Zhigancao Tang， derived from the Treatise on Cold Damage，is a classic and renowned formula for treating "intermittent and irregular pulse， and palpitations of the heart". It has an exquisite formulation. By replenishing Qi， nourishing Yin， activating Yang， and restoring the pulse， it achieves the dual supplementation of Yin and Yang， and the simultaneous treatment of Qi and blood. With the practical expansion by practitioners over successive dynasties， the application scope of this formula has been continuously expanding， extending from traditional cardiovascular diseases to diseases of multiple systems， fully reflecting the theoretical characteristics of traditional Chinese medicine （TCM） of "treating different diseases with the same method". Modern research shows that Zhigancao Tang not only has a remarkable curative effect on cardiovascular diseases but is also widely applied to diseases of the respiratory， nervous， digestive， endocrine， oncologic， gynecologic， and otorhinolaryngologic systems， demonstrating its interdisciplinary clinical application value. At the same time， research on the mechanism of action of Zhigancao Tang is also continuously deepening. The mechanisms by which it treats diseases involve multiple aspects， including anti-arrhythmic effects， myocardial protection， anti-fibrosis， antioxidative stress and anti‑inflammatory effects， regulation of glucose and lipid metabolism， enhancing hematopoietic function， and improving hemorheology. These mechanisms work synergistically to jointly regulate the physiological functions of the body and play a role in treating diseases. However， there are still some deficiencies in current research. For example， the sample size of some clinical trials is small， most of the mechanism studies are based on animal models or in vitro experiments， there is insufficient high-quality evidence from clinical trials， the composition of the compound formula is complex， and the pharmacodynamic material basis and the rules of compatibility still need to be deeply analyzed. By consulting relevant literature， this article systematically summarizes the modern clinical application and action mechanism of Zhigancao Tang， aiming to provide new ideas for its subsequent in-depth research and clinical application， promote the integrated development of classic TCM formulas and modern medicine， and further explore its great potential in clinical treatment.

Surface proteins play pivotal roles in physiological processes, including cell recognition, signal transduction, substance transport, and immune responses. However, challenges persist in characterizing abnormal surface proteins in disease states and identifying therapeutic targets, due to the low abundance of these proteins within the total proteome and the frequent presence of their complex glycosylation modifications. Recent years have witnessed the vigorous development of chemical proteomics, leading to the successful creation of various chemical probes for the labeling and characterization of cell surface proteins. These techniques have subsequently been applied to the detection of disease surface proteins and the discovery of corresponding targets. Surface protein characterization techniques based on chemical proteomics are discussed herein, focusing on the principles of amino acid-targeted labeling, proximity labeling, and glycoprotein capture. The novelty, advantages, and limitations of techniques such as targeted lysine labeling, peroxidase and photocatalytic proximity labeling, and chemical glycan capture and metabolic glycan labeling are elaborated, and their applications across various biological models and disease types are described, aiming to provide some reference for target discovery and drug development targeting surface proteins.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

[Objective]To analyze the application and compatibility rules of acupoints and reflex areas in foot massage for the treatment of insomnia through data mining technology,thereby providing an evidence-based basis for the clinical treatment of foot massage in patients with insomnia.[Methods]The literatures associated with the treatment of insomnia through foot massage were retrieved by computer from The Cochrane Library,Web of Science,Embase,PubMed,China National Knowledge Infrastructure,Wanfang,VIP,Chinese Biomedical Literature and other databases.The search period was set until January 1,2025.Excel 2016 software was employed to establish the database for the treatment of insomnia with foot massage,and SPSS 25.0 software was utilized to calculate the frequency of acupoints and reflection areas in the database.Association rules were analyzed by the Apriori module of SPSS Modeler 18.0 software.The association rules of acupoints,reflection areas and their compatibility were described.The association rules were visualized by using Cytoscape 3.9.1 and cluster analysis was visualized with Origin 2022,respectively.[Results]Finally,124 effective literatures were incorporated including 35 for massage treatment of the foot reflex area alone,42 for massage treatment of the foot point alone,and 47 for massage treatment of the combined area and point.The most frequently utilized foot reflex areas of foot massage were the brain,the abdominal nerve plexus,the kidney,the heart,etc.,and the foot points were Yongquan,insomnia points,Taixi,etc.,among which the foot points were mainly characterized by the foot Shaoyin kidney channel and the foot Jueyin liver channel.The five transport points were the most prevalent specific points.The statistical results indicated that the effect of multi-point and/or multi-zone compatibility treatment was superior.Compatibility analysis revealed that the efficacy of multi-point and/or multi-zone compatibility treatments was superior.Analysis result of 124 articles on insomnia treatment through foot massage demonstrated that the most supportive compatibitily for the treatment of insomnia by foot massage was brain-abdominal nerve plexus,which was consistent with the analysis results of 35 literatures on the treatment of insomnia by foot reflex area massage alone.Furthermore,an analysis of 42 articles on insomnia treatment through massage of foot acupoints indicated that Yongquan-Taixi was the most supportive foot acupoint combination.[Conclusion]The combination of Chinese and western medicine theories for guiding foot massage in the treatment of insomnia is highly recommended.Selecting points such as Yongquan,Taixi,insomnia points,brain,abdominal nerve plexus,kidney,heart,and others for the compatibility treatment effect of these areas is better.

Soy is a vital source of plant carbohydrates.However,it poses significant allergenic risks,particularly to young children and animals.Among the various proteins in soy,β-conglycinin,which con-stitutes approximately 30％of total soy carbohydrates,is a primary allergen.Undigested β-conglycinin can lead to intestinal damage by inhibiting cell growth,disrupting the cytoskeleton,and inducing apopto-sis.It can also enter the lymphatic and circulatory systems,triggering allergic reactions.Conventional ELISA methods for detecting β-conglycinin rely on polyclonal or monoclonal antibodies,which are limited by their large molecular weight,difficulty in accessing the protein core,and sensitivity to acidic and bas-ic conditions.To address these limitations,this study aimed to develop nanobodies(Nbs)against β-con-glycinin.Nbs,derived from the variable regions of heavy-chain antibodies found in camelids,have a mo-lecular weight approximately one-tenth that of conventional antibodies.They offer advantages such as small size,stable structure,high specificity,and strong affinity.A female alpacas was immunized five times using β-conglycinin,which showed a heavy chain antibody potency of 1∶16 000 by ELISA.Pe-ripheral blood lymphocytes were subsequently isolated and total RNA was extracted.The variable region of the heavy-chain antibody was amplified via PCR,and recombinant plasmids were constructed and transformed into the E.coli competency strain ER2738.The resulting library contained about 3.5×108 CFU/mL,which increased to 1.15×1012 PFU/mL after phage rescue,with a 100％Nbs gene insertion rate,indicating high diversity.Its Nbs phage output was significantly enriched by four rounds of solid-phase elution with an enrichment rate of 155.9.Four rounds of solid-phase panning yielded 35 positive clones,all of which shared the same amino acid sequence upon sequencing.The selected Nb was ex-pressed in a prokaryotic system,and its binding ability to β-conglycinin was confirmed using Western blotting and ELISA.The results demonstrated excellent specificity and affinity.This research lays the groundwork for developing a rapid and efficient detection method for β-conglycinin using Nbs,potentially enhancing food safety and allergen management.

Objective:To investigate the clinicopathological characteristics and genetic alterations of undifferentiated embryonal sarcoma of the liver (UESL).Methods:Three cases of UESL diagnosed in the Department of Pathology, the Third Affiliated Hospital of Sun Yat-sen University from 2020 to 2023 were retrospectively collected. The clinical, histomorphological, immunohistochemical, and genetic profiles were reviewed and analyzed.Results:The cohort comprised of three patients, including one male and two females, aged 7, 9, and 15 years, respectively. Tumor locations were in the right lobe of the liver in two cases, and in both the right and left lobes in one case. One case exhibited tumor rupture with hemorrhage. Gross examination revealed solid tumors in gray-red fleshy appearance, with areas of hemorrhage and necrosis. Microscopically, the tumor was composed of irregularly shaped spindle and polygonal cells arranged in bundles or sheets with varying density, scattered within a myxoid matrix containing giant tumor cells and eosinophilic globules. The tumor cells were positive for Vimentin, CD56, CD68, and bcl-2, with a Ki-67 index of 30%-80%. INI1 expression was retained, while p53 exhibited a mutant pattern. CKpan, CK7, CK19, EMA, HepPar-1, Arginase-1, AFP, CD34, S-100, Myogenin, and MyoD1 were negative. All three cases harbored TP53 missense mutations. Case 1 also showed MDM2 copy number amplification (class Ⅰ mutation), and case 2 exhibited a frameshift mutation in exon 10 of TSC2 (class Ⅱ mutation). Additionally, several class Ⅲ mutations were identified in all three cases. Germline testing for tumor-related genetic variants in case 2 revealed a missense mutation in exon 12 of DICER1, an in-frame insertion mutation in exon 8 of MSH2, and a missense mutation in exon 30 of TSC2.Conclusion:UESL is a rare malignant mesenchymal tumor of the liver, predominantly affecting children, with distinctive clinicopathological features and genetic alterations. TP53 mutations may play a key role in the pathogenesis of this tumor.

African swine fever(ASF)caused by African swine fever virus(ASFV)is a febrile,hem-orrhage and highly fatal infectious disease in pigs,which poses a serious threat to the global pig in-dustry.Currently,no vaccine is available for the prevention and control of ASF,and several ASF vaccines,including gene deletion attenuated live vaccines,live vector vaccines,and subunit vaccines are under the development stage in the laboratory research.As one of the most promising vaccines,live vector vaccine has the characteristic of safety and simulation of the pathogen natural infection to effectively stimulate the innate and adaptive immune responses,which becomes one of the hotspots in the research and development of novel ASF vaccines.This review focuses on the pro-gress in using modified viruses as vectors for ASF live vector vaccines,and aims to provide valua-ble information for future development of safe and effective ASF vector vaccines.

Objective To explore the application effect of foot massage based on the brain-gut axis theory in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and to provide references for improving patients' sleep quality and gastrointestinal symptoms.Methods A total of 88 patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,who were treated at a Blood Purification Center of a tertiary-A general hospital in Hangzhou,Zhejiang Province from April to September 2024,were selected as a study subjects.They were randomly divided into an experimental group and a control group using the random number table method,with 44 cases in each group.The experimental group received foot massage based on the guidance of the brain-gut axis theory in addition to conventional treatment and nursing care,while the control group received conventional treatment and nursing care only.The intervention lasted for 3 months.The differences in the Pittsburgh Sleep Quality Index(PSQI)scores,Gastrointestinal Symptom Rating Scale(GSRS)scores,traditional Chinese medicine(TCM)syndrome scores,and serum 5-hydroxytryptamine and melatonin levels between the 2 groups before and after the intervention were compared.Results During the study period,no cases were lost in the experimental group,while 5 cases were lost in the control group.Ultimately,44 cases were included in the experimental group and 39 cases in the control group.After the intervention,the PSQI scores,GSRS scores,and TCM syndrome scores in both groups were lower than those before the intervention,and those in the experimental group were lower than those in the control group.The serum 5-hydroxytryptamine and melatonin levels were higher than those before the intervention,and the levels in the experimental group were higher than those in the control group,with statistically significant differences(all P＜0.001).Conclusion Foot massage based on the brain-gut axis theory can improve gastrointestinal symptoms and TCM syndromes in patients with spleen-kidney yang deficiency syndrome undergoing maintenance hemodialysis and suffering from insomnia,and enhance their sleep quality.

Objective:To investigate the correlations between physical, psychological and social frailty in elderly patients with multimorbidity.Methods:This study utilized a mixed method. A questionnaire survey was conducted from February to June 2024, among elderly patients with multimorbidity attending 4 primary health care centers in urban Beijing selected by the convenience sampling method. The FRAIL Frailty Assessment Scale, WHO-5 Index of Well-Being Scale, and HALFT Scale were used to assess the patients′ physical, psychological, and social frailty, respectively. Spearman correlation analysis was used to analyze the correlation between different dimensions of frailty in elderly with multimorbidity. Logistic regression model was used to analyze the factors influencing physical, psychological and social frailty. The elderly with multimorbidity who were assessed to have at least 1 or more types of frailty in the quantitative study were selected for in-depth interviews in the form of online and offline combination. The topics of in-depth interview included the real experience of the different dimensions of frailty, the possible causes and the difficulties caused. The sample size was determined according to the principle of information saturation. Thematic analysis was used to summarize, code and analyze the interview data.Results:A total of 919 participants were included in the quantitative study, with a mean age of (74.09±6.03) years, 329(35.80%) were males and 590(64.20%) were females. The prevalence of physical, psychological, and social frailty was 17.85%(164/919), 21.44%(197/919), 11.21%(103/919), respectively. A total of 21 participants were included in the qualitative study, with a mean age (76.90±5.13)years, 5(23.81%) males and 16(76.19%) females. Spearman correlation analysis showed that physical and psychological frailty were moderately correlated ( r=0.311, P<0.001), psychological and social frailty were weakly correlated ( r=0.218, P<0.001), and physical and social frailty were weakly correlated ( r=0.267, P<0.001). Logistic regression analysis showed that the age, the number of multimorbidities, the psychological frailty and social frailty were the influencing factors for physical frailty (all P<0.05). The gender, number of multimorbidity, type of medication taken, physical frailty and social frailty were influencing factors of psychological frailty (all P<0.05). And age, number of multimorbidities, physical frailty and psychological frailty were influencing factors of social frailty (all P<0.05). A total of 3 themes were extracted through in-depth interviews, namely, "physical and psychological frailty are interrelated""physical and social frailty are interrelated", and "psychological and social frailty are interrelated". Conclusions:The physical, psychological, and social frailty in elderly patients with multimorbidity interacts with each other. Whereas the number of multimorbidities is a common risk factor for all three.

Objective:To analyze the current status, research hotspots, and development trends on the integration of primary care and prevention in China.Methods:This was a bibliometric analysis. Literature related to research on the integration of primary care and prevention in China was retrieved from CNIKI, Wanfang, VIP, Chinese Medical Journal Full Text Database, PubMed, and Web of Science for the period from January 1, 2015, to April 1, 2025. CiteSpace software was used to conduct a visual analysis of publication volume, authors and their collaborations, institutions, and keywords in the included literature.Results:A total of 292 domestic publications on the integration of primary healthcare and public health were analyzed. Research on primary healthcare-public health integration in China exhibited an overall upward trend from 2015 to 2025. Based on publication volume and temporal distribution, domestic research can be categorized into an exploratory phase (2015-2020) and a rapid development phase (2021-2025). The institutions publishing relevant research were predominantly universities and research centers, with a low institutional network density (0.013), indicating relative weak inter-institutional collaboration. The co-occurrence density among authors was 0.013 9. Collaboration predominantly occurred in small clusters, with limited cross-regional cooperation. Keywords that appeared frequently and had an intermediary centrality exceeding 0.1 included chronic diseases (0.40), public health (0.23),health management (0.18), and hypertension (0.17). Keyword clustering analysis showed that the top three categories mainly focused on public health, chronic diseases, and health management. Since 2024, emerging keywords with high burst intensity have included big data, health literacy, primary care hospitals, and infectious diseases.Conclusions:Research on the integration of medical and preventive care at the primary healthcare level in China has entered a stage of rapid development. Current research hotspots focus primarily on chronic disease management, the implementation status and barriers of primary healthcare and prevention integration models. Future research is expected to emphasize the application of intelligent technologies, and the enhancement of public health emergency response capacity.