BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.

OBJECTIVE: To explore the research history, hotspots and development trends of acupuncture and moxibustion in the treatment of gastroesophageal reflux disease（GERD）based on knowledge graph technology, and to provide references for clinical and basic research in this field. METHODS: The literature of acupuncture and moxibustion for gastroesophageal reflux disease was searched from the CNKI, Wanfang, VIP and SinoMed, from the establishment of the databases to December 31th, 2023. CiteSpace 6.2.R6 Advance was used to draw the knowledge graph of authors, institutions, keywords and other elements, and then perform the visual analysis. RESULTS: A total of 341 articles were included, with the number of publications showing an upward trend and the research types continually diversifying. A total of 832 authors and 308 institutions were analyzed, with XIE Sheng from the First Affiliated Hospital of Guangxi University of CM and BAI Xinghua from the Beijing University of CM as representative figures, forming core research teams. However, there was a lack of close collaboration between institutions, and no significant cross-regional research networks had been formed. A total of 192 keywords were included, forming 8 cluster labels, which mainly included 4 categories：treatment methods, disease types, TCM syndrome types, and literature types. The burst analysis showed that the methods of acupuncture and moxibustion in the treatment of gastroesophageal reflux disease had gradually become more integrated, the treatment methods had transitioned from simple acupuncture therapy to combined therapies with proton pump inhibitors or TCM decoctions, the disease types had become more refined, the focus of mechanism research had shifted from lower esophageal sphincter pressure and esophageal motility to changes in gastrointestinal hormone levels, and the research hotspots had gradually shifted from improving clinical symptoms to considering both mental and psychological states. Twenty-three high-frequency acupoints were obtained, forming 8 clusters of "acupuncture techniques-acupoints" for the treatment of gastroesophageal reflux disease with acupuncture and moxibustion, indicating a gradual enrichment of acupuncture and acupoint treatment protocols. CONCLUSION The research on acupuncture and moxibustion in the treatment of gastroesophageal reflux disease has gradually deepened, in the future, the cooperation among research teams should be strengthened, the quality of clinical research should be improved, more multi-dimensional mechanism research and horizontal comparative research of different acupuncture and moxibustion methods should be made, to provide a basis for clinical promotion and deeper exploration.
Humans ; Moxibustion/trends* ; Gastroesophageal Reflux/therapy* ; Acupuncture Therapy/trends*

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab 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 Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab 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 Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified 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.

Objective:To explore the correlation between periodontitis (PD) and chronic kidney disease (CKD) in adults, as well as the potential mechanisms involved.Methods:Data on PD and CKD from the National Health and Nutrition Examination Survey (NHANES) database between 1999 and 2014 were downloaded. Weighted univariate and multivariate logistic regression analyses were conducted to investigate the risk factors associated with PD and CKD, considering demographic and clinical indicators. Using publicly available genome-wide association study (GWAS) summary datasets for CKD and PD as outcome variables, as well as 731 immune cell phenotypes and 91 inflammatory proteins as exposure factors from the OPEN GWAS database, a two-sample Mendelian randomization (TSMR) analysis was performed using the inverse-variance weighted (IVW) method.Results:Seven demographic indicators including gender, age, race, education level, marital status, income, and health are related to the incidence of CKD and PD. Among them, the elderly (≥60 years old), poverty (poverty-income ratio <1.3), divorce or widowhood, and male ratio in the comorbidity group of CKD and PD [67.12% (833/1 241), 36.83% (457/1 241), 34.41% (427/1 241), and 57.78% (717/1 241) respectively] were significantly higher than those in the control group [23.71% (4 179/17 623), 29.17% (5 141/17 623), 18.16% (3 200/17 623), and 48.73% (8 587/17 623) respectively] (all P<0.001). Those with high educational level (university and above) and self-rated excellent health accounted for a relatively small proportion in the comorbidity group [14.10% (175/1 241) and 8.22% (102/1 241) respectively]. The prevalence of PD increased among individuals with abnormal renal function indices, including glomerular filtration rate, urine protein/creatinine ratio, serum creatinine, serum uric acid, and blood urea nitrogen. Univariate logistic regression analysis showed a positive correlation between the incidence of PD and CKD ( OR=2.14, 95 %CI: 1.90-2.42, P<0.001). Multivariate logistic regression analysis also indicated that PD and CKD were potential risk factors for each other (PD for CKD: OR=1.22, 95 %CI: 1.07-1.40, P=0.004; CKD for PD: OR=1.19, 95 %CI: 1.04-1.37, P=0.012). Furthermore, after adjusting the model based on demographic indicators, there was still a significant correlation between PD and CKD ( P=0.010). Mechanistically, the results of the TSMR analysis support the existence of a common risk factor mediated by immune cells between CKD and PD, namely the expression of CD64 on multiple innate immune cells mediates the occurrence of CKD and PD. The absolute count of CD64 + monocytes is associated with an increased risk for both CKD ( HR=1.11) and PD ( HR=1.07), while same tendency showed in the absolute count of CD64 + neutrophils for CKD ( HR=1.22) and PD ( HR=1.23). Conclusions:There is a positive correlation between CKD and PD, particularly moderate to severe PD, and the shared pathogenesis involves CD64 + monocytes in the circulatory system. Targeted interventions focusing on CD64 molecules or monocyte subsets may be beneficial.

Objective To investigate the effect of cisplatin treatment on the transcriptional level of human liver cancer cells by conducting transcriptome sequencing analysis after treating human liver cancer cell lines with differ-ent concentrations of cisplatin(CDDP).Methods Liver cancer cell lines HepG2 and Huh7 were incubated with cisplatin at different final concentrations of 0,20,50,100 and 200 μmol/L.After 12 hours,cell viability,immuno-fluorescence and RNA-sequencing(RNA-seq)were performed.Differential gene expression analysis(DEG),KEGG pathway analysis,and protein-protein interaction network analysis were conducted.Results Cisplatin de-creased cell viability and increased DNA damage in HepG2,Huh7 cells.Among the genes regulated after cisplatin treatment at different concentrations,59 genes were commonly up-regulated in both HepG2 and Huh7 cells,while 81 genes were commonly down-regulated.The commonly upregulated genes were mainly enriched in cancer initiation and progression pathways.The 81 commonly down-regulated genes were mainly enriched in Rap1 signaling pathway,Ras signaling pathway,signaling pathways regulating pluripotency of stem cells,axon guidance,and cell adhesion-related pathways.Survival analysis of key nodes in the protein-protein interaction network of commonly up-regulated and downregulated genes revealed a significant correlation between high expression of Jun proto-oncogene,AP-1 transcription factor subunit(JUN)and prolonged patient survival and a significant correlation between low ex-pression of growth arrest and DNA damage inducible alpha(GADD45A)and prolonged patient survival.Conclu-sions The study revealed common transcriptional changes in liver cancer cells under cisplatin treatment.Differential expression of JUN and GADD45A is a potential core mechanism to explain drug resistance.This conclusion provides some important prognostic indicators for clinical treatment.

Purpose/Significance To analyze the dynamic changes,influencing factors and weak links of e-health literacy of middle-aged and elderly people,so as to provide references for improving e-health literacy of middle-aged and elderly people.Method/Process A questionnaire survey is conducted among 505 middle-aged and elderly people in Guangzhou,and the results are analyzed by using SPSS 24.0.Result/Conclusion The average score of e-health literacy of middle-aged and elderly people is in the middle level;The weak link of e-health literacy is the lack of health information interaction and evaluation capacity.Individual factors are the primary factors that affect e-health literacy of middle-aged and elderly people.It is suggested to increase policy and financial support,carry out"the younger population helps the aging population"mode,and elderly-oriented transformation of digital health Apps.

Objective: To investigate the association of sugar sweetened beverage (SSB) consumption with insomnia and depressive symptoms among first grade middle school students from Yunnan Province, so as to provide evidence to guide interventions for the treatment of these symptoms in this population. Methods: From October to December 2022, 8 500 firstgrade middle school students from 11 counties in Yunnan Province were selected by cluster random sampling. Depressive symptoms, SSB consumption, and insomnia symptoms among students were evaluated by the Child Depression Scale (CDI), dietary frequency questionnaire, and Insomnia Severity Index (ISI). A Logistic regression model was employed to analyze the relationship between SSB consumption, insomnia, depressive symptoms, and their interaction effects among students. Results: The detection rate of depressive symptoms was 28.3%, and having insomnia symptoms ( OR=6.07, 95%CI =5.46-6.75), consuming carbonated beverages ( OR=1.20, 95%CI =1.08-1.34), tea ( OR=1.13, 95%CI =1.02-1.25), energy drinks ( OR=1.36, 95%CI =1.23-1.50), and other beverages ( OR=1.32, 95%CI =1.19-1.45) were positively correlated with depressive symptoms among first grade middle school students ( P < 0.05). Carbonated beverages (additive effect: OR=2.96, 95%CI =2.72-3.22, multiplicative effect: OR=4.75, 95%CI =4.25- 5.32 ), fruit drinks (additive effect: OR=2.61, 95%CI =2.40-2.82; multiplicative effect: OR=4.43, 95%CI =3.94-4.97), tea (additive effect: OR=2.70, 95%CI =2.47-2.89; multiplicative effect: OR=4.34, 95%CI =3.86-4.89), energy drinks (additive effect: OR=2.82, 95%CI =2.61-3.05; multiplicative effect: OR=4.48, 95%CI =3.92-5.12), sweetened milk (additive effect: OR= 2.73, 95%CI =2.06-2.96; multiplicative effect: OR=4.61, 95%CI =4.12-5.17) and other beverages (additive effect: OR= 2.73 , 95%CI =2.53-2.95; multiplicative effect: OR=4.56, 95%CI =4.00-5.20) had both additive and multiplicative effects with insomnia, and increased the risk of depressive symptoms in first grade middle school students ( P <0.01). Conclusions The interaction between the consumption of SSB and insomnia symptoms may increase the risk of depressive symptoms among first grade middle school students in Yunnan Province. It is necessary to advocate middle school students to reduce SSB intake, in order to decrease the occurrence of depressive symptoms among this population.

Objective: To investigate the effects of after school exercise service (referred to as the "after school ES") on physical health, so as to provide evidence for possible beneficial effect of after school ES. Methods: Students in the fourth grade of primary school were recruited from September 2021 to July 2022 in Changsha City and divided into the control group ( n =220) and the after school ES group ( n =220). The control group only participated in the regular physical education activities of the school. The after school ES group received after school ES for one academic year, 4 times a week, 40-50 minutes per time, for a total of 32 weeks. Body shape indicators such as height, weight and percentage of body fat, as well as physical fitness indicators such as 50 meter running, grip strength and progressive aerobic cardiovascular endurance run (PACER) were measured in September to October 2021 and June to July 2022, respectively. Independent sample t-test, Chi square test and two factors repeated measurement analysis of variance were used for statistical analysis of the data. Results: After one academic year, compared with the control group [(13.52±2.30)kg], muscle mass of primary school students in the after school ES group [(13.76±2.32)kg] significantly increased, while waist to hip ratio [(0.95±0.16)] and percentage of body fat [(20.17±7.43)%] significantly decreased compared to the control group [(1.01±0.21), (22.02±12.34)%]( F=330.70, 6.85, 4.33, P <0.05). The proportion of overweight and obesity in after school ES group decreased significantly from 19.5% to 12.3% ( χ 2=4.35, P <0.05). Compared with the control group, the scores of 50 meter running [(10.00±1.06, 10.21±0.83)s], 1 minute sit up [(33.25±8.24, 30.76±9.34)times], sitting and flexion [(14.53±7.50, 8.59±6.32)cm], 1 minute rope skipping [(125.01±30.50, 115.97±32.09)times], eyes closed and single legged standing [(30.00±34.72, 25.72±23.82)s], selective response time [(635.66±91.72, 652.79±120.42)ms] and VO 2max [(45.31± 1.02 , 43.67±0.85)mL/(kg〖 ·min)] in the after school ES group were significantly improved, with statistical significance ( F= 5.32 , 443.14, 97.23, 814.07, 36.49, 6.11, 396.91, P <0.05). Conclusions After school ES can improve body shape of primary school students, reduce the risk of overweight and obesity and enhance physical fitness. It is recommended that schools should appropriately increase after school ES to promote physical fitness of students.

Objective To explore the implementation effect of PDCA(plan-do-check-action)style training of severe ultrasound and hemodynamics in standardized training(residential training)for residents majoring in internal medicine on improving their clinical decision-making ability.Methods A retrospective research method was conducted,60 residents in Xinyang Central Hospital from July 2017 to July 2023 were selected as the research objects,and patients were randomly divided into experimental group and control group,with 30 residents in each group.After the routine entrance education,the experimental group applied the PDCA mode training of severe ultrasound and hemodynamics.The control group was trained with the training objectives and requirements of the department of critical care medicine in the contents and standards of standardized training for internal medicine residents for 2 months.At the end of the training period,the residents of the two groups were assessed and investigated by questionnaire,and the differences of theoretical knowledge assessment,clinical practice skills assessment,case assessment scores and satisfaction between the two groups were compared.Results The results of theoretical knowledge examination,diagnosis and differential diagnosis,and clinical decision-making in the experimental group were significantly higher than those in the control group(theoretical knowledge examination score:90.5±2.7 vs.85.7±3.8,diagnosis and differential diagnosis score:92.0±2.4 vs.87.9±3.7,clinical decision-making score:90.3±3.1 vs.85.5±3.9,all P<0.05),satisfaction with teaching methods,stimulating learning interest,firmly mastering knowledge,enhancing problem-solving ability,improving learning enthusiasm,improving clinical thinking ability and enhancing team consciousness was also significantly higher than that of the control group[teaching methods:80.0%(24/30)vs.46.7%(14/30),stimulate learning interest:83.3%(25/30)vs.56.7%(17/30),firmly mastering knowledge:80.0%(24/30)vs.40.0%(12/30),enhance problem-solving ability:70.0%(21/30)vs.43.3%(13/30),improving learning enthusiasm:83.3%(25/30)vs.50.0%(15/30),improving clinical thinking ability:60.0%(18/30)vs.40.0%(12/30),enhancing team consciousness:73.3%(22/30)vs.46.7%(14/30),all P<0.05].Conclusion The application of PDCA-style training of severe ultrasound and hemodynamics can help internal medicine residents master the basic theory and skills of severe diseases faster and better in the rotation of critical medicine departments,which is more conducive to improving the clinical decision-making ability of internal medicine residents.

Objective To deeply understand the psychological experience of patients with primary tumors participating in clinical trials,providing a reference basis for meeting the psychological needs of patients and improving the mental health level of patients with primary tumors.Methods From November 2021 to May 2022,13 patients with primary tumors participating in clinical trials were selected by target sampling method,semi-structured interviews were conducted,with Colaizzi 7-step analysis method was used to analyze the data.Results Four themes were extracted from the psychological experience of patients,namely the perception and attitudinal experience of clinical trials,complex and changeable emotional responses,experimental process adaptation,personal growth and transformation.Conclusion The psychological experience and related psychological problems of primary tumors patients participating in clinical trials cannot be ignored,the research team needs to help them complete role transformation and adaptation,pay attention to the experience of patients,improve mental health education programs according to the needs of this type of patients,and improve the quality of life of patients,then promote the development of cancer diagnosis and treatment in China.