1.Nanopackaged Astaxanthin Improves Demyelination in Multiple Sclerosis Model Mice by Scavenging Excessive Endogenous Formaldehyde
Wan-Jia LÜ ; Xin ZENG ; Zhi-Qian TONG ; Yang XING ; Xu YANG ; Mei-Na WU ; Ping MA
Progress in Biochemistry and Biophysics 2026;53(2):442-457
ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS); however, its underlying neurological pathogenic mechanisms remain incompletely understood. Endogenous formaldehyde (FA), a metabolic byproduct of methylation-demethylation cycles, has recently been implicated in neurotoxicity, oxidative damage, and cognitive impairment. This study aimed to investigate whether excessive FA contributes to myelin sheath demyelination in mice and to evaluate the protective effects and mechanisms of two FA-elimination strategies: sodium bisulfite (NaHSO3), a classical FA scavenger, and polyethylene glycol-modified astaxanthin nanoparticles (PEG-ATX@NPs), a brain-targeted nano-antioxidant formulation. MethodsA chronic demyelination model was established by feeding female C57BL/6J mice a diet containing 0.2% cuprizone (CPZ) for four weeks, followed by a two-week intervention period. Eighty mice were randomly assigned to four groups: NS (normal saline), CPZ+NS, CPZ+NaHSO3, and CPZ+PEG-ATX@NPs. Behavioral tests, including open-field, Y-maze, and pole-climbing assays, were conducted to assess locomotor activity, motor coordination, and working memory. FA levels in serum, corpus callosum, and spinal cord were measured using an Na-FA fluorescent probe and quantified via in vivo and ex vivo fluorescence imaging. Neuroinflammatory responses were evaluated by measuring TNF-α, IL-1β, and IL-6 levels using ELISA, while oxidative stress was assessed by reactive oxygen species (ROS) fluorescence intensity. Demyelination was examined via Luxol fast blue staining, and microglial activation was analyzed by Iba1 immunofluorescence. Correlation analyses were performed to explore relationships among FA levels, inflammatory cytokines, ROS intensity, and behavioral parameters. ResultsCompared with the NS group, mice in the CPZ+NS group exhibited significant weight loss, impaired motor coordination and memory, and markedly reduced myelin regeneration (P<0.05). FA levels and pro-inflammatory cytokines were significantly elevated in serum, corpus callosum, and spinal cord (P<0.05). FA-associated fluorescence in brain and spinal tissues, as well as ROS intensity across all tissues examined, also increased substantially (P<0.05). CPZ treatment induced pronounced microglial activation and severe demyelination in the corpus callosum (P<0.01). Both NaHSO3 and PEG-ATX@NPs effectively reduced FA accumulation in the brain and spinal cord, attenuated demyelination, suppressed microglial activation, decreased inflammatory cytokine levels, and improved motor and cognitive performance. These results confirm that CPZ induced severe demyelination accompanied by oxidative stress, neuroinflammation, and abnormal FA accumulation. Following intervention with either NaHSO3 or PEG-ATX@NPs, endogenous FA levels in the CNS were substantially reduced. Both treatments alleviated demyelination and significantly decreased the number of activated microglia. Levels of TNF-α, IL-1β, and IL-6 in serum, corpus callosum, and spinal cord were downregulated. Behavioral performance improved significantly, as evidenced by enhanced locomotor activity, better coordination, and improved memory function. These findings indicate that both FA-scavenging agents mitigate CPZ-induced biochemical and behavioral abnormalities. ConclusionThis study demonstrates that excessive endogenous FA is closely associated with cognitive impairment, inflammatory dysregulation, and demyelination in a CPZ-induced chronic demyelination mouse model. Clearing abnormally elevated FA effectively reduces neuroinflammation, suppresses microglial overactivation, decreases oxidative stress, and alleviates demyelination, ultimately improving motor and cognitive outcomes in mice. These results suggest that targeting endogenous FA represents a promising therapeutic strategy for MS and other demyelinating disorders. Further investigations are warranted to explore the long-term safety, dosage optimization, and molecular pathways involved in FA-mediated neurotoxicity.
2.Nanopackaged Astaxanthin Improves Demyelination in Multiple Sclerosis Model Mice by Scavenging Excessive Endogenous Formaldehyde
Wan-Jia LÜ ; Xin ZENG ; Zhi-Qian TONG ; Yang XING ; Xu YANG ; Mei-Na WU ; Ping MA
Progress in Biochemistry and Biophysics 2026;53(2):442-457
ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS); however, its underlying neurological pathogenic mechanisms remain incompletely understood. Endogenous formaldehyde (FA), a metabolic byproduct of methylation-demethylation cycles, has recently been implicated in neurotoxicity, oxidative damage, and cognitive impairment. This study aimed to investigate whether excessive FA contributes to myelin sheath demyelination in mice and to evaluate the protective effects and mechanisms of two FA-elimination strategies: sodium bisulfite (NaHSO3), a classical FA scavenger, and polyethylene glycol-modified astaxanthin nanoparticles (PEG-ATX@NPs), a brain-targeted nano-antioxidant formulation. MethodsA chronic demyelination model was established by feeding female C57BL/6J mice a diet containing 0.2% cuprizone (CPZ) for four weeks, followed by a two-week intervention period. Eighty mice were randomly assigned to four groups: NS (normal saline), CPZ+NS, CPZ+NaHSO3, and CPZ+PEG-ATX@NPs. Behavioral tests, including open-field, Y-maze, and pole-climbing assays, were conducted to assess locomotor activity, motor coordination, and working memory. FA levels in serum, corpus callosum, and spinal cord were measured using an Na-FA fluorescent probe and quantified via in vivo and ex vivo fluorescence imaging. Neuroinflammatory responses were evaluated by measuring TNF-α, IL-1β, and IL-6 levels using ELISA, while oxidative stress was assessed by reactive oxygen species (ROS) fluorescence intensity. Demyelination was examined via Luxol fast blue staining, and microglial activation was analyzed by Iba1 immunofluorescence. Correlation analyses were performed to explore relationships among FA levels, inflammatory cytokines, ROS intensity, and behavioral parameters. ResultsCompared with the NS group, mice in the CPZ+NS group exhibited significant weight loss, impaired motor coordination and memory, and markedly reduced myelin regeneration (P<0.05). FA levels and pro-inflammatory cytokines were significantly elevated in serum, corpus callosum, and spinal cord (P<0.05). FA-associated fluorescence in brain and spinal tissues, as well as ROS intensity across all tissues examined, also increased substantially (P<0.05). CPZ treatment induced pronounced microglial activation and severe demyelination in the corpus callosum (P<0.01). Both NaHSO3 and PEG-ATX@NPs effectively reduced FA accumulation in the brain and spinal cord, attenuated demyelination, suppressed microglial activation, decreased inflammatory cytokine levels, and improved motor and cognitive performance. These results confirm that CPZ induced severe demyelination accompanied by oxidative stress, neuroinflammation, and abnormal FA accumulation. Following intervention with either NaHSO3 or PEG-ATX@NPs, endogenous FA levels in the CNS were substantially reduced. Both treatments alleviated demyelination and significantly decreased the number of activated microglia. Levels of TNF-α, IL-1β, and IL-6 in serum, corpus callosum, and spinal cord were downregulated. Behavioral performance improved significantly, as evidenced by enhanced locomotor activity, better coordination, and improved memory function. These findings indicate that both FA-scavenging agents mitigate CPZ-induced biochemical and behavioral abnormalities. ConclusionThis study demonstrates that excessive endogenous FA is closely associated with cognitive impairment, inflammatory dysregulation, and demyelination in a CPZ-induced chronic demyelination mouse model. Clearing abnormally elevated FA effectively reduces neuroinflammation, suppresses microglial overactivation, decreases oxidative stress, and alleviates demyelination, ultimately improving motor and cognitive outcomes in mice. These results suggest that targeting endogenous FA represents a promising therapeutic strategy for MS and other demyelinating disorders. Further investigations are warranted to explore the long-term safety, dosage optimization, and molecular pathways involved in FA-mediated neurotoxicity.
3.Relationship between radial-ulnar ratio,lateral lunate angle of radius and height loss of radius after palmar locking plate surgery for distal radius fractures
Xing-jun LI ; Jun-jun SUN ; Bo ZHENG ; Jun ZHANG ; Zhi-fei JIAN ; Xiang ZHUO
Journal of Regional Anatomy and Operative Surgery 2025;34(6):505-511
Objective To investigate the relationship between the radial-ulnar ratio,lateral lunate angle of radius and height loss of radius after palmar locking plate internal fixation for distal radius fractures.Methods A total of 158 patients with distal radius fractures treated with palmar locking plate internal fixation in our hospital from March 2020 to September 2023 were selected.According to the height of radius loss after operation,the patients were divided into non-radius loss group(41 cases,<2 mm),mild to moderate radius loss group(32 cases,2 to 5 mm)and severe radius loss group(85 cases,>5 mm),and the clinical data of patients in the three groups were compared.Multivariate Logistic regression analysis was used to analyze the risk factors affecting height loss of radius.Locally weighted scatterplot smoothing(LOWESS)method was used to analyze the two-dimensional curve relationship of continuous variables.Restricted cubic spline(RCS)and threshold effect were used to analyze the relationship between the radial-ulnar ratio,lateral lunate angle of radius and height loss of radius after operation.Results The age of patients in the severe radius loss group was significantly higher than those in the non-radius loss group and the mild to moderate radius loss group(P<0.05),and the age of patients in the mild to moderate radius loss group was significantly higher than that in the non-radius loss group(P<0.05).Female patients and patients with osteoporosis and fracture type C were more likely to have height loss of radius(P<0.05).There were significant differences in patient-rated wrist evaluation(PRWE)score,disabilities of the arm,shoulder and hand(DASH)score,dorsal extension,palmar curvature,ulnar deviation,radial deviation,radial-ulnar ratio,and lateral lunate angle of radius of patients at 3 and 6 months after operation among three groups(P<0.001).The first prediction model based on age,gender,osteoporosis,fracture type,PRWE score,DASH score,dorsal extension,palmar curvature,ulnar deviation,and radial deviation and the second prediction model based on age,gender,osteoporosis,fracture type,PRWE score,DASH score,dorsal extension,palmar curvature,ulnar deviation,radial deviation,radial-ulnar ratio,and lateral lunate angle of radius were subjected to Hosmer-Lemeshow test showed good goodness of fit.LOWESS analysis showed that age,PRWE score,DASH score,dorsal extension,palmar curvature,ulnar deviation,radial deviation,radial-ulnar ratio,and lateral lunate angle of radius had a certain nonlinear relationship with the height loss of radius.RCS and threshold effect analysis showed that the probability of postoperative radius loss increased with the increase of radial-ulnar ratio in patients with distal radius fractures and radial-ulnar ratio≥13.254(P<0.001).The probability of postoperative radius loss decreased with the increase of the lateral lunate angle of radius in patients with distal radius fractures and lateral lunate angle of radius≤11.068°(P<0.001).Conclusion There was a positive correlation between the radial-ulnar ratio and the height loss of radius,and a negative correlation between the lateral lunate angle of radius and the height loss of radius after palmar locking plate internal fixation for distal radius fractures.
4.Global research status,hotspot analysis and trend outlook of tick-borne encephalitis
Xing-zhi FENG ; Yi-jia XU ; Qian-feng XIA ; Ya-jun LU
Chinese Journal of Zoonoses 2025;41(4):434-440
This study explored the current status,hotspots,and research trends in tick-borne encephalitis(TBE)worldwide.The bibliometric analysis and knowledge mapping software,VOSviewer,was used to conduct a comprehensive study of the literature in the field of TBE in the Web of Science database and the CNKI database,and to construct a research framework of the TBE field in order to demonstrate the association between the main keywords,research countries,research institutions and published journals in this field.A total of 2 046 English-language and 582 Chinese-language publications were included in this study,with an increasing trend of publication year by year.Keyword co-occurrence analysis showed that TBE and its viruses were the focus of research,along with infection,epidemiology,pathogen classification,prevalence,transmission,and clinical symptoms.The United States,Germany,and other countries were at the top of the list of publications and citations.Institutions such as the Russian Academy of Sciences and Medical University of Vienna were prominent contributors to TBE research.Journals represented by Ticks and Tick-borne Diseases were in the lead in terms of publications and citations and were important publications for research in this field.TBE research showed wide and vigorous trends worldwide.The study displayed the current status of research and the evolution of hot trends in this field,which provided us with strong support for examining TBE as a public health problem from a broader perspective and was also of great significance for promoting future in-depth research and formulating precise prevention and control strategies.
5.Exploring the sustainability of China's medical and health assistance and cooperation with Uganda
Ru-zhang JIANG ; Xiao-xing FU ; Jian JI ; Yi-hang LU ; Zhi-wei LENG
Chinese Journal of Health Policy 2025;18(2):69-75
Sustainability is a critical issue in China's medical and health assistance and cooperation with Africa.As China enters a new phase in this field,achieving sustainability presents both opportunities and challenges.Summarizing past successes and identifying barriers are of great practical significance for future development.This study examines the current state of China's medical and health assistance and cooperation with Uganda and finds that China has actively sought to integrate into local communities by collaborating with Ugandan medical institutions.However,several factors continue to constrain the sustainability of these efforts,including Uganda's fragmented public-private healthcare system heavily reliant on external aid,the personnel structure of Chinese medical teams,and linguistic and cultural barriers between China and Uganda.Based on official policy documents from both countries and field research findings,this study recommends supporting and assisting Uganda in establishing an independent healthcare system,with a particular focus on maternal and child health,youth health,and chronic disease management.Furthermore,strengthening cultural exchanges can contribute to the sustainable development of China-Uganda and broader China-Africa medical and health assistance and cooperation.
6.Moxibustion combined with low-dose tadalafil for diabetes mellitus-induced erectile dysfunction:A prospective,single-center,three-arm randomized controlled trial
Tao LIU ; Zhao-xu YANG ; Yan XU ; Qi ZHAO ; Xue LIU ; Xin-fei HUANG ; Zhi-xing SUN ; Yun CHEN ; Jian-huai CHEN
National Journal of Andrology 2025;31(1):55-60
Objective:To investigate the clinical efficacy of moxibustion(Mox)combined with low-dose tadalafil(TAD)in the treatment of diabetes mellitus-induced erectile dysfunction(DMED)with the syndrome of Qi deficiency and blood stasis.Meth-ods:According to the inclusion and exclusion criteria,we selected 90 patients with DMED for this trial and equally randomized them into a Mox,a TAD,and a Mox combined with TAD(Mox+TAD)group to be treated by mild Mox applied to the acupoints Zusanli,Sanyinjiao and Yinlingquan qd alt,oral medication with low-dose TAD at 5 mg per dose qd,and combination of the above two thera-pies,respectively,all for 4 weeks.We obtained from the patients their IIEF-5 scores,traditional Chinese medicine(TCM)symptoms scores,Erectile Hardness Scale(EHS)scores,corpus cavernosal hemodynamic indexes,and the peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)of the corpus cavernosal arteries before and after treatment,and compared them among the three groups.Results:The total effectiveness rate was significantly higher in the Mox+TAD(90.0%)than in the Mox(46.7%)and TAD groups(60.0%)(P<0.05).Compared with the baseline,the IIEF-5 and EHS scores were increased,while the TCM symptoms scores decreased in all the three groups after treatment,more significantly in the Mox+TAD group than in the other two(P<0.05).And the PSV and RI were remarkably increased,while the EDV decreased(P<0.05)in all the three groups(P<0.05)after treatment,with PSV even higher in the Mox+TAD than in the Mox and TAD groups(P<0.05).Conclusion:Moxi-bustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED,which can effectively improve the erectile function of the patients by increasing penile blood supply,benefiting qi and activating blood circulation.
7.Clinical efficacy observation of vital pulp therapy for mature permanent teeth with carious irreversible pulpitis
Zhi-ming QIN ; Jia-yang LI ; Hua-xing XU ; Zhi-fei MA ; Xiao-ling WEI
Fudan University Journal of Medical Sciences 2025;52(2):263-269
Objective To compare the pain relief and long-term clinical success rate of vital pulp therapy and root canal treatment in mature permanent teeth with carious irreversible pulpitis.Methods A total of 90 patients diagnosed with carious irreversible pulpitis in mature permanent teeth were collected at Shanghai Stomatological Hospital from Jan 2021 to Jun 2022.They were randomly divided into two groups:test group(n=45)undergoing vital pulp therapy(VPT)and control group(n=45)undergoing root canal treatment(RCT).Pain scores were recorded before treatment,24 hours after operation and 7 days after operation.We conducted clinical evaluation and imaging analysis at 1,6,and 12 months after the surgery,then compared the pain scores and treatment success rates between the two groups.Results Eighty-one patients,including 39 patients in group VPT aged(31.00±1.43)years old and 42 patients in group RCT aged(30.60±1.54)years old,received follow-up for more than 1 year,and the success rate of the test group and control was 97.44%and 95.24%.The pain degree of the two groups was reduced at 24 hours and 7 days after operation(P<0.05),and the pain score of the test group was reduced compared with that in the control group 7 days after operation(P<0.01).Conclusion Compared with root canal treatment,vital pulp therapy for mature permanent teeth with carious irreversible pulpitis can achieve good results in short-term pain evolution and long-term clinical success.
8.Early diagnostic value of Pentraxin-3 promoter methylation for compli-cated appendicitis
Feng-bo SUN ; Zhi-yuan XING ; Hong MA ; Jing-yuan CUI
Chinese Journal of Current Advances in General Surgery 2025;28(5):343-349
Objective:To investigate the early diagnosis value of Pentraxin-3(PTX-3)promoter methylation for complicated appendicitis.Methods:Patients with appendicitis and healthy physical examination from Qingdao Hiser Medical Group were selected as the research objects,and they were divided into complicated appendicitis group(CA),simple appendicitis group(SA)and healthy control group(HCs).Plasma PTX-3 levels,mRNA expression,promoter methylation status,and clinical parameters—including total bilirubin(TBIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(Alb),white blood cell count(WBC),neutrophil count(NEU),C-reactive protein(CRP),and procalcitonin(PCT)—were analyzed.in each group.Spearman correlation analysis was used to test the correlation of variables.Multivariate Logistic regression analysis was used to test the correlation between PTX-3 gene methylation and clinical parameters.The area under the receiver operating characteristic curve(AUC)was used to analyze the diagnostic value of PTX-3 methylation for CA.Results:The mRNA level and plasma concentration of PTX-3 in CA group were significantly higher than those in SA group and HCs group,while the methylation frequency of PTX-3 in CA group was significantly lower than that in SA group and HCs group(P<0.05).The methylation status of PTX-3 gene was significantly correlated with inflammatory markers(WBC,NEU,PCT,CRP)(P<0.05).Multivariate Logistic regression analysis showed that WBC,CRP and PCT were independent influencing factors of PTX-3 gene promoter methylation(P<0.05).Spearman correlation analysis showed that the PTX-3 mRNA level in peripheral blood of CA patients was negatively correlated with its methylation status(P<0.001).PTX-3 mRNA level was positively correlated with WBC,NEU,CRP and PCT levels(P<0.05).The sensitivity and specificity of PTX-3 gene methylation in the diagnosis of CA were 94.67%and 76.67%,re-spectively.When CA was diagnosed from SA patients,the AUCs of PTX-3 methylation were significantly higher than those of WBC,NEU,CRP and PCT(P<0.001).Conclusion:PTX-3 promoter methylation is involved in the pathogen-esis of AA by regulating the expression of PTX-3.It can be used to monitor the inflammatory state of patients with com-plicated appendicitis and serve as a non-invasive early diagnosis biomarker for complicated appendicitis.
9.Effect of pinocembrin on the malignant biological behavior of gastric can-cer cells by regulating the RhoA/ROCK signaling pathway
Rong PENG ; Ze-min ZHANG ; Zhi-qing WANG ; Bin LI ; Li-ping QING ; Jin-xing WANG
Chinese Journal of Current Advances in General Surgery 2025;28(8):601-606
Objective:Exploring the effect of Pinocembrin(Pino)regulating the Ras homolog gene family member A/Rho associated with curly helix binding protein kinase(RhoA/ROCK)signaling pathway of Ras homologous gene family members on the malignant biological behavior of gastric cancer cells.Methods:Cultivate human gastric cancer cells MGC803 with different concentrations of Pino(0~240μmol/L),detect cell survival rate using CCK-8 method,and screen for the optimal drug concentration.MGC803 cells were rseparated into MGC803 group(Control group),Pino-L group,Pino-M group,Pino-H group,and Pino-H+RhoA agonist CN03 group.The clone formation experiment was applied to detect the number of clones formed of cells in each group.Assessment of cell apoptosis using flow cytometry.Tran-swell invasion and migration experiments were used to detect the number of cells undergoing migration and invasion in each group;Detection of RhoA/ROCK signaling pathway and expression of epithelial mesenchymal transition related proteins in MGC803 cells using Western blot method.Results:Compared with the MGC803 group,the cell survival rate,clone formation number,migration cell number,and invasion cell number were all reduced in the Pino-L group,Pino-M group,and Pino-H group,and RhoA was also present in the cells,ROCK2,The expression levels of vimentin and N-cadherin gradually decreased(P<0.05),while the apoptosis rate and E-cadherin expression level gradually in-creased(P<0.05).The Pino-H+CN03 group reversed the trend of changes in the above indicators).Conclusion:Pino can prevent malignant biological behavior of gastric cancer cells,which may be related to the inhibition of the RhoA/ROCK signaling pathway.
10.Clinical efficacy observation of vital pulp therapy for mature permanent teeth with carious irreversible pulpitis
Zhi-ming QIN ; Jia-yang LI ; Hua-xing XU ; Zhi-fei MA ; Xiao-ling WEI
Fudan University Journal of Medical Sciences 2025;52(2):263-269
Objective To compare the pain relief and long-term clinical success rate of vital pulp therapy and root canal treatment in mature permanent teeth with carious irreversible pulpitis.Methods A total of 90 patients diagnosed with carious irreversible pulpitis in mature permanent teeth were collected at Shanghai Stomatological Hospital from Jan 2021 to Jun 2022.They were randomly divided into two groups:test group(n=45)undergoing vital pulp therapy(VPT)and control group(n=45)undergoing root canal treatment(RCT).Pain scores were recorded before treatment,24 hours after operation and 7 days after operation.We conducted clinical evaluation and imaging analysis at 1,6,and 12 months after the surgery,then compared the pain scores and treatment success rates between the two groups.Results Eighty-one patients,including 39 patients in group VPT aged(31.00±1.43)years old and 42 patients in group RCT aged(30.60±1.54)years old,received follow-up for more than 1 year,and the success rate of the test group and control was 97.44%and 95.24%.The pain degree of the two groups was reduced at 24 hours and 7 days after operation(P<0.05),and the pain score of the test group was reduced compared with that in the control group 7 days after operation(P<0.01).Conclusion Compared with root canal treatment,vital pulp therapy for mature permanent teeth with carious irreversible pulpitis can achieve good results in short-term pain evolution and long-term clinical success.

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