1.Effect of Hei Xiaoyaosan on Neuroinflammation and NLRP3/Caspase-1/GSDMD Signaling Pathway in APP/PS1 Mice
Jun ZHOU ; Mingcheng LI ; Yujie LYU ; Zhipeng MENG ; Yunyun HU ; Huping WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):124-133
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.
2.Current Situation, Trend, and Opportunity of Applying Blockchain to the Supply Chain of Orphan Drugs
Wenyan LI ; Yile YOU ; Jindong WU ; Xinrui LI ; Yunyun JIANG ; Shengfeng WANG
JOURNAL OF RARE DISEASES 2025;4(1):14-21
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.
3.Evaluation and prospect of clinical pharmacist instructor training reform oriented toward enhancing clinical teaching competence
Li YOU ; Jiancun ZHEN ; Jing BIAN ; Zhuo WANG ; Yunyun YANG ; Jin LU ; Jing LIU
China Pharmacy 2025;36(17):2085-2091
OBJECTIVE To summarize the implementation experiences of the China Hospital Association’s Clinical Pharmacist Instructor Training Program Reform, and to evaluate the effectiveness of the reform, thus continuously enhancing the quality and standards of clinical pharmacist instructor training. METHODS The study drew on project evaluation methodologies to summarize the main characteristics of the comprehensive system and new model for clinical pharmacist instructor training established through the reform by literature review. The “learning assessment” and “reaction assessment” were conducted by using Kirkpatrick’s four-level model of evaluation in order to evaluate the effectiveness of the clinical pharmacist instructor training reform through statistically processing and analyzing the performance data and teaching evaluation data of the instructor participants. Based on problem and trend analysis, the future development directions were anticipated for the reform of clinical pharmacist instructor training. RESULTS & CONCLUSIONS The latest round of clinical pharmacist instructor training reform initiated by the Chinese Hospital Association had initially established a four-pronged training system encompassing “recruitment, training, assessment, and management”. It had also forged a training 。 model “oriented towards enhancing clinical teaching competency, with practical learning and skill-based assessment conducted on clinical teaching sites as its core”. Following a period of over three years of gradual reform, the new training system and model became increasingly mature. In both 2023 and 2024, the participants achieved relatively high average total scores in their initial completion assessments [with scores of (84.05± 5.83) and (85.82±4.35) points, respectively]. They also reported a strong sense of gain from the training reform [with self- perceived gain scores of (4.80±0.44) and (4.85±0.39) points, respectively]. The operation and implementation effects of the reform were generally satisfactory. In the future, clinical pharmacist instructor training reforms should continue to address the issues remaining from the current phase, while aligning with global trends in pharmacy education and industry development. Additionally, sustained exploration and practice will be carried out around the core objective of “enhancing clinical teaching competence”.
4.Concordance and pathogenicity of copy number variants detected by non-invasive prenatal screening in 38,611 pregnant women without fetal structural abnormalities.
Yunyun LIU ; Jing WANG ; Ling WANG ; Lin CHEN ; Dan XIE ; Li WANG ; Sha LIU ; Jianlong LIU ; Ting BAI ; Xiaosha JING ; Cechuan DENG ; Tianyu XIA ; Jing CHENG ; Lingling XING ; Xiang WEI ; Yuan LUO ; Quanfang ZHOU ; Ling LIU ; Qian ZHU ; Hongqian LIU
Chinese Medical Journal 2025;138(4):499-501
5.Ion Robot-Assisted Bronchoscopy System and Its Applications.
Fei LI ; Zaozao WANG ; Xueyi LIU ; Qiaoqiao WANG ; Yunyun LI
Chinese Journal of Medical Instrumentation 2025;49(5):486-493
The peripheral pulmonary lesions are located far from the central airway and close to the pleura, so it is a challenge for clinical diagnosis of their nature through biopsy. Therefore, the Ion robot-assisted bronchoscopy system which has started its commercialization in China is proposed to diagnose and treat peripheral pulmonary lesions. The Ion system can be used for navigation, registration, biopsy and treatment. In this paper, the structural principle of the Ion system is expounded, and its technical advantages such as shape perception, slender catheter and flexible operation are summarized. It represents the latest development direction of the diagnosis and treatment of peripheral pulmonary lesions. Then, the clinical application and development status of the Ion system are analyzed and discussed in detail. Finally, the development trend of the robot-assisted bronchoscopy system is prospected, which provides new ideas for realizing the "integrated and one-stop" diagnosis and treatment services for peripheral pulmonary lesions based on this system.
Bronchoscopy/instrumentation*
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Humans
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Robotics
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Robotic Surgical Procedures
6.Pulmonary surfactant-biomimetic membranized coacervate injection for acute respiratory distress syndrome therapy.
Wei CHEN ; Qi XIE ; Zhanhao ZHOU ; Jia KANG ; Yuan GAO ; Haoyu ZHANG ; Samira BATUR ; Chuansheng FU ; Yunyun LI ; Conglian YANG ; Li KONG ; Zhiping ZHANG
Acta Pharmaceutica Sinica B 2025;15(11):5945-5965
Acute respiratory distress syndrome (ARDS) is the leading cause of respiratory failure with high morbidity and mortality. Pulmonary surfactant (PS)-based complementary therapies have exhibited potential for ARDS healing and applied as an adjunctive therapy strategy. Coacervate (Coac) has the characteristics of softness, deformability and excellent molecular enrichment properties, and has attracted extensive attention in the biomedical field. Here PS and coacervate were combined for the potential ARDS treatment. The Coac, fabricated from polyallylamine hydrochloride (PAH) and adenosine triphosphate (ATP) by simple mixing, exhibited soft droplet property and high enrichment for dexamethasone sodium phosphate (DSP). To avoid the fusion effect of membraneless coacervate and endow it with biological functions of PS, liposomes with PS-biomimetic lipid components (PS-lipo) were further introduced to construct PS-biomimetic membranized coacervate (DSP@PS-Coac). The DSP@PS-Coac demonstrated high lung targeting effect and significant penetration efficiency after intravenous injection. Furthermore, PS-lipo replenished the endogenous PS pool and facilitated the distribution of DSP in inflammatory cells in the lung. In the ARDS mouse model, PS-Coac and DSP exerted synergetic anti-inflammatory functions, via reducing the recruitment of inflammatory neutrophils and modulating macrophages into anti-inflammatory phenotype. The overall results confirmed that DSP@PS-Coac may provide a promising delivery option for the treatment of ARDS.
7.Expert consensus on classification and diagnosis of congenital orofacial cleft.
Chenghao LI ; Yang AN ; Xiaohong DUAN ; Yingkun GUO ; Shanling LIU ; Hong LUO ; Duan MA ; Yunyun REN ; Xudong WANG ; Xiaoshan WU ; Hongning XIE ; Hongping ZHU ; Jun ZHU ; Bing SHI
West China Journal of Stomatology 2025;43(1):1-14
Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans
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Cleft Lip/diagnosis*
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Cleft Palate/diagnosis*
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Consensus
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Prenatal Diagnosis
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Female
8.Progress of acute myeloid leukemia related gene mutations
Journal of Leukemia & Lymphoma 2025;34(2):125-128
Acute myeloid leukemia (AML) is an aggressive malignant tumor with high heterogeneity. It is characterized by rapid proliferation, dysapoptosis and impaired differentiation of leukemic blast cells. It can develop at any age. The complexity of the etiology, the diversity of mechanisms, and the variability of cytogenetics and genomics hid behind the development and evolution of AML, among which some specific cytogenetic and genomic abnormalities cause the high recurrence rate and drug resistance rate of clinical AML patients. At present, the clinical application of mutated genes has become a hot field in clinical medicine. This paper reviews the role of common mutated genes and molecular targeted therapy in order to provide help for clinical treatment.
9.Predictive value of serum CTSB and NOX4 levels for the prognosis of sepsis related acute kidney injury patients
Naixi JI ; Yunyun CUI ; Wenhao LIU ; Shangzhen LI ; Xiankui WANG ; Changqing YAO
International Journal of Laboratory Medicine 2025;46(18):2207-2211,2218
Objective To investigate prognostic value of serum levels of cathepsin B(CTSB)and NADPH oxidase 4(NOX4)in patients with sepsis associated acute kidney injury(S-AKI).Methods A total of 306 pa-tients with sepsis treated to the hospital from June 2023 to June 2024 were selected,including 192 patients with S-AKI(S-AKI group)and 114 patients without S-AKI(non-S-AKI group).According to the prognosis of S-AKI patients,they were divided into poor prognosis group(n=127)and non-poor prognosis group(n=65).The differences of CTSB and NOX4 in different groups were compared.Pearson analysis was conducted to analyze the correlation between CTSB,NOX4 and clinical indicators.The influencing factors of poor prognosis in S-AKI patients was analyzed according to multivariate Logistic regression.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of CTSB and NOX4 on the poor prognosis of S-AKI pa-tients.Results Th e serum levels of CTSB,NOX4 and serum creatinine(SCr)in S-AKI group were signifi-cantly higher than those in non-S-AKI group(P<0.05),while the mean arterial pressure and oxygenation in-dex were lower than those in non-S-AKI group(P<0.05).Serum levels of CTSB and NOX4 in patients with sepsis were positively correlated with SCr(P<0.05).Compared to non-poor prognosis group,the age,SCr,CTSB and NOX4 of patients in the poor prognosis group were higher,while the mean arterial pressure and ox-ygenation index were lower(P<0.05).The increased mean arterial pressure and oxygenation index were pro-tective factors for poor prognosis in S-AKI patients(P<0.05),and the increased age,SCr,CTSB and NOX4 levels were risk factors for poor prognosis in S-AKI patients(P<0.05).ROC curve showed that the area un-der the curve(AUC)of CTSB combined with NOX4 was significantly higher than AUC of single detection of CTSB and NOX4(Z=4.066,P<0.001,Z=3.801,P<0.001).Conclusion The serum levels of CTSB and NOX4 in S-AKI patients are elevated,and can indirectly reflect kidney function.CTSB combined with NOX4 can significantly improve the prediction efficiency of poor prognosis in S-AKI patients,which has potential ap-plication value for clinical treatment and nursing.
10.Exploration on the Onset of Acute Lymphoblastic Leukemia in Children Based on the Five-Circuit and Six-Qi Theory
Yunyun SUN ; Liang LI ; Leilei CHU ; Ke YANG ; Zhexiu JIANG ; Tian LIU ; Jianmin ZHANG ; Jian PAN ; Yanfang TAO
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(1):32-38
Objective To explore the five-circuit and six-qi features of birth time and onset time of children with acute lymphoblastic leukemia(ALL).Methods A total of 877 cases of children with ALL from Children's Hospital of Soochow University from June 2021 to February 2023 were collected,and their five-circuit and six-qi features of birth time and onset time were analyzed.And then the correlation of five-circuit and six-qi features of birth time and onset time with ALL was explored preliminarily,and the pathogenic characteristics of congenital factors and acquired pathogenic factors were revealed.Results(1)The children who were born in the year with the heavenly stems being bing(the 3rd of the ten heavenly stems)and ding(the 4th of the ten heavenly stems)and with the earthly branches being shen(the 8th of the twelve earthly branches)and you(the 9th of the twelve earthly branches)are prone to suffer from ALL,and the birth year of children with ALL had the five-circuit and six-qi features of the joining of guest circuit with dominant circuit being rebellious.ALL is commonly seen in the year with the heavenly stems being geng(the 7th of the ten heavenly stems)and xin(the 8th of the ten heavenly stems)and with the earthly branches being zi(the 1st of the twelve earthly branches)and chou(the 2nd of the twelve earthly branches),and the onset year of ALL in children had the five-circuit and six-qi features of the yearly circuit being gold-circuit and water-circuit,sitian-zaiquan yearly circuit qi being shaoyin monarch-fire with yangming dryness-gold,taiyin damp-earth with taiyang cold-water,and the qi-circuit assimilation relationship being celestial correspondence,same celestial correspondence,celestial correspondence in convergent year,disharmony,mildly-rebellious,and celestial restriction.Conclusion Gold-dryness and water-cold are the congenital factors and acquired pathogenic factors of ALL.The onset of ALL in children is closely related to qi insufficiency and qi stagnation of wood and fire in five-circuit and six-qi theory.

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