ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Objective: To assess the effect of transarterial embolization (TAE) for adhesive capsulitis (AC) by evaluating clinical outcomes and changes in inflammation using magnetic resonance imaging (MRI). Materials and Methods: Patients who had undergone TAE between August 2020 and August 2023 for AC refractory to conservative treatments without any invasive procedures for more than 3 months, and had undergone baseline and 3-month post-AC follow-up contrast-enhanced MRI evaluations, were included. A suspension mixture of 500 mg imipenem/cilastatin in 10 mL of iodinated contrast agent was used for TAE. MRI results were analyzed to assess periarticular capsule/ligament inflammation. Clinical assessments included pain scores using the numeric rating scale (NRS) and functional scores using the quick disabilities of the arm, shoulder, and hand (Quick DASH) questionnaire. Results: Twenty-five patients (female:male, 14:11; age, 54.9 ± 7.1 years) were included. Significant reductions in average NRS pain scores as well as improvements in Quick DASH scores and range of motion, including anterior flexion and abduction, were observed at 1, 3, and 6 months after TAE (all P < 0.001). MRI analyses revealed that TAE significantly decreased the grades of axillary recess capsule enhancement, rotator interval (RI) capsule T2 signal intensity, and RI capsule enhancement (all P ≤ 0.004). Conclusion TAE may be an effective and safe therapeutic approach for AC refractory to conservative treatments, alleviating pain and supporting functional recovery. The observed MRI findings suggest that the effectiveness of TAE for AC may be attributed to the reduction of inflammation and the elimination of angiogenesis.

BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

Objective: To assess the effect of transarterial embolization (TAE) for adhesive capsulitis (AC) by evaluating clinical outcomes and changes in inflammation using magnetic resonance imaging (MRI). Materials and Methods: Patients who had undergone TAE between August 2020 and August 2023 for AC refractory to conservative treatments without any invasive procedures for more than 3 months, and had undergone baseline and 3-month post-AC follow-up contrast-enhanced MRI evaluations, were included. A suspension mixture of 500 mg imipenem/cilastatin in 10 mL of iodinated contrast agent was used for TAE. MRI results were analyzed to assess periarticular capsule/ligament inflammation. Clinical assessments included pain scores using the numeric rating scale (NRS) and functional scores using the quick disabilities of the arm, shoulder, and hand (Quick DASH) questionnaire. Results: Twenty-five patients (female:male, 14:11; age, 54.9 ± 7.1 years) were included. Significant reductions in average NRS pain scores as well as improvements in Quick DASH scores and range of motion, including anterior flexion and abduction, were observed at 1, 3, and 6 months after TAE (all P < 0.001). MRI analyses revealed that TAE significantly decreased the grades of axillary recess capsule enhancement, rotator interval (RI) capsule T2 signal intensity, and RI capsule enhancement (all P ≤ 0.004). Conclusion TAE may be an effective and safe therapeutic approach for AC refractory to conservative treatments, alleviating pain and supporting functional recovery. The observed MRI findings suggest that the effectiveness of TAE for AC may be attributed to the reduction of inflammation and the elimination of angiogenesis.

Objective: To assess the effect of transarterial embolization (TAE) for adhesive capsulitis (AC) by evaluating clinical outcomes and changes in inflammation using magnetic resonance imaging (MRI). Materials and Methods: Patients who had undergone TAE between August 2020 and August 2023 for AC refractory to conservative treatments without any invasive procedures for more than 3 months, and had undergone baseline and 3-month post-AC follow-up contrast-enhanced MRI evaluations, were included. A suspension mixture of 500 mg imipenem/cilastatin in 10 mL of iodinated contrast agent was used for TAE. MRI results were analyzed to assess periarticular capsule/ligament inflammation. Clinical assessments included pain scores using the numeric rating scale (NRS) and functional scores using the quick disabilities of the arm, shoulder, and hand (Quick DASH) questionnaire. Results: Twenty-five patients (female:male, 14:11; age, 54.9 ± 7.1 years) were included. Significant reductions in average NRS pain scores as well as improvements in Quick DASH scores and range of motion, including anterior flexion and abduction, were observed at 1, 3, and 6 months after TAE (all P < 0.001). MRI analyses revealed that TAE significantly decreased the grades of axillary recess capsule enhancement, rotator interval (RI) capsule T2 signal intensity, and RI capsule enhancement (all P ≤ 0.004). Conclusion TAE may be an effective and safe therapeutic approach for AC refractory to conservative treatments, alleviating pain and supporting functional recovery. The observed MRI findings suggest that the effectiveness of TAE for AC may be attributed to the reduction of inflammation and the elimination of angiogenesis.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Objective: To assess the effect of transarterial embolization (TAE) for adhesive capsulitis (AC) by evaluating clinical outcomes and changes in inflammation using magnetic resonance imaging (MRI). Materials and Methods: Patients who had undergone TAE between August 2020 and August 2023 for AC refractory to conservative treatments without any invasive procedures for more than 3 months, and had undergone baseline and 3-month post-AC follow-up contrast-enhanced MRI evaluations, were included. A suspension mixture of 500 mg imipenem/cilastatin in 10 mL of iodinated contrast agent was used for TAE. MRI results were analyzed to assess periarticular capsule/ligament inflammation. Clinical assessments included pain scores using the numeric rating scale (NRS) and functional scores using the quick disabilities of the arm, shoulder, and hand (Quick DASH) questionnaire. Results: Twenty-five patients (female:male, 14:11; age, 54.9 ± 7.1 years) were included. Significant reductions in average NRS pain scores as well as improvements in Quick DASH scores and range of motion, including anterior flexion and abduction, were observed at 1, 3, and 6 months after TAE (all P < 0.001). MRI analyses revealed that TAE significantly decreased the grades of axillary recess capsule enhancement, rotator interval (RI) capsule T2 signal intensity, and RI capsule enhancement (all P ≤ 0.004). Conclusion TAE may be an effective and safe therapeutic approach for AC refractory to conservative treatments, alleviating pain and supporting functional recovery. The observed MRI findings suggest that the effectiveness of TAE for AC may be attributed to the reduction of inflammation and the elimination of angiogenesis.