Objective:To investigate the longitudinal stability of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Activity of Daily Living Scale (ADL).Methods:The longitudinal cognitive assessment results of 68 dementia patients admitted to the Dementia and Leukoencephalopathy Outpatient Clinic, Department of Neurology, Peking Union Medical College Hospital, from January 2021 to January 2024, were retrospectively analyzed, including the total and sub-items scores of the MMSE, MoCA, and ADL. Two different rules were applied to analyze the abnormality rates: rule 1, where the current test result being better than the previous one was considered an abnormality; rule 2, where the current test result being better than the previous average score was considered an abnormality (If a patient had only 2 cognitive assessments, rule 2 was considered the same as rule 1). Two rules were used to analyze the abnormality rates of the scales. The statistical analyses were repeated after excluding patients with possible anxiety and depression status.Results:In assessing the total score stability, MMSE showed the lowest abnormality rates [27.2% (31/114) under rule 1 and 29.8% (34/114) under rule 2], while MoCA had the highest abnormality rates [41.3% (26/63) and 46.0% (29/63), respectively]. The ADL abnormality rates were 27.7% (23/83) and 33.7% (28/83), respectively. Among MoCA sub-items, category cue, multiple choice cue, second memory trial, orientation, and clock showed higher abnormality rates [31.7%(20/63), 30.2%(19/63), 23.8%(15/63), 22.2%(14/63), 22.2%(14/63), respectively]. After excluding population with possible anxiety and depression status, the relative abnormality rates of MMSE and ADL sub-items did not significantly change, while the abnormality rate of orientation in MoCA sub-items decreased relatively.Conclusion:The MMSE and ADL exhibit good stability in long-term monitoring of dementia patients, serving as essential tools for assessing and following up cognitive changes.

Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70％of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66％antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.

This paper reviews the published articles of recent years on the application of deep learning methods in automatic localization of acupoint, and summarizes it from 3 key links, i.e. the dataset construction, the neural network model design, and the accuracy evaluation of acupoint localization. The significant progress has been obtained in the field of deep learning for acupoint localization, but the scale of acupoint detection needs to be expanded and the precision, the generalization ability, and the real-time performance of the model be advanced. The future research should focus on the support of standardized datasets, and the integration of 3D modeling and multimodal data fusion, so as to increase the accuracy and strengthen the personalization of acupoint localization.
Deep Learning ; Acupuncture Points ; Humans ; Neural Networks, Computer

OBJECTIVE: An intelligent moxibustion instrument based on electromyography was designed to evaluate the real-time therapeutic effect of moxibustion. METHODS: Taking Shenshu (BL23) as the subject, surface electromyography (sEMG) at the center and equidistant points of Shenshu (BL23) were collected. The characteristic parameters, integrated electromyography (iEMG) and root mean square (RMS) were calculated before and after moxibustion. After analyzing the effect of moxibustion, a function algorithm for the end-of-moxibustion was obtained. Using this algorithm and combined with STM32 technology, the control system of moxibustion instrument and the upper computer software were designed to achieve the precise control during moxibustion delivery. Finally, the function, stability and safety of the moxibustion instrument were verified through clinical trials to ensure its effectiveness in practical application. RESULTS: During one cycle of moxibustion at the center of Shenshu (BL23), the iEMG of sEMG decreased over time, meaning the decrease in muscle fatigue degree, and after one cycle of moxibustion, it elevated over time, showing the increase in muscle fatigue degree. RMS increased by 1.90% before and after moxibustion at the equidistant points of Shenshu (BL23), and the system indicated the end of moxibustion when RMS increased by 0.15%, and decreased by 0.13% at the center of Shenshu (BL23). The intelligent moxibustion instrument designed based on this algorithm can realize the function of mild moxibustion, and the effect of moxibustion can be evaluated by the real-time monitoring of RMS changes through the upper computer. During the operation of moxibustion instrument, moxa stick was fixed stably, remained a safe distance of 3 cm to 4 cm away from the skin surface. When the length of moxa stick was less than 5 cm left after ignited and the skin temperature exceeded the preset safety threshold of 48 ℃, the system was alarmed automatically. CONCLUSION The intelligent moxibustion instrument designed in the research can effectively evaluate the effect of moxibustion, and ensure the safety and stability during moxibustion delivery.
Humans ; Moxibustion/methods* ; Electromyography/instrumentation* ; Adult ; Male ; Female ; Young Adult ; Acupuncture Points ; Algorithms ; Middle Aged

Objective To investigate the effects of simulated-microgravity on the osteogenic differentiation,primary cilia status,cytoskeleton structure,and the YAP(Yes-associated protein)expression in primary osteoblasts.Methods Primary osteoblasts were isolated from the skull bones of neonatal Wistar rats and cultured in random positioning machine system to simulate the cellular effects of microgravity.The calcified nodules were stained with Arlizarin to assess the cellular mineralization ability,the primary cilia and cytoskeleton were detected by immunofluorescence staining of Arl13b/γ-Tubulin and α-Tubulin,respectively,and the expression of YAP was measured by western blot.Results The cellular osteogenic differentiation were markedly suppressed after treated with simulated microgravity for 24 h,and the ciliated cells decreased from(58.44±3.65)%to(15.76±1.84)%in parallel with a decline of average cilium length from(3.19±0.51)μm to(1.59±0.46)μm.In addition,simulated microgravity induced disassembly of microtubules.Notably,simulated microgravity interfered YAP expression and the inhibition of YAP into nucleus.Furthermore,knockdown of YAP expression in osteoblasts notably reduced primary cilia expression and inhibited osteogenic differentiation.Conclusion Primary cilia is a key organelle of osteoblasts in sensing microgravity and regulating osteogenic differentiation.Interference with YAP expression and inhibition of nuclear YAP entry may play an important role in the deaggregation of primary cilia induced by microgravity.

Objective To investigate the characteristics of laryngeal diadochokinesis(LDDK)in children with functional articulation disorder(FAD)using different corpus.Methods A total of 23 children with FAD and 21 typically developing(TD)children,aged 4-6,from Shanghai's general kindergartens were recruited.Five types of acoustic parameters were collected:average rate and jitter(％)of LDDK(/?a/,/ha/,/??/,/h?/),the diadochoki-nesis rate(/pataka/),the jitter and shimmer of the vowel/a/,maximum phonation time(MPT).Differences across different corpora of the LDDK were analyzed between the two groups.Results ① Between-group compari-son:the rate of/?a/was significantly lower in FAD children than in TD children(P＜0.05).② Different corpora comparison:the LDDK speed of/?a/-/ha/was significantly different for both groups,/?a/-/??/was significantly different in TD children,and/ha/-/h?/was significantly different in FAD children.The LDDK jitter of/ha/-/h?/was significantly different among FAD children.Conclusion The LDDK of children with FAD is weaker than the TD children,and both groups exhibiting varying abilities across different corpora.

Objective:To evaluate the diagnostic value of coronary angiography-derived fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) for identifying coronary functional abnormalities.Methods:This diagnostic study enrolled patients with clinically suspected or diagnosed coronary artery disease who underwent coronary angiography at Beijing Anzhen Hospital, TEDA International Cardiovascular Hospital, and Qilu Hospital of Shandong University between December 2021 and June 2022. All enrolled patients successfully underwent invasive wire-based FFR and IMR measurements during angiography. In a core laboratory, FFR and IMR for the target vessels were measured using artificial intelligence technology based on coronary angiographic images. Spearman correlation analysis was used to evaluate the correlation between angiography-derived FFR and wire-based FFR, and between angiography-derived IMR and wire-based IMR. Coronary hemodynamic abnormality was defined as FFR≤0.80; the diagnostic performance of angiography-derived FFR for identifying this abnormality was evaluated. Microcirculatory dysfunction was defined as IMR≥25; the diagnostic performance of angiography-derived IMR for identifying microcirculatory dysfunction was evaluated.Results:A total of 181 patients, aged (60.6±8.8) years, with 62 (34.3%) females, and 181 target vessels were included in the final analysis. Angiography-derived FFR showed a significant positive correlation with wire-based FFR ( r=0.78, P<0.001). For identifying coronary hemodynamic abnormality, angiography-derived FFR showed an accuracy of 89.0%, sensitivity of 88.8%, specificity of 89.1%, positive predictive value (PPV) of 88.8%, negative predictive value (NPV) of 89.1%, and an area under the receiver operating characteristic curve ( AUC) of 0.88. Angiography-derived IMR showed a significant positive correlation with wire-based IMR ( r=0.93, P<0.001). For identifying microcirculatory dysfunction, angiography-derived IMR demonstrated an accuracy of 89.5%, sensitivity of 86.8%, specificity of 90.2%, PPV of 70.2%, NPV of 96.3%, and an AUC of 0.95. Conclusion:Angiography-derived FFR and IMR exhibit strong correlations with their invasive wire-based counterparts and demonstrate high diagnostic value for assessing coronary hemodynamics and coronary microcirculatory function.