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.

OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal ; Humans

Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

ObjectiveTo investigate the therapeutic effect of Siegesbeckiae Herba water decoction （SWD） at different doses on atherosclerosis （AS） in a mouse model induced by a high-fat diet and analyze its potential mechanism of action. MethodsThirty-six male ApoE^-/- mice were randomly divided into six groups： blank control group， model group， low-dose， medium-dose， and high-dose SWD groups， and positive control group. Firstly， the AS mouse model was created by feeding mice a high-fat diet. After successful modeling， the low-， medium-， and high-dose SWD groups were intragastrically administered with SWD at 0.65， 1.3， 2.6 g·kg^-1， respectively. The positive control group was intragastrically administered with 30 mg·kg^-1 of atorvastatin calcium aqueous solution， while the blank and model groups received an equal volume of 0.9% sodium chloride solution via oral gavage， all administered for 12 weeks. During the administration period， the general condition of the mice was observed and recorded daily. Before sampling， color Doppler ultrasound was performed to observe the pathological changes in atherosclerotic plaques in the aortic wall of mice. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in aortic tissue in mice， and oil red O staining was used to detect the atherosclerotic plaque area in the aorta. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum lipid indices and the levels of interleukins （IL-1β， IL-4， IL-6， and IL-10） and tumor necrosis factor-α （TNF-α） in mice. Protein expression levels of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue were detected by Western blot. ResultsCompared with the blank control group， the model group showed a significant increase in body weight. The results of color Doppler ultrasound showed enhanced vascular wall echo， suggesting the presence of atherosclerotic plaques. HE staining showed foam cell aggregation， fibrous connective tissue proliferation， and vascular intima injury in the aortic tissue. Oil red O staining showed a significant increase in the plaque area in the aortic tissue （P<0.01）. ELISA results indicated significantly elevated levels of IL-1β， IL-6， TNF-α， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein （LDL） in mouse serum （P<0.01）， as well as significantly decreased levels of IL-4， IL-10， and high-density lipoprotein （HDL） （P<0.01）. Western blot results showed that the expression of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue increased significantly （P<0.01）. Compared with those in the model group， mice in the middle- and high-dose SWD groups showed significant weight loss. In the high-dose group， the aortic vascular wall echoes were weakened， and the atherosclerotic plaques were reduced. The aortic lesions of mice in the medium- and high-dose SWD groups were significantly alleviated. The plaque area percentage showed an inverse correlation with the administered dose in all groups treated with SWD （P<0.05）. In the medium-dose SWD group， serum levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）， while those of IL-4 and IL-10 were significantly increased （P<0.01）. In the high-dose SWD group， levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.01）， while IL-4， IL-10， and HDL were significantly increased （P<0.01）. The IKKα and IKKβ expression was significantly decreased in the low-dose SWD group （P<0.05）， and IKKα， IKKβ， and NF-κB p65 were significantly decreased in the medium- and high-dose SWD groups （P<0.05， P<0.01）. ConclusionSWD may exert therapeutic effects on AS by regulating the expression of related inflammatory factors through the NF-κB signaling pathway， thereby reducing inflammation， plaque area， and lipid content in the body.

Iodine speciations in aquatic environments are affected by dissolved oxygen,redox potential,microbial activity,organic matter decomposition,light reaction,etc.Accurate quantification of iodine speciation can not only help to understand the geochemical cycle of iodine,but also help to trace and study environmental processes.Based on the combination of ion chromatography(IC)and inductively coupled plasma mass spectrometry(ICP-MS),a rapid and sensitive method was established for determining the speciations of iodine in environmental water samples including seawater,river water,lake water,rainwater,groundwater,etc.The results presented here showed that IO3?and I?in seawater were quickly separated and measured within 120 s when using guard column AG22 and 8 mmol/L(NH4)2CO3 as the mobile phase.While for lake water,river water and precipitation samples with high soluble organically bond iodine(SOI),an AS22 separation column(250 mm×4 mm)connected with a guard column and using 50 mmol/L(NH4)2CO3 as mobile phase could effectively separate unknown SOI from IO3? to achieve accurate quantification of IO3?.For accurate correction of iodine measurement signal fluctuations,133Cs was directly added to the(NH4)2CO3 mobile phase as an internal standard.The SOI content was calculated by the total iodine concentrations minus the sum of IO3?and I?.The precision of the established iodine speciation analytical method was better than 3.5%,and the standard addition experiment showed that the analytical method was accurate.When the injection volume was 25 μL,the detection limits were 0.011?0.025 μg/L for IO3? and 0.023?0.031 μg/L for I?,respectively.The method was successfully used to analyze IO3?,SOI and I? in environmental water samples,such as seawater,river water,rainwater and groundwater.

Objective This study aims to develop an early in-hospital temperature management protocol for heat stroke patients and assess its effectiveness,providing guidance for rapid cooling and precise target temperature control.Methods The protocol was developed through a Delphi expert consultation combined with expert panel meetings.A multi-center,non-randomized,historical control study was conducted,utilizing convenience sampling to select heat stroke patients from the emergency departments of 7 tertiary hospitals in Zhejiang Province,China,between June and August 2024 as an experimental group.The protocol was implemented in this group,while the control group consisted of heat stroke patients treated between June and August 2022,prior to protocol implementation.Cooling rates,target temperature attainment rates,and clinical outcomes were compared between the 2 groups.Results The final protocol included 6 primary indicators,23 secondary indicators,and 56 tertiary indicators.After protocol implementation,the experimental group achieved a cooling rate of 0.08(0.05～0.09)℃/min within 0.5 hours,significantly higher than the control group,which had a rate of 0.04(0.02～0.06)℃/min(P＜0.001).The target temperature attainment rates at 0.5 hours and 2.0 hours were 55.93％and 98.31％,respectively,significantly higher than the rates of 15.87％and 61.11％in the control group(P＜0.001).The mechanical ventilation rate,hospitalization rate,ICU admission rate,and mortality rate in the experimental group were 25.42％,61.02％,44.07％,and 8.47％,respectively.Logistic regression analysis revealed that the early in-hospital temperature management protocol significantly reduced the risk of mechanical ventilation and hospitalization in heat stroke patients,with odds ratios(ORs)of 0.294 and 0.300,respectively(both P＜0.05).Conclusion The developed protocol for early in-hospital temperature management in heat stroke patients is scientific,systematic,and practical.It improves cooling rates and target temperature attainment,thereby enhancing the prognosis of heat stroke patients.

Objective This study explores the clinical correlation between different low-density lipoprotein cholesterol(LDL-C)levels and prognosis,providing evidence-based guidance for the development of personalized lipid-lowering goals.Methods Patients who underwent elective percutaneous coronary intervention(PCI)treatment at Beijing Anzhen Hospital from January 2020 to June 2023 and received lipid-lowering therapy with the addition of Evolocumab were selected.Based on the results of blood lipid rechecks 3 to 6 months after surgery,the patients were divided into five groups:low-density lipoprotein＜0.5 mmol/L,0.5 to＜1.0 mmol/L,1.0 to＜1.4 mmol/L,1.4 to＜1.8 mmol/L,and above 1.8 mmol/L.All patients were followed up for more than one year,and clinical conditions and major adverse cardiovascular events(MACE)were recorded.Results A total of 1 106 patients undergoing PCI were enrolled;after propensity score matching and exclusion of patients lost to follow up,550 remained(110 per group).During 12 months of follow-up,58 patients(10.5％)experienced a MACE,with incidence rising step-wise across LDL-C categories.In multivariable Cox models adjusted for age,sex,diabetes,hypertension,baseline LDL-C,follow-up LDL-C,estimated glomerular filtration rate(eGFR),and left ventricular ejection fraction,the hazard ratios[HR(95％CI)]for MACE,relative to the＜0.5 mmol/L group,were 1.810(0.507-6.454,P=0.361),3.036(0.945-9.749,P=0.062),5.228(1.737-15.735,P=0.003),7.708(2.633-22.565,P＜0.001)for LDL-C levels of 0.5 to＜1.0,1.0 to＜1.4,1.4 to＜1.8 and≥ 1.8 mmol/L,respectively.A restricted cubic spline model demonstrated a significant non-linear positive association between LDL-C and MACE(P-overall≤0.001;P-non-linear=0.008).Stratified analyses by age,sex,hypertension and diabetes showed consistent HR with no significant interactions(all P＞0.05).There were no statistically significant differences among the groups in the incidence of bleeding events,elevated creatinine levels,or abnormal liver function(all P＞0.05).Conclusions In patients using PCSK9 after PCI,there is a significant positive correlation between LDL-C levels and the risk of MACE,and no correlation was observed between different LDL-C levels and the risk of adverse events such as bleeding.

Objective:To study the incidence and epidemiological characteristics of tsutsugamushi disease in Ankang City, Shaanxi Province.Methods:From 2018 to 2023, data on tsutsugamushi disease cases reported by various medical institutions at all levels in Ankang City were collected through the China Disease Prevention and Control Information System. At the same time, individual epidemiological investigation of reported cases was carried out, and electronic medical records of patients were retrieved to verify their diagnosis. In 2023, the rodents and chigger mites were monitored in 3 townships with high incidence of tsutsugamushi disease in Ankang City by night clamping method, and the chigger mites rate and chigger mites index were calculated. Blood, liver, spleen and kidney samples of rodents were collected, DNA of blood and organ mixture was extracted, and quantitative real-time PCR was used to detect Orientia tsutsugamushi. Results:A total of 330 cases of tsutsugamushi disease were reported in Ankang City from 2018 to 2023, and the reported incidence rate increased from 0.56/100 000 in 2018 to 5.02/100 000 in 2023. Among them, 139 were males and 191 were females, with a sex ratio of 0.73∶1.00. The age was mainly 45 - 70 years old, accounting for 81.52% (269/330). The occupation was mainly farmers, accounting for 86.97% (287/330). The onset time was mainly concentrated from April to October, with a total of 317 cases, accounting for 96.06% (317/330). The main clinical manifestations were fever (93.20%, 274/294), ulcer or eschar (75.85%, 223/294), headache (44.56%, 131/294), and lymph node enlargement (44.22%, 130/294). The misdiagnosis rate at the first diagnosis was 73.81% (217/294). A total of 452 rodents were captured, of which 91 rodents carried chigger mites, and chigger mites rate was 20.13% (91/452). A total of 1 463 chigger mites were captured, and the chigger mites index was 3.24 (1 463/452). Quantitative real-time PCR was performed on blood and organ mixture samples collected from 452 rodents, and one of the organ mixture samples tested positive for Orientia tsutsugamushi. Conclusions:The incidence of tsutsugamushi disease in Ankang City is relatively high, and the overall incidence is on the rise. The cases are mainly female, middle-aged and elderly, and farmers, with a high misdiagnosis rate at the first diagnosis. There are chigger mites in rodents in townships with high incidence of tsutsugamushi disease.