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.

Systems theory emphasizes the multidimensional interactions among elements within a system and their dynamic changes over time， to provide a crucial theoretical framework and analytical tools for investigating the onset and evolution of mental disorders. From a complex systems perspective， this review examines the influence of multi-factor interaction networks on the development of depressive and anxiety disorders， and reviews research progress on early-warning signals based on dynamical systems theory for symptom prediction. This study specifically examines two system-oriented psychological interventions： acceptance and commitment therapy （ACT） and mindfulness-based intervention for emotional distress （MIED）. Building upon their respective psychopathological models， this review elucidates the multifactorial interaction of depressive and anxiety disorders at a transdiagnostic level， and further analyzes the mechanism through which core intervention strategies adjust the key factors to achieve clinical improvement. ［Funded by General Projects of National Natural Science Foundation of China （number， 32371138）］

ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

This study used the Appraisal of Guidelines Research & Evaluation-Health Systems （AGREE-HS） to demonstratively compare 34 global coronavirus disease-2019 （COVID-19） health systems guidance documents （HSGs） and 6 World Health Organization （WHO） standard HSGs. The comparison involved topic， participants， methods， recommendations， and implementability， with the aim of exploring the characteristics of emergency HSGs. The results showed that the emergency HSGs had an overall average score of 49%， with topic having the highest score， recommendations having the second highest score， and participants having the lowest score. The standard HSGs had an overall average score of 79%， with high scores in all items. The emergency HSGs had lower scores in participants， methods， recommendations， and implementability than the standard HSGs （P<0.001）， while the COVID-19 emergency HSGs developed by the WHO had higher score in topic than the standard HSGs （P<0.05）. Compared with those released by countries， the COVID-19 emergency HSG developed by the WHO showed superiority in all items and overall scores （P=0.000 2）. This indicates that emergency HSGs， represented by the COVID-19 emergency HSG， place equal emphasis on topic and recommendations as standard HSGs but have low requirements in terms of expert participation， evidence support， and comprehensive consideration in the time- and resource-limited context. They have the characteristics of prominent topics， clear purposes， orientation to demand， keeping up with the latest evidence， flexible adjustment， and timeliness， emphasizing immediate implementation effects， weakening long-term effects， and focusing on comprehensive benefits. Additionally， developers， types， and report completeness are important influencing factors.

The scientific rigor and efficacy of methodologies employed in drafting emergency health systems guidance documents （HSGs） are paramount in guaranteeing the quality， reliability， and applicability of HSGs. According to the Appraisal of Guidelines for Research and Evaluation- Health Systems （AGREE-HS）， we demonstratively assessed both global coronavirus disease-2019 （COVID-19） emergency HSGs and World Health Organization （WHO） standard HSGs to uncover the core attributes of methods employed in the development of emergency HSGs. Our evaluation findings revealed that across the five assessment items of AGREE-HS， methods in the 34 emergency HSGs evaluated ranked third， trailing behind topic and recommendations. Notably， criterion 2 （the best available and most contextually relevant evidence is considered） received the highest score， whereas criterion 5 （evidence of cost and cost-effectiveness of the potential options is described） scored the lowest. Compared with the WHO standard HSGs， the COVID-19 emergency HSGs exhibited low scores in methods （P<0.05）， which was reflected in nine criteria （P<0.05）， especially in criteria 1 （systematic and transparent methods are used to identify and review the evidence） and 9 （systematic and transparent methods are used to agree upon the final recommendations）. Among the COVID-19 emergency HSGs， that developed by the WHO achieved higher scores in eight out of all nine criteria， excluding criterion 8 （P<0.05）. The clinically relevant emergency HSGs had higher scores in the criteria 3 （the evidence base is current） and 8 （the rationale behind the recommendations is clear） than other types of emergency HSGs. Collectively， the methodology for developing emergency HSGs， represented by the COVID-19 emergency HSG， underscores evidence orientation and integrates expert consensus. It is characterized by adaptable evidence synthesis strategies， streamlined evidence review protocols， and contextual relevance， all of which are influenced by external， internal， and implementation-specific factors.

Objective To investigate the prevalence and molecular characteristics of Anaplasma infections in sheep and goats in Anhui Province in 2020, so as to provide insights into ovine anaplasmosis prevention and control. Methods A total of 355 fresh blood samples were collected from 7 sheep and goat farms in Linquan County of Fuyang City, Lixin County of Bozhou City, Yu'an District of Lu'an City, Wangjiang County of Anqing City, Nanling County of Wuhu City, and Tianchang City and Fengyang County of Chuzhou City in Anhui Province from June to December 2020. A. bovis and A. phagocytophilum 16S ribosomal RNA (16S rRNA) gene, A. ovis major surface protein 4 (MSP4) gene and A. capra citric acid synthase (gltA) gene were amplified using PCR assay in all blood samples, and the prevalence of A. bovis, A. phagocytophilum, A. ovis and A. capra infections was calculated in sheep and goats. In addition, the positive amplification products were sequenced and subjected to genetic evolutionary analysis. Results The overall prevalence of Anaplasma infections was 17.5% (62/355) in sheep and goats in Anhui Province, and the prevalence of A. bovis, A. phagocytophilum, A. ovis and A. capra infections was 2.8% (10/355), 2.5% (9/355), 2.5% (9/355), and 7.0% (25/355), while the prevalence of A. bovis and A. phagocytophilum, A. phagocytophilum and A. ovis, A. phagocytophilum and A. capra and A. bovis, A. phagocytophilum and A. ovis co-infections was 0.8% (3/355), 1.1% (4/355), 0.3% (1/355) and 0.3% (1/355), respectively. No Anaplasma was detected in the sheep and goat farms in Fengyang County, while at least three Anaplasma species were detected in other sheep and goat farms, with co-infections of multiple Anaplasma species identified. The prevalence of Anaplasma infections was 14.7% (24/163) in goats and 19.8% (38/192) in sheep, and the prevalence of Anaplasma infections was 31.0% (31/100) in goats and sheep under 6 months of age, and 12.2% (31/255) in goats and sheep at ages of 6 months and older, respectively. A. bovis, A. phagocytophilum, A. ovis and A. capra were identified in sheep and goats of different breeds and ages. Conclusions Multiple Anaplasma species infections were commonly prevalent in goats and sheep in Anhui Province in 2020, notably A. phagocytophilum, A. ovis and A. capra, which have zoonotic risks. Improved surveillance and prevention and control of Anaplasma infections are required in sheep and goats in Anhui Province.

Objective To assess the value of cardiac magnetic resonance(CMR)imaging for predicting adverse left ventricular remodeling in patients with ST-segment elevation myocardial infarction(STEMI).Methods We retrospectively analyzed the clinical data and serial CMR(cine and LGE sequences)images of 86 STEMI patients within 1 week and 5 months after percutaneous coronary intervention(PCI),including 25 patients with adverse LV remodeling and 61 without adverse LV remodeling,defined as an increase of left ventricular end-systolic volume(LVESV)over 15%at the second CMR compared to the initial CMR.The CMR images were analyzed for LV volume,infarct characteristics,and global and infarct zone myocardial function.The independent predictors of adverse LV remodeling following STEMI were analyzed using univariate and multivariate Logistic regression methods.Results The initial CMR showed no significant differences in LV volume or LV ejection fraction(LVEF)between the two groups,but the infarct mass and microvascular obstructive(MVO)mass were significantly greater in adverse LV remodeling group(P<0.05).Myocardial injury and cardiac function of the patients recovered over time in both groups.At the second CMR,the patients with adverse LV remodeling showed a significantly lower LVEF,a larger left ventricular end-systolic volume index(LVESVI)and a greater extent of infarct mass(P<0.001)with lower global peak strains and strain rates in the radial,circumferential,and longitudinal directions(P<0.05),infarct zone peak strains in the 3 directions,and infarct zone peak radial and circumferential strain rates(P<0.05).The independent predictors for adverse LV remodeling following STEMI included the extent of infarct mass(AUC=0.793,95%CI:0.693-0.873;cut-off value:30.67%),radial diastolic peak strain rate(AUC=0.645,95%CI:0.534-0.745;cut-off value:0.58%),and RAAS inhibitor(AUC= 0.699,95%CI:0.590-0.793).Conclusion The extent of infarct mass,peak radial diastolic strain rate,and RAAS inhibitor are independent predictors of adverse LV remodeling following STEMI.

Objective:To investigate the clinical features of chronic spontaneous urticaria (CSU) patients with angioedema (AE) .Methods:Clinical data were collected from adult outpatients with active CSU diagnosed and treated at the First Hospital of China Medical University from January 2019 to December 2021, and analyzed retrospectively. The data included gender, age, disease duration, the presence or absence of angioedema, urticaria activity score for one day, prior treatments, previous history, family history, laboratory test results, therapeutic effect, and adverse reactions. Their treatment regimens were based on the Chinese guidelines for the diagnosis and treatment of urticaria (2018) and the American guidelines for the diagnosis and management of urticaria (2014). Statistical analysis was carried out by using Mann-Whitney U test, two-independent-sample t test, Chi-square test, corrected Chi-square test, and Fisher's exact test. Results:A total of 131 CSU patients were collected, including 78 females and 53 males. Their age at the first visit was 44.6 ± 13.3 years, and the disease duration ( M[ Q1, Q3]) was 4.0 (2.0, 10.0) months. Among these CSU patients, there were 58 with AE and 73 without AE. The disease duration was significantly longer in the CSU patients with AE (6.0 [3.0, 24.0] months) than in those without AE (3.5 [2.0, 6.0] months; Z = -2.78, P = 0.005). The urticaria activity score for one day was also significantly higher in the CSU patients with AE (5.0 [3.0, 5.3] points) than in those without AE (4.0 [3.0, 5.0] points; Z = -2.63, P = 0.008). The CSU patients with AE showed a decreased proportion of patients completely controlled by licensed-dose second-generation H1-antihistamines (sgAHs) (8.6%, 5/58) compared with those without AE (24.7%, 18/73), but an increased proportion of patients uncontrolled by licensed-dose sgAHs (91.4%, 53/58) compared with those without AE (74.0%, 54/73; Z = -2.53, P = 0.011) ; there were no significant differences in the proportions of patients completely controlled or uncontrolled by updosed sgAHs alone or combinations of 2- to 4-fold equivalent-dose sgAHs, or in the proportions of patients completely controlled or uncontrolled by combination therapy with 4-fold equivalent-dose sgAHs and non-H1-antihistamines between the CSU patients with AE and those without AE ( P > 0.05) . Conclusion:Compared with the CSU patients without AE, the CSU patients with AE had a longer disease duration, higher disease activity, a lower proportion of patients completely controlled by licensed-dose sgAHs, and a higher proportion of patients uncontrolled by licensed-dose sgAHs.

Objective To assess the value of cardiac magnetic resonance(CMR)imaging for predicting adverse left ventricular remodeling in patients with ST-segment elevation myocardial infarction(STEMI).Methods We retrospectively analyzed the clinical data and serial CMR(cine and LGE sequences)images of 86 STEMI patients within 1 week and 5 months after percutaneous coronary intervention(PCI),including 25 patients with adverse LV remodeling and 61 without adverse LV remodeling,defined as an increase of left ventricular end-systolic volume(LVESV)over 15%at the second CMR compared to the initial CMR.The CMR images were analyzed for LV volume,infarct characteristics,and global and infarct zone myocardial function.The independent predictors of adverse LV remodeling following STEMI were analyzed using univariate and multivariate Logistic regression methods.Results The initial CMR showed no significant differences in LV volume or LV ejection fraction(LVEF)between the two groups,but the infarct mass and microvascular obstructive(MVO)mass were significantly greater in adverse LV remodeling group(P<0.05).Myocardial injury and cardiac function of the patients recovered over time in both groups.At the second CMR,the patients with adverse LV remodeling showed a significantly lower LVEF,a larger left ventricular end-systolic volume index(LVESVI)and a greater extent of infarct mass(P<0.001)with lower global peak strains and strain rates in the radial,circumferential,and longitudinal directions(P<0.05),infarct zone peak strains in the 3 directions,and infarct zone peak radial and circumferential strain rates(P<0.05).The independent predictors for adverse LV remodeling following STEMI included the extent of infarct mass(AUC=0.793,95%CI:0.693-0.873;cut-off value:30.67%),radial diastolic peak strain rate(AUC=0.645,95%CI:0.534-0.745;cut-off value:0.58%),and RAAS inhibitor(AUC= 0.699,95%CI:0.590-0.793).Conclusion The extent of infarct mass,peak radial diastolic strain rate,and RAAS inhibitor are independent predictors of adverse LV remodeling following STEMI.