ObjectiveDonkey hide is the sole legally designated raw material for the preparation of the traditional Chinese medicine Ejiao. The quality stability of donkey hide during preservation directly determines the efficacy and safety of Ejiao. This study focuses on the dynamic succession of microbial communities during the preservation of donkey hides from different origins, aiming to clarify the correlation between microbial biodiversity difference and the degradation profiles of hide collagen and critical biochemical components, thereby providing a theoretical foundation for developing targeted preservation strategies based on microbial regulation. MethodsDonkey hides originating from four different regions were subjected to an accelerated microbial aging assay to simulate the spoilage process. The microbial community succession was analyzed using high-throughput sequencing. Microstructure changes and pore structure characteristics were assessed by scanning electron microscopy and mercury intrusion porosimetry, respectively. Additionally, the content of major components, including lipids, proteins, and sugars were determined by biochemical methods. ResultsAfter 96 h of aging, the collagen fiber structure in Africa donkey hides (ADH) exhibited significant degradation and collapse, followed by Xinjiang donkey hides (XDH). Instead, the microstructure of Dong’e black donkey hides (DDH) and Peru donkey hides (PDH) remained relatively intact. The porosities of DDH, XDH, PDH, and ADH increased from 27.9%, 15.7%, 30.3%, and 46.2% to 36.5%, 52.6%, 42.8%, and 57.7%, respectively, during the aging process, which suggested that the originally compact fiber structure was disrupted by microbial aging. Fourier transform infrared spectrometer analysis revealed the amide bands in XDH exhibited relatively weak intensity, and no collagen amide I band was observed in ADH. Meanwhile, the lipid and protein contents decreased in all four types of donkey hides, indicating that these components served as the primary nutrient sources for the growth of microorganism. Notably, the most severe collagen degradation was observed in XDH and ADH. A substantial increase was detected in the total soluble sugar in PDH aging solution and hydroxyproline in the ADH aging solution, respectively. These results indicated that donkey hides exhibit distinct patterns of structural degradation and nutrient utilization. Furthermore, the viable cells number of donkey hides increased sharply after 48 h of aging. Metagenomic analysis revealed that the relative abundance of Euryarchaeota in ADH, PDH and XDH declining from initial 93.19%, 97.73% and 30.08% to 0.79%, 1.43% and 0.02% after 96 h, respectively. Conversely, a significantly increase was observed in the abundance of Bacillota, with a marked increase in ADH, peaking at 92.75%. Additionally, the abundance of Pseudomonadota in PDH increased from 0.10% to 87.84%, suggesting that Bacillota and Pseudomonadota may be key factors exacerbating donkey hide spoilage. Unlike the other three types of donkey hides, the dominant bacterial phylum in DDH shifted from Pseudomonadota to Bacteroidota, characterized by a substantial abundance increase of Bacteroidota from 0.13% to 44.22%. ConclusionRegional variation in origin significantly influence the microbial aging of donkey hides, leading to distinct patterns of structural deterioration and differential nutrient utilization. Therefore, implementing origin-specific preservation strategies, through the precisely controlling environmental factors to suppress harmful phyla such as Bacillota and Pseudomonadota, is crucial for enhancing the storage quality of donkey hides.

Objective To explore the application value of dual-phase dual-energy CT (DECT) perfusion imaging in preoperative lung function assessment of lung cancer patients. Methods Data were collected from patients with stageⅠA non-small cell lung cancer who underwent surgical treatment in the Department of Thoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, from November 2022 to June 2024. All patients underwent DECT perfusion imaging and pulmonary function testing (PFT) before surgery. PFT observation indicators included ventilation function indicators such as forced expiratory volume in one second (FEV1), forced vital capacity (FVC), 1-second rate (FEV1/FVC), maximal voluntary ventilation (MVV), and diffusion function indicators such as diffusing capacity for carbon monoxide (DLCO) and DLCO per liter of alveolar volume (DLCO/VA). The software eXamine was used to obtain quantitative parameters of DECT perfusion imaging, including volume parameters and perfusion parameters of both lungs and each lung lobe. The correlation between the volume parameters and perfusion parameters of both lungs and the ventilation and diffusion function indicators of the patients, as well as the differences in quantitative parameters of each lung lobe, was analyzed. Results The end-inspiration lung volume and biphasic volume difference were strongly positively correlated with FEV1 and FVC (r=0.636, r=0.682, r=0.614, r=0.624, P<0.001) and moderately positively correlated with MVV and DLCO (r=0.499, r=0.514, r=0.549, r=0.447, P<0.001); the end-expiration lung volume was weakly negatively correlated with DLCO/VA (r=−0.295, P=0.026); the volume ratio was positively correlated with FEV1, FVC, MVV, and MVV% (r=0.424, r=0.399, r=0.415, r=0.310, P<0.05); the end-inspiration iodine content was weakly positively correlated with DLCO/VA% (rs=0.292, P=0.030); the end-expiration iodine content was weakly positively correlated with FEV1, FVC, MVV, DLCO%, and DLCO/VA (r=0.307, r=0.299, r=0.295, r=0.366, r=0.320, P<0.05) and moderately positively correlated with DLCO (r=0.439, P<0.001); the end-inspiration iodine concentration was negatively correlated with FEV1, FVC, MVV, and MVV% (rs=−0.407, rs=−0.426, rs=−0.352, rs=−0.277, P＜0.05); the end-expiratory phase iodine concentration was moderately positively correlated with DLCO/VA (r=0.403, P=0.002); both the iodine concentration difference and the iodine concentration ratio were moderately positively correlated with FEV1, FEV1%, FVC, MVV, MVV% (P<0.05). The lung volume and iodine concentration ratio values were both highest in the left upper lung lobe and lowest in the right middle lung lobe; the differences in lung volume, lung volume ratio, intrapulmonary iodine content, and intrapulmonary iodine concentration were all highest in the lower lobes of both lungs and lowest in the middle lobe of the right lung. Conclusion Dual-phase DECT perfusion imaging can accurately assess overall lung function and quantify regional lung function.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

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.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

[Purpose]To analyze the results of breast cancer screening among women aged 45～74 in Chongqing from 2012 to 2022 and compare the risk of breast cancer among women with differ-ent characteristics.[Methods]The Urban Cancer Early Diagnosis and Treatment Program was con-ducted in Chongqing from 2012 to 2022,female residents aged 45～74 years old participated in breast cancer screening.The participants who were assessed as at high risk of breast cancer in the preliminary screening were advised to receive ultrasonography and mammography examination in designated hospitals.The study population was followed up annually to obtain information on their health outcomes.The high risk rate of breast cancer,compliance of further examination,the inci-dence density and breast cancer risk were calculated.[Results]A total of 207 891 women com-pleted the questionnaires survey and risk assessment,and 35 947 were assessed as the individuals with high risk of breast cancer with a high risk rate of 17.29％.Among them 14 713 received the imaging screening with a compliance rate of 40.93％.After a mean follow-up of(5.43±3.01)years,847 cases of breast cancer were diagnosed with a cumulative incidence rate of 407.43/105,an in-cidence density of 75.03/105 person-years(95％CI:70.15/105～80.26/105 person-years).Cox pro-portional hazards regression showed that the risk of breast cancer was higher in obese women than that in normal weight women(HR=1.26,95％CI:1.00～1.59);the risk of breast cancer was signifi-cantly higher in those with family history of breast cancer than that in those without family history(HR=1.69,95％CI:1.36～2.09).Compared with non-high-risk groups of breast cancer,the risk of breast cancer was increased in high-risk individuals who were screened or not screened(HR=1.36,95％CI:1.06～1.73 and HR=1.26,95％CI:1.01～1.56).[Conclusion]The breast cancer screening program combining primary risk assessment with ultrasonography and mammography for the high-risk groups can improve the detection rate,and the compliance rate of imaging screening need to be improved in the future and make accurate screening for people with high risk of breast cancer.

In order to comprehensively deepen the reform of medical insurance payment methods and explore the establishment of a medical insurance payment system with Chinese features,five representative cities have been selected for analysis:Jinhua City in Zhejiang Province,Xiamen City in Fujian Province,Suixi City in Anhui Province,TianjinCity,and Zhenjiang City in Jiangsu Province.These regions have been chosen due to their typical ambulatory care payment reform.It summarises the features of ambulatory care payment reforms in different regions regarding implementing agencies,covered crowds and types of illnesses,and payment methods.It is recommended that a reasonable scope of implementation be selected and the reform purpose and basic conditions should be taken into account to explore an appropriate ambulatory care payment reform.It is proposed that an innovative payment method reform be implemented to promote healthcare and prevention integration,and to incorporate a value-oriented paradigm,thereby realizing the benefits of the doctor and patient insurance.

Objective To investigate the effect of field angle on the results of in vivo dose validation of electronic portal imaging device(EPID)in patients.Methods Design the mold test and analyze the influence of different mold thicknesses and different frame angles on the 2D γ pass rate.Twenty-three patients who un-derwent radiotherapy in the Department of Radiotherapy of Jinhua Municipal Central Hospital from January to June 2023 were selected as the research object.In vivo dose verification was carried out during treatment to obtain 2D γ pass rate using same-day sector beam CT(FBCT)of planned CT and executive image guided(IG-RT)as reference images,and the influence of field angle on pass rate was analyzed.Results When the frame angle was unchanged,the area of the shooting field was larger than 17 cm×17 cm,and the 2D γ passing rate decreased with the increase of the thickness.The frame angle had no effect on the 2D γ pass rate when the mold thickness was constant.In clinical treatment data,the passage rate of 2D γ near 0°/180° was higher than that near 90°/270°(P＜0.05),and the passage rate near 90°/270° in the FBCT group was higher than that in the IGRT group(P＜0.05).The median passing rate of 3 mm 2D γ was 97.97％in 3％of the 23 patients.The non-IGRT group was 96.81％,the IGRT group was 97.89％,the FBCT group was 98.94％.There was a statistically significant difference in 2D γ passing rate between the non-IGRT group and the IGRT group(Z=-5.083,P＜0.05),and there was a statistically significant difference in 2D γ passing rate between the IGRT group and the FBCT group(Z=-10.657,P＜0.05).Conclusion Clinically,the difference of pass rate in vi-vo dose verification at different rack angles is mainly due to the difference of images within and between ses-sions.Using same-day FBCT as the reference image for in-vivo dose verification can improve the accuracy of pass rate and eliminate the influence of image difference between sessions.