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 investigate the improvement effects of Poria cocos polysaccharides(PCPs)on mouse nonalcoholic fatty liver disease(NAFLD).METHODS Forty-eight C57BL/6 mice were randomly divided into the blank group,the model group,the simvastatin group(4 mg/kg)and the high,medium and low dose PCPs groups(200,100 and 50 mg/kg),with 8 mice in each group.The NAFLD model was reproduced by 16 weeks feeding of high-fat and high-cholesterol diet,followed by 8 weeks administration of corresponding drug by gavage.The mice had their body mass and liver coefficient assessed;their levels of hepatic free fatty acid(FFA),and serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),γ-glutamyltransferase(γ-GT)and malondialdehyde(MDA)detected;their hepatic pathological changes and lipid deposition observed using HE staining,NAFLD activity score(NAS)and oil red O staining;and their hepatic protein expressions of Akt,mTOR,p-Akt,p-mTOR and SREBP-1c detected by Western blot.RESULTS Compared with the blank group,the model group demonstrated all increased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α.levels(P＜0.05,P＜0.01);decreased HDL-C level and activities of SOD and GSH-Px(P＜0.05,P＜0.01);more obvious hepatic pathological damage as revealed by increased NAS score(P＜0.01)and increased lipid deposition area(P＜0.01).Compared with the model group,the groups intervened with high or medium dose PCPs,or simvastatin displayed decreased body weight,liver coefficient,hepatic FFA level,and serum TC,TG,LDL-C,AST,ALT,γ-GT,MDA,IL-1β and TNF-α levels(P＜0.05,P＜0.01);increased HDL-C level and SOD,GSH-Px activities(P＜0.05,P＜0.01);decreased hepatic pathological damage as revealed by the decreased NAS score and lipid deposition area(P＜0.05,P＜0.01);and decreased hepatic protein expressions of p-Akt,p-mTOR and SREBP-1c protein(P＜0.05)as well.CONCLUSION PCPs can improve mouse NAFLD,and its mechanism may lie in their function in reversing abnormal lipid metabolism via Akt/mTOR/SREBP-1c signaling pathway.

Objective:To evaluate the feasibility of transjugular transcatheter tricuspid valve replacement (TTVR) using the LuX-Valve Plus system (Ningbo Jenscare Scientific, China) for the treatment of severe tricuspid regurgitation in real-world clinical settings.Methods:This prospective study enrolled 81 patients with severe ricuspid regurgitation (≥3+) who underwent TTVR with the LuX-Valve Plus system at the Department of Cardiology, West China Hospital of Sichuan University between May 2022 and March 2024. Among them, 44 patients were from a compassionate-use study, and 37 were from two premarket clinical trials. Baseline clinical data, preprocedural imaging, procedural outcomes, and postprocedural follow-up data were collected. The primary endpoint events included device success, procedural success, and 30 d composite adverse events.Results:The age of the cohort was (74.5±7.8) years, with 54 females (67%). Device success and procedural success rates were both 90% (73/81). Post-procedural tricuspid regurgitation improved, with a 6% (5/81) incidence of moderate-to-severe paravalvular leakage. The rate of permanent pacemaker implantation was 12% (10/81), of which 5% (4/81) had pre-existing indications for pacemaker implantation. Major bleeding events occurred in 10% (8/81) of patients, and the 30 d composite endpoint rate was 25% (20/81).Conclusion:TTVR using the LuX-Valve Plus system demonstrates promising feasibility for high-risk surgical patients with severe tricuspid regurgitation, effectively reducing or eliminating regurgitation with acceptable safety. However, challenges remain in reducing risks of major adverse events, including permanent pacemaker implantation and severe bleeding.

Objective:To explore the trend of mortality rates for female breast cancer in China and quantify the impact of demographic and non-demographic factors on the burden of breast cancer mortality.Methods:Mortality data for female breast cancer from 2013 to 2021 were extracted from the Chinese Cause of Death Monitoring Dataset, and the 2000 Chinese population census data were used to standardize the mortality rates. The Joinpoint software was employed to analyze the mortality trends by calculating the Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC). The population decomposition method was utilized to quantify the impact of changes in population age structure, population size, and non-demographic factors on the burden of breast cancer mortality.Results:From 2013 to 2021, the crude mortality rate for female breast cancer in China showed an increasing trend, with an AAPC of 2.3% (95% CI: 1.7%-2.9%). The standardized mortality rate remained relatively stable, with an AAPC of -0.2% (95% CI: -1.6%-1.3%). However, Joinpoint trend analysis indicated that the standardized mortality rate had a turning point in 2017, with a rapid increase before this year (APC: 3.9%, 95% CI: 1.1%-6.9%), and a rapid decline after this year (APC: -4.1%, 95% CI: -6.8% to -1.4%). The growth speed of crude mortality rates in rural areas was higher than that in urban areas, with AAPCs of 3.0% (95% CI: 2.4%-3.5%) and 1.3% (95% CI: 0.4%-2.2%), respectively. The standardized mortality rate in rural areas remained relatively stable, with an AAPC of 0.6% (95% CI: -1.0%-2.2%), while in urban areas, it showed a decreasing trend, with an AAPC of -1.1% (95% CI: -2.2%-0.0%). In the eastern, central, and western regions, the crude mortality rates all showed an increasing trend, with AAPCs of 1.7% (95% CI: 0.7%-2.8%), 3.8% (95% CI: 2.5%-5.2%), and 2.2% (95% CI: 0.5%-4.0%), respectively, while the standardized mortality rates remained relatively stable, with AAPCs of -0.3% (95% CI: -1.7%-1.2%), 0.6% (95% CI: -1.2%-2.4%), and 0.0% (95% CI: -2.2%-2.2%), respectively. Compared with 2013, the number of deaths in 2021 increased by 42.8%, of which changes in population age structure accounted for 21.3%, the age structure changes of urban and rural residents contributed 22.8% and 19.2%, respectively, to the whole changes caused by population age structure, while those in the eastern, central, and western regions contributed 20.6%, 24.3%, and 15.9%, respectively.Demographically, the changes in population size accounted for 18.3%, and non-demographic factors only accounted for 3.2%. Conclusions:From 2013 to 2021, the crude mortality rate for female breast cancer in China continued to rise, a trend mainly influenced by population age structure, with the fastest growth rates in crude mortality rates observed in rural areas and the central region. After adjusted for age structure, the standardized mortality rate for female breast cancer in China began to decline from 2017.

Medical ultrasound technology is widely used for diagnosis and therapy in clinical practice.Ultrasound probes,which are directly contact with patients,pose a potential risk of pathogen transmission.This expert consen-sus was developed by a multidisciplinary team based on international guidelines,standards in China,and the results of a national survey,aiming to reduce the risk of healthcare-associated infection through standardizing reprocessing of medical ultrasound probes,and formulating consensus recommendations with the Delphi method.The consensus clarifies the reprocessing principles for three types of ultrasound probes of different infection risks:external-use ul-trasound probes,interventional percutaneous ultrasound probes,and internal-use ultrasound probes,puts forward systematic suggestions on the reprocessing standards and disinfection levels of ultrasound probe isolation covers and coupling agents,the reprocessing procedures and methods of ultrasound probes,as well as architectural layout and management of reprocessing,so as to provide a scientific prevention and control framework for ensuring ultrasound diagnosis and therapy safety.

Cosmetics may be an important source of human exposure to per-and polyfluoroalkyl substances(PFASs),posing risks to human health.In this study,a nontarget screening method for PFASs in cosmetics was developed using ultra-high performance liquid chromatography-high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS)based on the Kendrick mass defect(KMD).The sample was extracted by ultrasonic assisted extraction prior to being analyzed by UHPLC-Q-Orbitrap HRMS.Acquisition of HRMS data was achieved in both full scan and data-dependent(Full MS/dd MS2)mode.The data collected by HRMS were imported into an in-lab built R script for processing.Samples retained the mass spectra peaks with KMD values in the range of 0.85-1 or 0-0.15 for in-and out-of-library matching;when KMD deviation(δKMD)<0.001 and CF 2 mass error(δMS)<15 ppm,it was considered as a potential PFASs homologues.According to matches of parent ions(MS),fragment ions(MS2)and retention time(RT)with the in-house built PFASs database,the screened and identified potential PFASs were categorized to 5 confidence levels(CL1-CL5).A total of 15 kinds of PFASs homologues with confidence level of CL3 and above were screened from 13 cosmetics products and 8 cosmetic raw materials,including perfluoroalkyl alcohol,hydroperfluoroalkyl sulfonic acid,chloroperfluoroalkyl sulfonic acid,etc.with concentrations ranging from 1.9 ng/g to 98.1 ng/g.The nontarget screening method could be used to screen and identify PFASs homologues feasibly and therefore provided data basis for management and control of PFASs addition in cosmetics.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an ¹⁸F-labeled PET tracer (QTFT) that targets the P2Y₁₂, a receptor highly expressed on anti-inflammatory microglia. [¹⁸F]QTFT exhibited high binding affinity to the P2Y₁₂ (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [¹⁸F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y₁₂ antagonist. Furthermore, [¹⁸F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y₁₂ in anti-inflammatory microglia. In a pilot clinical study, [¹⁸F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [¹⁸F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y₁₂ overexpressed in anti-inflammatory microglia.