ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

Objective: To investigate the role of ferroptosis in transfusion-related acute lung injury (TRALI) and evaluate the efficacy of the specific inhibitor Ferrostatin-1 (Fer-1), thereby to provide a basis for the prevention and treatment of TRALI. Methods: This study utilized a ”2-hit” model to induce TRALI in mice. The mouse model of TRALI was validated through survival curve analysis, lung tissue wet/dry weight ratio (W/D), myeloperoxidase (MPO) activity, and total protein concentration in lung tissue. Samples from the TRALI model group, LPS group, and control group (n=6) were collected. The occurrence of ferroptosis in TRALI was confirmed by measuring key ferroptosis indicators, including iron concentration in lung tissue, malondialdehyde (MDA) level, lipid peroxidation products (LPO) level, and expression levels of related proteins (GPX4, ACSL4). Additionally, a Fer-1 intervention group was added to evaluate its preventive and therapeutic effects. The survival rates and clinical symptoms of the four groups (n=6) were dynamically monitored, and the degrees of lung injury were assessed. Ferroptosis-related indicators were also measured to elucidate the protective mechanism of Fer-1. Results: A mouse model of TRALI was successfully established. Compared to the control and LPS groups, the TRALI group showed significantly higher levels of ferrous iron [(18.32±1.11) nmol/well, MDA [(14.68±0.96) μmol/L], and LPO [(1.60±0.02) μmol/L] in lung tissue (all P<0.01), along with a downregulation of GPX4 and an upregulation of ACSL4. Fer-1 pretreatment significantly reversed these abnormalities: the W/D ratio decreased to 4.01±0.43, and MPO activity significantly decreased [Fer-1 group: (21 606±4 235) pg/mL vs TRALI group: (30 724±2 616) pg/mL], the total protein concentration in lung tissue of the Fer-1 group decreased by approximately 40.8% compared to the TRALI group (all P<0.01). These changes indicate that the lung injury in mice was alleviated after treatment. Following Fer-1 intervention, ferrous iron concentration [(7.46±1.83) nmol/well] was restored to a level close to that of the control group [(5.48±0.70) nmol/well]. Lipid peroxidation tests further revealed that Fer-1 intervention reduced MDA and LPO levels by 35.8% and 29.4%, respectively (P<0.001). Additionally, the expression levels of GPX4 and ACSL4 proteins returned to near-normal levels in the treated mice (both P>0.05). Conclusion: The progression of TRALI is closely related to the activation of ferroptosis, characterized by iron overload, lipid peroxidation accumulation, and the imbalance of GPX4/ACSL4. Ferrostatin-1 significantly alleviates pulmonary edema and inflammatory damage by inhibiting the ferroptosis pathway, suggesting that targeting ferroptosis may provide a new therapeutic strategy for TRALI.

ObjectiveTo explore the efficacy-driving mechanism of Danhong injection （DHI） in the treatment of stable angina pectoris （SAP） based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency （AF） in the Seattle Angina Questionnaire （SAQ） that was obtained in the previous clinical trial， the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source， and then weighted gene co-expression network analysis （WGCNA） was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition， the On-modules （Z value below 0） were identified by Zsummary. The topological indicators such as density， centrality， and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level， respectively. In addition， the driver genes were screened by the personalized network control （PNC） algorithm. Finally， rat H9C2 cells were used to establish the model of hypoxia/reoxygenation （H/R）， which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP， and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally， the driver genes， Klotho and fibroblast growth factor 22 （FGF22）， in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data， this study determined the composition-activity relationship of target modules of DHI for SAP， which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.

AIM: To establish a method for quantitation of cefepime and avibactam in M-H broth, and applicated in the in vitro dynamic PK/PD model. METHODS: The cefepime was also determined using the high-performance liquid chromatography method (HPLC), the avibactam was also determined using the liquid chromatography-mass spectrometry (LC-MS/MS), an in vitro dynamic PK/PD model was established to study the PK/PD relationship of cefepime/avibactam against carbapenem resistant Klebsiella pneumoniae (CRKP). RESULTS: The linear ranges of cefepime and avibactam were good at (0.5-20) and (0.1-25) μg/mL (r=0.999), and the lower limit concentrations were 0.5 and 0.1 μg/mL. The extraction recoveries of cefepime and avibactam in M-H broth were 88.0%-101.7% and 90.9%-95.2%, the relative standard deviation of intra-day precision and inter-day precision were less than 5.2%. The concentration-time curves were well simulated by the PK/PD model. All observed concentrations in each experiment were in the range of 20% of the targeted values. For the CRKP of MIC=8 μg/mL and MIC=16 μg/mL, the colony decreased to 2.783Log10 CFU/mL and 1.325Log10 CFU/mL at the cefepime/avibactam 2.5 g q8 h administration after 24 h. CONCLUSION: The determination method of cefepime and avibactam in broth established in this study has high sensitivity and good stability. For the CRKP with MIC≤8 μg/mL,cefepime/avibactam showed that good anti-CRKP activity under routine administration in vitro dynamic PK/PD model.

Background::Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC.Methods::We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. Results::The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ESCC. Conclusion::The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.

Dysregulated RNA splicing events produce transcripts that facilitate esophageal squamous cell carcinoma (ESCC) progression, but how this splicing process is abnormally regulated remains elusive. Here, we unveiled a novel alternative splicing axis of BOLA3 transcripts and its regulator HNRNPC in ESCC. The long-form BOLA3 (BOLA3-L) containing exon 3 exhibited high expression levels in ESCC and was associated with poor prognosis. Functional assays demonstrated the protumorigenic function of BOLA3-L in ESCC cells. Additionally, HNRNPC bound to BOLA3 mRNA and promoted BOLA3 exon 3 inclusion forming BOLA3-L. High HNRNPC expression was positively correlated with the presence of BOLA3-L and associated with an unfavorable prognosis. HNRNPC knockdown effectively suppressed the malignant biological behavior of ESCC cells, which were significantly rescued by BOLA3-L overexpression. Moreover, BOLA3-L played a significant role in mitochondrial structural and functional stability. E2F7 acted as a key transcription factor that promoted the upregulation of HNRNPC and inclusion of BOLA3 exon 3. Our findings provided novel insights into how alternative splicing contributes to ESCC progression.
Female ; Humans ; Male ; Mice ; Alternative Splicing ; Cell Line, Tumor ; Disease Progression ; Esophageal Neoplasms/pathology* ; Esophageal Squamous Cell Carcinoma/pathology* ; Exons/genetics* ; Gene Expression Regulation, Neoplastic ; Heterogeneous-Nuclear Ribonucleoprotein Group C/metabolism* ; Prognosis ; RNA, Long Noncoding/metabolism* ; Animals

Objective:To explore the change trajectory and influencing factors of benefit finding of family caregivers of patients with lung cancer, so as to provide reference for formulating individualized intervention strategies.Methods:This study was a cross-sectional survey. From September 2021 to October 2022, 232 family caregivers of patients with lung cancer from General Hospital of PLA Central Theater Command and Tianyou Hospital affiliated to Wuhan University of Science and Technology were collected by convenience sampling method. The level of benefit finding of family caregivers was investigated at 1 month, 3 months and 6 month, after the patients were diagnosed. Growth Mixture Model was applied to identify distinct trajectory categories. Multinomial Logistic regressions were performed to analyze predictors of trajectory categories.Results:The overall level of benefit finding of family caregivers of lung cancer patients showed an upward trend over time ( F=83.06, P<0.01), from 1 month (47.02 ± 14.79) to 6 months (58.13 ± 13.18). Three categories of benefit finding trajectories were identified, named as "the high level-decline group" 12 cases, "the moderate level-stability group" 67 cases, and "the low level-elevation group" 153 cases. Univariate analysis showed that age and education level of family caregivers, average income per person in patient family, type of medical payment, whether the tumor was metastasized, the treatment method of the patient, whether they lived with the patient, and whether they had co-caregivers were related to the category of benefit finding trajectory ( χ2 values were 6.71-15.05, all P<0.05). Multivariate Logistic regression analysis showed that age and education level of family caregivers, average income per person in patient family, treatment method of the patient and whether they lived with the patients were the main influencing factors of benefit finding trajectory categories(all P<0.05). Conclusions:The benefit finding of family caregivers of lung cancer patients showed different trajectories with the time of diagnosis, and the overall level shows an upward trend. More than half of the family caregivers belong to the low level-elevation group. Medical staff should give family caregivers stage and specific nursing intervention according to the change trajectory of benefit finding and its influencing factors.

Objective To explore the differences between baduanjin and ninth set of broadcast gymnastics in their own pulse parameters before and after intervention for 12 weeks,and to provide objective indicators for the function of Baduanjin from the perspective of pulse diagnosis.Methods 60 healthy subjects were recruited,and 50 subjects were finally included according to the dropout criteria.The subjects were divided into the experimental group and the control group by the random number table method,and different interventions were adopted.Then,the pulse diagnosis of the two groups of subjects was collected,and the impact of the interventions on the viscera was judged by analyzing the Pulse Graph Parameters and contribution.Results The characteristic parameters of the experimental group include 8 time domain parameters(left Chi,left Guan,right Cun,etc.)and 9 frequency domain parameters(left Guan,left Chi,right Guan,etc.),which are mainly distributed in the left Cun,left Guan,left Chi,and right Guan;the characteristic parameters of the control group included 6 time domain parameters(left Cun,left Guan,right Chi,etc.)and 11 frequency parameters(left Guan,left Chi,right Guan,etc.),which were mainly distributed in left Chi,right Chi,and left Guan.Conclusion Practicing Baduanjin can significantly affect pulse diagram,and the accuracy and specificity after intervention are higher than those of the control group.Baduanjin has a certain influence on the circulation of qi and blood in the human meridians,and its mechanism of action may be related to affecting the overall circulation of qi and blood.In the experimental group,Baduanjin had a significant effect on the heart,liver,gallbladder,and kidneys,while the control group had the most obvious changes in the kidneys.For the overall intervention and coordination of the viscera,the Baduanjin group had better effects than the ninth broadcast gymnastics group.

Biology-guided radiotherapy (BgRT) is a novel technique of external beam radiotherapy, combining positron emission tomography-computed tomography (PET-CT) with a linear accelerator (LINAC). The key innovation is to utilize PET signals from tracers in tumor tissues for real-time tracking and guiding beamlets. Compared with a traditional LINAC system, a BgRT system is more complex in hardware design, software algorithm, system integration and clinical workflow. RefleXion Medical has developed the world's first BgRT system. Nevertheless, its actively advertised function, PET-guided radiotherapy, is still in the research and development phase. In this review study, we presented a number of issues related to BgRT, including its technical advantages and potential challenges.
Positron Emission Tomography Computed Tomography ; Radiotherapy Planning, Computer-Assisted/methods* ; Algorithms ; Particle Accelerators ; Biology ; Radiotherapy, Image-Guided/methods* ; Radiotherapy Dosage

Objective:To explore the effect and mechanism of taxifolin (TAX) on ameliorating cisplatin-induced renal oxidative damage.Methods:(1) Forty male C57BL/6 mice were divided into 4 groups: control group ( n=10), TAX group ( n=10), cisplatin group ( n=10) and cisplatin+TAX group ( n=10). The weight of mice in each group was measured. The level of serum creatinine (Scr) and blood urea nitrogen (BUN) was analyzed. Kidney histopathological change in mice was analyzed by HE staining. The pro-inflammatory cytokines levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured by enzyme linked immunosorbent assay. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were measured by multifunctional microplate reader. The expression of inflammatory factors, antioxidant genes, and peroxisome proliferator-activated receptor γ coactivator-1α ( PGC- 1) mRNA were measured by real-time PCR. Evaluation of mitochondrial function by measuring ATP level and mtDNA content. Determination of AMP-activated protein kinase (AMPK) and phosphorylated AMPK protein expression by Western blotting. (2) Evaluate the effect of taxifolin on chemotherapy of cisplatin by establishing Lewis lung cancer transplantation tumor C57BL/6 mice model. Results:Compared with the control group, the weight of the mice in the TAX group was not significantly reduced ( P>0.05), and there was no obvious kidney damage ( P>0.05), indicating that oral TAX had good safety. Compared with the cisplatin group, TAX could significantly delay cisplatin-induced the weight loss of mice, reduce the levels of Scr and BUN, and alleviate the pathological changes of kidney tissue (all P<0.05). TAX could reduce the levels of serum inflammatory factors IL-6 and TNF-α and the expression of renal inflammatory factors IL- 6, TNF- α and IL- 1β mRNA induced by cisplatin in mice (all P<0.05). TAX could significantly reduce the levels of ROS and MDA, and increase the activities of SOD, CAT and GSH in cisplatin-induced acute kidney injury mice (all P<0.01). Meanwhile, TAX could up-regulate the mRNA expression of UCP2, SOD2, CAT antioxidant genes and PGC- 1α in the kidneys of mice with acute kidney injury induced by cisplatin, and increase the levels of ATP and mtDNA in cisplatin-induced acute kidney injury mice (all P<0.01). Western blotting results showed that TAX significantly promoted the expression of phosphorylated AMPK protein in cisplatin-induced acute kidney injury mice ( P<0.01). In addition, through the establishment of Lewis lung cancer transplantation tumor C57BL/6 mice model, it was found that TAX had no significant effect on the anti-tumor efficacy of cisplatin. Conclusions:TAX can ameliorate cisplatin-induced renal oxidative damage, and its mechanism may be related to the activation of AMPK/PGC-1α pathway.