This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

Objective: To explore the feasibility of remotely obtaining complex information on traditional Chinese medicine (TCM) pulse conditions through voice signals. Methods: We used multi-label pulse conditions as the entry point and modeled and analyzed TCM pulse diagnosis by combining voice analysis and machine learning. Audio features were extracted from voice recordings in the TCM pulse condition dataset. The obtained features were combined with information from tongue and facial diagnoses. A multi-label pulse condition voice classification DNN model was built using 10-fold cross-validation, and the modeling methods were validated using publicly available datasets. Results: The analysis showed that the proposed method achieved an accuracy of 92.59% on the public dataset. The accuracies of the three single-label pulse manifestation models in the test set were 94.27%, 96.35%, and 95.39%. The absolute accuracy of the multi-label model was 92.74%. Conclusion Voice data analysis may serve as a remote adjunct to the TCM diagnostic method for pulse condition assessment.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

BACKGROUNDNominal atrioventricular (AV) interval in dual chamber pacemaker (DDD) is not the best AV delay in the majority of patients with atrioventricular block. To find a simple method for optimizing AV delay adjustment, we assessed surface electrocardiography (ECG) for optimizing AV delay during dual chamber pacing.

METHODSDDD pacemakers were implanted in 46 patients with complete, or almost complete, AV block. Optimal AV delay was achieved by programming an additional delay of 100 ms, to the width of intrinsic P wave or to the interval between pacing spike to the end of P wave on surface ECG. Left ventricular (LV) end diastolic and end systolic volumes, ejection fraction and diastolic parameters were measured by Doppler echocardiography during both nominal and optimal AV delay pacing.

RESULTSCompared to nominal AV delay setting, LV end diastolic volume increased [to (53.2 +/- 11.3) ml from (50.2 +/- 10.2) ml, P < 0.05], end systolic volume decreased [to (26.1 +/- 9.0) ml from (27.9 +/- 8.2) ml, P < 0.05] during adjusted AV delay pacing, resulting in an increase in LV ejection fraction [to (68.2 +/- 5.3)% from (64.5 +/- 4.3)%, P < 0.05]. LV diastolic filling and isovolumic relaxation time were not significantly changed.

CONCLUSIONOptimization of AV delay by surface ECG is a simple method to improve LV systolic function during dual chamber pacing.

Adult ; Aged ; Aged, 80 and over ; Atrioventricular Node ; physiopathology ; Cardiac Pacing, Artificial ; methods ; Electrocardiography ; methods ; Female ; Heart Block ; physiopathology ; therapy ; Humans ; Male ; Middle Aged ; Time Factors

OBJECTIVE To establish the implanted biofilm model of rabbit implant infection.METHODS SEP was cultured,purified,identified,and tested for the drug sensitivity and the biofilm production.Healthy adult rabbits were randomly divided into 4 groups,8 in each group.The stainless steel screws and washer UHMWPEs were implanted into the femoral condyle of the non-articular surface of the rabbit right stifle knee.The knee joints were inoculated with 1ml sterile saline,102,103 and 104 CFU SEP,respectively.Wounds were observed postoperatively.After the 14th days postoperation,the knee synovium of 32 rabbits sacrificed were taken out by aseptic technique and were cultured to determine whether the knees were infected and which concentration of SEP was the appropriate for causing knee joint infection.UHMWPEs from the appropriate ID group were observed to find whether there were biofilms on the surface by SEM and LCSM.RESULTS The bacterial strain was identified as SEP and could produce biofilm.Among the knee joints inoculated with 1ml saline,102,103 and 104 CFU SEP,the infective rate was 0,37.5%,100.0% and 100.0% and poor wound healing was in 0,1,2 and 4 rabbits,respectively.It showed 103 CFU of SEP was the appropriate ID.Biofilms were found on all UHMWPE surfaces from 103 CFU SEP group by SEM and LCSM.SEM showed SEP in the biofilms on the surface of UHMWPE was agglomerated and wrapped in the matrix.The structure of biofilms in which SEP radiated red fluorescence was inlaid in mucopolysaccharide stained green fluorescence was observed by LCSM.CONCLUSIONS The model provides an effective method to investigate the biofilm.

Objective To explore the liver toxicities of the VDLD scheme in children with malignant tumor.Methods In a prospective trial,the levels of serum total protein,albumin, globulin,rate of albumin/globuin alanine aminotransferase,aspartate transaminase,gamma glutamyltranspeptidase,total bile acid and alkaline phosphatase were tested in children with malignant tumour before and after VDLD scheme,and compared with each other.Results The concentration of the serum total bile acid was significantly increased after VDLD scheme than before(P