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.

OBJECTIVE To systematically evaluate the influential factors for all-cause mortality in patients with carbapenem-resistant Gram-negative bacteria （CR-GNB） treated with polymyxin B. METHODS PubMed， Embase， the Cochrane Library， Web of Science， Wanfang Data， VIP， CBM and CNKI were searched to collect clinical studies on all-cause death within 30 days or 28 days after treatment with polymyxin B in patients with CR-GNB infection from database establishment to July 2025. After literature screening， data extraction and evaluation of literature quality， meta-analysis was performed using RevMan 5.4 software. RESULTS A total of 12 studies were included， involving 1 326 patients， among whom 529 patients died， with a mortality rate of 39.89%. Meta-analysis results showed that combined with cardiovascular disease [OR＝2.06， 95%CI （1.37， 3.09）， P ＝0.005 ] ， increased Sequential Organ Failure Assessment （SOFA） score [OR＝1.20， 95%CI （1.07， 1.35）， P ＝0.003 ] ， mechanical ventilation [OR＝2.35， 95%CI （1.65， 3.34）， P ＜0.001 ] ， continuous renal replacement therapy （CRRT） [OR＝2.58， 95%CI （1.67， 3.97）， P ＜0.001 ] ， bloodstream infection [OR＝3.24， 95%CI （2.19， 4.78）， P ＜0.001 ] ， multiple-site infection [OR＝1.51， 95%CI （1.03， 2.20）， P ＝0.03 ] ， septic shock [OR＝3.19， 95%CI （1.94， 5.24）， P ＜0.001 ] ， use of vasoactive drugs [OR＝2.90， 95%CI （1.97， 4.27）， P ＜0.001 ] ， and the occurrence of acute kidney injury （AKI） [OR＝2.17， 95%CI （1.41， 3.36）， P ＜0.001 ] were risk factors for all-cause mortality in patients with CR-GNB infection treated with polymyxin B. Conversely， an extended duration of polymy xin B treatment [OR＝0.92， 95%CI （0.86， 0.99）， P ＝0.03 ] and early administration after CR-GNB infection [OR＝0.47， 95%CI （0.25， 0.85）， P ＝0.01 ] were protective factors. CONCLUSIONS Patients with cardiovascular disease， receiving mechanical ventilation or CRRT， having bloodstream infection， multiple-site infection or septic shock， combining with vasoactive drugs， with AKI and increased SOFA scores have a higher risk of all-cause mortality. Conversely， extending the duration of polymyxin B treatment （beyond 7 days） and early administration within 48 hours after confirmed CR-GNB infection can significantly reduce the risk of all-cause mortality.

Objective To investigate the drug resistance phenotype/genotype and virulence gene carrying status, serotype, and sequence typing (ST) of Campylobacter jejuni in Fengtai District in 2024. Methods The drug resistance phenotype was detected by agar dilution method, and serotyping was performed by real-time fluorescence quantitative polymerase chain reaction (PCR). The whole genome sequencing was used to analyze drug resistance genes, virulence genes, and other characteristics. Results Among the 35 Campylobacter jejuni strains analyzed, the antibiotics with the highest resistance rates were nalidixic acid and ciprofloxacin (both 82.86%), followed by tetracycline (74.89%). All strains exhibited a 100.00% sensitivity rate to erythromycin. The multiple drug resistance rate was 77.14%. The predominant drug resistance genes were gyrA-T86I (94.29%) and tetO (74.29%). The most common serotype was HS:2, accounting for 25 strains. A total of 132 virulence genes were detected. There were 12 clonal complexes (CC) and 24 ST types. Conclusion The drug resistance situation of Campylobacter jejuni in Fengtai District is relatively severe, and the drug resistance phenotype is related to specific genetic mutations to some extent. The serotypes are diverse, the virulence genes are complex, and the pathogenic potential is significant, posing a notable risk for inducing Guillain-Barré syndrome (GBS). The high number of ST types indicates substantial genetic diversity.

Objective To evaluate the brain injury in children with congenital diaphragmatic hernia(CDH)after surgery through examination methods such as amplitude-integrated electroencephalogram(aEEG),regional cerebral oxygen saturation(rSO2)and neonatal behavioral neurological assessment(NBNA),so as to clarify their diagnostic value.Methods A total of 83 full-term CDH children admitted to our hospital were retrospectively enrolled as the research subjects.According to the brain damage syndrome(BDS)diagnostic criteria,they were divided into brain injury group(n=36)and control group(n=47).We compared the general data of the neonates in the two groups,as well as the modified aEEG scores and rSO2 at admission,14 days after birth,and 28 days after birth.We compared the NBNA scores at 28 days after birth.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of the three tools for brain injury.Results The modified aEEG scores of the children in the brain injury group at each time point were lower than those in the control group.The rSO2 of the children in the brain injury group was lower than that in the control group at 14 days and 28 days after birth and recovered slowly.The NBNA scores also indicated that the neurodevelopment of the children in the brain injury group was significantly lower than that in the control group.The ROC curve showed that the areas under the curve of combined diagnosis exhibited the best diagnostic efficacy compared with rSO2 used alone at 28 days after birth,aEEG at 28 days after birth,and NBNA scores(the area under the curve:0.968 vs.0.701 vs.0.685 vs.0.870;sensitivity:92.0％ vs.53.7％ vs.87.8％ vs.95.1％;specificity:97.0％ vs.86.1％ vs.50.0％ vs.72.2％).Conclusion The combined application of the modified aEEG score,rSO2,and NBNA has high sensitivity and specificity in the diagnosis of brain injury in children with CDH;therefore,it is worthy of clinical promotion and application.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

ObjectiveTo investigate the effects of Zuoguiwan on osteoclast activation induced by breast cancer and its mechanism. MethodsTo simulate breast cancer-induced osteoclastic bone metastasis， RAW264.7 cells were cultured in conditioned medium containing 50% supernatant of MDA-MB-231 breast cancer cells. The dosages of Zuoguiwan used in the experiment were sera containing 5% and 10% Zuoguiwan. Tartrate-resistant acid phosphatase （TRAP） staining was used to detect osteoclast activation. Enzyme-linked immunosorbent assay （ELISA） was used to measure Cathepsin K secretion from RAW264.7 cells. Real-time quantitative polymerase chain reaction （PCR） was used to detect the mRNA expression levels of osteocalcin （OCN） and bone sialoprotein （BSP）. Immunoprecipitation was employed to detect the interaction between Runt-related transcription factor 2 （Runx2） and core binding factor β subunit （CBF-β）. Western blot was used to assess the protein expression of Runx2， phosphorylated Runx2 （p-Runx2）， extracellular signal-regulated kinases 1/2 （ERK1/2）， p-ERK1/2， p38 mitogen-activated protein kinase （MAPK）， p-p38 MAPK， and CBF-β. ResultsCompared with the blank group， the MDA-MB-231 cell supernatant group showed a significant increase in TRAP-positive cell counts and Cathepsin K secretion. Meanwhile， the expression levels of p-Runx2， Runx2-CBF-β interaction， BSP and OCN mRNA， p-p38 MAPK， and p-ERK1/2 proteins were significantly decreased （P<0.01）. Compared with the MDA-MB-231 cell supernatant group， Zuoguiwan-containing sera significantly reduced TRAP-positive cell counts and Cathepsin K secretion （P<0.01）， significantly increased p-Runx2， BSP and OCN mRNA expression， as well as p-p38 MAPK and p-ERK1/2 protein levels， and promoted the interaction between Runx2 and CBF-β （P<0.01）. No significant change in Runx2 expression was observed. Compared to the blank group， the BVD-523 group showed significantly lower expression of p-p38 MAPK and p-ERK1/2 proteins （P<0.01）. Compared with the BVD-523 group， both low and high concentration Zuoguiwan-containing sera groups showed significantly higher p-p38 MAPK expression （P<0.01）， and the high concentration Zuoguiwan group also exhibited a significant increase in p-ERK1/2 expression （P<0.01）， while no statistical difference was found in the low-dose group. ConclusionZuoguiwan inhibits osteoclast activation by inducing phosphorylation of the key transcriptional regulator Runx2 in intra-osteoclast bone formation， and this process is closely associated with the activation of the p38 MAPK/ERK signaling pathway.

Inflammatory response,immunosuppression,and drug sensitivity have been reported to have a significant correlation with the disulfidptosis levels in cancer patients.However,the value of disulfidpto-sis in colorectal cancer therapy remains unclear.Therefore,we classified the CRC cells into different cell types using single-cell sequencing data and cell-specific markers and analyzed their relationship with the cell disulfidptosis level.We found that the high disulfidptosis regions were concentrated in epithelial-like CRC cells.Further exploration using the disulfidptosis and programmed cell death 1 inhibitor therapy treated differential expression genes indicated that CRC patients with high disulfidptosis levels exhibited a lower risk profile and increased sensitivity to immunotherapy.By using the spatial transcriptomic analy-sis,we found that ubiquinol-cytochrome c reductase core protein 1(UQCRC1),a disulfidptosis-related gene,is highly expressed in epithelial-like CRC cells and co-localized with immune-infiltrated tumor re-gions.Additional bioinformatic analyses and experimental validation further confirmed that UQCRC1 was downregulated in CRC tissues.Overexpression of UQCRC1 suppressed CRC cell proliferation and migra-tion.These findings indicate that UQCRC1 is a potential target for CRC diagnosis and treatment.

Purpose To evaluate the diagnostic value of 18F-fluorodeoxyglucose(18F-FDG)PET/CT in differentiating primary lung cancer(PLC)from metastatic pulmonary breast cancer in breast cancer patients with solitary pulmonary lesion(SPL).Materials and Methods This retrospective analysis included 58 breast cancer patients with SPL in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2015 to August 2024.All patients had pathologically confirmed breast cancer with SPL and underwent PET/CT scans,including 36 cases of PLC and 22 cases of metastatic pulmonary breast cancer.Differences in clinical pathological features,high resolution CT morphological,and PET metabolic characteristics were analyzed.Multivariate Logistic regression was utilized to investigate independent predictive factors for SPL diagnosis.Results Statistically significant differences were observed between lesion density,nodule-lung interface,bubble sign,vascular convergence sign and pleural indentation sign(χ2=9.420,7.000,8.487,all P<0.05).PET/CT metabolic analysis revealed a significant difference in maximum standardized uptake value(SUVmax)between the two groups(Z=4.613,P<0.001).Multivariate analysis showed that bubble sign,pleural indentation sign and lower SUVmax were independent predictors for PLC.With an SUVmax threshold of 2.5,the area under the receiver operating curve(AUC)was 0.862,with a sensitivity of 90.9%,specificity of 77.8%and an accuracy of 82.8%.Combined analysis of high resolution CT and SUVmax demonstrated the highest diagnostic efficacy,with an area under the curve of 0.937,sensitivity of 90.9%,specificity of 94.4%and accuracy of 93.1%.Conclusion The presence of bubble sign,pleural indentation and SUVmax<2.5 suggests a high likelihood of PLC.Combined high resolution CT imaging features and PET metabolic characteristics significantly improve diagnostic accuracy for SPLs in breast cancer patients.

Copy number variation encompassing SNP plays an important role in IVD and precision medi-cine.As the most commonly used method,FISH could not overcome the probe cross-reactivity which is common when to detect SNP.Here we developed a quantitative and qualitative method on copy number variation encompassing SNP.In this study,the rs76711854 was used as an example to establish a quanti-tative method by advantage of probe cross-reactivity.The fragment encompassing rs76711854 and its downstream to 9 514 bp were amplified by PCR.The allelic genotypes were verified by Sanger sequen-cing.Different probes with or without cross-reactivity to be used via quantitative real-time PCR and digit-al PCR.The different clusters(2D)and fluorescence intensity layers(1D)exist by adding probe with cross-reactivity.The A/G ratio measured by digital PCR is 2︰1,which is verified by probe targeting to the SNP.The copy-number variant exists in the 9kb-long fragment upstream to the SNP of prostate cancer cell line but not in human endometrial adenocarcinoma cell line Ishikawa.The data suggest that there is a multi-copy variation at this locus in DU145 cells.The method applied here is based on one single cross-reactivity probe via digital PCR.