Irritable bowel syndrome （IBS） is a functional bowel disorder characterized primarily by abdominal pain and altered defecation habits. In recent years， traditional Chinese medicine （TCM） has made progress in multiple aspects of IBS research and treatment， including syndrome distribution， development of TCM formulas， clinical efficacy evaluation， external therapies， and psychosocial regulation. However， it still faces challenges such as over-reliance on symptomatic manifestations rather than biomarkers for diagnostic criteria， and the lack of high-quality evidence-based data supporting the efficacy of TCM formulas in treating IBS. This paper proposed that TCM diagnosis and treatment of IBS should adhere to the strategy of integrating the holistic concept with syndrome differentiation and treatment， combining TCM external therapies such as acupuncture， moxibustion and acupoint application）， and emphasizing individualized diagnosis and treatment for psychosomatic abnormalities. Future research should integrate multi-omics technologies， artificial intelligence and other methods to deepen the understanding of the pathogenesis of IBS and the mechanisms of TCM formulas， so as to promote the standardization and internationalization of TCM in the diagnosis and treatment of IBS.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objective To propose a multiple regression-variational auto-encoders(MR-VAE)model to realize precise and non-invasive prediction of intra-abdominal pressure(IAP)in critically ill patients.Methods At first,a dataset was constructed by retrospectively analysing baseline characteristics and clinical indicators of 100 critically ill patients admitted to the Intensive Care Unit of Daping Hospital of Army Medical University between 30 August 2019 and 30 March 2021.Then,a MR-VAE prediction model was developed by integrating a feedforward neural network for supervised regression onto a variational autoencoder(VAE)framework and incorporating multiple regression strategies to mitigate feature interference.Finally,the MR-VAE model had its performance evaluated by its comparison with five classical models including support vector machines(SVM),convolutional neural networks(CNN),Scikit-learn integrated model(SIM),multi-layer perceptron(MLP)and K-nearest neighbors(KNN),and its prediction accuracy verified by testing the data of 10 randomly selected patients.Results The MR-VAE model behaved the best when compared with the five classical models,with a mean squared error(MSE)of 0.207,a root mean square error(RMSE)of 0.454,a mean absolute error(MAE)of 0.361,a median absolute deviation(MAD)of 0.243,an explained variance score(EVS)of 0.814 and a R2of 0.823,which also outperformed the five models in fitting performance,convergence and final loss.In random sample testing,the MR-VAE model exhibited high consistency between predicted and actual values.Conclusion The MR-VAE model proposed can accurately predict IAP,which has great potential in reducing the repeated measurements of IAP in critically ill patients and providing new ideas for the early diagnosis and treatment of IAH.

Objective To investigate the characteristics and clinical significance of serum immunoglob-ulins in patients with Cronkhite-Canada syndrome(CCS).Methods This retrospective study included CCS patients admitted to Peking Union Medical College Hospital from December 2009 to September 2024 who under-went serum immunoglobulin testing.Clinical manifestations and ancillary examination results were analyzed ret-rospectively.Results Fifty-two patients were included(male:36[69.2%],female:16[30.8%]),with median onset age of 60(54-64)years and median diagnostic delay of 5(3-12)months.Common manifesta-tions included diarrhea(86.5%),abdominal pain(40.4%),hematochezia(19.2%),weight loss(86.5%),nail malnutrition(100.0%),pigmentation(88.5%),hair loss(84.6%),and hypogeusia(69.2%).Serum IgG reduction occurred in 21 patients(50.0%),while total IgE elevation was observed in 20(71.4%).Elevated serum IgG4 levels were noted in 11 patients(23.4%),with no significant clinical differences between IgG4-elevated and normal groups.IgG4 levels showed no statistical difference between active(n=43)and remission(n=27)groups.The hair loss rate was significantly higher in the total IgE-ele-vated group than that in the normal total IgE group(P=0.0383).Conclusions CCS patients exhibit periph-eral blood immunoglobulin disorders,with elevated IgE levels correlating with hair loss.This suggests an im-mune-mediated mechanism may underlie hair loss in CCS.

BACKGROUND:The pathogenesis of osteoporosis is closely related to the immune system.A comprehensive and in-depth study of the relationship between immunity and osteoporosis is crucial for understanding and treating the disease.OBJECTIVE:To investigate the role of immune cells in osteoporosis using single-cell sequencing technology.METHODS:Femoral head tissue samples from osteoporosis and non-osteoporosis patients were downloaded from GEO database and analyzed using single-cell sequencing.Data analysis,including cell clustering,functional enrichment,pseudotime trajectory,and cell interaction analyses,was performed using R4.3.0 and software packages such as Seurat v.4.3,monocle(2.28.0),and CellChat.The femoral head tissues of patients with femoral neck fracture who underwent artificial hip replacement surgery were obtained,including two cases of osteoporosis patients and two cases of non-osteoporosis patients.Immunohistochemical staining was used to detect the protein expression of CCL13 and CCL18.qPCR was used to detect the immunoglobulin heavy constant γ-4,immunoglobulin λ constant 3,human class Ⅱ major histocompatibility complex DRβ1,and CD83 mRNA expression.Western blot was used to detect the protein expression of receptor-type tyrosine protein phosphatase C,CD22,and CD99.RESULTS AND CONCLUSION:Transcriptomic analysis identified 10 cell clusters,including osteoclasts,myeloid cells,T cells,osteoblasts,macrophages,monocytes,erythrocytes,B cells,bone marrow mesenchymal stem cells,and mast cells.There was an increase in the ratio of osteoclasts to T cells and a decrease in the ratio of osteoblasts to B cells in the femoral head tissue of the osteoporosis group.Among the B-cell subpopulations,the proportion of B-cells of taxa 1,3(BC1,BC3)in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group,and the proportion of B-cells of taxa 2(BC2)was less than that of the non-osteoporosis group.BC1 was enriched significantly for labels such as regulation of adaptive immune response,somatic recombination of immune receptors,and modulation of lymphocyte-mediated immunity,while BC3 was enriched significantly for labels such as regulation of immunoglobulin production,response to type Ⅱ interferon,apoptotic processes involving cysteine endopeptidases,and cytotoxicity.The communication intensity between B-cell subtype BC1 and osteoblasts in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group,while the communication intensity between BC3 and BC1 was also increased.The communication between BC3 and BC1 was significantly enriched in the CD22-receptor-type tyrosine protein phosphatase C pathway;the communication between BC1 and osteoblasts was mainly enriched in the CD99-CD99 pathway;and the communication between BC3 and osteoblasts was also highly enriched in the CD99-CD99 pathway.Protein expression of CCL13,CCL18,receptor-type tyrosine protein phosphatase C,CD22,CD99,immunoglobulin heavy constant γ-4,immunoglobulin λ constant 3,human class Ⅱ major histocompatibility complex DRβ1,and CD83 mRNA were higher in femoral tissues of the osteoporosis group than those of the non-osteoporosis group(P＜0.05).To conclude,specific B cell subpopulations can influence the differentiation and apoptosis of osteoblasts in the femoral tissue of osteoporosis patients.

Objective To investigate the effects of governor vessel pushing manipulation on behavioral outcomes in valproic acid(VPA)-induced autism spectrum disorder(ASD)rats and explore its underlying mechanisms using prefrontal RNA sequencing(RNA-Seq).Methods Nine Sprague-Dawley pregnant rats at gestational day 12.5 were divided into two groups,six received intraperitoneal VPA injection(600 mg/kg)for modeling,and three received saline.Male offspring at postnatal day 21 were evaluated using the three-chamber social test and open field test to validate the ASD model.VPA-induced male offspring were randomly assigned to the model group(n=5)or tuina group(n=5),while saline offspring formed the blank group(n=5).The blank group and model group received no intervention,while the tuina group underwent governor vessel pushing manipulation stimulation along the governor vessel using a custom device,twice a day for 14 days,totaling 28 times.Post-intervention,behavioral assessments included social index(SI)and social preference index(SPI)in the three-chamber test,total distance traveled and central zone time in the open field test,marble-burying test for stereotyped behaviors,and Nissl staining for prefrontal cortical neuron survival.RNA-Seq identified differentially expressed genes(DEGs)in the prefrontal cortex,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Real time fluorogenic quantitative PCR(RT-qPCR)validated DEGs,and Western blotting analyzed proteins in enriched pathways.Results Pre-intervention,both model and tuina groups showed reduced SI,SPI,total distance,and central zone time compared to the blank group(P<0.05),confirming successful modeling.Post-intervention,the model group exhibited lower SI,SPI,total distance,central zone time,increased marble-burying(P<0.05),and fewer Nissl bodies(P<0.01)versus the blank group.Compared to the model group,the tuina group displayed improved SI,SPI,total distance,central zone time(P<0.05),reduced marble-burying(P<0.05),and increased Nissl bodies(P<0.01).RNA-Seq revealed 213 prefrontal DEGs(181 upregulated,32 downregulated)in the tuina group.GO analysis highlighted cellular components,while KEGG identified 181 pathways,with 67 significantly enriched(P<0.05),notably the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway.RT-qPCR confirmed decreased collagen type Ⅰ alpha 2(Col1α2),transforming growth factor-α(TGF-α),epidermal growth factor receptor 3(ErbB3),and serum/glucocorticoid regulated kinase 2(Sgk2)(P<0.05),and increased hepatic growth factor(Hgf)(P<0.01)in the model group,reversed by governor vessel pushing manipulation.Western blotting showed reduced prefrontal NRG1,ErbB3,nNOS,PI3K,AKT,p-nNOS,p-PI3K,and p-AKT in the model group(P<0.05),which were upregulated by tuina.Conclusion Governor vessel pushing manipulation ameliorates social deficits,anxiety,stereotyped behaviors,and neuronal loss in ASD rats,potentially via activation of the PI3K/AKT signaling pathway.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

OBJECTIVE: Human brucellosis is a serious public health concern in the Xilingol League, Inner Mongolia; however, the epidemic trends are unclear. METHOD: In this study, Joinpoint regression analysis and spatiotemporal analysis were applied to investigate the epidemic evolution of human brucellosis. RESULT: From 2004 to 2023, a total of 35,747 cases were reported, with an annual average of 1787.35 cases and an annual average incidence rate of 176.04/100,000. The incidence increased from 173.96/100,000 in 2004 to 500.71/100,000 in 2009 and fluctuated to 61.43/100,000 in 2023. Three epidemic join points were observed in which the disease experienced an alternative rise and fall, peaking in 2009 (APC = 21.73, P > 0.001) and 2020 (APC = 21.51, P > 0.001). The disease showed a persistent decline trend in lentitude (AAPC = -5.30, P > 0.001), suggesting challenges in disease control and a higher risk of rebound. The most cases were reported in Xilinhot City ( n = 4,777), followed by 4,391 in Sonid Left Banner, and 4,324 in Abaga Banner. Spatiotemporal analysis revealed two high clusters (CI and CII) from 2005 to 2012, the high cluster encompassing eight counties and shifting from north to south. CONCLUSION The present analysis highlights that human brucellosis has decreased significantly in the Xilingol League, but the epidemic is still severe; further implementation of a strict control program is necessary.
China/epidemiology* ; Humans ; Brucellosis/epidemiology* ; Epidemics ; Spatio-Temporal Analysis ; Incidence ; Cluster Analysis

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To propose a multiple regression-variational auto-encoders(MR-VAE)model to realize precise and non-invasive prediction of intra-abdominal pressure(IAP)in critically ill patients.Methods At first,a dataset was constructed by retrospectively analysing baseline characteristics and clinical indicators of 100 critically ill patients admitted to the Intensive Care Unit of Daping Hospital of Army Medical University between 30 August 2019 and 30 March 2021.Then,a MR-VAE prediction model was developed by integrating a feedforward neural network for supervised regression onto a variational autoencoder(VAE)framework and incorporating multiple regression strategies to mitigate feature interference.Finally,the MR-VAE model had its performance evaluated by its comparison with five classical models including support vector machines(SVM),convolutional neural networks(CNN),Scikit-learn integrated model(SIM),multi-layer perceptron(MLP)and K-nearest neighbors(KNN),and its prediction accuracy verified by testing the data of 10 randomly selected patients.Results The MR-VAE model behaved the best when compared with the five classical models,with a mean squared error(MSE)of 0.207,a root mean square error(RMSE)of 0.454,a mean absolute error(MAE)of 0.361,a median absolute deviation(MAD)of 0.243,an explained variance score(EVS)of 0.814 and a R2of 0.823,which also outperformed the five models in fitting performance,convergence and final loss.In random sample testing,the MR-VAE model exhibited high consistency between predicted and actual values.Conclusion The MR-VAE model proposed can accurately predict IAP,which has great potential in reducing the repeated measurements of IAP in critically ill patients and providing new ideas for the early diagnosis and treatment of IAH.