the methylation levels of DMRs associated with MIR10B, DMRTA2, HOPX, TFAP2B and MARCH11 in cancer tissues were significantly higher than those in adjacent non-cancerous tissues [11.200(4.305, 27.088) vs 2.650(1.298, 4.645), Z=?4.539, P<0.05; 18.610(13.600, 33.025) vs 8.675(5.488, 13.085), Z=?4.554, P<0.05; 17.600(2.183, 76.015) vs 1.085(0.898, 1.835), Z=?5.131, P<0.05; 5.250(3.220, 7.693) vs 3.495(2.165, 4.383), Z=?2.861, P<0.05; 11.515(7.525, 21.033) vs 7.830(5.518, 11.488), Z=?2.440, P<0.05 ], and the differences were statistically significant. Conclusions:Lung adenocarcinoma tissue exhibits different methylation patterns compared with adjacent normal lung tissue. The identified DMRs are involved in the regulation of several key pathways. Results from the TCGA cohort and an independent validation group support the potential diagnostic value of DMRs such as MIR10B, DMRTA2, HOPX, TFAP2B, and MARCH11 in lung adenocarcinoma, though their clinical application requires further validation.

[Objective]To observe the effect of electroacupuncture on the expression of glucose transporter 4(GLUT4)of skeletal muscle in rats with type-2 diabetes mellitus,and to elucidate the mechanism of electroacupuncture on blood glucose regulation.[Methods]Twenty-four rats with type-2 diabetes were randomly divided into blank control group,exercise intervention group and electroacupuncture group,with 8 rats in each group.Rats in blank control group did normal activities.After 1 week of adaptation,rats in exercise intervention group began to run on the treadmill for 2 weeks.The rats in electroacupuncture group were adapted for 1 week,and then the electroacupuncture was placed at the Zhusanli acupoint on both sides with continuous wave stimulation for 2 weeks.Fasting blood glucose and insulin resistance index(IRI)were detected before and after the treatment,and the GLUT4 level of rat muscle cells was detected after the treatment.[Results]Compared with before intervention,the fasting blood glucose level of rats with type-2 diabetes in exercise intervention group and electroacupuncture group reduced significantly after intervention(P<0.001,P=0.028),and the IRI was reduced significantly(P<0.001,P<0.001).The differences of fasting blood glucose level and IRI were significant among the three groups after intervention(P<0.001).The difference of level of GLUT4 was also significant among the three groups after intervention(P<0.001).[Conclusion]Electroacupuncture stimulation can significantly decrease the level of blood glucose and IRI,and regulate the level of GLUT4 in skeletal muscle,which may be an important mechanism of regulation.

Objective To establish and validate a Nomogram model for predicting the overall survival(OS)of the patients with intrahepatic cholangiocarcinoma(ICC)based on domestic multicenter data,and screen the beneficiaries of adjuvant chemotherapy based on the prediction model.Methods From December 2011 to December 2017,the data of 278 patients with postoperative pathological diagnosis of ICC from 4 medical centers in our country were collected retrospectively COX regression model was used to screen the independent risk factors of OS and constructed a Nomogram model.This model was used to stratify the risk of OS for all patients and to screen the beneficiaries of adjuvant chemotherapy.Results A total of 278 patients were enrolled,and 23 cases(8.3%)received adjuvant chemotherapy.COX multivariate analysis showed that drinking history,ECOG score,method of hepatectomy,lymph node status,number of tumors,and tumor differentiation were independent risk factors for postoperative OS.The Nomogram model had a C-index of 0.690(95%CI:0.646-0.734)in the training cohort and 0.740(95%CI:0.863-0.617)in the validation cohort.According to risk stratification by Nomogram model,in the high-risk group there was a statistically significant difference in survival between adjuvant chemotherapy and non-adjuvant chemotherapy(P=0.033),whereas in the low-risk group,there was no significant difference in survival(P=0.59).Conclusions Nomogram model based on independent risk factors of OS demonstrated excellent predictive capability for survival and could be used to screen,and identify the patients with ICC who benefit from adjuvant chemotherapy.

Purpose To establish a non-invasive model for predicting axillary lymph node metastasis(ALNM)based on breast cancer related metabolic parameters.Materials and Methods A total of 158 patients diagnosed as breast cancer in Meizhou People's Hospital from January 1,2016 to March 30,2023 were selected,and all of them underwent whole-body PET/CT examination in our department before operation.Metabolic parameters of primary breast cancer[maximum standard uptake value(SUVmax),metabolic volume,total glycolysis(TLG)],highest axillary lymph node uptake SUVmax(SUVmaxALN),axillary lymph node short diameter and clinical related indexes[age,maximum tumor diameter,pathological type and tumor location]were obtained.According to the surgical and pathological results,the patients were divided into ALNM positive[ALNM(+)]group and ALNM negative[ALNM(-)]group.The relationship between the parameters of the two groups was analyzed,the best influencing factors were screened out,and binary Logistic regression was used to establish a prediction model to obtain the primary metabolic parameters of breast cancer.Results There were significant differences in TLG,metabolic volume,axillary lymph node short diameter and SUVmaxALN between ALNM(+)group and ALNM(-)group(Z=-3.924--1.812,all P<0.05),but there were no significant differences in age,tumor maximum diameter,pathological type,tumor location,primary focus SUVmax and SUVavg(all P>0.05).Multivariate Logistic regression analysis showed that TLG of breast cancer primary focus and SUVmaxALN could be used as independent risk factors of ALNM of breast cancer,and the regression model established by using these two factors was Logit(P)=0.142+0.443×SUVmaxALN-0.013×TLG.The area under the curve of ALNM prediction model based on TLG and SUVmaxALN was 0.769(95%CI 0.691-0.841,P<0.001).Conclusion TLG of breast cancer primary focus and SUVmaxALN can be used as independent predictors of ALNM of breast cancer,and the prediction model based on these two factors can predict ALNM well.This non-invasive method may have a certain application prospect in clinic.