Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

Objective To evaluate the application value of artificial intelligence (AI) in the quality control of mammographic images and explore its feasibility for improving image quality. Methods A retrospective analysis was conducted on 500 mammographic images from 125 female patients. These images were acquired in December 2024 at the Department of Radiology, Obstetrics and Gynecology Hospital of Tongji University by two junior technologists with qualification certificate for junior radiologic technologists and ≤ 2 months of independent operation. The reference standard was the evaluation by a panel of senior experts comprising one associate chief radiologist and two intermediate radiologic technologists with over 10 years of experience in mammography. The evaluation was based on nine criteria within an AI quality control system. The correlation and consistency (Kappa test) of the assessment outcomes were compared among the junior technologist group, the AI quality control group, and the panel group. Additionally, the differences in the proportions of high-, medium-, and low-quality images rated by the three groups were analyzed. After one month of AI assistance, 200 images from 50 additional patients acquired by the same two junior technologists in January 2025 were collected. The area under the receiver operating characteristic curve and 95% confidence interval (95%CI) were calculated for the assessment performance of the junior technologist group before and after AI assistance. Differences were compared using the DeLong test. Changes in the disqualification rates for the nine criteria were analyzed. Results In consistency analysis, the AI quality control group showed high consistency with the panel group across multiple key criteria, with Kappa values ranging from 0.41 to 1.00. In contrast, the consistency between the junior technologist group and the panel group was generally low, with Kappa values ranging from 0.13 to 0.49. In comparison of image quality classification, no significant differences were observed in image quality classification between the AI group and the panel group (P>0.05). However, the proportion of images rated as high quality by the junior technologist group was significantly higher, while the proportions rated as medium and low quality were significantly lower, compared to those rated by the panel group (P<0.05). After AI assistance, the area under the receiver operating characteristic curve for the assessment performance of junior technologist group increased significantly from 0.56 (95%CI: 0.51-0.61) to 0.91 (95%CI: 0.87-0.94) (P<0.001). The disqualification rates for skin folds, incomplete inclusion of the pectoralis major muscle, and nipple not in profile decreased significantly. Conclusion AI demonstrates assessment capability comparable to the panel group in mammographic quality control. AI effectively enhances the quality of images acquired by junior technologists through real-time, objective feedback.

Objective To evaluate the application value of artificial intelligence (AI) in the quality control of mammographic images and explore its feasibility for improving image quality. Methods A retrospective analysis was conducted on 500 mammographic images from 125 female patients. These images were acquired in December 2024 at the Department of Radiology, Obstetrics and Gynecology Hospital of Tongji University by two junior technologists with qualification certificate for junior radiologic technologists and ≤ 2 months of independent operation. The reference standard was the evaluation by a panel of senior experts comprising one associate chief radiologist and two intermediate radiologic technologists with over 10 years of experience in mammography. The evaluation was based on nine criteria within an AI quality control system. The correlation and consistency (Kappa test) of the assessment outcomes were compared among the junior technologist group, the AI quality control group, and the panel group. Additionally, the differences in the proportions of high-, medium-, and low-quality images rated by the three groups were analyzed. After one month of AI assistance, 200 images from 50 additional patients acquired by the same two junior technologists in January 2025 were collected. The area under the receiver operating characteristic curve and 95% confidence interval (95%CI) were calculated for the assessment performance of the junior technologist group before and after AI assistance. Differences were compared using the DeLong test. Changes in the disqualification rates for the nine criteria were analyzed. Results In consistency analysis, the AI quality control group showed high consistency with the panel group across multiple key criteria, with Kappa values ranging from 0.41 to 1.00. In contrast, the consistency between the junior technologist group and the panel group was generally low, with Kappa values ranging from 0.13 to 0.49. In comparison of image quality classification, no significant differences were observed in image quality classification between the AI group and the panel group (P>0.05). However, the proportion of images rated as high quality by the junior technologist group was significantly higher, while the proportions rated as medium and low quality were significantly lower, compared to those rated by the panel group (P<0.05). After AI assistance, the area under the receiver operating characteristic curve for the assessment performance of junior technologist group increased significantly from 0.56 (95%CI: 0.51-0.61) to 0.91 (95%CI: 0.87-0.94) (P<0.001). The disqualification rates for skin folds, incomplete inclusion of the pectoralis major muscle, and nipple not in profile decreased significantly. Conclusion AI demonstrates assessment capability comparable to the panel group in mammographic quality control. AI effectively enhances the quality of images acquired by junior technologists through real-time, objective feedback.

Objective To evaluate the application value of artificial intelligence (AI) in the quality control of mammographic images and explore its feasibility for improving image quality. Methods A retrospective analysis was conducted on 500 mammographic images from 125 female patients. These images were acquired in December 2024 at the Department of Radiology, Obstetrics and Gynecology Hospital of Tongji University by two junior technologists with qualification certificate for junior radiologic technologists and ≤ 2 months of independent operation. The reference standard was the evaluation by a panel of senior experts comprising one associate chief radiologist and two intermediate radiologic technologists with over 10 years of experience in mammography. The evaluation was based on nine criteria within an AI quality control system. The correlation and consistency (Kappa test) of the assessment outcomes were compared among the junior technologist group, the AI quality control group, and the panel group. Additionally, the differences in the proportions of high-, medium-, and low-quality images rated by the three groups were analyzed. After one month of AI assistance, 200 images from 50 additional patients acquired by the same two junior technologists in January 2025 were collected. The area under the receiver operating characteristic curve and 95% confidence interval (95%CI) were calculated for the assessment performance of the junior technologist group before and after AI assistance. Differences were compared using the DeLong test. Changes in the disqualification rates for the nine criteria were analyzed. Results In consistency analysis, the AI quality control group showed high consistency with the panel group across multiple key criteria, with Kappa values ranging from 0.41 to 1.00. In contrast, the consistency between the junior technologist group and the panel group was generally low, with Kappa values ranging from 0.13 to 0.49. In comparison of image quality classification, no significant differences were observed in image quality classification between the AI group and the panel group (P>0.05). However, the proportion of images rated as high quality by the junior technologist group was significantly higher, while the proportions rated as medium and low quality were significantly lower, compared to those rated by the panel group (P<0.05). After AI assistance, the area under the receiver operating characteristic curve for the assessment performance of junior technologist group increased significantly from 0.56 (95%CI: 0.51-0.61) to 0.91 (95%CI: 0.87-0.94) (P<0.001). The disqualification rates for skin folds, incomplete inclusion of the pectoralis major muscle, and nipple not in profile decreased significantly. Conclusion AI demonstrates assessment capability comparable to the panel group in mammographic quality control. AI effectively enhances the quality of images acquired by junior technologists through real-time, objective feedback.

ObjectiveTo investigate the potential mechanisms and pathways through which Gandouling （GDL） exerts its effects in the treatment of liver fibrosis in Wilson disease. MethodsSixty male SD rats were randomly divided into six groups： the normal group， the model group， the GDL low-， medium-， and high-dose groups （0.24， 0.48， 0.96 g·kg^-1）， and the penicillamine group （90 mg·kg^-1）， with 10 rats in each group. A copper-loaded Wilson disease rat model was established by gavage administration of 300 mg·kg^-1 copper sulfate pentahydrate to all groups except the normal group. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathomorphological changes in the liver. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of hyaluronic acid （HA）， laminin （LN）， procollagen type-Ⅲ peptide （PC-Ⅲ）， and collagen type-Ⅳ （C-Ⅳ）. Transmission electron microscopy was used to examine the ultrastructure of liver tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the expression levels of liver tissues and serum exosomal long noncoding RNA H19 （LncRNA H19）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR）. Western blot analysis was performed to assess the expression levels of PI3K， Akt， mTOR， and their phosphorylated forms， as well as autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3B （LC3-Ⅱ/LC3-Ⅰ） in liver tissues. Beclin1 and LC3-Ⅱ fluorescence signal intensity was observed by immunofluorescence. ResultsCompared with the normal group， the model group exhibited inflammatory cell infiltration in hepatocytes， unclear nuclear boundaries with cell cleavage and necrosis， and collagen fiber deposition around confluent areas. The levels of HA， LN， PC-Ⅲ， and C-Ⅳ were significantly elevated （P<0.01）. Transmission electron microscopy revealed an increased number of autophagic vesicles， with autophagic lysosomes exhibiting a single-layer membrane structure following degradation of most envelopes. Expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ were significantly increased （P<0.01）， and fluorescence signals of Beclin1 and LC3-Ⅱ were markedly enhanced. The protein expression levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were reduced （P<0.01）， while LncRNA H19 expression was increased （P<0.01）， and mRNA expression levels of PI3K， Akt， and mTOR were decreased （P<0.01）. After treatment with GDL， the degree of liver fibrosis was significantly improved， with decreased levels of HA， LN， PC-Ⅲ， and C-Ⅳ. The number of autophagic vesicles was significantly reduced， and expression levels of Beclin1 and LC3-Ⅱ/LC3-Ⅰ proteins were lower （P<0.01）. The fluorescence signals of Beclin1 and LC3-Ⅱ weakened dose-dependently. The protein levels of PI3K， Akt， mTOR， p-PI3K， p-Akt， and p-mTOR were elevated （P<0.01）， while the expression level of LncRNA H19 was reduced （P<0.01）. Furthermore， the mRNA expression levels of PI3K， Akt， and mTOR increased （P<0.05， P<0.01）. ConclusionGDL may alleviate liver fibrosis and reduce liver injury by regulating the PI3K/Akt/mTOR autophagy signaling pathway via LncRNA H19.

ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease （AD） from cell apoptosis mediated by the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa B （NF-κB） signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group， a sham group， a model group， a donepezil hydrochloride （0.45 mg·kg^-1） group， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline， while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 （Aβ_1-42） solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Western blot was employed to determine the protein levels of PI3K， Akt， and NF-κB. A cell model of AD was established by co-culturing Aβ_1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 （CCK-8） assay and flow cytometry （FC）， respectively. ResultsAnimal experiments showed that compared with the blank group， the model group had a prolonged escape latency （P<0.01）， a reduced number of crossing platforms （P<0.01）， disarrangement and a reduced number of hippocampal neurons， up-regulated expression of Bax and Caspase-3， down-regulated expression of Bcl-2 （P<0.01）， decreased p-PI3K/PI3K and p-Akt/Akt levels， and an increased p-NF-κB/NF-κB level （P<0.01）. Compared with the model group， donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms （P<0.05， P<0.01）， improved the arrangement and increased the number of hippocampal neurons， down-regulated the expression levels of Bax and Caspase-3， up-reguated the expression level of Bcl-2 （P<0.05， P<0.01）， increased the p-PI3K/PI3K and p-Akt/Akt levels （P<0.05， P<0.01）， and reduced the p-NF-κB/NF-κB level （P<0.05， P<0.01）. Cell experiments showed that compared with the blank group， the model group exhibited an increased apoptosis rate （P<0.01）. Compared with the model group， the serum containing Hei Xiaoyaosan at various doses improved the cell viability （P<0.01）， and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis （P<0.01）. ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis， while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.

ObjectiveTo observe the effects of Hei Xiaoyaosan on the learning and memory abilities of Alzheimer's disease model mice （APP/PS1 mice）， and to explore its mechanism through the inflammatory cascade mediated by nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 （NLRP3）/cysteine aspartate-specific protease （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsSPF-grade 4-month-old APP/PS1 mice were randomly divided into the model group， MCC950 group， and Hei Xiaoyaosan high-， medium-， and low-dose groups. C57BL/6J mice were used as the blank group. After 7 days of adaptive feeding， mice in each group were intervened. The Hei Xiaoyaosan high-， medium-， and low-dose groups were given corresponding doses by gavage （25.79， 12.90， 6.45 g·kg^-1·d^-1）， the MCC950 group was intraperitoneally injected with 10 mg·kg^-1·2 d^-1， and the blank group received the same volume of physiological saline by gavage. After 90 days of intervention， the learning and memory abilities were assessed using the Y maze and Morris water maze tests. The structural changes of hippocampal neurons were observed by hematoxylin-eosin （HE） staining. The expression of amyloid precursor protein （APP） in the hippocampal CA3 region was detected by immunohistochemistry. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin （IL）-10， IL-18， and IL-1β in the hippocampus. Western blot was applied to detect the protein expression of NLRP3， Caspase-1， GSDMD， and GSDMD-N in the hippocampus. Immunofluorescence was used to detect the co-localization of GSDMD-N and ionized calcium-binding adapter molecule-1 （Iba-1） in the hippocampus. Results① In the Y maze test， compared with the blank group， the spontaneous alternation rate of the model group was significantly reduced （P<0.01）. Compared with the model group， the spontaneous alternation rate in the Hei Xiaoyaosan high- and low-dose groups was significantly increased （P<0.01）. ② In the Morris water maze test， during the 1-4 days of the location navigation test， the escape latency time of mice decreased with the extension of training time. On day 4， compared with the blank group， the model group showed a significantly increased escape latency （P<0.05）. Compared with the model group， the MCC950 group and the Hei Xiaoyaosan low-dose group showed significantly reduced escape latency （P<0.05）. In the spatial exploration experiment， compared with the blank group， the number of platform crossings in the model group was significantly reduced （P<0.01）. Compared with the model group， the Hei Xiaoyaosan low-dose group showed significantly increased platform crossings （P<0.05）. ③ HE staining showed that， compared with the blank group， the hippocampal CA3 cells of the model group were damaged， arranged loosely and irregularly， swollen， with unclear boundaries， and the nuclei were pyknotic and deeply stained. MCC950 and all doses of Hei Xiaoyaosan improved the hippocampal CA3 cell damage in APP/PS1 mice to varying degrees. ④ Immunohistochemical results indicated that， compared with the blank group， the expression of APP in the hippocampal CA3 region was significantly increased in the model group （P<0.01）. MCC950 and all doses of Hei Xiaoyaosan could reduce the expression of APP in the hippocampal CA3 region of APP/PS1 mice （P<0.01）. ⑤ ELISA results showed that the levels of IL-18 and IL-1β in the hippocampus of mice in the model group were significantly increased， and IL-10 levels were significantly reduced （P<0.01）. Compared with the model group， the IL-18 levels in the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were significantly reduced （P<0.01）. IL-1β levels in the hippocampus of the MCC950 group and Hei Xiaoyaosan high-， medium-， and low-dose groups were significantly decreased （P<0.01）. The IL-10 levels in the hippocampus of the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were increased （P<0.05， P<0.01）. ⑥ Western blot results showed that compared with the blank group， the protein levels of NLRP3， Caspase-1， GSDMD， and GSDMD-N in the hippocampus of the model group were significantly elevated （P<0.01）. Compared with the model group， the content of NLRP3 and Caspase-1 in the hippocampus of the treated groups was decreased （P<0.05， P<0.01）. The content of GSDMD in the hippocampus of the Hei Xiaoyaosan high-， medium-， and low-dose groups was reduced （P<0.05， P<0.01）， and the content of GSDMD-N in the hippocampus of the Hei Xiaoyaosan medium- and low-dose groups was decreased （P<0.05， P<0.01）. ⑦ Immunofluorescence results showed that， compared with the blank group， the co-expression of GSDMD-N and Iba-1 in the hippocampus of the model group was significantly increased （P<0.01）. Compared with the model group， the co-expression of GSDMD-N and Iba-1 in the treated groups was significantly reduced （P<0.01）. ConclusionHei Xiaoyaosan may regulate the NLRP3/Caspase-1/GSDMD signaling pathway to affect the release of inflammatory factors， alleviate neuroinflammation，improve hippocampal histopathological changes，and improve learning and memory deficits，thus providing potential therapeutic benefits for Alzheimer's disease.

The exploration and pilot studies of applying blockchain to drug supply chain show great potential in promoting information sharing, collaboration competence among the actors, regulatory efficiency, and etc. In the future, with the help of blockchain, the optimization of the entire supply chain for orphan drugs is expected to be realized. However, there is no such exploration in China at present. This paper systematically sorts out the whole process of supply chain for orphan drugs and the existing problems of the chain. The article concludes that at present, blockchain is mainly used in the " circulation" and " use" of the drug supply chain. It helps to improve the traceability of drugs, to cope with the problem of counterfeit drugs, to enable actors of the drug supply chain to form a collaborative network in optimizing resource allocation, and to improve the operation and supervision efficiency of the supply chain. In the future, the application faces challenges such as high costs in system conversion, lack of personnel awareness, and incomplete supporting systems. Based on the three dimensions of technology, practice, and research, this paper also looks into the future and suggests for the future use of blockchain in the supply chain of orphan drugs by constructing a practice model, the so called DI-GIVE (Digital, Intelligence, Government′s supervision, Innovation, Views of variety, Evaluation-based) hoping to innovate the supply chain of orphan drugs and to ensure the drug use for the patients with rare diseases in China.

Objective To study the role and influence of basic Alkaline ceramidase 1 on mucosal barrier and immune regulation in ulcerative colitis(UC).Methods Acer1 knockout mice(Acer1 KO)were constructed,and the UC model was induced by continuous drinking water of sodium dextran sulfate(DSS)for 7 days,and the severity of symptoms of UC disease in C57 and Acer1 KO mice was compared.The expression levels of intestinal mucosal barriers(ZO-1,Occludin,Claudin,JAMA)were detected by RT-PCR and immunohistochemistry.Systemic immune response levels(IL-1b、IL-6、IL-23、IL-17、IL-10,and TNF-a)were assessed by ELISA and intestinal inflammatory infiltration levels(TNF-a、IL-1b、IL-6、IL-17、IL-21,etc.)were assessed by RT-PCR.Results There was no significant difference between C57 and Acer1 KO mice in free drinking water.In the DSS induced UC model,compared with C57 mice,the survival rate of Acer1 KO mice decreased,the weight decreased significantly,the mechanical barrier and mucus barrier protein expression levels decreased significantly,the intes-tinal epithelial barrier was seriously damaged,the inflammatory response was strong,and the cytokine infiltration was obvious,with statistical differences(P<0.05).Conclusion Acer1 can inhibit inflammatory infiltration by maintaining the integrity of intestinal mucosal barrier,preventing endotoxin,and delaying the progression of UC.