Traditional Chinese medicine (TCM) features complex compatibility mechanisms involving multi-component, multi-target, and multi-pathway interactions. This study presents an interpretable graph artificial intelligence (GraphAI) framework to quantify such mechanisms in Chinese herbal formulas (CHFs). A multidimensional TCM knowledge graph (TCM-MKG; https://zenodo.org/records/13763953) was constructed, integrating seven standardized modules: TCM terminology, Chinese patent medicines (CPMs), Chinese herbal pieces (CHPs), pharmacognostic origins (POs), chemical compounds, biological targets, and diseases. A neighbor-diffusion strategy was used to address the sparsity of compound-target associations, increasing target coverage from 12.0% to 98.7%. Graph neural networks (GNNs) with attention mechanisms were applied to 6,080 CHFs, modeled as graphs with CHPs as nodes. To embed domain-specific semantics, virtual nodes medicinal properties, i.e., therapeutic nature, flavor, and meridian tropism, were introduced, enabling interpretable modeling of inter-CHP relationships. The model quantitatively captured classical compatibility roles such as "monarch-minister-assistant-guide," and uncovered TCM etiological types derived from diagnostic and efficacy patterns. Model validation using 215 CHFs used for coronavirus disease 2019 (COVID-19) management highlighted Radix Astragali-Rhizoma Phragmitis as a high-attention herb pair. Mass spectrometry (MS) and target prediction identified three active compounds, i.e., methylinissolin-3-O-glucoside, corydalin, and pingbeinine, which converge on pathways such as neuroactive ligand-receptor interaction, xenobiotic response, and neuronal function, supporting their neuroimmune and detoxification potential. Given their high safety and dietary compatibility, this herb pair may offer therapeutic value for managing long COVID-19. All data and code are openly available (https://github.com/ZENGJingqi/GraphAI-for-TCM), providing a scalable and interpretable platform for TCM mechanism research and discovery of bioactive herbal constituents.

AIM:To investigate the impact of Kir2.1 channels on abnormal spontaneous pacemaker activities induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:Human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)were transfected with lentiviral particles containing sequences for human Kir2.1,the Kir2.1-E224G mutant,or Kir4.1.Patch clamp techniques were employed to examine the effects of low extracellular potassium concentration([K+]e)of 1 mmol/L on the resting membrane potentials and whole-cell currents of the cells in each group,assessed via both current and voltage clamp modes.RESULTS:Under conditions of 1 mmol/L[K+]e,cur-rent clamp data revealed that hiPSC-CMs overexpressing Kir2.1 channels exhibited both hyperpolarized and depolarized resting membrane potentials,with the depolarized state triggering abnormal pacemaker activities.In contrast,cells overex-pressing the Kir2.1-E224G mutant or Kir4.1 channels displayed only hyperpolarized resting membrane potentials.Voltage clamp analysis indicated that hiPSC-CMs overexpressing Kir2.1 channels produced"N"-shaped whole-cell currents,whereas cells expressing the Kir2.1-E224G mutant or Kir4.1 exhibited typical K+currents.CONCLUSION:Kir2.1 channels play a crucial role in mediating hypokalemia-induced abnormal spontaneous pacemaker activities in human car-diomyocytes through their inward rectification properties.

Traditional Chinese medicine(TCM)features complex compatibility mechanisms involving multi-component,multi-target,and multi-pathway interactions.This study presents an interpretable graph artificial intelligence(GraphAI)framework to quantify such mechanisms in Chinese herbal formulas(CHFs).A multidimensional TCM knowledge graph(TCM-MKG;https://zenodo.org/records/13763953)was constructed,integrating seven standardized modules:TCM terminology,Chinese patent medicines(CPMs),Chinese herbal pieces(CHPs),pharmacognostic origins(POs),chemical compounds,biological targets,and diseases.A neighbor-diffusion strategy was used to address the sparsity of compound-target associations,increasing target coverage from 12.0％to 98.7％.Graph neural networks(GNNs)with attention mechanisms were applied to 6,080 CHFs,modeled as graphs with CHPs as nodes.To embed domain-specific semantics,virtual nodes medicinal properties,i.e.,therapeutic nature,flavor,and me-ridian tropism,were introduced,enabling interpretable modeling of inter-CHP relationships.The model quantitatively captured classical compatibility roles such as"monarch-minister-assistant-guide",and uncovered TCM etiological types derived from diagnostic and efficacy patterns.Model validation using 215 CHFs used for coronavirus disease 2019(COVID-19)management highlighted Radix Astragali-Rhi-zoma Phragmitis as a high-attention herb pair.Mass spectrometry(MS)and target prediction identified three active compounds,i.e.,methylinissolin-3-O-glucoside,corydalin,and pingbeinine,which converge on pathways such as neuroactive ligand-receptor interaction,xenobiotic response,and neuronal func-tion,supporting their neuroimmune and detoxification potential.Given their high safety and dietary compatibility,this herb pair may offer therapeutic value for managing long COVID-19.All data and code are openly available(https://github.com/ZENGJingqi/GraphAI-for-TCM),providing a scalable and inter-pretable platform for TCM mechanism research and discovery of bioactive herbal constituents.

Objective:To retrospectively analyze the efficacy and feasibility of surgical management in patients with cervical dysphagia secondary to Diffuse idiopathic skeletal hyperostosis(DISH)of the cervical spine.Methods:A retrospective analysis was conducted on 6 patients who presented with dysphagia as the primary symptom, were diagnosed with cervical DISH, and underwent surgical treatment in the Department of Otorhinolaryngology Head and Neck Surgery of The Second Xiangya Hospital of Central South University from January 2018 to February 2024. There were 5 males and 1 female, aged from 65 to 78 years (70.2±4.7 years). The duration of dysphagia prior to admission was 13 to 18 months (14.7±2.2 months). All patients had the symptom of dysphagia, and at least one other clinical manifestation of cervical DISH (dyspnea, restricted neck mobility, sleep apnea, odynophagia). One patient had undergone tracheotomy due to laryngeal obstruction before surgery. Surgical intervention was performed after failure of conservative management in all patients. All patients underwent anterior cervical osteophyte resection via the Smith-Robinson approach without concomitant spinal fusion. In the patient with prior tracheotomy for airway obstruction, epiglottoplasty and right arytenoidectomy were performed simultaneously. The swallowing function was evaluated by water swallow test, FEES, M. D. Anderson Dysphagia Inventory. Clinical and imaging evaluations were conducted for follow-uppostoperatively. Preoperative and 30-day post operative data were statistically analyzed using paired samples t-test.Results:Cervical computed tomography revealed osteophyte involvement from C2 to T1 with a median of 4 vertebral segments affected. The most frequently involved vertebral segments were C4-C6 (all 6 patients were involved). The anteroposterior diameter of the most prominent osteophyte was 12.0 to 20.0 mm (16±3.1 mm). The time to resumption of a regular diet was 6 to 20 days(12.7±5.3 days), and the time to remove the nasogastric tube was 8 to 25 days(15.2±6.2 days). In the patient with prior tracheotomy, the tracheostomy tube was successfully decannulated 30 days after initial tube capping following conversion to a metal tube. All cervical DISH-related symptoms except for limited neck mobility improved postoperatively. Both water swallow test and the Rosenbek Penetration-Aspiration Scale showed significant improvement postoperatively. At 30 days postoperatively, MDADI scores significantly improved in all domains: l global (73.33±10.33), emotional (85.56±8.35), functional (83.33±5.89), and physical (82.08±6.60). No major perioperative complications occurred. and the length of hospital stay was 7 to 10 days (7.8±1.2 days). The follow-up time was 12 to 84 months (43.7±27.2 months). All patients maintained sustained symptom relief, with no evidence of osteophyte recurrence during follow-up.Conclusion:Cervical DISH is an under-recognized causes of dysphagia in elderly patients and warrants attention from otolaryngologists. For patients erefractory to conservative treatment, anterior resection of cervical osteophytes via the Smith-Robinson approach is a safe, minimally invasive procedure with favorable short-and long-term outcomes in improving swallowing function.

AIM:To investigate the impact of Kir2.1 channels on abnormal spontaneous pacemaker activities induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:Human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)were transfected with lentiviral particles containing sequences for human Kir2.1,the Kir2.1-E224G mutant,or Kir4.1.Patch clamp techniques were employed to examine the effects of low extracellular potassium concentration([K+]e)of 1 mmol/L on the resting membrane potentials and whole-cell currents of the cells in each group,assessed via both current and voltage clamp modes.RESULTS:Under conditions of 1 mmol/L[K+]e,cur-rent clamp data revealed that hiPSC-CMs overexpressing Kir2.1 channels exhibited both hyperpolarized and depolarized resting membrane potentials,with the depolarized state triggering abnormal pacemaker activities.In contrast,cells overex-pressing the Kir2.1-E224G mutant or Kir4.1 channels displayed only hyperpolarized resting membrane potentials.Voltage clamp analysis indicated that hiPSC-CMs overexpressing Kir2.1 channels produced"N"-shaped whole-cell currents,whereas cells expressing the Kir2.1-E224G mutant or Kir4.1 exhibited typical K+currents.CONCLUSION:Kir2.1 channels play a crucial role in mediating hypokalemia-induced abnormal spontaneous pacemaker activities in human car-diomyocytes through their inward rectification properties.

Objective:To retrospectively analyze the efficacy and feasibility of surgical management in patients with cervical dysphagia secondary to Diffuse idiopathic skeletal hyperostosis(DISH)of the cervical spine.Methods:A retrospective analysis was conducted on 6 patients who presented with dysphagia as the primary symptom, were diagnosed with cervical DISH, and underwent surgical treatment in the Department of Otorhinolaryngology Head and Neck Surgery of The Second Xiangya Hospital of Central South University from January 2018 to February 2024. There were 5 males and 1 female, aged from 65 to 78 years (70.2±4.7 years). The duration of dysphagia prior to admission was 13 to 18 months (14.7±2.2 months). All patients had the symptom of dysphagia, and at least one other clinical manifestation of cervical DISH (dyspnea, restricted neck mobility, sleep apnea, odynophagia). One patient had undergone tracheotomy due to laryngeal obstruction before surgery. Surgical intervention was performed after failure of conservative management in all patients. All patients underwent anterior cervical osteophyte resection via the Smith-Robinson approach without concomitant spinal fusion. In the patient with prior tracheotomy for airway obstruction, epiglottoplasty and right arytenoidectomy were performed simultaneously. The swallowing function was evaluated by water swallow test, FEES, M. D. Anderson Dysphagia Inventory. Clinical and imaging evaluations were conducted for follow-uppostoperatively. Preoperative and 30-day post operative data were statistically analyzed using paired samples t-test.Results:Cervical computed tomography revealed osteophyte involvement from C2 to T1 with a median of 4 vertebral segments affected. The most frequently involved vertebral segments were C4-C6 (all 6 patients were involved). The anteroposterior diameter of the most prominent osteophyte was 12.0 to 20.0 mm (16±3.1 mm). The time to resumption of a regular diet was 6 to 20 days(12.7±5.3 days), and the time to remove the nasogastric tube was 8 to 25 days(15.2±6.2 days). In the patient with prior tracheotomy, the tracheostomy tube was successfully decannulated 30 days after initial tube capping following conversion to a metal tube. All cervical DISH-related symptoms except for limited neck mobility improved postoperatively. Both water swallow test and the Rosenbek Penetration-Aspiration Scale showed significant improvement postoperatively. At 30 days postoperatively, MDADI scores significantly improved in all domains: l global (73.33±10.33), emotional (85.56±8.35), functional (83.33±5.89), and physical (82.08±6.60). No major perioperative complications occurred. and the length of hospital stay was 7 to 10 days (7.8±1.2 days). The follow-up time was 12 to 84 months (43.7±27.2 months). All patients maintained sustained symptom relief, with no evidence of osteophyte recurrence during follow-up.Conclusion:Cervical DISH is an under-recognized causes of dysphagia in elderly patients and warrants attention from otolaryngologists. For patients erefractory to conservative treatment, anterior resection of cervical osteophytes via the Smith-Robinson approach is a safe, minimally invasive procedure with favorable short-and long-term outcomes in improving swallowing function.

Objective To establish a nomogram for overall survival rate after liver resection for primary small hepatocellular carcinoma based on SEER data and external validation of Chinese data. Methods The data of 1809 patients, registered in National Cancer Institute SEER database in 2004-2015, who underwent hepatectomy for primary small hepatocellular carcinoma were extracted as modeling group, and 158 patients with small hepatocellular carcinoma who underwent hepatectomy in Affiliated Hospital of North Sichuan Medical College from 2010 to 2017 were collected as validation group. The univariate Cox risk regression analysis, lasso regression analysis, and multivariate Cox hazard regression analysis were used to investigate the influencing factors for OS after hepatectomy in patients with small hepatocellular carcinoma. A nomogram was established based on the independent influencing factors for OS, and index of concordance (C-index), calibration curves, and receiver operating characteristic (ROC) curve were used to analyze the predictive ability of the nomogram. The Kaplan-Meier survival analysis and the log-rank test were used to investigate the difference in survival between the high- and low-risk groups. Results The multivariate Cox hazard regression analysis showed that sex (hazard ratio [ HR ]=1.22, 95% confidence interval [ CI ]: 1.05-1.41, P =0.010), Seer stage ( HR =1.51, 95% CI : 1.23-1.85, P < 0.001; HR =10.31, 95% CI : 2.53-42.04, P =0.001), tumor diameter ( HR =1.22, 95% CI : 1.06-1.39, P =0.004), vascular invasion or metastasis ( HR =1.43, 95% CI : 1.24-1.65, P < 0.001), and alpha-fetoprotein ( HR =1.33, 95% CI : 1.16-1.54, P < 0.001) were independent risk factors for OS after hepatectomy for small hepatocellular carcinoma. The modeling group had a C-index of 0.621, and its area under the ROC curve at 1, 2, and 3 years was 0.666(95% CI 0.628-0.704), 0.678(95% CI 0.647-0.708), and 0.663(95% CI : 0.635-0.690), respectively; the validation group had a C-index of 0.718, and its area under the ROC curve at 1, 2, and 3 years was 0.695(95% CI : 0.593-0.797), 0.781(95% CI : 0.706-0.856), and 0.759(95% CI 0.669-0.848), respectively. Risk stratification was performed based on the nomogram, and the Kaplan-Meier survival analysis showed that for both the modeling group and the validation group, the low-risk group had a significantly better prognosis than the high-risk group ( P < 0.01). Conclusion The model established for survival rate after liver resection for primary small hepatocellular carcinoma can predict the 1-, 2-, and 3-year OS rates and can thus be used in clinical practice in China.

Lysyl oxidase (LOX) family is a group of copper-containing amine oxidases composed of LOX and LOX-like proteins (LOXL1, LOXL2, LOXL3, and LOXL4). It is overexpressed in tumor tissue and promotes tumor metastasis through covalent cross-linking of extracellular matrix, with the functions of cell growth control, tumor inhibition, senescence, and chemotaxis. In recent years, more and more evidence has shown that LOX family members play a key role in the pathogenesis of hepatocellular carcinoma (HCC), suggesting that they have great potential as therapeutic targets. This article reviews the role of LOX family members in the development and progression of HCC and the intervention effect of traditional Chinese medicine extracts on HCC by regulating LOX family, in order to provide a reference for further research on the prevention and treatment of HCC.

Objective To establish an Early Warning System for Recurrence Scoring after Radical Resection of BCLC stage 0/A Primary Liver Cancer (PLC-EWSPRS), and to investigate its predictive value. Methods A retrospective analysis was performed for the clinical data of 232 patients with BCLC stage 0/A liver cancer who underwent radical resection in Affiliated Hospital of Chuanbei Medical College from January 2009 to January 2015, and according to the presence or absence of recurrence within 5 years after surgery based on telephone or outpatient follow-up data, the patients were divided into recurrence group with 103 patients and non-recurrence group with 129 patients. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test or Fisher's exact test was used for comparison of categorical data between groups. The indices with statistical significance were included in the binary logistic regression analysis to investigate the risk factors for recurrence of BCLC stage 0/A liver cancer after surgery. Two points were assigned for independent risk factors and one point was assigned for risk factors to establish the PLC-EWSPRS system. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the diagnostic efficiency of this system. Results Compared with the non-recurrence group, the recurrence group had significantly higher levels of aspartate aminotransferase and alanine aminotransferase (ALT) and a significantly lower level of albumin (Alb) before surgery ( Z =3.864 and 4.587, t =-5.628, all P < 0.001), as well as a significantly higher proportion of patients with positive HBsAg, capsular invasion, microvascular invasion (MVI), tumor diameter ≥5 cm, liver cirrhosis (moderate-to-severe), non-R0 resection, or death within 5 years ( χ 2 =35.539, 22.325, 13.398, 7.130, 4.312, 4.034, and 18.527, all P < 0.05). The regression analysis showed that preoperative Alb < 40 g/L (odds ratio [ OR ]=5.796, P < 0.001), preoperative ALT ≥40 U/L ( OR =3.029, P =0.002), MVI ( OR =3.981, P =0.003), positive HBsAg ( OR =7.829, P < 0.001), capsular invasion ( OR =5.357, P < 0.001), and non-R0 resection ( OR =3.048, P =0.018) were independent risk factors for recurrence of BCLC stage 0/A liver cancer within 5 years after surgery. According to the assignment criteria of the PLC-EWSPRS system, the recurrence group had the lowest score of 2 points and the highest score of 14 points, while the non-recurrence had the lowest score of 0 point and the highest score of 11 points, and the recurrence group had a significantly higher score than the non-recurrence group ( P < 0.05). The ROC curve analysis showed that the PLC-EWSPRS system had an AUC of 0.918 (95% confidence interval [ CI ]: 0.883-0.953, P < 0.001) in predicting recurrence within 5 years after surgery in patients with BCLC stage 0/A liver cancer undergoing radical resection, and subgroup analysis showed that the system had an AUC of 0.796 (95% CI : 0.695-0.896, P =0.002), 0.859 (95% CI : 0.791-0.927, P < 0.001), and 0.944 (95% CI : 0.839-1.000, P =0.044), respectively, in predicting recurrence within 5 years after surgery in patients with a low score of 0-5 points, a moderate score of 6-10 points, and a high score of 11-14 points. Conclusion The PLC-EWSPRS system has a good value in predicting the recurrence of BCLC stage 0/A liver cancer within 5 years after surgery and thus has important guiding significance for postoperative reexamination and treatment strategy for patients with BCLC stage 0/A liver cancer undergoing radical resection.

Acute-on-chronic liver failure (ACLF) is a life-threatening disease with a high risk of multiple organ failure, sepsis, and death. ACLF activates innate and acquired immune responses in human body and thus leads to the progression of persistent systemic inflammatory response syndrome and multiple organ dysfunction, leading to the high mortality rate of this disease. Dysregulated immune response plays a key role in disease progression, and immunotherapy may help to target immune-mediated organ damage and inhibit the progression of liver failure. This article reviews the role and mechanism of drugs and means with a potential immune regulatory effect in ACLF, in order to provide a reference for immunotherapy for ACLF.