Objective: To evaluate the incremental vaccine effectiveness (VE) of two dose of the mumps containing vaccine (MuCV) in chidren, so as to provide a basis for optimizing mumps immunization strategies. Methods: A 1∶2 frequency matched case-control study was conducted by using reported mumps cases in childcare centers or schools from Lu an, Hefei, Ma anshan and Huainan cities of Anhui Province from September 1, 2023 to June 30, 2024, as a case group(383 cases). And healthy children in the same classroom were selected as a control group(766 cases). The MuCV immunization histories of participants were collected to estimate the incremental VE of the second dose of MuCV against mumps. Group comparisons were performed using the Chi square test or t-test. For matched case-control pairs, the Cox regression model was employed to calculate the odds ratio (OR) with 95% confidence interval (CI) for two dose MuCV vaccination and to estimate the incremental vaccine effectiveness (VE). Results: There were no statistically significant differences between the case and control groups regarding gender, age, dosage of MuCV vaccination and the time interval since the last dose vaccination( χ 2/t=0.05, 0.20, 0.94, -0.02, P >0.05). The proportions of the case and control groups vaccinated with two doses of MuCV were 26.63% and 29.37%, respectively, and the overall incremental VE of the second dose of MuCV was 40.73% (95% CI=3.03%-63.77%, P <0.05). Subgroup analyses revealed that the incremental VE for children with a period of ≥1 year between the two doses of MuCV was 54.13% (95% CI=1.90%-78.56%, P <0.05), while for children with a period of <1 year, it was 30.63% (95% CI=-28.59%-62.58%, P >0.05). The incremental VE of the second dose of MuCV was 30.36% (95% CI=-25.95%-61.50%, P >0.05) in kindergarten children and 66.73% (95% CI=14.92%-86.99%, P <0.05) in elementary and secondary school students. The incremental VE was 28.78% (95% CI=-27.46%-60.21%, P >0.05) within five years of the last dose of MuCV vaccination and 66.07% (95% CI=-41.56%-91.87%, P >0.05) for vaccinations administered beyond five years. Conclusions The second dose of MuCV may offer additional protection for children; however, extending the interval between two dose of MuCV (<1 year) has shown limited incremental protective effects. Therefore, it is crucial to consider optimizing current immunization strategies for mumps.

With the technological innovation and the advances in information technology, acupuncture-moxibustion is on the path of modernization and high-quality development. The research on ancient acupuncture-moxibustion literature has been gradually transformed from traditional sorting and digital research to intelligent knowledge services, so as to realize the deep integration of ancient acupuncture-moxibustion knowledge with the needs of modern clinical practice and scientific research. Guided by the characteristics of acupuncture-moxibustion knowledge and based on the knowledge meta-theory, the in-depth analytical indexing and knowledge organization are conducted on more than 400 kinds of ancient acupuncture-moxibustion literature. Taking ancient literature of meridian symptoms/manifestations as an example, thematic literature research and database construction are carried out. Integrated with database, cloud platform, knowledge domain mapping and other technologies, the sharing service platform of ancient acupuncture-moxibustion knowledge is constructed. As a result, the research and development achievements can be adopted by the researchers in the field of basic theory, clinical practice and research of acupuncture-moxibustion. Finally, through the way of "digital reconstruction + intelligent application", the path and paradigm of digital research of ancient acupuncture-moxibustion literature are explored to provide the references for the innovative utilization of ancient acupuncture-moxibustion literature.
Moxibustion/history* ; Humans ; Acupuncture Therapy/history* ; History, Ancient ; Knowledge

OBJECTIVE: To organize and display systematically the ancient medical records of stroke treated with acupuncture and moxibustion based on the knowledge element theory of information technology, so as to provide the path and paradigm for the construction of ancient acupuncture and moxibustion knowledge model. METHODS: The medical records of stroke treated with acupuncture and moxibustion were collected from the monographs of acupuncture and moxibustion and tuina, medical reports, the ancient works of traditional Chinese medicine of comprehensive collection and clinical disorders of each medical department, from the pre-Qin period to the late Qing Dynasty, collected in Zhonghua Yidian (Canon of Chinese Medicine), the fifth edition. Using "knowledge processing platform of ancient Chinese medicine books", the medical records of stroke treated with acupuncture and moxibustion in ancient time were deeply analyzed and indexed. With the MS SQL Server database adopted, the indexing results were exported into logical data; and Neo4j database was employed to build the knowledge graph of stroke treatment with acupuncture and moxibustion in ancient time. RESULTS: There were 43 medical records in 18 ancient books that met the inclusion criteria, and a logical structure was organized and composed of 65 knowledge bodies, 462 knowledge elements, 1,413 semantic types and 315 semantic associations. CONCLUSION Based on the knowledge element theory, the medical records of stroke treated with acupuncture and moxibustion in ancient time have been explored, and the logical data formed can accurately reflect the knowledge of the different attributes inside these medical records. It displays the knowledge organization category from the overall to the local. The knowledge graph generated according to the logical data is conducive to presenting the ancient acupuncture knowledge in view of the "vertical and horizontal" dimensions.
Moxibustion/history* ; Humans ; Acupuncture Therapy/history* ; Stroke/history* ; History, Ancient ; Medical Records ; China

"Jingmai binghou" (meridian symptoms) is not the original term in ancient works, and it is proposed in modern teaching materials of acupuncture. It refers to "the diseases caused by the invasion of pathogenic factors into meridians", and "diseases of the affected meridians", recorded in jingmai (Meridian) of Lingshu (Miraculous Pivot). The proposal of this term is related to the academic tendency of textbook writers and the influence of TCM policy in China. Through collating and analyzing the records of meridian disorders in ancient works, it is found that besides the classic "meridian symptoms", many zangfu disorders, the disorders along the running course of meridian based on meridian differentiation, collateral disorders and the disorders of the exterior-interior relationship of meridians should be classified as meridian disorder. In order to accurately express the rich content of "Jingmai binghou", from the perspective of terminology normalization, it is believed that the expression as "meridian-collateral dominated disease" may reflect its connotation more comprehensively.
Meridians ; Humans ; China ; Terminology as Topic ; History, Ancient ; Acupuncture Therapy/history* ; Medicine, Chinese Traditional/history*

This paper presents a textual research on the author, year of composition, basic content, and academic value of Zhenjiu Neipian (Inner Analects of Acupuncture and Moxibustion). This acupuncture-moxibustion work was written by DA Zhongguang, alias Jiang Shang Wai Shi, a renowned painter and calligrapher of the Qing Dynasty. The work was compiled around the reign of Emperor Kangxi (1661-1692). It includes four parts. The first part covers general theories and needle-forging techniques; the second part introduces meridian and acupoint diagrams and the verses of acupoints; the third part is the verses of contraindications of acupuncture and moxibustion; and the fourth part discusses reinforcing and reducing techniques. Zhenjiu Neipian is mainly based on Dou's acupuncture books, Pu Ji Fang (Formulas for Universal Relief), Lei Jing Tu Yi (Pictorial Appendices to 'The Classified Classic'), Zhenjiu Dacheng (The Great Compendium of Acupuncture and Moxibustion), Gu Jin Yi Tong Da Quan (The Complete Compendium of Ancient and Modern Medical Works), Zi Hui (Dictionary of Chinese Characters) , and Ling's acupuncture books. Zhenjiu Neipian preserves some lost writings in lost medical books such as Dou's acupuncture books and Ling's acupuncture books. In addition, it plays an important role in acupoint selection methods, acupuncture and moxibustion techniques, and the indications of acupoints, presenting a high literature and clinical value. This book is an invaluable acupuncture-moxibustion book for studying Ling's acupuncture techniques.
Humans ; China ; Acupuncture Therapy/history* ; Moxibustion/history* ; History, 17th Century ; Acupuncture/education* ; Books/history* ; Acupuncture Points

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

BACKGROUND:Astrocytes play an important role in the pathology of central nervous system diseases.The phenotypic and functional changes in astrocytes suggest that it may be an effective therapeutic target for central nervous system diseases.Our previous studies have confirmed that astragaloside can inhibit the lipopolysaccharide-induced astrocyte inflammatory response.Whether astragaloside can regulate the phenotype and function of astrocytes through Notch-1 and its downstream signaling pathway remains unclear. OBJECTIVE:To explore the effect of astragaloside on astrocyte activation and inflammatory response induced by inflammation and its possible mechanism. METHODS:Cerebral cortex astrocytes derived from neonatal C57BL/6 mouse were cultured in vitro.CCK-8 assay was used to determine the optimum concentration of astragaloside and Notch active inhibitor DAPT.The astrocytes were divided into five groups:PBS group,lipopolysaccharide group,lipopolysaccharide + astragaloside group,lipopolysaccharide + DAPT group and lipopolysaccharide + DAPT + astragaloside group.The secretion level of inflammatory factors was detected by ELISA,and the level of nitric oxide was detected by Griess method.The astrocytes and splenic mononuclear cells were co-cultured in Transwell chamber to observe the migration of CD4T cells.The expression of astrocyte activation marker GFAP,A1 marker C3 and A2 marker S100A10 as well as Notch 1 and Jag-1 was detected by immunofluorescence staining.The expressions of CFB,C3,S100A10,PTX3,Notch-1,Jag-1,and Hes were detected by western blot assay. RESULTS AND CONCLUSION:(1)According to the results of CCK8 assay,the final concentration of astragaloside was selected as 25 μmol/L and the final concentration of DAPT was 50 μmol/L for follow-up experiments.(2)Compared with PBS group,interleukin-6,interleukin-12 and nitric oxide secretion levels in the lipopolysaccharide group were significantly increased(P<0.05,P<0.05,P<0.01).Compared with the lipopolysaccharide group,interleukin-6(all P<0.05),interleukin-12(P>0.05,P<0.05,P<0.05)and nitric oxide(P<0.05,P<0.01,P<0.01)secretion significantly reduced in the lipopolysaccharide + astragaloside group,lipopolysaccharide +DAPT group,lipopolysaccharide + DAPT + astragaloside group.(3)Compared with the PBS group,the expression of GFAP that is the marker of activated astrocytes and the migration of CD4 T cells were significantly increased in the lipopolysaccharide group(P<0.01).Compared with the lipopolysaccharide group,astrocyte activation was significantly inhibited and CD4 T cell migration was significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group(P<0.05,P<0.05,P<0.01).(4)Compared with the PBS group,the expressions of A1 markers C3 and CFB in the lipopolysaccharide group were increased(P<0.01,P<0.05),and the expressions of A2 markers S100A10 and PTX3 were decreased(P<0.01,P<0.05).Compared with the lipopolysaccharide group,C3(all P<0.01)and CFB(both P<0.05)were significantly reduced and S100A10(all P<0.01)and PTX3(P<0.05,P<0.05 and P>0.05)were increased in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(5)Compared with the PBS group,the expressions of Jag-1,Notch-1 and Hes in the lipopolysaccharide group were significantly increased(all P<0.01).Compared with the lipopolysaccharide group,the expressions of Jag-1(all P<0.01),Notch-1(all P<0.01)and Hes(P<0.05,P<0.01 and P<0.01)were significantly reduced in the lipopolysaccharide + astragaloside,lipopolysaccharide +DAPT,lipopolysaccharide + DAPT + astragaloside group.(6)The results indicate that astragaloside can promote the transformation of astrocytes from A1 to A2 by regulating Notch-1 signaling pathway,reduce the secretion of inflammatory factors and the migration of CD4 T cells,and thus inhibit astrocyte activation and inflammatory response.

Studies have shown that vertebral artery hypoplasia(VAH)is associated with posterior circulation ischemic stroke,but it is difficult to distinguish VAH from atherosclerotic stenosis in cerebrovascular angiography and other imaging examinations,and there is currently no unified diagnostic standard for intracranial VAH.The authors reviewed the definition and incidence of intracranial VAH from the aspects of autopsy and imaging,and summarized its relationship with posterior circulation ischemic stroke,in order to improve the clinicians'understanding of intracranial VAH.

Objective To investigate the effect of imatinib on the growth of A549 non-small cell lung cancer transplanted tumors and the expression of PDGFB and PDGFRβ proteins in tumor tissues and stroma in nude mice and to explore the underlying tumor suppression mechanism. Methods A transplantation tumor model of A549 non-small cell lung cancer was established in nude mice. The mice were then randomly divided into four groups: control group (0.9%NaCl), low-dose imatinib group (50 mg/(kg·d)), medium-dose imatinib group (100 mg/(kg·d)), and high-dose imatinib group (200 mg/(kg·d)). The effect of different concentrations of imatinib administered by continuous gavage on tumor growth was observed for 28 days. HE staining was performed to observe the pathological changes of tumor tissues. The expression of PDGF/PDGFR pathway-related proteins and the phosphorylation levels of AKT and ERK1/2 proteins in tumor tissues were detected by Western blot analysis. Double immunofluorescence staining was used to detect the expression of PDGFB and PDGFRβ proteins in the tumor stroma. Results Imatinib inhibited the growth of A549 non-small cell lung cancer cells in nude mice, suppressed the expression of PDGFB in tumor tissues, and decreased the phosphorylation levels of PDGFRβ, AKT, and ERK1/2. The expression of PDGFB and PDGFRβ in tumor stromal fibroblasts of the administered group was significantly lower than that of the control group. Conclusion Imatinib exhibits a pronounced inhibitory effect on A549 xenografts of nude mice with non-small cell lung cancer, and its antitumor mechanism may involve the downregulation of PDGFB and PDGFRβ expression in tumor stromal fibroblasts.

Objective:To evaluate the value of pretreatment 18F-fluorodeoxyglucose (FDG) PET/CT-based heterogeneity for early prediction of targeted therapy outcome in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Methods:From May 2012 to April 2018, 29 patients (all females, median age: 52 (32-69) years) who had HER2 positive metastatic breast cancer and underwent pretreatment 18F-FDG PET/CT in Fudan University Shanghai Cancer Center were retrospectively enrolled. All patients received trastuzumab as first-line treatment and were followed up for 6-87 (median time: 35) months. The relations between clinicopathologic parameters or PET/CT-based parameters and progression-free survival (PFS)/overall survival (OS) were analyzed with Cox univariate analysis. The parameters with P≤0.01 were further analyzed with Cox multivariate analysis. Optimal cut-off values were determined by time-dependent receiver operating characteristic (ROC) curve analysis. The survival analyses were estimated by Kaplan-Meier method and log-rank test. Results:The median OS of the 29 patients was 30 (6-83) months, and the median PFS was 10 (2-29) months. The PET/CT-based heterogeneity index(HI), including the maximum standardized uptake value (SUV max) ratio (SUV max-R; hazard ratio ( HR)=8.6, 95% CI: 2.7-27.8, P<0.001), the mean standardized uptake value (SUV mean)-2.5 (the cut-off value of standardized uptake value (SUV)=2.5) ratio (SUV mean-2.5-R; HR=2.6, 95% CI: 1.2-5.9, P=0.020), the metabolic tumor volume(MTV)-2.5 ratio(MTV-2.5-R; HR=2.4, 95% CI: 1.1-5.2, P=0.030), and the total lesion glycolysis(TLG)-2.5 ratio(TLG-2.5-R; HR=3.2, 95% CI: 1.4-7.4, P=0.008) of the lesion with the highest SUV max to that with the lowest SUV max, were significantly associated with PFS. None of the parameters was significantly associated with OS (all P>0.05). Multivariate analysis showed that the SUV max-R was the only independent predictor for PFS ( HR=6.8, 95% CI: 1.8-26.1, P<0.01). Area under the ROC curve for SUV max-R was 0.747. With a cut-off value of 1.8, SUV max-R could effectively distinguish the benefit from non-benefit population treated with trastuzumab (15.0 vs 7.0 months; χ2=18.68, P<0.01). Conclusion:Pretreatment 18F-FDG PET/CT-based HI has potential value for early prediction of first-line trastuzumab treatment outcome in patients with HER2 positive metastatic breast cancer.