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”.

ObjectiveThis paper aims to systematically collect and organize ancient and modern clauses and studies containing Xieqingwan， excavate and analyze the key information of Xieqingwan， and provide a reference for facilitating the development of the classic formula Xieqingwan. MethodsThe composition， dosage， decocting methods， usage， and other key information of Xieqingwan in ancient traditional Chinese medicine books were collected and analyzed by means of literature research and metrological methods. The modern clinical application of Xieqingwan was summarized. ResultsA total of 42 pieces of effective data involving 32 ancient traditional Chinese medicine books were collected. Xieqingwan was first recorded in Xiaoer Yaozheng Zhijue. The drug origin of this formula is basically clear in the ancient traditional Chinese medicine books. The modern drug usage and decocting method were as follows： Angelicae Sinensis Radix， Gentianae Radix et Rhizoma， Chuanxiong Rhizoma， Gardenia seeds， Radix et Rhizoma Rhei， Notopterygii Rhizoma et Radix， and Saposhnikoviae Radix were grounded to fine powder， decocted with honey， and finally formed into pills with the size of a chicken head （1.5 g）. It was suggested that half a pill or one pill were taken for one dose with warm Lophatheri decoction and sugar. The indications and clinical application had developed from the recordings in Xiaoer Yaozheng Zhijue and evolved from pediatrics to ophthalmic otolaryngology， neurology， dermatology， digestion， and respiratory diseases. The main pathogenesis of these diseases is heat in the liver meridian and is treated. The effect of Xieqingwan is "clearing away heat and toxicity， removing fire and relaxing the bowels， and dispersing swelling and relieving pain". It is recommended to use the corresponding preparation methods in the 2020 Edition of Pharmacopoeia of the People's Republic of China. Modern clinical studies are centered around the clinical application of Xieqingwan， which is often modified and used in treating Tourette syndrome， herpes， febrile convulsion， sleepwalking， and insomnia. ConclusionThis paper conducts a thorough textual research of the key information of Xieqingwan， induces its historic evolution， and confirms its key information， so as to provide a reference for the future development of Xieqingwan.

Parkinson's disease(PD)is one of the most common neurodegenerative disorders.Recent evidence implicates pyroptosis as one of the pathogenic mechanisms in central nervous system disorders,although its specific mechanisms remain unclear.In this study,SH-SY5Y cells were transfected with py-roptosis-related proteins GSDME full-length(GSDME-F)or GSDME-N terminal(GSDME-N)plasmids revealed that GSDME-N significantly reduced mitochondrial membrane potential(P＜0.0001).To inves-tigate the mechanism by which GSDME mediates mitochondrial dysfunction,Western blotting analysis demonstrated that transfection with GSDME-N plasmids significantly increased BAX expression and en-hanced its translocation to mitochondria in both HEK 293T and SH-SY5Y cells(P＜0.05).SH-SY5Y cells treated with varying concentrations of rotenone(ROT)exhibited GSDME cleavage,elevated BAX expression(P＜0.05),increased mitochondrial BAX aggregation(P＜0.05),and reduced mitochondrial membrane potential(P＜0.01),as confirmed by Western blotting and JC-1 staining.Concurrently,MTT assays assessing cell viability and lactate dehydrogenase(LDH)release assays indicated that ROT in-duced these processes prior to pyroptosis.Furthermore,in a ROT-induced mouse PD model,ROT trig-gered GSDME cleavage,enhanced BAX expression,caused dopaminergic neuronal damage,and induced motor deficits.In summary,this study demonstrates that GSDME-N exacerbates mitochondrial damage and increases cytotoxicity by upregulating BAX expression and facilitating its mitochondrial translocation.This study provides novel insights into the role of GSDME in PD pathogenesis and suggests potential avenues for therapeutic intervention.

Objective To investigate the feasibility and safety of transradial approach(TRA)for carotid artery stenting(CAS)using single-layer braided carotid stents with a microporous dense mesh design.Methods A retrospective consecutive series of patients with carotid artery stenosis who underwent CAS via TRA using single-layer braided microporous dense mesh stents admitted to the Department of Neurology,Linyi People's Hospital,Shandong Second Medical University were included from December 2022 to April 2023.General and clinical data,lesion characteristics,procedural metrics,periprocedural conditions,and follow-up outcomes were collected from the patients.General and clinical data including sex,age,medical history(hypertension,diabetes,coronary artery disease),and preoperative modified Rankin scale(mRS)score.Lesion characteristics included stenosis location,normal lumen diameters distal and proximal to the stenosis,stenosis rate,lesion length,and aortic arch type.Procedural metrics included successfully guided catheter placement,stent deployment,retrieval of the embolic protection device and residual stenosis rate.Periprocedural conditions included periprocedural complications(within 72 hours included puncture site bleeding,symptomatic radial artery occlusion,new cerebral infarctions on diffusion-weighted imaging,and cardio-cerebrovascular events[angina,acute myocardial infarction,cerebral infarction,cerebral hemorrhage])and length of hospital stay.The mRS scores at 1 and 6 months after surgery were recorded via telephone follow-ups.At 12 months after surgery,outpatient carotid color Doppler ultrasound was performed to evaluate in-stent restenosis.Results(1)Ten patients(9 male,1 female)aged 57-72 years,with a median age of 70(62,71)years were included.Among them,9 had hypertension,2 had diabetes,and 1 had coronary artery disease.Four patients had symptomatic carotid stenosis:2 presented with hemiparesis,1 with mild dysarthria,and 1 with transient ischemic attack.Preoperative mRS scores among symptomatic patients were 0(1 patient),1(2 patients),and 2(1 patient).The remaining 6 patients had asymptomatic stenosis,all with preoperative mRS scores of 0.(2)Two patients had left internal carotid artery(ICA)stenosis,and 8 had right ICA stenosis.The mean stenosis degree was(79.9±7.1)％,and the mean lesion length was(16.8±5.7)mm.The mean normal distal and proximal lumen diameter of the stenosed blood vessel were(5.1±0.5)mm and(8.1±0.8)mm,respectively.One patient had a type Ⅰ aortic arch,8 patients had type Ⅱ,and 1 patient had type Ⅲ.Among the 8 patients with right ICA stenosis,4 underwent direct catheterization of the right common carotid artery using a glidewire,while the other 4 required exchange technique for guide catheter placement.Both left-sided lesions were treated using exchange technique.Guide catheter placement and stent deployment were successful in all cases.No difficulties were encountered in embolic protection device retrieval.The mean residual stenosis rate was(21.6±6.7)％.(3)The mean postoperative hospital stay was(1.8±0.9)days.No puncture site bleeding or symptomatic radial artery occlusion occurred.One patient experienced a cerebrovascular event due to a pontine perforator artery infarction,presenting with diplopia and impaired left eye adduction,likely caused by postoperative hypotension and hypoperfusion.This patient had an immediate postoperative mRS score of 2 at discharge,which improved to 0 at 6 months.The other 9 patients showed no change in mRS scores compared to preoperative assessments,and no new cerebral infarctions were detected within 72 hours after surgery.At 12-month follow-up,carotid color Doppler ultrasound revealed no in-stent restenosis in any patient.Conclusions CAS performed via TRA using single-layer braided microporous dense mesh stents appears to be feasible and safe.However,this study is a single-center,retrospective analysis with a small sample size.Larger prospective randomized controlled trials are needed to validate these findings.

Parkinson's disease(PD)is one of the most common neurodegenerative disorders.Recent evidence implicates pyroptosis as one of the pathogenic mechanisms in central nervous system disorders,although its specific mechanisms remain unclear.In this study,SH-SY5Y cells were transfected with py-roptosis-related proteins GSDME full-length(GSDME-F)or GSDME-N terminal(GSDME-N)plasmids revealed that GSDME-N significantly reduced mitochondrial membrane potential(P＜0.0001).To inves-tigate the mechanism by which GSDME mediates mitochondrial dysfunction,Western blotting analysis demonstrated that transfection with GSDME-N plasmids significantly increased BAX expression and en-hanced its translocation to mitochondria in both HEK 293T and SH-SY5Y cells(P＜0.05).SH-SY5Y cells treated with varying concentrations of rotenone(ROT)exhibited GSDME cleavage,elevated BAX expression(P＜0.05),increased mitochondrial BAX aggregation(P＜0.05),and reduced mitochondrial membrane potential(P＜0.01),as confirmed by Western blotting and JC-1 staining.Concurrently,MTT assays assessing cell viability and lactate dehydrogenase(LDH)release assays indicated that ROT in-duced these processes prior to pyroptosis.Furthermore,in a ROT-induced mouse PD model,ROT trig-gered GSDME cleavage,enhanced BAX expression,caused dopaminergic neuronal damage,and induced motor deficits.In summary,this study demonstrates that GSDME-N exacerbates mitochondrial damage and increases cytotoxicity by upregulating BAX expression and facilitating its mitochondrial translocation.This study provides novel insights into the role of GSDME in PD pathogenesis and suggests potential avenues for therapeutic intervention.

Objective To investigate the feasibility and safety of transradial approach(TRA)for carotid artery stenting(CAS)using single-layer braided carotid stents with a microporous dense mesh design.Methods A retrospective consecutive series of patients with carotid artery stenosis who underwent CAS via TRA using single-layer braided microporous dense mesh stents admitted to the Department of Neurology,Linyi People's Hospital,Shandong Second Medical University were included from December 2022 to April 2023.General and clinical data,lesion characteristics,procedural metrics,periprocedural conditions,and follow-up outcomes were collected from the patients.General and clinical data including sex,age,medical history(hypertension,diabetes,coronary artery disease),and preoperative modified Rankin scale(mRS)score.Lesion characteristics included stenosis location,normal lumen diameters distal and proximal to the stenosis,stenosis rate,lesion length,and aortic arch type.Procedural metrics included successfully guided catheter placement,stent deployment,retrieval of the embolic protection device and residual stenosis rate.Periprocedural conditions included periprocedural complications(within 72 hours included puncture site bleeding,symptomatic radial artery occlusion,new cerebral infarctions on diffusion-weighted imaging,and cardio-cerebrovascular events[angina,acute myocardial infarction,cerebral infarction,cerebral hemorrhage])and length of hospital stay.The mRS scores at 1 and 6 months after surgery were recorded via telephone follow-ups.At 12 months after surgery,outpatient carotid color Doppler ultrasound was performed to evaluate in-stent restenosis.Results(1)Ten patients(9 male,1 female)aged 57-72 years,with a median age of 70(62,71)years were included.Among them,9 had hypertension,2 had diabetes,and 1 had coronary artery disease.Four patients had symptomatic carotid stenosis:2 presented with hemiparesis,1 with mild dysarthria,and 1 with transient ischemic attack.Preoperative mRS scores among symptomatic patients were 0(1 patient),1(2 patients),and 2(1 patient).The remaining 6 patients had asymptomatic stenosis,all with preoperative mRS scores of 0.(2)Two patients had left internal carotid artery(ICA)stenosis,and 8 had right ICA stenosis.The mean stenosis degree was(79.9±7.1)％,and the mean lesion length was(16.8±5.7)mm.The mean normal distal and proximal lumen diameter of the stenosed blood vessel were(5.1±0.5)mm and(8.1±0.8)mm,respectively.One patient had a type Ⅰ aortic arch,8 patients had type Ⅱ,and 1 patient had type Ⅲ.Among the 8 patients with right ICA stenosis,4 underwent direct catheterization of the right common carotid artery using a glidewire,while the other 4 required exchange technique for guide catheter placement.Both left-sided lesions were treated using exchange technique.Guide catheter placement and stent deployment were successful in all cases.No difficulties were encountered in embolic protection device retrieval.The mean residual stenosis rate was(21.6±6.7)％.(3)The mean postoperative hospital stay was(1.8±0.9)days.No puncture site bleeding or symptomatic radial artery occlusion occurred.One patient experienced a cerebrovascular event due to a pontine perforator artery infarction,presenting with diplopia and impaired left eye adduction,likely caused by postoperative hypotension and hypoperfusion.This patient had an immediate postoperative mRS score of 2 at discharge,which improved to 0 at 6 months.The other 9 patients showed no change in mRS scores compared to preoperative assessments,and no new cerebral infarctions were detected within 72 hours after surgery.At 12-month follow-up,carotid color Doppler ultrasound revealed no in-stent restenosis in any patient.Conclusions CAS performed via TRA using single-layer braided microporous dense mesh stents appears to be feasible and safe.However,this study is a single-center,retrospective analysis with a small sample size.Larger prospective randomized controlled trials are needed to validate these findings.

The epicanthus is mainly manifested by a wide intercanthal distance and a short palpebral fissure,which affects the aesthetics of eyes.The epicanthus correction is of great significance in improving eye shape and facial aesthetics.However,scar formation and hyperplasia after surgery in the surgical area have been bothering doctors and patients,and how to prevent or alleviate scar after epicanthus correction is still a difficult problem to be solved in clinic.Therefore,this article summarizes the prevention and treatment of scar after epicanthus correction based on the current research status at home and abroad,in order to provide a reference for clinic.

Abstract Gurrently, healthy behaviors are the cornerstone of both physical and mental wellbeing,and more researches are focusing on improving behaviors to alleviate depression among children and adolescents. Based on the concept of 24 h movement behaviors proposed in recent years, the study examines the relationship among physical activity, sedentary behavior, sleep and depressive symptoms in children and adolescents. The research suggests that physical activity could effectively alleviate depression among children and adolescents, and its effectiveness is influenced by factors including type, intensity, duration and frequency of physical activity. Excessive sedentary behavior may increase depressive symptoms, and the impacts of different types, durations, and frequencies of sedentary behavior on depressive symptoms among children and adolescents vary. In addition to its direct impact on depression, sleep could also serve as a mediator among physical activity, sedentary behavior and depression, and there is also a crowdingout effect of time between physical activity and sedentary behavior. Future research should focus on the mechanisms and pathways underlying how 24 h movement behaviors affecting depression among children and adolescents, in order to provide more accurate solutions for the prevention and treatment of depression.