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”.

Objective To investigate the efficacy and safety of the Corheart 6 left ventricular assist system in patients with end-stage heart failure. Methods A retrospective study was conducted on patients with end-stage heart failure who were treated with Corheart 6 left ventricular assist system from March 2022 to June 2024 in 4 hospitals in Jiangsu Province. The efficacy of the device was evaluated by comparing changes in clinical indicators at preoperative, discharge, 3-month postoperative, and 6-month postoperative timepoints, including the New York Heart Association (NYHA) functional classification, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic diameter (LVEDD). The safety of the device was assessed by analyzing the intraoperative position and orientation of the blood pump inlet cannula, as well as the incidence of adverse events. Results In this study, 39 patients were collected, including 34 males and 5 females with a mean age of (56.4±12.5) years, ranging from 20 to 75 years. There was no operative death. There was no death in postoperative 3 months with a survival rate of 100.0%. There were 3 deaths in 6 months postoperatively, with a survival rate of 92.3%. All patients had a preoperative NYHA cardiac function classification of class Ⅳ. The NYHA cardiac function class of the patients improved (P<0.05) at discharge, 3 and 6 months after surgery when compared to the preoperative period. LVEF was significantly higher at 3 months after surgery than that during the preoperative period (P<0.05). LVEDD was significantly smaller at discharge, 3 and 6 months after surgery than that during the preoperative period (P<0.05). The safety evaluation's findings demonstrated that all 39 patients' intraoperative blood pump inlet tubes were oriented correctly, the artificial blood vessel suture sites were appropriate, there were no instances of device malfunction or pump thrombosis, or instances of bleeding or hemolysis, and the rate of the remaining adverse events was low. Conclusion With a low rate of adverse events and an excellent safety profile, the Corheart 6 left ventricular assist system can efficiently enhance cardiac function in patients with end-stage heart failure. It also has considerable clinical uses.

OBJECTIVE To promote the application of drones in emergency rescue and related fields， expand “low-altitude+ medical” rescue services， and advance the standardization of “low-altitude+medical” distribution services. METHODS The Consensus on Low-altitude Transport and Delivery Services for Emergency Medicines via Drones （2025 Edition） （hereinafter referred to as the Consensus） was jointly initiated by the Division of Therapeutic Drug Monitoring， Chinese Pharmacological Society and the Expert Committee on Precision Medication of the Guangdong Pharmaceutical Association. Guangzhou Red Cross Hospital served as the leading unit， organizing 53 multidisciplinary experts nationwide to participate in drafting and reviewing. A nominal group technique was employed to discuss and finalize the consensus outline， resulting in a preliminary draft. Delphi method was employed， and 11 external review experts were invited to conduct the evaluation. After the experts’ opinions were analyzed and integrated， the Consensus was finalized. RESULTS & CONCLUSIONS The finalized Consensus includes its purpose， principles， and applicable scenarios， basic requirements， and operational procedures for low-altitude transport and delivery of emergency medications； distribution requirements and precautions for controlled substances， fragile medications， and temperature-sensitive medications； and recommendations for emergency medications supplies suitable for the low-altitude transportation and distribution. The release of this Consensus is expected to provide guidance and support for the standardization of “low-altitude+medical” distribution services and the application of low-altitude economy in the healthcare sector.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

BACKGROUND:Percutaneous retrograde screws and minimally invasive percutaneous plates are extensively used in the treatment of unilateral pubic ramus fractures.However,the above internal fixations have the disadvantages of mistakenly penetrating the hip joint and damaging the medial pelvic trophoblastic artery.A new type of retrograde superior pubic ramus intramedullary nail offers advantages,such as fewer radiographic exposures and shorter surgery times,but the validation of the biomechanical properties of the three endoprostheses is lacking.OBJECTIVE:To compare the biomechanical differences post-treatment of upper and lower pubic ramus fractures using percutaneous retrograde screws,minimally invasive percutaneous plates,and retrograde superior pubic ramus intramedullary nail under various conditions through finite element analysis.METHODS:Pelvic CT data were collected from one volunteer and imported into Mimics 20,Geomagic Wrap 2021,and SolidWorks 2019 to create geometric models of three types of internal fixation for treating unilateral pubic ramus fractures:hollow screw group,plate group,and intramedullary nail group.Each model was imported into Ansys 2022 software,where it was set up in vertical,book-opening,and shear conditions for preprocessing and calculation to compare and analyze the mechanical stability of the implants.RESULTS AND CONCLUSION:(1)In vertical conditions,the biomechanical stability of the hollow screw treatment for unilateral pubic fractures was superior to that of the steel plate and intramedullary nail,with the smallest peak stress in the implant,which was four times lower compared to the other two groups.(2)In book-opening conditions,the steel plate treatment for unilateral pubic fractures showed better biomechanical stability,particularly in reducing stress at the fracture ends of the upper pubic branch,with stress values five times higher in the other two groups.(3)In shear conditions,the intramedullary nail treatment for unilateral pubic fractures exhibited good biomechanical stability,maintaining the best pelvic displacement,with a 25％greater displacement observed in the other two groups.(4)These findings reveal the biomechanical differences of different implants:the peak stress of implants is the smallest under vertical working conditions with percutaneous retrograde screws.Minimally invasive percutaneous plates reduce the stress at the broken end of superior pubic branch under open-book working condition.Retrograde superior pubic ramus intramedullary nail of superior pubic branch maintains pelvic displacement under shear working condition.The surgeon can combine the biomechanical differences of the implants with the actual situation of pubic injury in clinical practice to make the best implant treatment.

Objective To systematically evaluate the effectiveness and acceptability of antidepressant drugs in the treatment of postpartum depression(PPD).Methods The PubMed,Cochrane Library,Embase,Web of Science,China National Knowledge Infrastructure(CNKI),Wanfang Database,VIP Journals of Chinese Scienc were searched,and Chinese Biomedical Literature Service System(SinoMed)database until November 2023.Screen randomized controlled trials(RCTs)of antidepressant drugs for the treatment of PPD.The treatment group was given antidepressant drugs,and the control group was given placebo or another antidepressant drug.Meta-analysis of effectiveness and acceptability is performed using Stata 17.0 software.Results A total of 27 RCTs with a total of 2 202 patients were included.The results of meta-analysis showed:The top three efficacy relative to placebo were mirtazapine[odds ratio(OR)=2.25,95％confidence interval(CI)=(1.20-3.30),P＜0.05],nortriptyline[OR=1.50,95％CI=(0.55-2.44),P＞0.05],venlafaxine[OR=1.35,95％CI=(0.13-2.56),P＞0.05].Acceptability is compared with placebo in the top three Chinese herbal medicine[OR=0.47,95％CI=(-0.72-1.66),P＞0.05],nortriptyline[OR=-0.08,95％CI=(-1.16-1.33),P＞0.05],venlafaxine[OR=-0.12,95％CI=(-1.47-1.24),P＞0.05].Conclusion Nortriptyline,venlafaxine,trazodone,and duloxetine are effective in treating PPD without obvious adverse drug reactions.

Programmed cell death protein 1(PD-1)and its ligand,programmed cell death 1 ligand 1(PD-L1),represent a pair of prototypical immune checkpoint that plays a critical role in tumor immune evasion.However,the development of targeted therapeutics against these two proteins is limited by their low levels and high glycosylation modifications in eukaryotic cells.In this study,we designed two func-tional but truncated variants of PD-1(PD-133-150)and PD-L1(PD-L1 19-239);and subcloned them into eukaryotic expression vectors using golden gate assembly technology.Using these vectors,we achieved high level yields of these two proteins in transiently-transfected HEK-293T cells.After one-step affinity purification,the yields of PD-133-150 and PD-L119 239 proteins reached 5 mg and 3 mg per liter of cell cul-ture medium,with over 95％purity.Using biolayer interferometry and flow cytometry analysis,we deter-mined the binding kinetics,equilibrium constants,and the cellular binding activities of these proteins.Compared with the PD-1 extracellular domain expressed in insect or E.coli cells,the PD-133-150 purified from HEK-293T cells has a 24-fold and a 50-fold increase in its binding affinity to PD-L1.In addition,the dissociation rate of the binding decreased to less than l/400th of the original rate.Thus,we speculate that N-glycosylation could modulate the PD-1/PD-L1 interactions.Together,we established an effective eukaryotic expression and purification platform for functional characterization of PD-133150/PD-L119239 in-teractions,thereby providing high-quality molecular tools for PD-1/PD-L1 antibody screening and im-mune checkpoint research.

Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.

Objective:To investigate the effect of risk forewarning hierarchical management on mental state,major adverse cardiovascular events(MACE)and quality of life in patients with acute coronary syndrome after percutane-ous coronary intervention(PCI).Methods:This randomized controlled study enrolled 152 patients with acute coro-nary syndrome who underwent PCI in the First Hospital of Qinhuangdao between July 2021 and June 2023.Patients were randomly divided into control group(n=76,conventional intervention program)and intervention group(n=76,additional risk forewarning hierarchical management).After 3-month intervention,mental state[Hamilton anxiety scale(HAMA)and Hamilton depression scale(HAMD)scores],health literacy[perceived knowledge scale for coronary heart diseases(PKS-CHD)score],quality of life[Seattle angina questionnaire(SAQ)score]and in-cidence of MACE were compared between the two groups.Results:Compared to those in the control group,patients in the intervention group had significantly higher total score of PKS-CHD[(35.08±3.59)points vs.(30.53±3.85)points],SAQ dimensional scores of physical limitation[(15.24±1.73)points vs.(13.26±1.45)points],an-ginal stability[(16.84±1.39)points vs.(15.18±1.48)points],disease perception[(17.00±1.46)points vs.(14.34±1.93)points],anginal frequency[(18.55±1.18)points vs.(16.11±1.39)points]and treatment satis-faction[(17.12±1.45)points vs.(14.04±1.93)points](P＜0.001 all),and significantly lower HAMA score[(11.89±1.64)points vs.(13.55±1.56)points],HAMD score[(12.61±1.76)points vs.(16.42±1.92)points]and the incidence of MACE(8.00％vs.28.38％)(P＜0.001 all).Conclusion:Risk forewarning hierarchical man-agement may effectively relieve patients'negative emotions,improve their health literacy and quality of life,and significantly reduce the risk of MACE in patients with acute coronary syndrome after PCI.