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”.

AIM To study the effect of Zuogui Pills on improving ovarian function in rats with premature ovarian failure(POF)by regulating autophagy.METHODS Seven rats were randomly selected as the blank group,and the remaining rats were injected with cisplatin(4.0 mg/kg)intraperitoneally to establish POF model.The success of the model was evaluated by observing the changes of estrous cycle.Twenty-one successful model of rats were randomly divided into model group and estradiol group(0.01 mg/mL)and Zuogui Pills group(1.85 g/kg),with 7 rats in each group,the drug was administered continuously for 21 days.Serum E2,FSH and LH levels were detected by ELISA;HE staining was used to observe the pathological morphology of ovarian tissue;immunohistochemical(IHC)method was used to detect the protein expressions of LC3B,SIRT1 and FoxO1 in ovarian tissues;RT-qPCR method was used to detect the mRNA expressions of LC3B,Beclin-1 and Atg5 in ovarian tissues;the protein expressions of SIRT1,FoxO1 and Ac-FoxO1 in ovarian tissue was detected by Western blot.RESULTS Compared with the blank group,the ovarian index of the model group decreased(P＜0.01);serum FSH and LH levels increased(P＜0.01)and E2 level decreased(P＜0.01);the structure of ovary is disordered,especially atresia follicle;the mRNA expressions of LC3B,Beclin-1 and Atg5 in ovarian tissue increased(P＜0.01),while the protein expressions of LC3B and Ac-FoxO1 increased(P＜0.01),while the protein expressions of SIRT1 and FoxO1 decreased(P＜0.01).Compared with the model group,the ovarian index of rats in estradiol group and Zuogui Pills group increased(P＜0.01);serum FSH and LH levels decreased(P＜0.01)and E2 level increased(P＜0.01);the number of primordial follicles in ovary increased and the number of atresia follicles decreased;the mRNA expressions of LC3B,Beclin-1 and Atg5 in ovarian tissue decreased(P＜0.01),while the protein expressions of LC3B and Ac-FoxO1 decreased(P＜0.01),while the protein expressions of SIRT1 and FoxO1 increased(P＜0.01).CONCLUSION Zuogui Pills may inhibit autophagy by activating SIRT1/FoxO1 signaling pathway,thus improving the pathological state of POF rats,regulating the level of sex hormones in rats,restoring endocrine balance,enhancing ovarian reserve function,promoting the normal development of follicles and delaying the progress of POF.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Objective:To explore the genetic etiology for a child presenting with motor retardation, language delay, intellectual disability, and dysmorphic features.Methods:A child presented at Linyi People′s Hospital in June 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were obtained from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variant was validated by Sanger sequencing. Amniotic fluid samples were obtained from the mother′s subsequent pregnancies for prenatal diagnosis. This study has been reviewed and approved by the Medical Ethics Committee of Linyi People′s Hospital (Ethics No.: 202402-H-034).Results:The proband was a 2-year-old girl showing developmental delays in motor, language, and intellectual domains, strabismus, hypertelorism, hearing impairment, obesity, and brachymesophalangy of the fifth finger. Magnetic resonance imaging revealed abnormalities of the white matter. Chromosomal microarray analysis (CMA) identified a 15q26.3 duplication (chr15: 101562020_102060896×3) inherited from her mother. WES has uncovered a heterozygous c. 1931A>G (p.Tyr644Cys) variant in the FBXO11 gene. Sanger sequencing confirmed the variant to be de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic. Prenatal diagnosis revealed that the fetuses from the mother′s second and third pregnancies did not harbor the same variant. Conclusion:The c. 1931A>G (p.Tyr644Cys) variant of the FBXO11 gene probably underlay the abnormal phenotype in the child. Based on its genotype and phenotype, the proband was diagnosed with Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities.

Objective To analyze the changes in optical coherence tomography angiography (OCTA) parameters in patients with essential hypertension，and to explore the effect of blood pressure on OCTA parameters. Methods A total of 164 patients with essential hypertension were selected and divided into controlled blood pressure group (n=92) and uncontrolled blood pressure group (n=72). OCTA examination was performed on the optic disc and macula of all patients, and the right eyes were selected for analysis. Results There were no significant differences in retinal nerve fiber layer (RNFL) thickness, radial peripapillary capillary (RPC) total vascular density, RPC total small vessel density, perifovea superficial capillary plexus (SCP) vascular density, and perifovea deep capillary plexus (DCP) vascular density between the two groups of patients. There were no significant differences in foveal avascular zone (FAZ) area, FAZ diameter, and fovea retinal thickness between the two groups of patients. The density of the parafovea SCP, parafovea DCP, and fractal dimension (FD) in the uncontrolled blood pressure group were significantly lower than those in the controlled blood pressure group (P＜0.05). Multiple linear regression analysis showed that elevation of blood pressure was a independently related factor of reduced parafovea DCP density (P＝0.026), while there was no correlation between the uncontrolled blood pressure and parafovea SCP density and FD level. Conclusions The blood pressure level is correlated with the parafovea DCP density, while has no correlation with other OCTA parameters in hypertension patients.

Purpose Chemical exchange saturation transfer(CEST)imaging is used to study the changes of glutamate metabolism in the hippocampus of rats with chronic unpredictable mild stress(CUMS)model,so as to evaluate the clinical reference value of glutamate acid CEST(GluCEST)imaging results.Materials and Methods Twenty-two male SD rats were enrolled,and were divided into CUMS and healthy groups.Rats in CUMS group were further divided into the non-treatment group(n=7)and the ketamine treatment group(n=8).Seven healthy rats were randomly selected as control group.CEST imaging scans were performed using 7T small animal magnetic resonance and glutamate concentrations were measured in both hippocampi.The difference of hippocampal GluCEST value and glutamate concentration between control group and CUMS non-treatment group,CUMS ketamine treatment group and CUMS non-treatment group was analyzed,respectively.Results Compared with the control group,the hippocampal GluCEST value in CUMS non-treatment group was increased(left:t=2.8,P=0.015;right:t=3.0,P=0.011),while the hippocampal GluCEST value of rats in CUMS ketamine treatment group was decreased compared with CUMS non-treatment group(left:t=2.3,P=0.037;right:t=2.5,P=0.028).Conclusion GluCEST imaging can provide high spatial resolution images and accurately evaluate the changes of glutamate metabolism in hippocampus of rats with depression,which is conducive to monitoring the abnormal signals of hippocampal neurons caused by depression.

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Gentianopsis barbata (G. barbata) represents a significant plant species with considerable ornamental and medicinal value in China. This investigation sought to elucidate the primary constituents within the plant and investigate their pharmacological properties. Fifty triterpenoids (1-50), including nine previously undescribed compounds (1, 2, 7, 10, 20, 28, 29, 37, and 41) were isolated and characterized from the whole plants of G. barbata. Notably, compounds 1 and 2 exhibited the novel 3,4;9,10-diseco-24-homo-cycloartane triterpenoid skeleton. The isolated triterpenoids demonstrated substantial anti-inflammatory activity through inhibition of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) cytokine secretion in LPS-induced RAW264.7 macrophages, and hepatoprotective effects by preventing tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in HepG2 cells. These results demonstrate both the presence of diverse triterpenoids in G. barbata and their therapeutic potential for inflammatory and hepatic conditions, providing scientific evidence supporting the clinical application of this traditional Mongolian medicinal plant.
Triterpenes/isolation & purification* ; Mice ; Anti-Inflammatory Agents/isolation & purification* ; Animals ; Humans ; RAW 264.7 Cells ; Hep G2 Cells ; Interleukin-6/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Medicine, Mongolian Traditional ; Macrophages/immunology* ; Protective Agents/isolation & purification* ; Liver/drug effects* ; Gentianaceae/chemistry* ; Plant Extracts/chemistry* ; Molecular Structure