1.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.
2.Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics
Yu-long CHEN ; You ZHAI ; Xiao-yan WANG ; Wei-xia LI ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Xiao-fei CHEN ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Kun LI ; Jin-fa TANG ; Ming-liang ZHANG
Acta Pharmaceutica Sinica 2024;59(2):382-394
Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and
3.A cross-sectional study on the relationship between 24-hour activities and depressive symptoms in vocational school students
Biao-Qian TANG ; Bo-Hao CHEN ; Yi-Yang LI ; Han-Qing LIU ; Shu-Qing XU ; Shu-Mei WANG
Fudan University Journal of Medical Sciences 2024;51(2):159-165
Objective An isotemporal substitution model was used to explore the associations between activities including 10 minutes per day of physical activity(PA),sedentary behavior(SB),and sleep(SLP),and depressive symptoms among vocational school students with and without depressive symptoms.Methods Questionnaire survey was conducted on grade one to grade three students attending vocational schools in Shanghai and Jiangsu Province from Dec 2021 to Jan 2022.Fourteen schools were selected using the convenience cluster sampling method.The selected students were categorized into depressive symptoms group and non-depressive symptoms group according to the Centre for Epidemiologic Studies Depression Scale(CES-D)scores.Results A total of 40 339 questionnaires were collected,of which 10 086 were able to clearly remember the time of physical activity in the past week,and 8 149 were valid after data cleaning.According to the valid questionnaires,5 496 students(67.44%)were in the non-depressive symptoms group and 2 653(32.56%)were in the depressive symptoms group.The mean age of the students were(16.70±1.19)years.In the non-depressive symptoms group,substituting moderate physical activity(MPA)for all the other behaviors was negatively associated with CES-D scores,while substituting vigorous physical activity(VPA)for MPA and SB was positively associated with CES-D scores.In the depressive symptoms group,substituting walking,SB,and SLP with MPA was negatively associated with CES-D scores,respectively.The associations of MPA substituted for walking,SB,and SLP with CES-D scores were much stronger in the depressive symptoms group than in the non-depressive symptoms group.Conclusion The detection rate of depressive symptoms was high among vocational students.Substituting MPA for walking,SB,and SLP were negatively associated with CES-D scores,with a stronger association observed in the depressive symptoms group than in the non-depressive symptoms group.
4.Effect of high intensity focused ultrasound treatment on ovarian reserve capacity in adenomyosis
Yi-Lin QIAN ; Hui-Xian CHEN ; Qing-Yue CHEN ; Dong-Qin HE ; Shu-Jing CHEN
Chinese Medical Equipment Journal 2024;45(1):67-70
Objective To explore the impact of high intensity focused ultrasound(HIFU)treatment on ovarian reserve capacity in adenomyosis.Methods Clinical data of 106 adenomyosis patients who underwent HIFU treatment from May 2019 to December 2020 at some hospital were analyzed retrospectively.All the patients were treated with HIFU,and color Doppler ultrasonography was performed before and after 6 months of treatment,respectively.The resistance index,pulsatility index,vascularization index,blood flow index,vascularization blood flow index and sinus follicle number were obtained,and serum anti-Mullerian hormone(AMH),follicle-stimulating hormone(FSH)and luteinizing hormone(luteinizing hormone)were measured.The correlation between serum AMH levels and FSH and LH levels was analyzed.SPSS 21.0 statistical software was used for data analysis.Results After 6 months of treatment serum FSH,LH,value of FSH/LH,resistance index and pulsatility index significantly decreased while vascularization index,blood flow index,vascularization blood flow index,number of sinus follicles,and serum AMH level obviously increased when compared with those before treatment,with the differences being statistically significant(P<0.05).Serum AMH levels were negatively correlated with FSH and LH levels(r=-0.448,-0.527,P<0.05)after 6 months of treatment.Conclusion HIFU treatment reduces sex hormone levels,elevates serum AMH levels and sinus follicle number,and may improve ovarian reserve capacity in patients with adenomyosis.[Chinese Medical Equipment Journal,2024,45(1):67-70]
5.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
6.Exploring the risk "time interval window" of sequential medication of Reduning injection and penicillin G injection based on the correlation between biochemical indexes and metabolomics characteristics
Ming-liang ZHANG ; Yu-long CHEN ; Xiao-yan WANG ; Xiao-fei CHEN ; Hui ZHANG ; Ya-li WU ; Liu-qing YANG ; Shu-qi ZHANG ; Lu NIU ; Ke-ran FENG ; Wei-xia LI ; Jin-fa TANG
Acta Pharmaceutica Sinica 2024;59(7):2098-2107
Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.
7.Clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma
Boen WANG ; Siyuan CHEN ; Qing SHI ; Muchen ZHANG ; Hongmei YI ; Lei DONG ; Li WANG ; Shu CHENG ; Pengpeng XU ; Weili ZHAO
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(9):1162-1168
Objective·To analyze the clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma(DLBCL),including clinical characteristics,pathological characteristics,gene mutation profiles,and prognostic factors.Methods·One hundred and forty-nine patients with kidney-involved DLBCL,admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from July 2005 to November 2021,were retrospectively analyzed for their clinicopathological data,survival and prognostic factors,which included therapeutic methods,clinical outcomes,staging,etc.Gene mutation profiles were evaluated by targeted sequencing of 54 lymphoma-related genes.Prognostic factors were also analyzed based on the information mentioned above.Results·A total of 149 kidney-involved DLBCL cases were included,of which 89 patients(58.4%)were aged over sixty,121 patients(81.2%)were staged Ann Arbor Ⅲ?Ⅳ,27 patients(18.1%)had an Eastern Cooperative Oncology Group(ECOG)performance status of two or more,121 patients(81.2%)had elevated serum lactate dehydrogenase(LDH)level,111 patients(74.5%)had extranodal invasion in at least two organs and 131 patients(87.9%)scored over 2 points on the international prognosis index(IPI).The estimated 5-year overall survival(OS)rate and progression-free survival(PFS)rate of kidney-involved DLBCL patients were 52.2%and 50.4%respectively.Univariate analysis revealed that elevated serum LDH levels were an adverse prognostic factor for both OS(P=0.048)and PFS(P=0.033).In pathological characteristics,145 patients(97.3%)belonged to DLBCL,not otherwise specified(NOS)and 39 patients(26.3%)belonged to germinal center B-cell(GCB)according to Hans classification.Among 144 patients who could be evaluated for clinical outcomes,87 patients(60.4%)got complete response(CR).Targeted sequencing data from 75 kidney-involved DLBCL patients showed high mutation frequency in PIM1(n=23,31%),MYD88(n=22,29%),CD79B(n=21,28%)and KMT2D(n=18,24%),with CD79B mutation indentified as an adverse prognostic factor for OS in patients with kidney-involved DLBCL(P=0.034).Conclusion·Elevated serum LDH level is an adverse prognostic factor in patients with kidney-involved DLBCL.The prognosis of patients with CD79B mutations is poor.
8.Treatment and pharmaceutical care of a case of follicular lymphoma with persistent positive SARS-Cov-2
Jie-Qing ZHANG ; Xiao-Fen YE ; Qian-Zhou LYU ; Xiao-Yu LI ; Shu-Jing CHEN
Fudan University Journal of Medical Sciences 2024;51(4):632-637,642
SARS-CoV-2 has posed a significant threat to a subset of the patient population.The occurrence of hematological malignancies and tumor treatment can lead to immunosuppression in patients,which significantly increases the risk of serious complications,severe incidence and mortality after SARS-CoV-2 infection.The treatment of a patient with follicular lymphoma infected with SARS-CoV-2 was described in detail.The patient remained positive for RT-PCR tests during the hospitalization for nearly 90 days.After undergoing 5 rounds of antiviral treatment,along with glucocorticoid anti-inflammatory therapy,low-molecular-weight heparin for anticoagulation,antibiotics for infection control,and respiratory support through the use of a ventilator,the patient eventually obtained negative result of the RT-PCR test.Subsequently,the patient was successfully weaned from mechanical ventilation and discharged.By summarizing the treatment process of this case,we hoped to provide reference and experience for future clinical diagnosis and treatment.
9.Effect of Simo decoction on the regulation of NLRP3/Caspase-1/GSDMD signal pathway on duodenal microinflammation in rats with functional dyspepsia
Qin LIU ; Xiao-Yuan LIN ; Ling-Feng YANG ; Qian LUO ; Yun-Zong HAN ; Si-Qing CHEN ; Hai-Yue ZHANG ; Shu ZHOU ; Sai-Nan ZHOU
The Chinese Journal of Clinical Pharmacology 2024;40(1):67-71
Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)%,(29.16±8.37)%,(48.77±6.10)%,(48.35±6.04)%,(48.20±3.49)%and(39.24±4.20)%;the small intestinal propulsion rates were(82.01±7.55)%,(41.95±9.53)%,(64.61±10.18)%,(75.04±9.76)%,(60.58±7.13)%and(45.89±7.40)%;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P<0.01 or P<0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.
10.Study on the Correlation Between Sleep Status and Traditional Chinese Medicine Constitution Types of Sub-healthy Population in Lingnan Area
Bai-Shu CHEN ; Jin-Ling LONG ; Yan CHEN ; Qing-Song ZHANG ; Yi LUO ; Shu-Hui CHEN ; Ying-Zhen LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(7):1676-1681
Objective To explore the correlation between sleep status and traditional Chinese medicine(TCM)constitution types of sub-healthy population in Lingnan area.Methods From May 2022 to May 2023,an investigation was carried out in a sub-healthy population of 688 persons who lived in Shenzhen for more than 5 years,had no serious cardiovascular disease and were confirmed by the sub-health rating scale.The questionnaire survey of Pittsburgh Sleep Quality Index(PSQI)scale and the TCM constitution classification rating scale was conducted,and multiple linear regression analysis was performed to explore the correlation between the sleep status and TCM constitution types.Results(1)A total of 688 questionnaires were released,of which 19 were lost to follow-up,and 669 were responded.After weeding out the 29 invalid questionnaires,640 valid questionnaires were finally included for the analysis.(2)According to the PSQI score,the population was divided into excellent sleep group(total PSQI score<8)of 350 cases and poor sleep group(total PSQI score≥8)of 290 cases.The item scores of time for falling asleep,sleep time and sleep disorder as well as the total PSQI score of the excellent sleep group were significantly lower than those of the poor sleep group(P<0.05 or P<0.01).(3)The persons with excellent sleep usually had the balanced constitution(86.86%),while the persons with poor sleep often had the biased constitution(79.64%).The top three biased constitution types in the persons with poor sleep were damp-heat constitution(15.52%),phlegm-damp constitution(13.79%)and qi-stagnation constitution(13.10%).(4)Multiple linear regression analysis showed that the time for falling asleep was positively correlated with phlegm-damp constitution and qi-stagnation constitution(P<0.01),and was negatively correlated with balanced constitution(P<0.05);the sleep efficiency was positively correlated with damp-heat constitution and inherited special constitution(P<0.05 or P<0.01),and was negatively correlated with balanced constitution(P<0.05);sleep disorder was positively correlated with qi-stagnation constitution and yin-deficiency constitution(P<0.01);hypnotic drugs were positively correlated with yin-deficiency constitution(P<0.01);daytime dysfunction was positively correlated with phlegm-damp constitution(P<0.05).Conclusion The sleep status of sub-healthy population in Lingnan area has a certain correlation with TCM constitution types.Damp-heat constitution,phlegm-damp constitution,qi-stagnation constitution,yin-deficiency constitution,balanced constitution and inherited special constitution are the six constitution types that affect sleep status.It is of great significance to guide the sub-healthy population to achieve the purpose of prevention before illness by improving their constitution after the identification of TCM constitution types.

Result Analysis
Print
Save
E-mail