ChuanWu (CW), the dried mother root of Aconitum carmichaelii Debx., is a well-known traditional Chinese medicine (TCM) recognized for its potent efficacy but inherent toxicity, primarily due to its alkaloid content. Traditional and modern detoxification methods for CW include proper processing, rational compatibility, and specialized decoction techniques, among which honey-boiled CW is particularly distinctive. However, research on the detoxification mechanism of honey-boiled CW remains limited. This study investigated this mechanism by analyzing alkaloid transformation and supramolecular aggregation. Honey-boiled and water-boiled CW preparations were compared. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze CW alkaloids, specifically diester alkaloids (DDAs), monoester alkaloids (MDAs), and non-esterified diterpenoid alkaloids (NDAs). Transmission electron microscopy was employed to observe and identify supramolecular aggregates in the honey-boiled CW decoction. In vivo absorption of water-boiled, honey-boiled, and NADES-boiled CW was compared. Median lethal dose (LD₅₀) tests assessed toxicity, including hepatotoxicity and nephrotoxicity. In vitro experiments evaluated the safety, anti-inflammatory, and analgesic effects of CW-medicated serum on RAW264.7 cells, with in vivo validation in mice. Results showed that honey promoted the conversion of highly toxic DDAs to less toxic MDAs and prevented MDAs from hydrolyzing into NDAs. Honey-boiled CW formed approximately 250 nm supramolecular aggregates that encapsulated MDAs, inhibiting their conversion to NDAs. These encapsulated MDAs acted as a stable delivery system with higher bioavailability than free benzoylmesaconine. Subsequent mouse experiments confirmed that honey-boiled CW significantly increased the LD₅₀ of CW while reducing hepatotoxicity and nephrotoxicity. Additionally, honey-boiled CW significantly improved cell safety and enhanced anti-inflammatory and analgesic effects. Our findings reveal that honey-boiled CW exhibits a potent detoxification mechanism by influencing alkaloid transformation and facilitating the formation of supramolecular aggregates. This study lays the groundwork for developing detoxification or synergistic strategies within honey-boiled TCM.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective To investigate the risk factors and establish a line graph model for diabetic retinopathy(DR)and diabetic macular edema(DME)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 446 patients with T2DM admitted to our hospital from June 2017 to January 2020 were selected and divided into DR/DME group(n=80)and T2DM group(n=366)according to whether they were complicated with DR and DME.Univariate and multivariate analysis were performed on the clinical data to obtain the influencing factors,and a nomogram model was constructed to evaluate the model.Results The DM duration,proportion of short axial length,FPG,HbA1c,TC and LDL-C in the DR/DME group were higher than those in the T2DM group,and the age and eGFR were lower than those in the T2DM group(P<0.05).DM duration(OR 16.380,95%CI 10.697～29.133),eGFR(OR 13.510,95%CI 5.393～33.863),HbA1c(OR 2.820,95%CI 1.064～5.610)and short axial length(OR 7.062,95%CI 1.153～43.265)were the influencing factors of DR and DME in T2DM patients.The AUC of the nomogram model was 0.906.The consistency index(0.957)and calibration curve showed that the model had good discrimination and consistency.Conclusions The DM duration,eGFR,HbA1c and short eye axis are closely related to DR and DME in T2DM patients,and the column line graph model based on this analysis has high predictive efficacy.

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 investigate the risk factors and establish a line graph model for diabetic retinopathy(DR)and diabetic macular edema(DME)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 446 patients with T2DM admitted to our hospital from June 2017 to January 2020 were selected and divided into DR/DME group(n=80)and T2DM group(n=366)according to whether they were complicated with DR and DME.Univariate and multivariate analysis were performed on the clinical data to obtain the influencing factors,and a nomogram model was constructed to evaluate the model.Results The DM duration,proportion of short axial length,FPG,HbA1c,TC and LDL-C in the DR/DME group were higher than those in the T2DM group,and the age and eGFR were lower than those in the T2DM group(P<0.05).DM duration(OR 16.380,95%CI 10.697～29.133),eGFR(OR 13.510,95%CI 5.393～33.863),HbA1c(OR 2.820,95%CI 1.064～5.610)and short axial length(OR 7.062,95%CI 1.153～43.265)were the influencing factors of DR and DME in T2DM patients.The AUC of the nomogram model was 0.906.The consistency index(0.957)and calibration curve showed that the model had good discrimination and consistency.Conclusions The DM duration,eGFR,HbA1c and short eye axis are closely related to DR and DME in T2DM patients,and the column line graph model based on this analysis has high predictive efficacy.

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.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective To explore the changes of hepatic and pancreatic fat content in patients with type 2 diabetes mellitus(T2DM)using quantitative MRI,and to discuss the relationship with pancreatic β-cell function and bone mineral density(BMD).Methods A total of 118 patients with T2DM(T2DM group)were selected as the research subjects.At the same time,100 healthy control(HC)(HC group)who received physical examination were selected.All patients were examined with MRI.Hepatic fat fraction(HFF)and pancreatic fat fraction(PFF)were detected using the iterative decomposition of water and fat with echo asymmetry and least square estimation quantitation(IDEAL-1Q)technology.The homeostasis model assessment of β-cell function(HOMA-β)and homeostasis model assessment of insulin resistance(HOMA-IR)were performed.BMD of L2-L4,femoral neck and total hip were measured by dual-energy X-ray absorptiometry.The correlations among HFF,PFF and HOMA-β,HOMA-IR and BMD of L2-L4,femoral neck and total hip were analyzed by Pearson method.Results HFF and PFF in the T2DM group[(14.12±2.19)％and(8.23±1.60)％]were higher than those in the HC group[(5.30±0.83)％and(4.36±0.85)％],with statistically significant differences(P＜0.05).HOMA-βand BMD of L2-L4,femoral neck and total hip in the T2DM group[14.50±3.63,(0.92±0.13)mg/cm3,(0.77±0.10)mg/cm3 and(0.83±0.12)mg/cm3]were lower than those in the HC group[25.22±5.43,(1.05±0.23)mg/cm3,(0.85±0.18)mg/cm3 and(0.91±0.20)mg/cm3].HOMA-IR in the T2DM group(3.56±1.22)was higher than that in the HC group(1.90±0.45).The differences were statistically significant(P＜0.05).Pearson correlation analysis found that HFF and PFF were negatively correlated with HOMA-β and BMD of L2-L4,femoral neck and total hip,and were positively correlated with HOMA-IR(P＜0.05).Conclusion MRI can be used to quantitatively evaluate hepatic and pancreatic fat content in patients with T2DM.In addition,hepatic and pancreatic fat content are closely related to pancreatic HOMA-β,HOMA-IR and BMD.

Objective:To compare the clinical efficacies of O-arm combined with CT three-dimensional navigation system assisted screw placement versus manual screw placement in treating lower cervical fracture and dislocation.Methods:A retrospective cohort study was used to analyze the clinical data of 41 patients with lower cervical fracture and dislocation, who were treated in Honghui Hospital, Xi′an Jiaotong University from May 2021 to February 2022. The patients included 26 males and 15 females, aged 31.5-48.6 years [(41.5±15.0)years]. The injured segments were C 3 in 3 patients, C 4 in 12, C 5 in 13, C 6 in 10 and C 7 in 3. Nineteen patients were treated with cervical pedicle screws by O-shaped arm combined with CT three-dimensional navigation system (navigation group, 76 screws) and 22 by bare hands (traditional group, 88 screws). The total operation time, effective operation time, single nail placement time, single screw correction times, screw distance from anterior cortex, intraoperative blood loss, intraoperative fluoroscopic radiation dose, incision length and length of hospital stay were compared between the two groups, and the height of intervertebral space, Cobb angle, interbody slip distance and American Spinal injury Association (ASIA) grade were compared before operation and at 3 days after operation. Visual analogue score (VAS), Japanese Orthopedic Association (JOA) score, and neck dysfunction index (NDI) were evaluated before operation, at 3 days, 3 months after operation and at the last follow-up. Accuracy of screw placement and incidence of complications (adjacent facet joint invasion, infection, screw loosening) were detected as well. Results:All the patients were followed up for 11.1-13.9 months [(12.5±1.4)months]. The total operation time, intraoperative blood loss, intraoperative fluoroscopic radiation dose and incision length in the navigation group were more or longer than those in the traditional group (all P<0.05). The effective operation time, single nail placement time, single nail correction times and screw distance from anterior cortex in the navigation group were markedly less or smaller than those in the traditional group (all P<0.05). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). There were significant improvements in the height of intervertebral space, Cobb angle and interbody slip distance between the two groups at 3 days after operation (all P<0.05). There was no significant difference in the height of intervertebral space, Cobb angle, interbody slip distance or ASIA grade between the two groups before operation or at 3 days after operation (all P>0.05). Compared with pre-operation, the VAS, JOA score and NDI were significantly improved in both groups at 3 days, 3 months after operation and at the last follow-up (all P<0.05), with further improvement with time. There was no significant difference in VAS between the two groups before operation or at 3 months after operation (all P>0.05), but it was markedly lower in the navigation group compared with the traditional group at 3 days after operation and at the last follow-up (all P<0.05). There were no significant differences in JOA score or NDI between the two groups before operation or at 3 days and 3 months after operation (all P>0.05), but both were lower in the navigation group compared with the traditional group at the last follow-up (all P<0.05). The accuracies of placement of grade 0 and grade 0+1 screws were 92.0% (70/76) and 96.6% (73/76) in the navigation group, respectively, which were markedly higher than 88.7% (78/88) and 93.5% (82/88) in the traditional group (all P<0.05). The rates of adjacent facet joint invasion of A, B, and C degrees were 71.2% (54/76), 28.8% (22/76) and 0% (0/76) in the navigation group, respectively, while the invasion rates were 60.5% (53/88), 32.3% (28/88) and 7.3% (7/88) in the traditional group ( P<0.05). No screw loosening was noted in the navigation group, but the screw loosening rate was 9.1% (8/88) in the traditional group ( P<0.01). Conclusion:Compared with manual screw placement, O-arm combined with CT three-dimensional navigation system assisted screw placement for lower cervical fracture and dislocation has the advantages of shorter effective operation time, quicker screw placement, stronger screw holding force, better cervical stability, slighter postoperative pain, higher screw placement accuracy, and lower facet joint invasion and screw loosening rates.