OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

ObjectiveTo develop an assessment tool for apraxia of speech (AOS) of Chinese Putonghua speakers and test its reliability and validity. MethodsThe Chinese Apraxia of Speech Assessment and Diagnostic Tool (CAADT) was developed based on the Apraxia of Speech Rating Scale 3.5, combined with the linguistic characteristics of Chinese and clinical experience. The tool consistsed of eleven items across three sections: articulation, prosody and alternating motion rates. Six experts evaluated the content validity. From November, 2024 to May, 2025, 51 patients with post-stroke AOS (experimental group) and ten patients with post-stroke aphasia without AOS (control group) were recruited from Anhui Wannan Rehabilitation Hospital (the Fifth People's Hospital of Wuhu), and tested with CAADT. Reliability was assessed using Cronbach's α coefficient, Kendall's coefficient of concordance W and Pearson correlation coefficient. Validity was evaluated using the content validity index (CVI) and Spearman correlation coefficient. Discriminative effect was analyzed using the receiver operating characteristic (ROC) curve. ResultsThe Cronbach's α coefficients for the articulation and prosody sections and the total scale were all > 0.9, while it was 0.454 for the alternating motion rates. Inter-rater reliability was good (W ≥ 0.598, P < 0.001). Test-retest reliability showed high positive correlations for the three sections and the total score between the two assessments (r ≥ 0.84, P < 0.001). The scale-level CVI was 0.95, and the item-level CVI ≥ 0.83. The Spearman correlation coefficients among the sections ranged from 0.30 to 0.70. ROC analysis revealed an area under the curve of 0.953, with a cut-off value of 11, yielding a sensitivity of 0.92 and a specificity of 0.90. ConclusionCAADT demonstrates good reliability, validity and discriminative effect, which can be used for clinical assessment and auxiliary diagnosis of Chinese Putonghua speaking patients with post-stroke AOS.

OBJECTIVE:Neuromuscular exercise is a new comprehensive rehabilitation therapy in recent years,but its effect on knee osteoarthritis is still controversial.The purpose of this paper is to systematically evaluate the efficacy of neuromuscular exercise on knee osteoarthritis pain and function. METHODS:The randomized controlled trials addressing neuromuscular exercise in the treatment of knee osteoarthritis pain and function were retrieved from PubMed,Cochrane Library,Embase,EBSCO,CNKI,Web of Science,China Biomedical Database(CBM),VIP,and WanFang Database.The retrieval time ranged from database inception to October 2023.The neuromuscular training group(experimental group)was given neuromuscular training or neuromuscular training as the main intervention;the control group was a blank group or given conventional rehabilitation.Outcome indicators included the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,walking time,knee stability,and the maximum number of knee flexion in 30 seconds.The risk of bias was evaluated by the Cochrane Collaboration tool and the Physiotherapy Evidence Database.Meta-analysis was performed using RevMan 5.4 software. RESULTS:A total of 11 randomized controlled trials were included,and 628 samples were extracted.The results of Meta-analysis showed that the experimental group was superior to the control group in terms of WOMAC pain score[standardized mean difference(SMD)=0.38,95%confidence interval(CI):0.08-0.69,P=0.01],knee stability(SMD=0.57,95%CI:0.23-0.92,P=0.001),the maximum number of knee joint flexion in 30 seconds(SMD=0.35,95%CI:0.05-0.65,P=0.02),and WOMAC physical function score(SMD=-0.79,95%CI:-1.30 to-0.28,P=0.002).In both groups,walking speed was increased and walking ability was improved in patients with knee osteoarthritis,but there was no significant difference(walking time:SMD=-0.22,95%CI:-0.48-0.03,P=0.09). CONCLUSION:Neuromuscular exercise can effectively improve knee joint pain,enhance the stability of the knee joint,and promote functional recovery in patients with knee osteoarthritis.However,more high-quality randomized controlled trials are still needed to further confirm the research.

Aim To explore the mechanism by which dioscin regulates IL-17+γδT cells in the treatment of arthritis.Methods A collagen-induced arthritis(CIA)model was established in DBA/1 mice using bovine type Ⅱ collagen.The mice were randomly divid-ed into the CIA model group,methotrexate(MTX)positive control group,and dioscin low-dose(Dioscin-L),medium-dose(Dioscin-M),and high-dose(Dios-cin-H)groups.After intervention,the therapeutic effects were evaluated using scoring methods.Joint pathological damage was analyzed by hematoxylin and eosin(HE)staining.The levels of anti-collagen-spe-cific antibodies and the pro-inflammatory cytokine IL-17 were measured by ELISA.The expressions of γδT cells and their subtypes,as well as the secretion level of IL-17,were detected by flow cytometry.Results Dioscin significantly reduced the arthritis severity score in collagen-induced arthritis(CIA)mice,alleviated joint pathological damage,inhibited the production of IL-17 by splenic lymphocytes and the levels of anti-col-lagen-specific antibodies total IgG and IgG3,and de-creased the proportion of γδT cells in the lymph nodes,splenic γδT cells,and the Vδ4+T-cell subset.The level of IL-17 produced by the Vδ4 subtype in the lymph nodes of the intervention groups was lower than that in the model group,but the difference was not sta-tistically significant.Conclusion Dioscin has signifi-cant therapeutic effect on CIA,and its mechanism may be through the inhibition of γδT cells,but it is unlikely to be related to IL-17 derived from γδT cells.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

Objective To explore the effect of bone grafting combined with locking plate fixation on the postoperative rehabilitation of patients with comminuted proximal humerus fractures.Methods A total of 84 patients with comminuted proximal humerus fractures who underwent surgery at Armed Forces Jiangxi General Hospital from January 2022 to July 2024 were enrolled.Using a randomized digital table method,the patients were divided into conventional group(n=42)and combined group(n=42).The combined group received bone grafting combined with locking plate fixation,while conventional group underwent single locked plate internal fixation.Perioperative indicators,shoulder joint function,range of motion,quality of life,and complications were compared between two groups.Results Compared with conventional group,intraoperative blood loss,surgical duration were longer while fracture healing time and hospitalization period were shorter in combined group,as well as postoperative drainage volume was lower(P＜0.05).Shoulder joint function of combined group was better than that of conventional group(P＜0.05).At 3 months after surgery,the short form health survey(SF-36)scores of patients in both groups were higher than those before surgery,and the SF-36 score of combined group was higher than that of conventional group(P＜0.05).The total incidence of complications in combined group was lower than that in conventional group,and the difference was statistically significant(P＜0.05).Conclusion Bone grafting combined with locking plate fixation for comminuted proximal humerus fractures is more safe,can shorten hospitalization time and fracture healing time,promote shoulder joint function improvement,improve patients' shoulder joint activity and quality of life.

AIM To evaluate the quality of Rubi Fructus.METHODS UPLC-Q-TOF-MS/MS was adopted in the component identification,after which the HPLC fingerprints were established,cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition.and the contents of chlorogenic acid,ferulic acid,ellagic acid,isoquercitrin,kaempferol-3-O-rutinoside,astragalin,tiliroside quercetin,kaempferol were determined.RESULTS Total 34 constituents were identified.There were 19 common peaks in the fingerprints for 31 batches of medicinal materials with the similarities of more than 0.8.Wild varieties and cultivated varieties,and medicinal materials from different producing areas could be distinguished;4 principal components demonstrated the accumulative variance contribution rate of 84.142％;8 differential components were screened,2 of which were ellagic acid and astragalin.Ellagic acid and astragalin displayed higher contents in the wild varieties than those in the cultivated varieties(P＜0.05,P＜0.01).CONCLUSION UPLC-Q-TOF-MS/MS,HPLC fingerprints combined with content determination can be used for the quality control of Rubi Fructus.

Objective To investigate correlations of the ratio of specific brain region volume to total brain volume(ratio％),standard uptake value(SUV)of specific brain region based on 18F-FDG PET/MR examination in Alzheimer disease(AD)patients,as well as the relationship between changes of these two.Methods Fifty AD patients were retrospectively collected.Based on FDG PET/MR,the ratio％and the mean SUV(SUVmean)of 40 specific brain regions were obtained,and the correlation between ratio％and SUVmean for each region were evaluated.According to a database of normal brains,Z-scores for ratio％and SUVmean were calculated to represent structural and functional changes in AD patients,and the correlation between these 2 Z-scores was assessed.Results Correlations were found between ratio％and SUVmean,also between Z-scores of these two parameters in 29 brain regions(r=0.288 to 0.778,all P＜0.05).Among them 7 brain regions,i.e.bilateral middle temporal gyrus,right fusiform gyrus,right hippocampus,right precuneus,left lingual gyrus and right parahippocampal gyrus exhibited correlation coefficients greater than 0.6.Conclusion There were some relationships between brain structural and metabolic functions and their changes in AD patients showed on FDG PET/MR.