Baoding People's Hospital

This study aimed to examine the clinical characteristics of Chinese patients with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGLD) and identify the prevalent mutations in the HMGCL gene among these patients. The clinical features, biochemical parameters, imaging findings, and genetic variations in 16 previously documented Chinese patients with HMGLD, along with one newly reported case in this study, were comprehensively analyzed. Within the cohort of Chinese patients with HMGLD, 76.5% were diagnosed during infancy, while 35.3% were identified through newborn screening protocols. Acute metabolic disturbances were reported in 88.2% of patients, with neurological manifestations—particularly coma and unconsciousness—presenting as the initial symptoms in 58.9% of cases, and vomiting occurring in 52.9%. Imaging revealed white matter abnormalities in 47.1% of patients and basal ganglia alterations in 17.6%. The homozygous c.122G > A mutation emerged as the predominant genetic variant among Chinese patients with HMGLD, followed by the c.252 + 1G > A mutation. HMGLD is a rare metabolic disorder with significant mortality rates, highlighting the necessity for early diagnosis to prevent metabolic crises. This study is the first to report a case of adolescent-onset HMGLD and characterize the clinical presentation of Chinese patients with the disorder. The study additionally identified a novel homozygous c.133 C > T/p.Gln45Ter mutation in the HMGCL gene.

Abstract Objective To investigate the risk factors for preoperative deep vein thrombosis (DVT) in patients with peri-ankle fractures and to develop a machine learning-based prediction model for preoperative DVT risk. Methods A retrospective study was conducted involving 1000 patients with peri-ankle fractures. Predictors were selected using Lasso regression, and the dataset was randomly split into a training set and a validation set at a 7:3 ratio. Four models—Logistic Regression, Decision Tree, Random Forest, and XGBoost—were constructed and internally validated using the Bootstrap method. Model performance was compared using metrics including the area under the ROC curve (AUC), calibration curves, decision curve analysis, and the F1 score. The optimal model was interpreted using the SHAP method. Results Four predictors were identified: age, BMI, preoperative waiting time, and D-dimer level. The XGBoost model demonstrated the best performance, with an AUC of 0.827 in the validation set. SHAP analysis confirmed that higher values of these four features contributed positively to the model's predictions, aligning with clinical knowledge and ensuring a transparent and credible decision-making process. Conclusion The XGBoost-based prediction model exhibits favorable performance and interpretability. It delineates core risk factors to guide targeted nursing interventions and holds potential for translation into a clinical decision-support tool, offering a novel strategy for the precise prevention of preoperative DVT.

To develop a pre-percutaneous microwave ablation (PMWA) model combining conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) for predicting non-perfused volume ratio (NPVR) ≥ 80% in patients with uterine fibroids. This multicentre, retrospective study enrolled 276 patients with pathologically confirmed uterine fibroids (training/validation = 140/136). CUS features (maximum diameter, pre-operative volume, location, echo), CEUS parameters (maximum intensity: IMAX), and ablation parameters (energy, time, energy per unit volume [EPV], and time per unit volume [TPV]) were analysed. Multivariate logistic regression identified predictors, and model performance was assessed using the area under the receiver operating characteristic curve (AUC) and clinical decision curve analysis. Multivariate analysis identified four independent predictors: maximum diameter (odds ratio [OR] = 0.47, p < 0.001), IMAX (OR = 0.34, p = 0.013), energy (OR = 1.01, p = 0.002), and TPV (OR = 0.69, p < 0.001).The prediction model performed well in both the training (AUC = 0.79, 95% confidence interval [CI] = 0.71-0.87) and validation (AUC = 0.70, 95%CI = 0.61-0.79) datasets. P values for the Hosmer-Lemeshow test were 0.263 and 0.980, respectively, and the Brier Score was 0.184. This study established a prediction model based on CUS features, CEUS perfusion parameters, and ablation parameters to evaluate the efficacy of PMWA for uterine fibroids; NPVR ≥ 80% can be predicted using the nomogram. This model enables accurate prediction of the efficacy of PMWA for uterine fibroids, providing profound guidance for pre-operative assessment and intraoperative management in clinical practice and facilitating personalised, precision treatment.

Abstract Background: Dalpiciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, has shown significant efficacy and a favorable safety profile when combined with endocrine therapy for advanced hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Building on this evidence, the present study evaluated the efficacy and safety of neoadjuvant dalpiciclib plus letrozole compared with standard chemotherapy in patients with high-risk HR+/HER2- early breast cancer. Methods: DARLING-02 was a multicenter, randomized, phase II non-inferiority trial (NCT06107673). Key eligibility criteria included women aged ≥18 years; Eastern Cooperative Oncology Group performance status 0-1; clinical stage T1c-2N1-2 or T3-4N0-2; estrogen receptor (ER) expression ≥50%; HER2- status; and Ki-67 level ≤30%. Patients were randomized 1:1 to receive 24-week treatment. The experimental arm received dalpiciclib 150 mg orally once daily (3 weeks on, 1 week off) plus letrozole 2.5 mg orally once daily. The control arm received epirubicin 100 mg/m2 plus cyclophosphamide 500 mg/m2 intravenously on day 1 every 3 weeks for 4 cycles, followed by docetaxel 100 mg/m2 intravenously on day 1 every 3 weeks for 4 cycles. The primary endpoint was objective response rate (ORR), assessed per Response Evaluation Criteria in Solid Tumors, version 1.1. Results: Between August 2023 and April 2025, 170 patients were screened; 158 met the eligibility criteria and were randomized to the dalpiciclib-letrozole (n = 80) or chemotherapy (n = 78) group. At the data cut-off date (September 17, 2025), 9 patients in the experimental arm and 10 in the control arm were still on neoadjuvant therapy. Among patients with completed short-term efficacy assessment, the ORR was 69.0% (49/71) with dalpiciclib-letrozole and 70.5% (48/68) with chemotherapy; total pathological complete response (tpCR) rate was 5.6% (4/71) and 1.5% (1/68), respectively. The proportion of patients with Preoperative Endocrine Prognostic Index (PEPI) score ≥4 was higher in the chemotherapy group (74.6% [44/59]) than in the dalpiciclib-letrozole group (53.3% [32/60]). Grade ≥3 adverse events were predominantly hematological toxicities and occurred less frequently with dalpiciclib-letrozole than with chemotherapy (decreased white blood cell count: 36.4% [28/77] vs 64.0% [39/61]; decreased neutrophil count: 74.0% [57/77] vs 86.9% [53/61]). Conclusions: These findings support dalpiciclib plus letrozole as a promising neoadjuvant option for patients with high-risk HR+/HER2- early breast cancer and warrant confirmation in phase III trials. Citation Format: C. Geng, L. Zhang, C. Yang, T. Zhou, L. Ma, R. Luo, Z. Song, Y. Qi, J. Yang, X. Wang, J. Han, J. Ma, Z. Zhang, Y. Li, C. Gao, L. Yang, J. Yu. Neoadjuvant Dalpiciclib Plus Letrozole Versus Standard Chemotherapy in High-Risk HR+/HER2- Negative Breast Cancer (DARLING-02): A Randomized Phase II Trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-13-08.

Telemedicine has been introduced as a new and effective method in dealing with public health challenges, improving access to health care, and reducing healthcare costs in today's world. In order to solve the problems of a single access network and the unknown network status of the telemedicine system in complex environments, a multi-link aggregation algorithm based on link priority (MLA-LP) was proposed. Firstly, the network parameters, such as packet loss rate (PLR) and round-trip time (RTT), of each link were obtained, and then MLA-LP was realized by using the congestion control algorithm based on sender and the traffic allocation algorithm based on link priority. Finally, the MLA-LP algorithm was tested on the test platform based on HoloWAN 1200 network simulator. The comparison algorithm was the multilink aggregation algorithm based on the weightedround-robin algorithm (MLA-WRR). MLA-LP algorithm has higher uplink throughput than MLA-WRR under the same link PLR and delay. When the link is suddenly abnormal (burst packet loss, delay, etc.), the MLA-LP algorithm could quickly avoid the abnormal link and transfer traffic within 2 s; In the mobile scenario, compared with a single network and MLA-WRR algorithm, MLA-LP algorithm has the best video transmission effect, with an average delay of 136 ms, an average bit rate of 2.31 Mbps, an average PLR of 0.04%, and video jamming times close to 0. The MLA-LP algorithm could effectively aggregate link bandwidth and quickly avoid abnormal links, ensuring the robustness of the access network.In order to solve the problems of a single access network and the unknown network status of telemedicine system in complex environment, a MLA-LP was proposed. MLA-LP algorithm has higher uplink throughput and could quickly avoid the abnormal link and transfer traffic within 2 s, ensuring the robustness of the access network.

ABSTRACTObjective:To evaluate the effectiveness of integrating case-based learning (CBL) with the flipped classroom approach in the standardized residency training of ultrasound physicians.Methodology:This was a retrospective study. A total of 26 residents undergoing standardized ultrasound residency training at Baoding NO.1 Central Hospital between January to August 2024 were enrolled in this study. Participants were randomly assigned to an experimental group (n= 13) and a control group (n= 13). The experimental group received CBL and flipped classroom instruction, while the control group was taught using traditional methods. Theoretical examination scores, perceived learning outcomes and teaching satisfaction were compared between the two groups.Results:The experimental group achieved significantly higher theoretical examination scores than the control group (p< 0.05). Participants in the experimental group also demonstrated significantly improved learning outcomes and reported higher satisfaction with the teaching methods compared with those in the control group (p< 0.05, respectively).Conclusion:The teaching approach combining CBL and the flipped classroom model may enhance clinical reasoning, stimulate learning motivation, foster innovation and contribute to the overall effectiveness of standardized ultrasound residency training.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder with unclear molecular mechanisms, complicating early diagnosis and treatment. This study aimed to identify hub genes and pathways driving RA pathogenesis and assess their therapeutic potential. Gene expression datasets related to RA were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and analyzed by functional enrichment and protein-protein interaction network construction. Machine learning approaches, including LASSO regression, random forest, and SVM-RFE, were used to screen hub genes. Pathway associations were explored using Gene Set Enrichment Analysis (GSEA). Experimental validation was performed in collagen-induced arthritis (CIA) rat models and MH7A synovial fibroblast cells through Western blot and functional assays. A total of 106 DEGs were identified in RA synovial tissues, including 76 upregulated and 30 downregulated genes. Enrichment analyses revealed involvement in cytokine-cytokine receptor interaction, lymphocyte-mediated immunity, and immunoglobulin complexes. SDC1 emerged as a key hub gene across all three machine learning methods. GSEA indicated its significant correlation with the JAK-STAT pathway. In CIA rats, SDC1 expression was markedly elevated alongside p-JAK2 and p-STAT3 levels. Silencing SDC1 in MH7A cells reduced cell proliferation, decreased p-JAK2 and p-STAT3 expression, and promoted apoptosis. This study identifies SDC1 as a central hub gene in RA pathogenesis through activation of the JAK2-STAT3 signaling pathway. These findings highlight SDC1 as a potential biomarker for early diagnosis and a promising target for therapeutic intervention, providing new insights into RA management.

Myocardial infarction (MI) is one of the leading causes of death globally, and stress-aggravated cardiac injury exacerbates patient prognosis. The study aimed to clarify the role of notoginsenoside R1 (NR) in the myocardial infarction-induced differential gene 2 (CRIF1)/PINK1-Parkin complex by using a restrain stress-exacerbated MI rat model. Male Sprague Dawley rats were subjected to coronary artery ligation followed by treatment with NR (2.5, 5, or 10mg/kg, p.o.) for 10days post-surgery. NR significantly enhanced cardiac function (elevated LVEF (left ventricular ejection fraction), LVFS (left ventricular fractional shortening), LVEDD (left ventricular end diastolic diameter), LVESD (left ventricular end systolic diameter)) and attenuated serum markers of myocardial damage (LDH (lactate dehydrogenase), CK-MB (creatine kinase myocardial band), CPK (creatine phosphokinase), cTnT (cardiac troponin T), cTnI (cardiac Troponin I)). It brought the imbalanced electrolyte status back to equilibrium, increased antioxidants, and decreased inflammatory mediators and apoptotic markers. In addition, NR suppressed NF-κB (nuclear kappa B factor) and NOX (NADPH oxidase 1) isoforms but increased the expression of PINK1-Parkin-associated mitochondrial quality control genes and cardiac remodeling markers at mRNA levels. These results indicate that NR exerts cardioprotection by inhibiting oxidative stress, inflammation, and apoptosis via the coordinated regulation of NF-κB/NOX/PINK1-Parkin signaling. However, additional protein-level validation (Western blot) and pathway inhibition studies together with the mechanistic confirmation are warranted in order to promote a causal role and translational potential.

The advantages, mechanisms, and advances in nanocomposites for delivering bioactive substances in bone tissue engineering were systematically reviewed. This review provides a comprehensive analysis by conducting an in-depth retrieval of relevant literature and integrating it with related work from our research team. Capitalizing on their inherent size effects and tunable structures, nanocomposites exhibit high drug-loading capacity and controlled/targeted delivery, allowing for the co-delivery of diverse molecules. This smart delivery capability, responsive to specific pathological or external cues, facilitates on-demand precision release to execute multiple therapeutic functions, including osteogenesis, antibacterial action, and immunomodulation. Nanocomposites demonstrate high delivery efficiency and controlled release kinetics, with the potential for future clinical translation of their multi-signal responsive and spatiotemporally precise drug release capabilities.

Here, we systematically investigated the effects of EDA1 variants on apoptosis, migration, and adhesion in ameloblast-like LS8 cells and identified downstream effectors of the EDA-NF-κB pathway through RNA sequencing (RNA-seq) combined with in vivo and in vitro validation. LS8 cells were transiently transfected with four constructs: wild-type (Wt) EDA1, nonsyndromic tooth agenesis-associated EDA1 variant (EDA1-A259E), X-linked hypohidrotic ectodermal dysplasia-associated EDA1 variant (EDA1-H252L), or empty vector control (pCMV-C-FLAG). We used flow cytometry, wound-healing assay, and cell counting kit 8 assay to assess cell apoptosis, migration, and adhesion, respectively. High-throughput RNA-seq was used to identify differentially expressed genes, which were subsequently validated through quantitative polymerase chain reaction and immunoblotting. Spatiotemporal Fosb expression patterns were comparatively analyzed in Wt and Tabby mouse tooth germs through in situ hybridization by using RNAscope. Wt EDA1 transiently enhances cellular migratory capacity, a function compromised in the pathogenic EDA1 variants. The EDA-NF-κB pathway operates through FOSB-mediated transcriptional regulation, as evidenced by coordinated suppression of Fosb expression at transcriptional and translational levels in the mutant models. Therefore, FOSB is a candidate downstream effector in EDA1-mediated odontogenesis. These results provide mechanistic insights into ectodermal dysplasia pathogenesis.