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.

Smoking is the leading preventable risk factor for disease and death worldwide. Tobacco and its smoke contain a complex mix of over 9 500 chemical substances, including oxidative gases, heavy metals, and 83 known carcinogens. Long-term smoking is a significant risk factor for respiratory diseases such as acute lung injury, emphysema, and pulmonary fibrosis. Damage to alveolar epithelial cells (AECs) is a common pathological feature in these smoking-related lung diseases. AECs, which line the surface of the alveoli, play a crucial role in preventing overexpansion or collapse, secreting cell factors and surfactants, containing abundant mitochondria, and being essential for lung tissue maturation, gas exchange, metabolism, and repair after damage. Damage to these cells can lead to pulmonary edema and alveolar collapse. Cigarette smoke (CS) can disrupt alveolar epithelial cell function through various pathways, resulting in cell death, tissue damage, and the development of lung diseases.This review summarizes recent research on the damage caused by CS to AECs, showing that CS can promote cell death and damage through induction of oxidative stress, autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, inflammation, and epithelial-mesenchymal transition. It also affects the proliferative function of alveolar type II epithelial cells. The review highlights that CS-induced oxidative stress is a key factor in causing various types of damage, with TRP ion channels serving as important triggers. Inhibiting CS-induced oxidative damage can significantly prevent cell death and subsequent diseases such as pulmonary emphysema. The activation of the same pathway induced by CS can lead to different types of cell damage, potentially encouraging the development of different diseases. CS can either directly induce or indirectly promote cell inflammation through endoplasmic reticulum stress, mitochondrial dysfunction, and senescence. There are interconnected relationships between these mechanisms, and SIRT1 is an important protein in preventing CS-induced AECs damage. Increasing SIRT1 activity can alleviate CS-induced autophagy, endoplasmic reticulum stress, and senescence in various cell damages; its substrate NAD⁺ is already used clinically, and its effectiveness in COPD treatment deserves further exploration. The impact of CS on cells varies based on concentration: lower concentrations stimulate stress responses or apoptosis, while higher concentrations lead to apoptosis or necrosis through various mechanisms, ultimately impairing lung epithelial function. When external stimuli exceed the cells’ self-healing capacity, they can cause damage to cells, lung epithelial barriers, and alveoli, promoting the development of related lung diseases. Key proteins that play a protective role may serve as potential targets to mitigate cell damage.This review provides insights into the various mechanisms through which CS induces damage to AECs, covering important transcription factors, DNA repair proteins, and membrane channel proteins, paving the way for the study of new mechanisms and pathways. However, there are still unanswered questions, such as the need for further exploration of the upstream pathways of CS-induced autophagy in AECs and the intrinsic mechanisms of CS in enhancing the stem cell properties of AECs and its relationship to the occurrence of lung cancer.It is expected that this article will provide a theoretical basis for future research on the mechanisms of lung epithelial cell damage caused by CS or its individual components and inspire clinical strategies for the prevention and treatment of smoking-related lung diseases.

As the global population continues to age, the incidence of Alzheimer’s disease (AD), one of the most common neurodegenerative diseases, continues to rise significantly. As the disease progresses, the patient’s daily living abilities gradually decline, potentially leading to a complete loss of self-care abilities. According to estimates by the Alzheimer’s Association and the World Health Organization, AD accounts for 60%-70% of all other dementia cases, affecting over 55 million people worldwide. The case number is estimated to double by 2050. Despite extensive research, the precise etiology and pathogenesis of AD remain elusive. Researchers have a profound understanding of the disease’s pathological hallmarks, which include amyloid plaques and neurofibrillary tangles resulting from the abnormal phosphorylation of Tau protein. However, the exact causes and mechanisms of the disease are still not fully understood, leaving a vital gap in our knowledge and understanding of this debilitating disease. A crucial player that has recently emerged in the field of AD research is the α7 nicotinic acetylcholine receptor (α7nAChR). α7nAChR is composed of five identical α7 subunits that form a homopentamer. This receptor is a significant subtype of acetylcholine receptor in the central nervous system and is widely distributed in various regions of the brain. It is particularly prevalent in the hippocampus and cortical areas, which are regions associated with learning and memory. α7nAChR plays a pivotal role in several neurological processes, including neurotransmitter release, neuronal plasticity, cell signal transduction, and inflammatory response, suggesting its potential involvement in numerous neurodegenerative diseases, including AD. In recent years, the role of α7nAChR in AD has been the focus of extensive research. Emerging evidence suggests that α7nAChR is involved in several critical steps in the disease progression of AD. These include involvement in the metabolism of amyloid β-protein (Aβ), the phosphorylation of Tau protein, neuroinflammatory response, and oxidative stress. Each of these processes contributes to the development and progression of AD, and the involvement of α7nAChR in these processes suggests that it may play a crucial role in the disease’s pathogenesis. The potential significance of α7nAChR in AD is further reinforced by the observation that alterations in its function or expression can have significant effects on cognitive abilities. These findings suggest that α7nAChR could be a promising target for therapeutic intervention in AD. At present, the results of drug clinical studies targeting α7nAChR show that these compounds have improvement and therapeutic effects in AD patients, but they have not reached the degree of being widely used in clinical practice, and their drug development still faces many challenges. Therefore, more research is needed to fully understand its role and to develop effective treatments based on this understanding. This review aims to summarize the current understanding of the association between α7nAChR and AD pathogenesis. We provide an overview of the latest research developments and insights, and highlight potential avenues for future research. As we deepen our understanding of the role of α7nAChR in AD, it is hoped that this will pave the way for the development of novel therapeutic strategies for this devastating disease. By targeting α7nAChR, we may be able to develop more effective treatments for AD, ultimately improving the quality of life for patients and their families.

Objective To compare the fidelity of chronic obstructive pulmonary disease(COPD)models established using two methods:exposure to cigarette smoke(CS)and exposure to motor vehicle exhaust(MVE)in rats.Methods Twenty-four male SD rats were randomly divided into control,CS-exposed(CS),and MVE-exposed(MVE)groups,with 8 rats per group.Rats in CS and MVE groups were exposed to CS or MVE,respectively,to induce COPD models.After COPD model established,lung function of each group was assessed.Bronchoalveolar lavage fluid(BALF)was collected to measure inflammatory cell counts,levels of inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor(TNF)-α,and expression levels of mucin 5AC(MUC5AC).Lung tissue sections were stained with hematoxylin and eosin(HE)to observe pulmonary tissue and airway pathological changes.Periodic acid-Schiff(PAS)staining was used to detect goblet cell hyperplasia in airways.Results Compared with control group,rats in CS and MVE groups showed significantly increased inspiratory resistance(RI),total lung capacity(TLC),and lung static compliance(Cchord)(P<0.05),while expiratory flow parameters FEV50/FVC were significantly decreased(P<0.05).Compared with MVE group,rats in CS group had significantly higher RI,TLC,and Cchord(P<0.05),and lower FEV50/FVC(P<0.05).HE staining of lung tissues showed that mean linear intercept(MLI)was significantly higher in both CS and MVE groups compared with control group(P<0.05),with CS group having higher MLI than MVE group(P<0.05).BALF analysis revealed that white blood cells,neutrophils,macrophages,lymphocytes,IL-6,and TNF-α levels were significantly higher in both CS and MVE groups compared with control group(P<0.05),and inflammatory cell counts,IL-6,and TNF-α levels were higher in CS group compared with MVE group(P<0.05).PAS staining of lung tissues indicated that goblet cells in large airways were significantly increased in both CS and MVE groups compared with control group(P<0.05),with CS group showing higher goblet cell counts than MVE group(P<0.05).Expression levels of MUC5AC in BALF were significantly higher in both CS and MVE groups compared with control group(P<0.05),with CS group having significantly higher MUC5AC levels than MVE group(P<0.05).Conclusions Exposure to CS or MVE can establish a rat model of COPD,with CS exposure better mimicking characteristics of acute exacerbation of COPD compared to MVE exposure.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Hematopoietic Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; T-Lymphocytes ; Immunotherapy, Adoptive ; Antigens, CD19

Objective: To investigate the clinical significance of pathological diagnosis and genetic abnormalities detection of gastrointestinal stromal tumor (GIST) using endoscopic biopsy. Methods: Patients with GIST diagnosed by endoscopic biopsy (from January 1st, 2016 to August 1st, 2018, at Zhongshan Hospital, Fudan University) were included in this study. This retrospective study evaluated the histopathologic and immunohistochemical (IHC) features, genetic abnormalities of the tumors and the treatment and clinical course of the patients. Results: Totally 4 095 cases of GIST were collected, among which 67 patients (67/4 095, 1.6%) underwent endoscopic biopsy. Forty-eight patients (71.6%) were male and 19 (28.4%) were female, with a mean age of 61 years (range 31-90 years). Fifty-nine lesions were located in stomach and eight in duodenum. Of all the 67 cases, 47 were spindle type, 14 were epithelioid type, and 6 mixed type. IHC staining showed the positive rates were 100.0% (64/64) for DOG1, 98.4% (62/63) for CD117, 87.5% (56/64) for CD34, 3.6% (2/56) for S-100 protein, 12.1% (7/58) for α-SMA, 12.3% (7/57) for desmin and 4.0% (2/50) for CKpan. Morphologically, 34 cases were malignant; three cases (all epithelioid type) were originally misdiagnosed as poorly differentiated carcinoma; missed-diagnosis were found in four cases (spindle type) due to the insufficient diagnostic tumor cells. The genetic abnormality detection rate in the biopsy tissue was 38.8% (26/67),among them two patients were lost to follow up after biopsy, 33 patients received surgical resection, 16 cases underwent operation after neoadjuvant therapy and 16 patients with advanced disease underwent continuous imatinib therapy, with the genetic testing rate of 6.1% (2/33), 10/16 and 14/16, respectively. Conclusions: Endoscopic biopsy is a useful but rare method for the preoperative diagnosis of GIST. For majority of biopsy, accurate pathological diagnosis and auxiliary examination can be completed to guide clinical treatment. A thorough history in combination with endoscopic finding is essential to avoid misdiagnosis (epithelioid type) and missed diagnosis (spindle type) in suspicious cases. Genetic testing should be recommended in patients who will undergo targeted therapy after endoscopic biopsy, and it can provide valuable information and guidance for clinical treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Gastrointestinal Stromal Tumors/pathology* ; Retrospective Studies ; Clinical Relevance ; Imatinib Mesylate ; Biopsy ; S100 Proteins

From the perspective of market classification of Cnidii Fructus, this paper revealed the scientific connotation of evaluating the quality grade of Cnidii Fructus by its appearance traits. Thirty batches of Cnidii Fructus in different grades were selected as the research objects. The canonical correlation analysis and principal component analysis(PCA) were used to explore the measurement values of 15 appearance traits and intrinsic content indexes. The results of correlation analysis showed that except the aspect ratio, the 5 appearance trait indexes(length, width, 1 000-grain weight, broken grain weight proportion, and chroma) and 9 internal content indexes(the content of moisture, total ash, acid insoluble ash, osthole, imperatorin, 5-methoxy psoralen, isopimpinellin, xanthotoxin, and xanthotol) showed significant correlation to varying degrees. In addition, there was a significant positive correlation between the first typical variable U_1 composed of appearance traits and the first typical variable V_1 composed of internal content indexes(CR_1=0.963, P<0.01). The results of PCA showed that the classification results of appearance traits for 30 batches of Cnidii Fructus were consistent with the actual information of the samples. Under the same analysis conditions, 30 batches of Cnidii Fructus were reclassified by 9 groups of internal content indexes, and the analysis results were consistent. From the classification standard of the appearance traits of the system study, the statistical results of 6 appearance traits of Cnidii Fructus showed a correlation with grades. There was a good correlation between the appearance and the internal content of Cnidii Fructus, and the appearance quality effectively predicted the level of the internal content. There is a certain scientific basis for the quality classification of Cnidii Fructus by main appearance traits. Appearance classification can replace quality grading to realize the "quality evaluation through morphological identification" of Cnidii Fructus.
Fruit ; Phenotype ; Principal Component Analysis ; Social Group

Objective: To investigate the efficacy of humanized anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 64 patients with SR-aGVHD between June 2019 and October 2020 in Suchow Hopes Hematology Hospital were enrolled in this study. Humanized anti-CD25 monoclonal antibodies 1 mg·kg(-1)·d(-1) were administered on days 1, 3, and 8, and then once per week according to the disease progression. Efficacy was assessed at days 7, 14, and 28 after humanized anti-CD 25 treatment. Results: Of the 64 patients with a median age of 31 (15-63) years, 38 (59.4%) were male and 26 (40.6%) were female. The overall response (OR) rate of the humanized CD25 monoclonal antibody in 64 patients with SR-aGVHD on days 7, 14, and 28 were 48.4% (31/64), 53.1% (34/64), and 79.7% (51/64), respectively. Liver involvement is an independent risk factor for poor efficacy of humanized CD25 monoclonal antibody for SR-aGVHD at day 28 (OR=9.588, 95% CI 0.004-0.291, P=0.002). The median follow-up time for all patients was 17.1 (0.2-50.8) months from the start of humanized CD25 monoclonal antibody therapy. The 1- and 2-year OS rates were 63.2% (95% CI 57.1% -69.3%) and 52.6% (95% CI 46.1% -59.1%), respectively. The 1- and 2-year DFS rates were 58.4% (95% CI 52.1% -64.7%) and 49.8% (95% CI 43.4% -56.2%), respectively. The 1- and 2-year NRM rates were 28.8% (95% CI 23.1% -34.5%) and 32.9% (95% CI 26.8% -39.0%), respectively. The results of the multifactorial analysis showed that liver involvement (OR=0.308, 95% CI 0.108-0.876, P=0.027) and GVHD grade Ⅲ/Ⅳ (OR=9.438, 95% CI 1.211-73.577, P=0.032) were independent risk factors for OS. Conclusion: Humanized CD25 monoclonal antibody has good efficacy and safety for SR-aGVHD. This study shows that SR-aGVHD with pretreatment grade Ⅲ/Ⅳ GVHD and GVHD involving the liver has poor efficacy and prognosis and requires early intervention.
Adult ; Female ; Humans ; Male ; Middle Aged ; Acute Disease ; Antibodies, Monoclonal/therapeutic use* ; Graft vs Host Disease/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Retrospective Studies ; Salvage Therapy/methods* ; Steroids ; Adolescent ; Young Adult

Our previous study has shown that p66^Shc plays an important role in the process of myocardial regeneration in newborn mice, and p66^Shc deficiency leads to weakened myocardial regeneration in newborn mice. This study aims to explore the role of p66^Shc protein in myocardial injury repair after myocardial infarction in adult mice, in order to provide a new target for the treatment of myocardial injury after myocardial infarction. Mouse myocardial infarction models of adult wild-type (WT) and p66^Shc knockout (KO) were constructed by anterior descending branch ligation. The survival rate and heart-to-body weight ratio of two models were compared and analyzed. Masson's staining was used to identify scar area of injured myocardial tissue, and myocyte area was determined by wheat germ agglutinin (WGA) staining. TUNEL staining was used to detect the cardiomyocyte apoptosis. The protein expression of brain natriuretic peptide (BNP), a common marker of myocardial hypertrophy, was detected by Western blotting. The results showed that there was no significant difference in survival rate, myocardial scar area, myocyte apoptosis, and heart weight to body weight ratio between the WT and p66^ShcKO mice after myocardial infarction surgery. Whereas the protein expression level of BNP in the p66^ShcKO mice was significantly down-regulated compared with that in the WT mice. These results suggest that, unlike in neonatal mice, the deletion of p66^Shc has no significant effect on myocardial injury repair after myocardial infarction in adult mice.
Animals ; Mice ; Body Weight ; Cicatrix/metabolism* ; Mice, Knockout ; Myocardial Infarction/genetics* ; Oxidative Stress ; Shc Signaling Adaptor Proteins/metabolism* ; Src Homology 2 Domain-Containing, Transforming Protein 1/metabolism*