The pathogenesis of neurodegenerative diseases (NDDs) is fundamentally linked to complex and profound alterations in metabolic networks within the brain, which exhibit marked spatial heterogeneity. While conventional bulk metabolomics is powerful for detecting global metabolic shifts, it inherently lacks spatial resolution. This methodological limitation hampers the ability to interrogate critical metabolic dysregulation within discrete anatomical brain regions and specific cellular microenvironments, thereby constraining a deeper understanding of the core pathological mechanisms that initiate and drive NDDs. To address this critical gap, spatial metabolomics, with mass spectrometry imaging (MSI) at its core, has emerged as a transformative approach. It uniquely overcomes the limitations of bulk methods by enabling high-resolution, simultaneous detection and precise localization of hundreds to thousands of endogenous molecules—including primary metabolites, complex lipids, neurotransmitters, neuropeptides, and essential metal ions—directly in situ from tissue sections. This powerful capability offers an unprecedented spatial perspective for investigating the intricate and heterogeneous chemical landscape of NDD pathology, opening new avenues for discovery. Accordingly, this review provides a comprehensive overview of the field, beginning with a discussion of the technical features, optimal application scenarios, and current limitations of major MSI platforms. These include the widely adopted matrix-assisted laser desorption/ionization (MALDI)-MSI, the ultra-high-resolution technique of secondary ion mass spectrometry (SIMS)-MSI, and the ambient ionization method of desorption electrospray ionization (DESI)-MSI, along with other emerging technologies. We then highlight the pivotal applications of spatial metabolomics in NDD research, particularly its role in elucidating the profound chemical heterogeneity within distinct pathological microenvironments. These applications include mapping unique molecular signatures around amyloid β‑protein (Aβ) plaques, uncovering the metabolic consequences of neurofibrillary tangles composed of hyperphosphorylated tau protein, and characterizing the lipid and metabolite composition of Lewy bodies. Moreover, we examine how spatial metabolomics contributes to constructing detailed metabolic vulnerability maps across the brain, shedding light on the biochemical factors that render certain neuronal populations and anatomical regions selectively susceptible to degeneration while others remain resilient. Looking beyond current applications, we explore the immense potential of integrating spatial metabolomics with other advanced research methodologies. This includes its combination with three-dimensional brain organoid models to recapitulate disease-relevant metabolic processes, its linkage with multi-organ axis studies to investigate how systemic metabolic health influences neurodegeneration, and its convergence with single-cell and subcellular analyses to achieve unprecedented molecular resolution. In conclusion, this review not only summarizes the current state and critical role of spatial metabolomics in NDD research but also offers a forward-looking perspective on its transformative potential. We envision its continued impact in advancing our fundamental understanding of NDDs and accelerating translation into clinical practice—from the discovery of novel biomarkers for early diagnosis to the development of high-throughput drug screening platforms and the realization of precision medicine for individuals affected by these devastating disorders.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Objective:To explore therapeutic effect of sacubitril valsartan sodium combined with Wenxin granule in the treatment of hypertension complicated with paroxysmal atrial fibrillation(AF)and its effect on cardiac electro-physiological structure.Methods:A total of 116 patients with hypertension and paroxysmal atrial fibrillation treated in our hospital from Oct 2021 to Nov 2022 were consecutively selected.According to random number table,they were divided into Wenxin granule group(received Wenxin granule treatment based on routine antihypertensive ther-apy)and combined treatment group(received sacubitril valsartan sodium combined Wenxin granule therapy based on routine antihypertensive therapy)with 58 cases in each group,and both groups were consecutively treated for six months.Clinical symptom score,AF burden,P wave duration,P wave dispersion,left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd)and left ventricular ejection fraction(LVEF)were compared between two groups before and after treatment.Results:After treatment,compared with Wenxin granule group,there were significant reductions in clinical symptom score[(1.66±0.69)scores vs.(1.40±0.53)scores],AF burden[4.43(1.65)％vs.1.62(3.50)％],P wave duration[(112.17±6.46)ms vs.(109.29±8.59)ms],P wave dispersion[(32.47±8.11)ms vs.(29.02±7.49)ms]and LAD[(34.83±3.41)mm vs.(33.40±3.74)mm]in combined treatment group(P＜0.05 or＜0.01).There were no significant difference in LVEDd and LVEF between two groups,P＞0.05 both.Conclusion:Sacubitril valsartan sodium combined with Wenxin granule can significantly im-prove clinical symptoms and atrial fibrillation burden,reduce the susceptibility to atrial fibrillation,and inhibit atrial electrical remodeling and structural remodeling in patients with hypertension complicated with paroxysmal atrial fi-brillation.

Chronic exertional compartment syndrome (CECS) of the lower extremities is a common clinical condition characterized by exercise-induced pain in the extremities, which is predominantly observed in people who take an active part in sports, such as athletes. It is mainly presented as post-exercise pain in the lower extremities, probably accompanied by numbness and limb weakness, etc., affecting the patients′ life and work. The symptoms of CECS in the lower limbs are usually present after physical activities of a certain intensity, making them difficult to be identified through routine outpatient physical examination, and likely to be misdiagnosed and underdiagnosed. Furthermore, the absence of universally accepted and unified treatment standards for CECS of the lower extremities complicates the decision-making process regarding the necessity of surgical intervention and choice of surgical approach in the clinical practice. For this purpose, recent developments in the diagnosis and treatment of CECS of the lower extremities were reviewed to provide reference for its standardized diagnosis and treatment.

Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Objective To evaluate the effect of endoscopic laryngeal mask on perioperative airway management and postoperative recovery in patients undergoing gastric endoscopic submucosal dissection(ESD).Methods Ninety patients,aged 18-64 years,BMI 18-25 kg/m2,ASA physical statusⅠorⅡ,who underwent elective gastric ESD were randomly divided into two groups:the endoscopic laryngeal mask group(group E)and the endotracheal tube group(group C),45 patients in each group.After induction of general anesthesia,group E received endoscopic laryngeal mask airway ventilation,and the endoscope was inserted through the endoscopic channel of the laryngeal mask,group C received tracheal intubation,and the endoscopy was inserted through the mouth.The successful time and one-time success rate of intubation,and the insertion time and withdrawal rate of endoscopy were recorded.The operative time,extubation time and PACU residence time were recorded.HR,MAP were recorded when the patient entered the room(T0),at the time of intubating(T1),inserting gastroscopy(T2),exiting gastroscopy(T3),extubation(T4),and leaving PACU(T5).The average airway pressure and peak airway pressure at T1-T3 were recorded.The airway sealing pressure and endoscopic view grading system(EVGS)grading of group E were recorded before and after changing the position,and at the end of surgery.The adverse reactions and the satisfaction of anesthesiologists and gastroenterologists were recorded.Results Compared with T0,HR and MAP were significantly increased at T1 and T4 between the two groups(P＜0.05).Compared with group C,the suc-cessful time of intubation,the extubation time,and PACU residence time were significantly shortened,HR and MAP were significantly decreased at T1 and T4,the incidence of choking cough during extubation,post-operative pharyngeal pain,and hoarseness were significantly decreased(P＜0.05).There were no signifi-cant differences in the one-time success rate of intubation,the insertion time and withdrawal rate of endosco-py between the two groups.Endoscopic laryngeal mask showed good sealing and alignment in group E.Conclusion Endoscopic laryngeal mask could shorten the success time of establishment of artificial airway in patients with gastric ESD,without interfering with digestive endoscopy operations,shorten extubation time and PACU retention time,maintain intraoperative hemodynamic stability,and reduce adverse reactions.

Objective:To understand the current status of pubertal sexual characteristics development of girls aged 6-18 years in Tongzhou District of Beijing and to compare the differences in sexual characteristics development among girls characterized as thin, normal, overweight, and obese.Methods:A cross-sectional survey was conducted among 2 844 girls aged 6-18 years in Tongzhou District of Beijing from September 2022 to July 2023. The developmental stages of breast and pubic hair were assessed on site, and menarche status was inquired. Weight and height were measured. The girls were subsequently characterized into thin, normal, overweight and obese groups. Basic information (including family and personal history) was obtained through questionnaires. Probit probability unit regression was applied to calculate the age of each Tanner stage of sexual characteristics development and the age of menarche. The χ 2 test was applied to compare the counting data between two or multiple groups. Results:A total of 2 844 girls were surveyed and 2 704 girls met the inclusion criteria, resulting in a valid response rate of 95.1%. Among these girls, 1 105 (40.9%) were aged 6-9 years, 1 053 (38.9%) were aged 10-13 years, and 546 (20.2%) were aged 14-18 years. The of height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and body mass index-for-age Z-score (BAZ) were 0.46(-0.23,1.16), 0.69(-0.16,1.67), and 0.67(-0.27,1.73) respectively. The prevalences of thin, overweight, and obesity were respectively 1.7% (45/2 704), 17.3% (467/2 704), and 19.9% (538/2 704), respectively. There were 45 girls in the thin group, 1 654 girls in the normal weight group, 1 005 girls in the overweight and obesity group. The age of Tanner stage breast 2 (B2), Tanner stage pubic hair 2 (P2), and menarche was 9.0 (95% CI 8.9-9.1), 10.5 (95% CI 10.4-10.6), and 11.4 (95% CI 11.3-1.5) years, respectively. The current status of breast and pubic hair maturity in girls with pubertal development shows that 64.6% (1 211/1 874) of these girls had breast development preceding pubic hair development, 32.4% (607/1 874) had concurrent breast and pubic hair development, and 3.0% (56/1 874) had pubic hairs development preceding breast development. The interval age between B2 and B5 was 4.7 (95% CI 4.6-4.8) years, between P2 and P5 was 4.5 (95% CI 4.4-4.6) years, and between B2 and menarche was 2.4 (95% CI 2.3-2.5) years. The ages of sexual characteristics development in overweight and obese groups were earlier than that in normal and thin groups. The ages of B2 in thin, normal, overweight, and obese groups were 10.0 (95% CI 9.5-10.6), 9.3 (95% CI 9.2-9.4), and 8.6 (95% CI 8.4-8.7) years, respectively. The age of menarche in thin, normal, overweight, and obese groups were 13.1 (95% CI 12.4-13.7), 11.6 (95% CI 11.4-11.7), and 11.1 (95% CI 11.0-11.2) years, respectively. The interval ages between B2 and B5 and between P2 and P5 was 4.5 and 4.1 years, respectively in the overweight and obese groups, and those in normal group and thin group was 4.7 and 4.5 years, 4.6 and 4.7 years, respectively. Conclusions:The ages of sexual characteristics development and menarche tend in Tongzhou District of Beijing to be earlier than that being reported of Beijing's survey 20 years ago. Girls characterized as overweight and obese not only start puberty at an earlier age than girls of normal weight, but also have a shorter developmental process.

Objective To evaluate the feasibility,reliability and validity of the symptom identification scale for kidney yang deficiency syndrome.Methods The symptom identification scale for kidney yang deficiency syndrome developed in previous research was administered to 200 vascular cognitive impairment patients from September 2020 to September 2022 to assess feasibility through recall rate,completion rate,and completion time;reliability was measured using retest reliability,split-half reliability,homogeneity reliability,and inter-rater reliability;and validity was evaluated based on discriminant and structural validity.Results A total of 200 scales were sent out,and all of them cooperated and were completed and retrieved within 20 min.The results of reliability analysis showed that the retest reliability of the scale was 0.828 for the dimension of yang deficiency and 0.718 for the dimension of kidney qi deficiency;the Spearman-Brown coefficient of split-half reliability was 0.784;the Cronbach coefficient of the dimension of yang deficiency was 0.799,and the Cronbach coefficient of the dimension of kidney qi deficiency in the homogeneity reliability was 0.670.The results of the analysis showed that the differences between the kidney yang deficiency syndrome group and the non-kidney yang deficiency syndrome group in the yang deficiency dimension,kidney qi deficiency dimension scores and total scale scores in the discriminant validity were statistically significant(P<0.001);the KMO value in the structural validity was 0.842,and a total of two factors with eigenvalues greater than 1 were extracted,with a cumulative variance contribution rate of 58.227%.Conclusion The symptom identification scale for kidney yang deficiency syndrome demonstrates adequate reliability and validity,potentially enhancing the prediction of kidney yang deficiency in vascular cognitive impairment.However,the validity of the scale is somewhat limited and requires further refinement for clinical application.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.