1.Influencing factors for recompensation and its impact on the prognosis in patients with decompensated liver cirrhosis
Danqing XU ; Haiwen LI ; Huan MU ; Yingyuan ZHANG ; Caifen SA ; Li LIU ; Yongrui YANG
Journal of Clinical Hepatology 2026;42(1):90-100
ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated liver cirrhosis, as well as the impact of recompensation on the prognosis of such patients, and to provide a basis for early identification of high-risk patients in clinical practice. MethodsA retrospective analysis was performed for the clinical data of patients who attended The Third People’s Hospital of Kunming from January 2016 to December 2022 and were diagnosed with decompensated liver cirrhosis due to hepatitis B, hepatitis C, alcoholic hepatitis, and autoimmune hepatitis, and they were divided into recompensation group and persistent decompensation group. To control for confounding factors, whether recompensation occurred was used as the rouping variable,and BMI, alcohol consumption history, HIV infection history, TG, CHOL, LDL, and HDL were used as covariates. The propensity score was calculated, and 1:1 nearest neighbor matching was performed with a caliper value of 0.1. After propensity score matching, the recompensation group and the persistent decompensation group with relatively balanced covariates were obtained. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for recompensation; the “rms” package was used to establish a nomogram; the receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC); the Hosmer-Lemeshow test was used to assess the goodness of fit of the model; the “Calibration Curves” package was used to plot calibration curves for model assessment. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison of survival curves. ResultsAmong the 863 patients with decompensated liver cirrhosis, 305 experienced recompensation, resulting in an incidence rate of 35.3%. After PSM, 610 cases were successfully matched, with 305 cases in each group. The univariate and multivariate Cox regression analyses showed that etiology (hepatitis C: hazard ratio[HR]=0.288, P=0.002); male(HR=0.701, P=0.016), age(HR=0.988, P=0.047), hemoglobin (HGB)(HR=1.006, P=0.017), and CD4 T cell(HR=1.001,P=0.047), TIPS procedure (HR=1.808,P=0.042) were independent influencing factors for recompensation in patients with decompensated liver cirrhosis. During follow-up, 116 patients died of liver disease-related causes, with 27 patients (8.85%) in the recompensation group and 89 (15.95%) in the persistent decompensation group; 109 patients developed HCC, with 23 patients (7.54%) in the recompensation group and 86 (15.41%) in the persistent decompensation group. The Kaplan-Meier survival curves showed significant separation between the patients with different states of compensation in terms of liver disease-related mortality rate and the incidence rate of HCC, and the Log-rank test showed that there were significant differences between the two groups in liver disease-related mortality rate (χ2=9.023, P=0.003) and the incidence rate of HCC (χ2=10.526, P=0.001). ConclusionEtiology,sex,age,TIPS,HGB,and CD4 T cell are independent influencing factors for recompensation in patients with decompensated liver cirrhosis. There is a significant difference in the incidence rate of recompensation between decompensated liver cirrhosis patients with different etiologies, and female patients and patients with a younger age,a history of TIPS, a higher HGB level, and a higher CD4 lymphocyte count are more likely to experience recompensation. Recompensation is the key to improving the long-term prognosis of patients and can significantly reduce long-term liver disease-related mortality rate and the incidence rate of HCC.
2.Efficacy and safety of Babaodan Capsule in patients with chronic hepatitis B virus infection comorbid with gallbladder polyps
Qianqian NIU ; Huan CHEN ; Ying ZHENG ; Chunyan GOU ; Chen XU ; Li LI ; Xinxin WANG ; Jianping LIU ; Zhaolan LIU ; Xiuhui LI
Journal of Clinical Hepatology 2026;42(2):304-311
ObjectiveTo investigate the efficacy and safety of Babaodan Capsule (BBD) in the treatment of patients with chronic hepatitis B virus (HBV) infection with damp-heat in the liver and gallbladder comorbid with gallbladder polyps. MethodsA randomized, double-blinded, placebo-controlled single-center trial was conducted among 120 patients with chronic HBV infection who were admitted to Beijing YouAn Hospital, Capital Medical University, from August 2020 to April 2023, and they were divided into treatment group (BBD) and control group (placebo), with 60 patients in each group. The course of treatment was 24 weeks, and follow-up assessments were conducted every 4 weeks. The primary outcome measures were the number and maximum diameter of gallbladder polyps (assessed by ultrasound), and the secondary outcome measures included traditional Chinese medicine (TCM) syndrome score, blood lipid levels, and liver function parameters. The independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups; the Wilcoxon rank-sum test was used for comparison of ranked data between two groups; the generalized estimating equation was used to analyze repeated measures data. ResultsAfter 8 weeks of treatment, the treatment group had a significantly smaller diameter of polyps and a significantly lower number of polyps than the control group (Z=-1.76 and -1.80, both P<0.05), and after 24 weeks of treatment, the treatment group had a significantly higher polyp reduction rate than the control group (30.51% vs 10.91%, P<0.05). The subgroup analysis showed that patients receiving combined antiviral therapy, male patients, patients with a diameter of polyps of <5 mm, and patients with multiple polyps tended to achieve significantly greater benefits. At week 8 of treatment, the treatment group had a significantly better TCM syndrome score than the control group (Z=-2.35, P<0.05); after treatment, compared with the control group, the treatment group had a significantly greater increase in high-density lipoprotein (Z=-1.85, P<0.05) and significantly lower levels of alanine aminotransferase (Z=-2.06, P <0.05), aspartate aminotransferase (Z=-2.13, P<0.05), total bilirubin (Z=-2.12, P<0.05), and direct bilirubin (Z=-3.09, P<0.05). No serious adverse events were reported in either group. ConclusionBBD can effectively reduce the size of gallbladder polyps, improve TCM syndrome score, and reduce the level of bilirubin in patients with chronic HBV infection with damp-heat in the liver and gallbladder, with a favorable safety profile, and it may be more suitable for patients receiving combined antiviral therapy and specific subgroups (male patients, patients with a diameter of polyps of <5 mm, and patients with multiple polyps.
3.Neuroprotective effect and mechanism of eleutheroside B on Parkinson’s disease model mice by regulating the IKKβ/NF-κB signaling pathway
Xiaoli WANG ; Hua RONG ; Siwen PAN ; Chunlei YU ; Tianjiao XU ; Yu SUN ; Huan CONG ; Yu PANG ; Gang CHEN ; Xiaoming LI
China Pharmacy 2026;37(8):998-1002
OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B (ELB) on Parkinson’s disease (PD) model mice by regulating the IκB kinase β (IKKβ)/nuclear factor-κB (NF-κB) signaling pathway. METHODS Fifty mice were randomly divided into normal control group, model group, positive control group (selegiline hydrochloride, 10 mg/kg), and ELB low-dose and high-dose groups (80, 160 mg/kg), with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration, the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 30 mg/kg, for five consecutive days to establish the chronic PD model. After the last administration for 24 h, six mice were randomly selected from each group to test their behavioral abilities; detect the levels of interleukin-1β (IL-1β), IL-10, tumor necrosis factor-α (TNF-α) in brain tissue and their mRNA expressions were measured, and positive expression of tyrosine hydroxylase (TH), protein expressions of TH, α -synuclein ( α -syn), ionized calcium-binding adaptor molecule 1 (Iba-1), as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group, rotarod endurance time and climbing score of each administration group (except for the ELB low-dose group) were increased significantly ( P <0.05), while the levels and mRNA expressions of IL-1β, TNF-α, α -syn, and Iba-1, as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly (except for TNF-α in the ELB low-dose group). Conversely, the level and mRNA expression of IL-10 (except for the ELB low-dose group), TH positive expression and protein expressions were significantly increased ( P <0.05). Typical neurodegenerative pathological changes, such as neuronal karyopyknosis, mitochondrial swelling and vacuolization, and endoplasmic reticulum dilation, all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway, alleviating inflammatory responses, reducing abnormal α -syn aggregation and neuronal loss, and further improving motor dysfunction in PD mice.
4.Construction of a nomogram model for clinical cure of chronic hepatitis B with a low level of hepatitis B surface antigen treated with pegylated interferon α-2b
Yingyuan ZHANG ; Huan MU ; Lixian CHANG ; Danqing XU ; Yuanzhen WANG ; Chunyun LIU ; Weikun LI ; Huangchenghao ZHANG ; Chunyan MOU ; Li LIU
Journal of Clinical Hepatology 2026;42(5):1038-1047
ObjectiveTo investigate the predictive factors for HBsAg clearance in chronic hepatitis B (CHB) patients with a low level of hepatitis B surface antigen (HBsAg) treated with pegylated interferon α-2b (PEG-IFN-α-2b), to establish a combined predictive model and a nomogram based on multiple factors, and to provide a reference for formulating individualized treatment regimens and predicting treatment outcome in clinical practice. MethodsA retrospective analysis was performed for 167 CHB patients with HBsAg <1 500 IU/mL who attended The Third People’s Hospital of Kunming from January 2022 to January 2024 and were treated with PEG-IFN-α-2b. According to whether clinical cure was achieved, the patients were divided into HBsAg clearance group and HBsAg non-clearance group. Related data were collected, including general information and serological/biochemical/virological indicators at different time points during treatment. The independent samples t-test was used for comparison of normally distributed continuous data, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data; the chi-square test was used for comparison of categorical data. The multivariate logistic regression analysis was used to identify independent influencing factors. The receiver operating characteristic (ROC) curve was used to assess the value of indicators used alone or in combination in predicting clinical cure, and calibration curves were plotted to assess the risk prediction model. ResultsThe univariate analysis showed that there were significant differences between the two groups in age (t=-6.839, P<0.05), history of nucleos(t)ide analogue treatment for over 1 year (χ2=59.339, P<0.05), genotype (χ2=4.610, P<0.05), nonalcoholic fatty liver disease (χ2=5.319, P<0.05), hepatitis B virus DNA status before treatment (χ2=60.861, P <0.05), compensated liver cirrhosis (χ2=10.960, P<0.05), HBeAg status before treatment (χ2=19.060, P<0.05), a history of interferon treatment (χ2=8.162, P<0.05), presence of interferon antibodies after treatment (χ2=12.858, P<0.05), HBsAg level before treatment (Z=-7.412, P<0.05), alanine aminotransaminase (ALT) level at baseline (Z=-6.117, P<0.05), ALT level at 12 weeks of treatment (Z=-7.171, P<0.05), platelet count (PLT) at 24 weeks of treatment (Z=-3.622, P<0.05), and thyroid stimulating hormone (TSH) level at 24 weeks of treatment (Z=-2.830, P<0.05). The multivariate logistic regression analysis showed that age (odds ratio [OR]=1.230, P=0.007), history of nucleos(t)ide analogue treatment for over 1 year (OR=0.008, P=0.011), HBeAg status before treatment (OR=0.003, P=0.012), HBsAg level before treatment (OR=1.005, P=0.014), ALT level at baseline (OR=0.949, P=0.014), ALT level at 12 weeks of treatment (OR=0.969, P=0.016), PLT at 24 weeks of treatment (OR=0.969, P=0.022), and TSH level at 24 weeks of treatment (OR=3.608, P=0.045) were independent influencing factors for HBsAg clearance at 48 weeks of treatment in CHB patients with HBsAg <1 500 IU/mL. The Hosmer-Lemeshow goodness-of-fit test yielded χ2=1.398, P=0.994, indicating that the model had good fitting. The Bootstrap method was used to perform internal validation of the nomogram model, and there was a good degree of fitting between the calibration curve and the ideal curve, with a mean absolute error of 0.029. The ROC curve analysis showed that the combination of predictive factors had an area under the ROC curve of 0.982 (95% confidence interval: 0.961 — 0.999), with a sensitivity of 94.10% and a specificity of 93.10%, suggesting that the nomogram model had a good discriminatory ability. For the CHB patients with HBsAg <1 500 IU/mL and different features, further analysis of HBsAg clearance rate at 48 weeks of treatment showed an HBsAg clearance rate of 69.60% for those with HBsAg ≤67.65 IU/mL before treatment, 58.30% for those with a baseline ALT level of ≥62.50 U/L, 68.30% for those with an ALT level of ≥92.50 U/L at 12 weeks of treatment, 42.40% for those with PLT ≥104×109/L at 24 weeks of treatment, and 48.30% for those with a TSH level of ≤1.38 μIU/mL at 24 weeks of treatment, with significant differences between the two groups (all P<0.001). ConclusionAge, history of nucleos(t)ide analogue treatment for over 1 year, HBeAg status before treatment, HBsAg level before treatment, baseline ALT level, ALT level at 12 weeks of treatment, PLT level at 24 weeks, and TSH level at 24 weeks of treatment are independent predictive factors. The combined prediction nomogram model constructed in this study has a relatively high value in predicting clinical cure at 48 weeks of PEG-IFN-α-2b treatment in CHB patients with HBsAg<1 500 IU/mL, thereby providing a reference for selecting suitable treatment population and predicting clinical cure.
5.Value of albumin-bilirubin, easy albumin-bilirubin, and platelet-albumin-bilirubin scores in predicting the prognosis of patients with HCV-associated hepatocellular carcinoma
Huan MU ; Yingyuan ZHANG ; Danqing XU ; Yuanqiang HE ; Chunyan MOU ; Chunyun LIU ; Li LIU
Journal of Clinical Hepatology 2025;41(5):921-926
ObjectiveTo investigate the value of albumin-bilirubin (ALBI), easy albumin-bilirubin (EZ-ALBI), and platelet-albumin-bilirubin (PALBI) scores in predicting 2-year survival in patients with HCV-associated hepatocellular carcinoma (HCV-HCC). MethodsA retrospective analysis was performed for the clinical data of 174 patients with HCV-HCC who were admitted to The Third People’s Hospital of Kunming from January 2020 to January 2022, and the patients were followed up till 2 years after admission. According to the follow-up results, the patients were divided into survival group with 95 patients and death group with 79 patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for the survival of HCV-HCC patients. The Kaplan-Meier method was used to plot survival curves and analyze the 2-year survival rate of HCV-HCC patients with different EZ-ALBI grades, and the log-rank test was used for comparison between groups. ResultsThere were significant differences between the survival group and the death group in platelet count, aspartate aminotransferase (AST), total bilirubin, albumin (Alb), alpha-fetoprotein (AFP), prealbumin, prothrombin time, international normalized ratio, PALBI score, ALBI score, EZ-ALBI score, Model for End-Stage Liver Disease (MELD) score, HCV genotype, peritoneal effusion, and vascular invasion (all P<0.05). The univariate Cox regression analysis showed that AST, Alb, AFP, ALBI score, EZ-ALBI score, PALBI score, MELD score, Barcelona Clinic Liver Cancer Staging, and peritoneal effusion were influencing factors for the survival of patients (all P<0.05), and the multivariate Cox regression analysis showed that EZ-ALBI score (hazard ratio [HR]=1.850, 95% confidence interval [CI]: 1.054 — 3.247, P=0.032) and peritoneal effusion (HR=1.993, 95%CI: 1.030 — 3.858, P=0.041) were independent risk factors for the survival of HCV-HCC patients. The survival curve analysis showed that the patients with EZ-ALBI grade 1/2/3 had a 2-year survival rate of 90.9%, 60.2%, and 32.2%, respectively, and there was a significant difference in cumulative survival rate between the patients with different EZ-ALBI grades (χ2=26.294, P<0.001). ConclusionEZ-ALBI score and the presence or absence of peritoneal effusion can be used as predictors of the survival of HCV-HCC patients.
6.Prrx1 promotes mesangial cell proliferation and kidney fibrosis through YAP in diabetic nephropathy.
Liu XU ; Jiasen SHI ; Huan LI ; Yunfei LIU ; Jingyi WANG ; Xizhi LI ; Dongxue REN ; Sijie LIU ; Heng WANG ; Yinfei LU ; Jinfang SONG ; Lei DU ; Qian LU ; Xiaoxing YIN
Journal of Pharmaceutical Analysis 2025;15(10):101247-101247
Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.
7.Anti-inflammatory and hepatoprotective triterpenoids from the traditional Mongolian medicine Gentianopsis barbata.
Huizhen CHENG ; Huan LIU ; Xiaoyu QI ; Yuzhou FAN ; Zhongzhu YUAN ; Yuanliang XU ; Yanchun LIU ; Yan LIU ; Kai GUO ; Shenghong LI
Chinese Journal of Natural Medicines (English Ed.) 2025;23(9):1111-1121
Gentianopsis barbata (G. barbata) represents a significant plant species with considerable ornamental and medicinal value in China. This investigation sought to elucidate the primary constituents within the plant and investigate their pharmacological properties. Fifty triterpenoids (1-50), including nine previously undescribed compounds (1, 2, 7, 10, 20, 28, 29, 37, and 41) were isolated and characterized from the whole plants of G. barbata. Notably, compounds 1 and 2 exhibited the novel 3,4;9,10-diseco-24-homo-cycloartane triterpenoid skeleton. The isolated triterpenoids demonstrated substantial anti-inflammatory activity through inhibition of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) cytokine secretion in LPS-induced RAW264.7 macrophages, and hepatoprotective effects by preventing tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in HepG2 cells. These results demonstrate both the presence of diverse triterpenoids in G. barbata and their therapeutic potential for inflammatory and hepatic conditions, providing scientific evidence supporting the clinical application of this traditional Mongolian medicinal plant.
Triterpenes/isolation & purification*
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Mice
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Anti-Inflammatory Agents/isolation & purification*
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Animals
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Humans
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RAW 264.7 Cells
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Hep G2 Cells
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Interleukin-6/genetics*
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Tumor Necrosis Factor-alpha/genetics*
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Medicine, Mongolian Traditional
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Macrophages/immunology*
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Protective Agents/isolation & purification*
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Liver/drug effects*
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Gentianaceae/chemistry*
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Plant Extracts/chemistry*
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Molecular Structure
9.Efficacy and safety of coblopasvir hydrochloride combined with sofosbuvir in treatment of patients with genotype 3 hepatitis C virus infection
Yingyuan ZHANG ; Huan MU ; Danqing XU ; Chunyan MOU ; Yuanzhen WANG ; Chunyun LIU ; Weikun LI ; Li LIU
Journal of Clinical Hepatology 2025;41(6):1075-1082
ObjectiveTo investigate the efficacy and safety of the direct-acting antiviral agents coblopasvir hydrochloride/sofosbuvir (CLP/SOF) regimen used alone or in combination with ribavirin (RBV) in the treatment of patients with genotype 3 hepatitis C virus (HCV) infection in terms of virologic response rate, liver function recovery, improvement in liver stiffness measurement (LSM), and adverse drug reactions, and to provide a reference for clinical medication. MethodsA total of 98 patients with genotype 3 HCV infection who attended The Third People’s Hospital of Kunming from January 2022 to December 2023 were enrolled, and according to the treatment method, the patients were divided into CLP/SOF+RBV treatment group with 55 patients and CLP/SOF treatment group with 43 patients. The patients were observed in terms of rapid virologic response at week 4 (RVR4), sustained virologic response (SVR), previous treatment experience, underlying diseases, laboratory and imaging indicators, and adverse reactions during treatment. The course of treatment was 12 weeks, and the patients were followed up for 12 weeks after drug withdrawal. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the Friedman test was used for comparison within each group at different time points, and the Bonferroni method was used for further comparison and correction of P value; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for SVR12. ResultsBefore treatment, there were significant differences between the CLP/SOF+RBV treatment group and the CLP/SOF treatment group in terms of LSM, total bilirubin (TBil), gamma-glutamyl transpeptidase (GGT), HCV genotype, and the presence or absence of liver cirrhosis and compensation (all P<0.05). The 98 patients with genotype 3 HCV infection had an RVR4 rate of 81.6% and an SVR12 rate of 93.9%. The patients with genotype 3a HCV infection had an RVR4 rate of 84.44% and an SVR12 rate of 97.78%, while the patients with genotype 3b HCV infection had an RVR4 rate of 79.25% and an SVR12 rate of 90.57%. There were significant differences in RVR4 and SVR12 rates between the patients without hepatocellular carcinoma and those with hepatocellular carcinoma, there was a significant difference in RVR4 rate between the patients without HIV infection and those with HIV infection, and there was a significant difference in SVR12 rate between the previously untreated patients and the treatment-experienced patients (all P<0.05). The univariate Logistic regression analysis showed that treatment history, hypertension, hepatocellular carcinoma, ascites, albumin (Alb), and platelet count were influencing factors for SVR12 (all P<0.05), and the multivariate Logistic regression analysis showed that hepatocellular carcinoma (odds ratio=0.034, 95% confidence interval: 0.002 — 0.666, P=0.026) was an independent influencing factor for SVR12. After treatment with CLP/SOF combined with RBV or CLP/SOF alone, the patients with genotype 3 HCV infection showed gradual reductions in the liver function parameters of TBil, GGT, and alanine aminotransferase (all P<0.05) and a gradual increase in the level of Alb (P<0.05). As for renal function, there were no significant changes in blood urea nitrogen and creatinine after treatment (P>0.05). For the patients with or without liver cirrhosis, there was a significant reduction in LSM from baseline after treatment for 12 weeks (P<0.05). Among the 98 patients with genotype 3 HCV infection, 9 tested positive for HCV-RNA at 12 weeks after treatment, 2 showed no response during treatment, 4 showed virologic breakthrough, and 3 experienced recurrence. The overall incidence rate of adverse events during treatment was 17.35% for all patients. ConclusionCLP/SOF alone or in combination with RBV has a relatively high SVR rate in the treatment of genotype 3 HCV infection, with good tolerability and safety in patients during treatment, and therefore, it holds promise for clinical application.
10.The Application of Spatial Resolved Metabolomics in Neurodegenerative Diseases
Lu-Tao XU ; Qian LI ; Shu-Lei HAN ; Huan CHEN ; Hong-Wei HOU ; Qing-Yuan HU
Progress in Biochemistry and Biophysics 2025;52(9):2346-2359
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.

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