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.

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.

ObjectiveTo investigate the role of disco interacting protein 2 homolog B （DIP2B） in the proliferation， migration， and invasion processes of gastric cancer cells. MethodsBioinformatic analysis was performed using public datasets， including TCGA， GEPIA and TIMER2.0， to assess DIP2B expression and its clinical prognostic value in gastric cancer. DIP2B expression levels in gastric cancer cell lines were validated by Western blot and RT-qPCR. A DIP2B knockdown cell model was established via siRNA mediated gene silencing， and the knockdown efficiency was confirmed. Cell proliferation was assessed using real-time cellular analysis （RTCA） and colony formation assays. Cell migration and invasion were evaluated by Transwell assays， while flow cytometry was employed to detect changes in apoptosis and cell cycle distribution. ResultsDIP2B was significantly upregulated in gastric cancer cells and correlated with poor prognosis in patients （P<0.05）. The experimental results revealed that DIP2B knockdown markedly suppressed the proliferation， migration， and invasion of gastric cancer cells， while promoting apoptosis and inducing cell cycle arrest （P<0.05）. ConclusionDIP2B is highly expressed in gastric cancer and associated with unfavorable prognosis. Knockdown of DIP2B inhibits the proliferation， migration， and invasion of gastric cancer cells and promotes apoptosis， suggesting that DIP2B may serve as a potential prognostic biomarker and therapeutic target for gastric cancer.

OBJECTIVES: To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism. METHODS: MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin. RESULTS: The IC₅₀ of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio. CONCLUSIONS DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Apoptosis/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/metabolism* ; Cell Line, Tumor ; Artemisinins/pharmacology* ; Female ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Survivin

Blue light inactivation technology, particularly at the 405 nm wavelength, has demonstrated distinct and multifaceted mechanisms of action against both Gram-positive and Gram-negative bacteria, offering a promising alternative to conventional antibiotic therapies. For Gram-positive pathogens such as Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus (MRSA), the bactericidal effects are primarily mediated by endogenous porphyrins (e.g., protoporphyrin III, coproporphyrin III, and uroporphyrin III), which exhibit strong absorption peaks between 400-430 nm. Upon irradiation, these porphyrins are photoexcited to generate cytotoxic reactive oxygen species (ROS), including singlet oxygen, hydroxyl radicals, and superoxide anions, which collectively induce oxidative damage to cellular components. Early studies by Endarko et al. revealed that (405±5) nm blue light at 185 J/cm² effectively inactivated L. monocytogenes without exogenous photosensitizers, supporting the hypothesis of intrinsic photosensitizer involvement. Subsequent work by Masson-Meyers et al. demonstrated that 405 nm light at 121 J/cm² suppressed MRSA growth by activating endogenous porphyrins, leading to ROS accumulation. Kim et al. further elucidated that ROS generated under 405 nm irradiation directly interact with unsaturated fatty acids in bacterial membranes, initiating lipid peroxidation. This process disrupts membrane fluidity, compromises structural integrity, and impairs membrane-bound proteins, ultimately causing cell death. In contrast, Gram-negative bacteria such as Salmonella, Escherichia coli, Helicobacter pylori, Pseudomonas aeruginosa, and Acinetobacter baumannii exhibit more complex inactivation pathways. While endogenous porphyrins remain central to ROS generation, studies reveal additional photodynamic contributors, including flavins (e.g., riboflavin) and bacterial pigments. For instance, H. pylori naturally accumulates protoporphyrin and coproporphyrin mixtures, enabling efficient 405 nm light-mediated inactivation without antibiotic resistance concerns. Kim et al. demonstrated that 405 nm light at 288 J/cm² inactivates Salmonella by inducing genomic DNA oxidation (e.g., 8-hydroxy-deoxyguanosine formation) and disrupting membrane functions, particularly efflux pumps and glucose uptake systems. Huang et al. highlighted the enhanced efficacy of pulsed 405 nm light over continuous irradiation for E. coli, attributing this to increased membrane damage and optimized ROS generation through frequency-dependent photodynamic effects. Environmental factors such as temperature, pH, and osmotic stress further modulate susceptibility, sublethal stress conditions (e.g., high salinity or acidic environments) weaken bacterial membranes, rendering cells more vulnerable to subsequent ROS-mediated damage. The 405 nm blue light inactivates drug-resistant Pseudomonas aeruginosa through endogenous porphyrins, pyocyanin, and pyoverdine, with the inactivation efficacy influenced by bacterial growth phase and culture medium composition. Intriguingly, repeated 405 nm exposure (20 cycles) failed to induce resistance in A. baumannii, with transient tolerance linked to transient overexpression of antioxidant enzymes (e.g., superoxide dismutase) or stress-response genes (e.g., oxyR). For Gram-positive bacteria, porphyrin abundance dictates sensitivity, whereas in Gram-negative species, membrane architecture and accessory pigments modulate outcomes. Critically, ROS-mediated damage is nonspecific, targeting DNA, proteins, and lipids simultaneously, thereby minimizing resistance evolution. The 405 nm blue light technology, as a non-chemical sterilization method, shows promise in medical and food industries. It enhances infection control through photodynamic therapy and disinfection, synergizing with red light for anti-inflammatory treatments (e.g., acne). In food processing, it effectively inactivates pathogens (e.g., E. coli, S. aureus) without altering food quality. Despite efficacy against multidrug-resistant A. baumannii, challenges include device standardization, limited penetration in complex materials, and optimization of photosensitizers/light parameters. Interdisciplinary research is needed to address these limitations and scale applications in healthcare, food safety, and environmental decontamination.

Objective:To investigate the therapeutic effect of platelet-rich plasma(PRP)combined with Xianling Gubao Capsule on rats with osteoarthritis(OA)and the changes in the levels of related factors.Methods:Anterior cruciate ligament transection was performed to establish a rat model of OA,and after modeling,the rats were randomly divided into control group,model group,Xianling Gubao Capsule group,PRP group,and Xianling Gubao Capsule+PRP group,with 10 rats in each group.After intervention,ELISA was used to measure the serum levels of IL-1β and TNF-α;knee articular cartilage was collected,and qPCR and Western blot were used to measure the mRNA and protein expression levels of MMP3,MMP13,Col2,Aggrecan,and p-p38;Micro-CT was used to assess the changes in bones around the knee joint;HE staining and SF staining were used to observe the changes in knee articular cartilage.Results:ELISA showed that PRP combined with Xianling Gubao Capsule significantly reduced the serum levels of the inflammatory factors such as IL-1β and TNF-α(P<0.05).The results of qPCR and Western blot showed that PRP combined with Xianling Gubao Capsule significantly reduced the expression levels of MMP3,MMP13,and p-p38 and increased the expression levels of Col2 and Ag-grecan in knee articular cartilage(P<0.05).Micro-CT,HE staining,and SF staining showed a certain degree of improvement in knee articular cartilage degeneration in the Xianling Gubao Capsule+PRP group(P<0.05).Conclusion:PRP combined with Xianling Gubao Capsule exerts a therapeutic effect on rats with OA,possibly by regulating the p38MAPK signaling pathway.

Objective To investigate the correlation between apathy and imaging markers in pa-tients with aCSVD.Methods A total of 143 patients diagnosed with aCSVD and hospitalized in the Department of Neurology of the First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology from August 2023 to August 2024 were continu-ously included as the study objects.According to MAES,they were divided into an apathetic group(MAES score＞14,68 cases)and a non-apathetic group(MAES score ≤14,75 cases).The clinical data and imaging markers were compared between the two groups.Results The apathetic group had significantly older age and larger ratio of hypertension,but shorter years of education and lower MAES score than the non-apathetic group(P＜0.05,P＜0.01).The apathetic group also had notably higher Fazekas score of white matter hyperintensity(WMH),larger recent small sub-cortical infarct(RSSI),lacunar infarct(LI),and perivascular space(PVS)in the basal ganglia and the centrum semiovale,more obvious cerebral atrophy and cerebral microbleed(CMB),and high-er total imaging burden score when compared with the non-apathetic group(P＜0.01).In the aCSVD patients,the MAES score was positively correlated with WMH Fazekas score,RSSI,LI,basal ganglia PVS,centrum semiovale PVS,cerebral atrophy,CMB,and total imaging burden score(P＜0.01).WMH Fazekas score was an independent risk factor for apathy in the aCSVD patients(OR=2.218,95％CI:1.343-3.664,P=0.002).Conclusion The higher the score of ima-ging markers in patients with aCSVD,the more severe the apathy.

AIM To study the chemical constituents from Radix Puerariae Lobatae from Anhui province and their in vitro lipid-lowering activity.METHODS D101 macroporous resin,silica gel,MCI,and semi-preparative HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The lipid accumulation model was established by palmitic acid-induced hepatocyte AML12,and the in vitro lipid-lowering activity was evaluated.RESULTS Twenty-one compounds were isolated and identified as carboxymethyl isoferulate(1),methyl(E)feruloylglycolate(2),ariscucurbin-A(3),trans-p-coumaroygly colic acid(4),indole-3-carboxaldehyde(5),β-sitosterol(6),puerol A(7),pueroside C(8),cumoestrol(9),dihydrofurocoumarin(10),decuroside V(11),psoralen dimer(12),bergapten dimer(13),isoliquiritigenin(14),neoliquiritin(15),calycosin(16),daidzein(17),3,4,7-trihydroxyisoflavone(18),ononin(19),genistein(20),genistin(21).Compounds 1-4、7-10、13 and 17-19 significantly inhibited lipid accumulation in AML12 cells,and compound 9 inhibited PPAR-γ expression.CONCLUSION Compounds 1-6,10-13 are isolated from Pueraria genus for the first time.Compounds 1-4,7-10,13 and 17-19 have good lipid-lowering activity.

Objective To investigate the role and mechanism of AMP-activated protein kinase(AMPK)in regulating mitochondrial function and cardiomyocyte injury in sepsis.Methods Forty Balb/c mice were randomly divided into four groups:Sham group(n=10),Sham+5-aminoimidazole-4-carboxamide ribonucleotide(AICAR)group(n=10),CLP group(n=10),and CLP+AICAR group(n=10).A sepsis mouse model was established through cecal ligation and puncture(CLP).Echocardiography and histological analysis were used to assess sepsis-induced cardiac injury.Neonatal rat cardiomyocytes(NRCMs)were incubated with lipopolysaccharide(LPS)(10 μg/mL)for 24 h to induce an in vitro sepsis model,and treated with AICAR.Mitochondrial function and dynamics were assessed by using Western blotting,enzyme-linked immunosorbent assay(ELISA),and immunofluorescence assays.Results Compared with the Sham group,AMPK expression in the myocardial tissue of CLP mice was significantly reduced(P<0.05).Compared with the CLP group,AMPK expression in the CLP+AICAR group was significantly increased(P<0.05).Survival analysis showed that CLP led to a high mortality rate(～60％ ),while AICAR treatment significantly improved the survival rate of CLP mice(P<0.05).Compared with the Sham group,cardiac output(CO),stroke volume(SV),and left ventricular end-diastolic volume(LVEDV)were significantly decreased in the CLP group(P<0.05),while left ventricular posterior wall systolic(LVPWs)and left ventricular posterior wall thickness(LVPWd)were significantly increased(P<0.05).AICAR treatment alleviated the cardiac dysfunction induced by CLP.Compared with the CLP group,mitochondrial size and the number of mitochondrial cristae in the myocardial tissue of CLP+AICAR group mice were significantly increased(P<0.05),while DHE fluorescence intensity and the number of TUNEL-positive cells were significantly reduced(P<0.05).Compared with the LPS group,ATP production,mitochondrial respiration rate,and complex Ⅰ,Ⅱ,and Ⅲ activities in NRCMs of the LPS+AICAR group were significantly increased(P<0.05),while mitochondrial and cytoplasmic ROS levels were significantly reduced(P<0.05).Compared with the control group,mitochondrial size in NRCMs of the LPS group was significantly reduced(P<0.05),while Bax and Caspase-3 expression,as well as mitochondrial fission index,were significantly increased(P<0.05),and these changes were mitigated by AICAR(P<0.05).Conclusion AMPK plays a crucial role in maintaining cardiac function and mitigating septic myocardial injury by regulating mitochondrial structure and function,energy metabolism,oxidative stress,and apoptosis.

Objective:Interpret the key differences between the China Health-care Security Diagnosis Related Groups(CHS-DRG)2.0 and CHS-DRG 1.1,and provide reference for optimizing management strategies in medical institutions.Methods:Text analysis was used to import the CHS-DRG 2.0 and 1.1 grouping scheme dictionary data into the SQL database in a structured table format using SQL Server 2014.The key differences between the two schemes in grouping structure,grouping rules,grouping results,and other aspects were identified.Results:CHS-DRG 2.0 version added 26 groups,deleted 3 groups,and refined 10 groups into 20 groups for 14 clinical specialties at the ADRG level compared to CHS-DRG 1.1.Some group codes,names,and grouping rules were adjusted;Adjusted some grouping conditions and grouping results at the DRG level.Conclusion:CHS-DRG 2.0 version has improved grouping efficiency compared to CHS-DRG 1.1,solved some clinical bottleneck problems,and standardized the role of clinical diagnosis in grouping from the perspective of resource consumption.However,it has not completely solved the grouping problems of multi disease co treatment,multi disease treatment,and combined surgery.The adjustment of DRG weights and rates,the follow-up of related supporting policy reforms,and the negative effects of DRG will still pose challenges for medical institutions.