ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.

OBJECTIVE: To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS: Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS: The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans ; Lymphoma, T-Cell, Peripheral/pathology* ; Prognosis ; Retrospective Studies ; Central Nervous System Neoplasms/pathology* ; Neoplasm Invasiveness ; Male ; Female ; Central Nervous System/pathology* ; Middle Aged ; Adult

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective To compare the differences in virulence-related factor aspartate protease,biofilm formation,and gene expression among clinical isolates of Candida parapsilosis(C.parapsilosis).Methods Gene sequencing and microsatellite typing(MT)method were adopted to identify C.parapsilosis isolated from patients with clinical fungal infection.The production of secreted aspartate protease and biofilm formation ability of each strain were de-tected,and the expression of biofilm formation related-genes BCR1,EFG1,and HWP1,as well as aspartate prote-ase virulence genes SAPP1,SAPP2,SAPP3 were compared among the strains.Results A total of 8 clinically iso-lated C.parapsilosis strains were collected,all of which were identified as genotype Ⅰ.Based on microsatellite ty-ping results,8 clinical strains were divided into 4 microsatellite types.G1,G2,and G3 strains isolated from the urine,peripherally inserted central catheters(PICC),and blood of patient A were of different subtypes.J1,J2,J3,J4,and J5 strains were of the same type,and isolated from blood specimens of patient B at different periods.All 8 clinical strains could form biofilm,and their biofilm formation ability was higher than that of the standard strain of C.parapsilosis(ATCC 22019).G1,G3 and J5 strains had strong biofilm formation ability,J1,J2,J3,and J4 strains had moderate biofilm formation ability,and G2 strain had weak biofilm formation ability.All of the eight clinical isolates secreted aspartate protease,and their in vitro expression levels of the enzyme were higher than that of the standard strain(ATCC 22019).G3,G1,and G2 strains showed low,moderate,and high in vitro enzyme expression respectively,with statistical differences(all P＜0.05).Enzyme expressed moderately in J1 and J5 strains,and highly in J2,J3,and J4 strains.Difference between moderate and high expressions was statistically significant(P＜0.05).The expression levels of biofilm formation genes BCR1,EFG1,and HWP1 in various strains isolated from patients A and B increased.In strains isolated from patient A,the expression level of EFG1 gene in G1 strain was higher than that in G2 strain(P＜0.05).There was no statistically significant difference in BCR1,EFG1,and HWP1 gene expression levels among strains isolated from patient B.The expression levels of as-partate protein genes(SAPP1,SAPP2,and SAPP3)in various strains isolated from patients A and B increased.The expression levels of SAPP1 and SAPP2 in strain G1 were higher than those in G2 and G3(both P＜0.05).There was no statistically significant difference in the expression levels of SAPP1,SAPP2,and SAPP3 genes in strains from patient B.Conclusion Clinical isolates of C.parapsilosis have higher biofilm formation and aspartate protease production abilities than standard strain.The expression of virulence factors varies among strains isolated from different specimens,while there is no significant difference in the expression of virulence factors among strains isolated at different periods.Patients may have been infected with different MT types of C.parapsilosis in multiple sites during the same period.

OBJECTIVE: To retrospectively analyze the clinical efficacy of anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex repair and ACL reconstruction combined with ALL reconstruction in the treatment of anterior cruciate ligament injuries with high-grade pivot shift. METHODS: From January 2018 to June 2022, 49 patients combined ACL and ALL injuries with high-grade pivot shift were retrospectively studied from three hospitals, 29 of them underwent ACL reconstruction with anterolateral complex repair (repair group), including 23 males and 6 females with an average age of (27.5±4.8) years old, ranged from 20 to 37 years old;the injured sides were 13 on the left and 16 on the right, and 11 patients were suffered with meniscus injury. The other 20 patients underwent ACL and ALL reconstruction (reconstruction group) including 17 males and 3 females with the mean age of (27.1±4.5) years old, ranged from 20 to 38 years old;the injured sides were 8 on the left and 12 on the right, and 6 patients were suffered with meniscus injury. Knee stability (pivot shift test, KT-2000), range of motion, knee function (Lysholm scoring scale, Cincinnati sports activity scale (CSAS) scoring scale, and Tegner activity level score between two groups were compared. RESULTS: A total of 49 patients were followed up, the repair group receiving 13 to 20(15.3±1.8) months and the reconstruction group receiving 12 to 21(16.0±2.2) months. There was no statistically significant difference in the preoperative pivot shift test grading distribution between two groups (P>0.05). At the last postoperative follow-up, there were 24 patients with grade 0 and 5 patients with grade 1 in the repair group, and there were 18 patients with grade 0 and 2 patients with grade 1 in the reconstruction group, there is no significant difference in the distribution of axial shift test grading between two groups(P>0.05). The preoperative KT-2000 tibial displacement of two groups were (9.39±0.77) mm (repair group) and (9.14±0.78) mm (reconstruction group) respectively, with no statistically significant difference (P>0.05). At the final postoperative follow-up, there were 24 patients with KT-2000 tibial displacement <3 mm and 5 patients with 3 to 5 mm in the repair group, while 18 patients with <3 mm and 2 patients with 3 to 5 mm in the reconstruction group, KT-2000 tibial displacement distribution of two groups was no significant difference (P>0.05), but the KT-2000 tibial displacement in the reconstruction group (1.30±0.86) mm was significantly smaller than that in the repair group (1.99±1.11) mm (P<0.05). The final postoperative follow-up range of motion of the contralateral side knee between two groups was no significant difference (P>0.05). The range of motion of the suffering knee in the repair group was less than that in the reconstruction group (P<0.05). There was no significant difference in preoperative Lysholm and CSAS scores between two groups (P>0.05). At the final postoperative follow-up, both groups showed significant improvement in Lysholm and CSAS scores, while the Lysholm and CSAS scores of the reconstruction group were better than those of the repair group, and the difference was statistically significant (P<0.05). Significant differences was found in Tegner scores between two groups, which 16 patients in the repair group returned to their pre-injury activity level, and 17 patients in the reconstruction group returned to their pre-injury level (P<0.05). CONCLUSION Compared to anterolateral complex repair, combined ACL and ALL reconstruction in the treatment of ACL injuries with high-grade pivot shift results in better knee joint function and stability. This is advantageous in reducing the risk of ACL reconstruction failure.
Humans ; Male ; Female ; Adult ; Anterior Cruciate Ligament Reconstruction/methods* ; Anterior Cruciate Ligament Injuries/surgery* ; Young Adult ; Retrospective Studies ; Anterior Cruciate Ligament/surgery* ; Range of Motion, Articular

Objective:To evaluate the efficacy of daily use of a test emollient combined with topical glucocorticoids applied at the weekend for delaying the recurrence of atopic dermatitis (AD) in children during the maintenance period.Methods:A randomized, blank-controlled, multicenter clinical study was conducted in children with moderate AD from Beijing Children′s Hospital, Capital Medical University, Children′s Hospital of Chongqing Medical University and Shenzhen Children′s Hospital from March 2021 to February 2022. A total of 127 children aged 0 - 12 years with moderate AD were treated with topical glucocorticoids combined with emollients during the run-in period, 112 out of them achieved the investigator′s global assessment (IGA) score ≤ 1 point, and then the 112 patients were randomly divided into a test group (56 cases) and a control group (56 cases) at a ratio of 1∶1. Patients in the test group received treatment with a test emollient twice a day in combination with topical glucocorticoids applied at the weekend, and those in the control group were only treated with topical glucocorticoids at the weekend. Patients in the two groups were followed up at baseline, week 2 (± 3 d), week 4 (± 5 d), and week 12 (±7 d), as well as at the time of AD relapse, and the effect of the test emollient on the remission rate of AD in children during the maintenance period was evaluated, so were its effects on the dosage of topical glucocorticoids, pruritus, sleep, and skin pH. The occurrence of treatment-related adverse events was evaluated and recorded at the same time. Study endpoints were defined as AD relapse during the maintenance period, end of 12-week follow-up, or occurrence of serious adverse events. Comparisons of efficacy indicators between groups were conducted by using chi-square test, Kaplan-Meier survival analysis, Satterthwaite t′ test and Mann-Whitney U test. Results:In the full-analysis set, 45 (80.36%) patients with AD maintained remission in the test group (56 cases) and 30 (53.57%) in the control group (56 cases), and the remission rate difference between the two groups was 26.79% (95% confidence interval [ CI]: 10.09%, 43.49%; χ2 = 9.11, P = 0.003) ; the 12-week follow-up during the maintenance period showed that the time to first relapse was 75.05 ± 25.07 days in the test group, which was significantly longer than that in the control group (49.55 ± 33.92 days, t′ = 4.52, P < 0.001). At the study endpoint, the test group showed significantly decreased AD disease severity score (eczema area and severity index [EASI] score: 0.00 [0.00, 1.20] points vs. 0.60 [0.00, 4.00] points), pruritus visual analog scale (VAS) score (0.00 [0.00, 2.00] points vs. 2. 00 [0.00, 10.00] points), and sleep VAS score (0.00 [0.00, 0.00] points vs. 1.00 [0.00, 4.00] points) compared with the control group ( Z = -2.77, 2.43, 3.48, P = 0.006, = 0.015, < 0.001, respectively), while there was no significant difference in the pH value at the lesional sites between the test group and control group ( t = 0.97, P = 0.335). For the group aged 0 - 2 years, the average daily glucocorticoid dosage at the weekend in AD children during the maintenance period was significantly lower in the test group than in the control group ( Z = -1.97, P = 0.049) ; for the group aged >2 - 12 years, there was no significant difference in the average daily glucocorticoid dosage at the weekend between the two groups ( Z = -0.25, P = 0.802). During the study period, no significant difference was observed in the incidence of treatment-related adverse events between the test group (2/56, 3.57%) and control group (3/56, 5.36%; P = 1.000), and no serious adverse events occurred. Conclusion:Compared with the weekend treatment with topical glucocorticoids alone, the daily use of the test emollient combined with topical glucocorticoids at the weekend could markedly improve the remission rate of AD, prolong the time to relapse, and reduce the disease severity at relapse in children with AD during the maintenance period, which provides a new option for maintenance treatment of children with AD.

Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hy-perplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+ PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the tran-scriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.

Objective To investigate the mechanism by which Liraglutide improves the inflammatory response in metabolic associated fatty liver disease(MAFLD)by regulating the interferon gene stimulating factor(STING)signaling pathway.Methods 20 male C57BL/6J mice were randomly divided into normal diet group(NC),Liraglutide intervention group(NC+Lir group),high fat diet group(HFD group)and Liraglutide intervention high fat diet group(HFD+Lir group),with 5 in each group.Mouse primary hepato-cytes(MPHs)were divided into normal control(Con)group,Liraglutide intervention group(Con+Lir group),palmitic acid group(PA group)and Liraglutide intervention PA group(PA+Lir group).The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)in serum and triglyceride(TG)contents in liver were detected.HE and oil red O staining were used to observe the pathological changes in the liver and to calculate the MAFLD activity score(NAS).The mRNA expression levels of STING,IL-1β and TNF-α in tissues and cells were detected by qRT-PCR.The protein expression levels of STING,p-IRF3 and IFN-β were detected by Western blot.Results Body weight,liver tissue weight,serum ALT,AST,liver TG,steatosis,lobular inflammation and balloon-like NAS in HFD group were higher than those in NC group(P＜0.05 or P＜0.01).Body weight,liver tissue weight,serum ALT,AST,liver TG,steatosis,lobular inflammation and balloon-like NAS in HFD+Lir group were lower than those in HFD group(P＜0.05 or P＜0.01).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in liver of HFD group were higher than those of NC group(P＜0.05).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in HFD+ Lir group were lower than those in HFD+ Lir group(P＜0.05).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in PA group were higher than those in Con group(P＜0.01).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in PA+Lir group were lower than those in PA group(P＜0.05 or P＜0.01).Conclusion Liraglutide ameliorates the high-fat-induced inflammation responses in MAFLD by regulating the STING signaling pathways.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Humans ; Muscle Proteins/genetics* ; Carrier Proteins/genetics* ; Syndrome