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 analyze the characteristics of pediatric medicines with priority review and approval for marketing in China,providing a reference for promoting enterprise R&D and production,as well as improving the supply guarantee mechanism for pediatric medicines.METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval,Pharnexcloud biomedical database,and National Medical Insurance Drug Directory,this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing.RESULTS As of June 30,2024,a total of 68 pediatric medicines had been approved through the priority review and approval process,covering 12 therapeutic areas,with oral dosage forms accounting for 64.71％.The median time from application to inclusion in priority review was 35.50 days,with an average of 41.69 days.The median time from inclusion in priority review to market approval was 1.24 years,with an average of 1.42 years.This included 12 domestic new medicines,21 domestic generic medicines,35 imported medicines,as well as 29 pediatric-specific medicines and 21 orphan medicines.Additionally,31 of these medicines had been included in the medical insurance catalog,representing a proportion of 45.59％.CONCLUSIONS Currently,a trend of differentiated competition is emerging between domestic and imported pediatric medicines.The therapeutic areas for pediatric medicines are continuously expanding,and the dosage forms are becoming more tailored to children's needs.However,there are still issues such as slow progress in new medicine development,insufficient stability in the medicine review and approval process,and a need to increase the proportion of medicines included in medical insurance.

Aim To investigate the effect of chrysoeriol on pulmonary vascular remodeling in pulmonary hyper-tension by animal experiments combined with cell ex-periments,and to explore its potential therapeutic tar-gets by network pharmacology.Methods The target of chrysoeriol was collected in Targetnet,SEA and SwissTargetPrediction database.Pulmonary arterial hy-pertension(PAH)targets were collected in the Dis-GeNET and GeneCards databases,and PPI network map was drawn in the STRING database,and key tar-gets were screened.The GO and KEGG pathway en-richment analysis was carried out through DAVID data-base and Weishengxing platform.AutoDock software was used for molecular docking of key core targets.The PAH model of rats was constructed,and the pulmo-nary hemodynamics and vascular remodeling were de-tected by echocardiography,HE and Masson staining.Primary pulmonary smooth muscle cells were extracted,and the effects of drugs on pathway proteins were de-tected in vitro.Results The results of network phar-macology showed that chrysoeriol exerted therapeutic effects on pulmonary hypertension by affecting key tar-gets such as AKT1,SRC,EGFR,MMP9 and gsk3 β,and signaling pathways such as EGFR and PI3K-AKT.Molecular docking showed that chrysoeriol had good binding ability with 5 key target genes.Animal experi-ments showed that the pulmonary hemodynamic func-tion of PAH rats was significantly improved after ad-ministration of chrysoeriol.The remodeling of small pulmonary arteries was significantly reduced.Cell ex-periments showed that chrysoeriol could inhibit the ex-pression of proliferation,migration and phenotypic transformation genes.Conclusion Chrysoeriol may play a role in the treatment of pulmonary hypertension through multiple targets.

Objective:To analyze the epidemiological characteristics of cases involving monkey injuries at medical institutions surrounding Qianlingshan Park in Guiyang City, and to provide a reference basis for preventive measures to reduce monkey injuries and standardized post-exposure treatment.Methods:A retrospective cross-sectional study was conducted, collecting 1 900 cases of monkey-induced injuries in Qianlingshan Park treated at the outpatient clinic of Guizhou Provincial Center for Disease Control and Prevention and the Department of Surgery at Qianling Hospital, Guiyang City, from 2021 to 2024. Statistical analysis was performed using Pearson′s chi-square test.Results:Total of 1 900 cases of monkey-related injuries in Qianlingshan Park were collected from 2021 to 2024. The exposure time distribution exhibited significant seasonality, with 48.58% of cases occurring during July and August, totaling 923 cases, indicating a peak in the summer. There were 774 male patients and 1 126 female patients, with a ratio of 1∶1.45.and significant differences were observed between different age groups and genders (χ2=195.00, P<0.001), with the highest number of cases occurring in the 0-9 and 20-29 age groups, accounting for 22.05%(419 cases) and 21.79%(414 cases), respectively. The upper limbs were the most common injury site, accounting for 50.84% of the total cases(966 cases in total), with significant differences between gender and injury location (χ2=22.00, P<0.001), Among females, the proportion of injuries to the upper and lower limbs (30.11% and 16.47%, respectively) was higher than that among males (20.74% and 8.63%, respectively). The majority of injuries were classified as Grade Ⅲ, making up 57.38% of cases(1 069 cases in total). Self-treatment after exposure was the most common approach(60.44%), with significant differences observed between wound severity and treatment method (χ2=6.90, P=0.032), Patients with Grade Ⅱ and Grade Ⅲ wounds were more likely to choose self-management (26.84% and 33.23%, respectively) than outpatient management (15.14% and 24.15%). Approximately 98.05% (1 863 cases) of monkey-injured patients had received rabies vaccinations. Conclusions:This study analyzes monkey-related injuries in Qianlingshan Park from 2021 to 2024, clarifying the temporal distribution of injuries, demographic characteristics, injury sites, and treatment methods. The findings provide references for optimizing human-monkey conflict management and the prevention and control of zoonotic diseases in urban ecological parks.

AIM:To investigate the effects of urolithin A on motor function and muscle fibrosis in dystrophin-deficient mdx mice,a model of Duchenne muscular dystrophy.METHODS:Twelve 26-week-old SPF male dystrophin gene deficient C57BL/10ScSnJNju-Dmdem3Cd4/Gpt(mdx)mice were randomly divided into model group and urolithin A treatment group,with 6 mice in each group.Additionally,six wild-type SPF male mice were selected as the normal con-trol.The motor ability of the mice was evaluated by pole climbing test,inverted suspension test,grip strength test and en-durance test.The body mass,mitochondrial relative copy number,ATP level and malondialdehyde(MDA)level were compared among the mice in different groups.Hematoxylin-eosin staining,Masson staining and immunohistochemistry were performed to analyze the atrophy and pathological changes of the gastrocnemius muscle.RESULTS:Compared with normal control group,the mdx mice in model group exhibited significantly impaired motor function,as evidenced by pro-longed pole-climbing time(P<0.01),reduced suspension time and forelimb/hindlimb grip strength(P<0.01),and in-creased number of electrical stimuli required to induce movement(P<0.01).Additionally,mitochondrial relative copy number and ATP level were significantly decreased(P<0.01),while MDA level was significantly elevated(P<0.01).Histological analysis revealed marked inflammatory cell infiltration and extensive tissue fibrosis in the gastrocnemius mus-cle.In contrast,urolithin A treatment significantly improved motor performance(P<0.01),attenuated inflammatory cell infiltration and muscle fibrosis,increased mitochondrial copy number,restored ATP level(P<0.05),and reduced MDA level(P<0.01).CONCLUSION:Urolithin A ameliorates motor dysfunction and alleviates muscle fibrosis in mdx mice,suggesting its potential therapeutic benefits for Duchenne muscular dystrophy.

BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

Objective:To investigate the mediating role of psychological capital between the perception of decent work and work engagement among Operating Room nurses, and to provide insights for improving their work engagement.Methods:From December 2023 to February 2024, a total of 307 Operating Room nurses from four class ⅢGrade A hospitals in Beijing, Chongqing, Dalian, and Zhuhai were recruited using convenience sampling. Data were collected using a general information questionnaire, Work Engagement Scale, Decent Work Scale, and Nurses' Psychological Capital Scale. Pearson correlation analysis was conducted to examine the relationships among psychological capital, perception of decent work, and work engagement. Structural equation modeling and mediation analysis were performed using AMOS 24.0 software.Results:A total of 307 questionnaires were distributed, and 301 valid responses were collected, with an effective response rate of 98.05%. The mean scores for work engagement, perception of decent work, and psychological capital were (41.01±10.76), (67.30±17.86), and (93.30±15.15), respectively. Work engagement was positively correlated with both the perception of decent work and psychological capital (all P<0.01), and the perception of decent work was positively correlated with psychological capital ( P<0.01). Psychological capital partially mediated the relationship between the perception of decent work and work engagement, with the mediating effect accounting for 62.63%. Conclusions:Psychological capital plays a partial mediating role between the perception of decent work and work engagement among Operating Room nurses. Nursing managers can enhance nurses' work engagement by improving their perception of decent work and strengthening their psychological capital.

Chinese-foreign joint education program of clinical medicine is an important means to achieve the globalization of medical education. Chongqing Medical University and University of Leicester in the UK have jointly established a Chinese-foreign joint education program of clinical medicine to achieve the integration of Chinese and British cultivation concepts, management systems, teaching resources, teacher teams, evaluation systems, and multiculturalism. They have also constructed an internal teaching quality assurance system with the main contents of the improvement of management mechanisms, the formulation of training programs, the construction of teaching staff, the design of syllabuses, the curriculum assessment system, and teaching quality evaluation, as well as an external teaching quality assurance system with the core components of clinical medicine accreditation, Chinese-foreign joint education program evaluations, international quality audits, and professional quality monitoring. Both systems can help to comprehensively improve teaching quality.

Objective:To establish a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for accurate determination of plasma Lyso-GL-3 concentration.Method:Solid phase extraction technology was used to process plasma samples, and under positive ion mode and multiple reaction monitoring (MRM) conditions, LC-MS/MS was used to determine the concentration of Lyso-GL-3. The linear range, detection and quantification limits, accuracy, precision, matrix effect, carrier effect of the method, and plasma sample stability were validated. And the accuracy of Lyso-GL-3 positive patients was compared by combining enzymatic and genetic testing results.Result:Lyso-GL-3 had good linearity in the range of 1.25-400 nmol/L. The detection limit and quantification limit were 0.15 nmol/L and 0.50 nmol/L, respectively. The spiked recovery rate was 88.78%-108.96%. The coefficient of variation ( CV) for intra batch precision, inter batch precision, and matrix effect were all less than 15%, the result of carrier effect was 0.55%. Plasma samples could be stably stored for 30 days under refrigeration conditions. The clinical conformity of the patient was 100%. Conclusion:The established LC-MS/MS detection method for plasma Lyso-GL-3 concentration takes 2.5 minutes, which is simple, fast, accurate, and reliable.