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.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

OBJECTIVE To stimulate the debridement and dressing process under the approximately real clinical scene by fluorescence labeling and understand the contamination status of the operators' bodies and their surround-ings so as to improve the strategies.METHODS A total of 41 trainees were recruited from Enterostomal Therapist Nursing Education Program of Peking University School of Medicine and International School of Wound Thera-pists of Peking University First Hospital in 2023.The examination was designed by stimulating the debridement and dressing operations with fluorescence labeling,the orange was used to simulate the wound of the patients,and the pad towel was placed under the orange to represent the contaminated surroundings of the wound.A round le-sion area with diameter of 2 cm was uniformly marked on the surface of the orange peel by the operators,the trai-nees were asked to remove the lesion tissues and take dressings.The fluorescent powders were smeared evenly on the orange and pad towel before the examination,and no fluorescence labeling for the surroundings was guaranteed.The trainees were required to wear hats,masks,isolation gowns and gloves during the operations,and take off the gloves and trace the scope of fluorescent contamination with ultraviolet radiator after the examina-tion.RESULTS The contamination rate was 92.68％for the trainees' bodies,100.00％for their surroundings.The hands and forearms were the most severe contaminated body sites,and the contamination rates were 85.37％(35/41)and 34.15％(14/41),respectively.The downside of the pad towel was the most frequently contaminated area of the surroundings,with the proportion of 90.24％(37/41);the right side of the pad towel was the area with the contamination disseminated farthest,with the median distance of dissemination 13.50 cm.In addition,the dressing change carts of 75.61％(31/41)of the trainees were contaminated.CONCLUSIONS The operations of de-bridement and dressing change may lead to varying degrees of contamination of their bodies and surroundings.It is necessary to strengthen the hand hygiene and protective isolation during the process of dressing change and pay attention to the disinfection of the dressing change carts so as to minimize the risk of hospital-associated infec-tions.

Three evaluation methods were recommended for the key properties of the intravascular catheter lubricating coating such as stability,lubricity and integrity,including insoluble particle test method,friction test procedure and appearance detection method.Fifteen batches of microcatheters produced by different manufacturers were selected for testing to clarify the three methods in test principle,step,result,characteristic.References were provided for the design,production,evaluation and regulation of intravascular catheters with lubricant coatings.[Chinese Medical Equipment Journal,2025,46(1):66-72]

OBJECTIVE To stimulate the debridement and dressing process under the approximately real clinical scene by fluorescence labeling and understand the contamination status of the operators' bodies and their surround-ings so as to improve the strategies.METHODS A total of 41 trainees were recruited from Enterostomal Therapist Nursing Education Program of Peking University School of Medicine and International School of Wound Thera-pists of Peking University First Hospital in 2023.The examination was designed by stimulating the debridement and dressing operations with fluorescence labeling,the orange was used to simulate the wound of the patients,and the pad towel was placed under the orange to represent the contaminated surroundings of the wound.A round le-sion area with diameter of 2 cm was uniformly marked on the surface of the orange peel by the operators,the trai-nees were asked to remove the lesion tissues and take dressings.The fluorescent powders were smeared evenly on the orange and pad towel before the examination,and no fluorescence labeling for the surroundings was guaranteed.The trainees were required to wear hats,masks,isolation gowns and gloves during the operations,and take off the gloves and trace the scope of fluorescent contamination with ultraviolet radiator after the examina-tion.RESULTS The contamination rate was 92.68％for the trainees' bodies,100.00％for their surroundings.The hands and forearms were the most severe contaminated body sites,and the contamination rates were 85.37％(35/41)and 34.15％(14/41),respectively.The downside of the pad towel was the most frequently contaminated area of the surroundings,with the proportion of 90.24％(37/41);the right side of the pad towel was the area with the contamination disseminated farthest,with the median distance of dissemination 13.50 cm.In addition,the dressing change carts of 75.61％(31/41)of the trainees were contaminated.CONCLUSIONS The operations of de-bridement and dressing change may lead to varying degrees of contamination of their bodies and surroundings.It is necessary to strengthen the hand hygiene and protective isolation during the process of dressing change and pay attention to the disinfection of the dressing change carts so as to minimize the risk of hospital-associated infec-tions.

Three evaluation methods were recommended for the key properties of the intravascular catheter lubricating coating such as stability,lubricity and integrity,including insoluble particle test method,friction test procedure and appearance detection method.Fifteen batches of microcatheters produced by different manufacturers were selected for testing to clarify the three methods in test principle,step,result,characteristic.References were provided for the design,production,evaluation and regulation of intravascular catheters with lubricant coatings.[Chinese Medical Equipment Journal,2025,46(1):66-72]

The construction method and simulation parameter settings for the discrete element model of Jianwei Xiaoshi Granules, as the primary material of Jianwei Xiaoshi Tablets, are not yet clear. The accuracy of the simulation model significantly influences the dynamic response characteristics between granules. Therefore, it is necessary to calibrate the parameters to improve the accuracy of the simulation parameters. Using the repose angle of Jianwei Xiaoshi Granules as the response value, the response surface methodology was employed to optimize and calibrate the discrete element parameters. Physical experiments were conducted to determine the physical properties of Jianwei Xiaoshi Granules. Based on the Hertz-Mindlin with Johnson-Kendall-Roberts(JKR) V2 model and virtual simulation methods, a repose angle determination model was constructed in EDEM software. The repose angle was measured using image analysis and numerical fitting methods. The Plackett-Burman experiment was used to screen the initial parameters for significance in the discrete element simulation. The significant parameters were then subjected to a steepest ascent experiment to determine the optimal parameter range. Furthermore, based on the Box-Behnken experiment, a second-order regression equation between significant parameters and repose angle was established, with the repose angle of 37.64° in the physical experiment as the target value. The regression equation was optimized and solved. The significance screening experiment revealed that the granule-granule static friction coefficient, granule-granule rolling friction, and granule-steel plate rolling friction of Jianwei Xiaoshi Granules significantly influenced the simulated repose angle. The optimal parameter combination was found to be 0.330, 0.222, and 0.229. The simulation results with this optimal parameter combination showed that there was no significant difference between the simulated repose angle and the repose angle obtained in the physical experiment, with a relative error of 0.05%, which further validated the reliability of the calibrated discrete element parameters for Jianwei Xiaoshi Granules.
Drugs, Chinese Herbal/chemistry* ; Calibration ; Computer Simulation

Identification of critical material attributes(CMAs) is a key issue in the quality control of large-scale TCM products like Jianwei Xiaoshi Tablets. This study focuses on the granules of Jianwei Xiaoshi Tablets, using tablet tensile strength as the primary quality attribute. A method for identifying the CMAs and a design space for the granules were established, along with a predictive model for the granule CMAs based on Fourier transform near-infrared spectroscopy(FT-NIR). First, granules of Jianwei Xiaoshi Tablets with different properties were prepared using a partial factorial design method from the design of experiments(DOE). The powder properties of the granules were measured. An orthogonal partial least squares(OPLS) model was established to correlate the powder properties with tensile strength. Based on the characteristics of the comprehensive variables extracted by OPLS, the independent variables with the greatest explanatory power for tensile strength were identified. FT-NIR technology was then employed to establish a predictive model for the granule CMAs. The final CMAs identified were hygroscopicity, moisture content, D_(50), collapse angle, mass flow rate, and tapped density. The coefficients of determination of the prediction set(R■) and relative percentage deviation(RPD) of the prediction set for flowability, D_(50), and moisture content were 0.891, 0.994, and 0.998; and 2.97, 12.4, and 20.7, respectively. The established OPLS model clearly identified the impact of various factors on tensile strength, demonstrating good fit results. The model exhibited high prediction accuracy and can be used for the rapid and accurate determination of CMAs in granules of Jianwei Xiaoshi Tablets.
Drugs, Chinese Herbal/chemistry* ; Tablets/chemistry* ; Tensile Strength ; Quality Control ; Spectroscopy, Fourier Transform Infrared ; Spectroscopy, Near-Infrared

OBJECTIVE: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. METHODS: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B-IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. RESULTS: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change -13.67, 95% CI -22.70 to -4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). CONCLUSION The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694).
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Middle Aged ; Female ; Lung Neoplasms/pathology* ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Chemotherapy, Adjuvant ; Patient Reported Outcome Measures ; Quality of Life ; Aged ; Postoperative Period ; Prospective Studies