The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

Objective To investigate the relationship between cyclin A2 (CCNA2) and the prognosis of colon cancer, and its possible mechanism from the perspective of immune infiltration. Methods We downloaded the transcriptome data of colon cancer patients from The Cancer Genome Atlas database. Clinicopathological feature analysis and survival analysis were performed based on the expression levels of CCNA2. A total of 75 specimens of colon cancer and normal tissues were collected, and the expression level of CCNA2 was analyzed using immunohistochemical methods. Multivariate analysis was conducted to explore its relationship with clinicopathological features. Gene Set Enrichment Analysis (GSEA) was used to assess the potential molecular functions of CCNA2 in colon cancer. CIBERSORT algorithm was applied to calculate the correlation between CCNA2 and immune-cell infiltration in colon cancer. Results Database and immunohistochemical analyses indicated that CCNA2 was expressed at a significantly higher level in colon cancer tissues than normal tissues (P<0.001). The overall survival, disease-specific survival, and progression-free interval were all longer in the group with high CCNA2 expression than the group with low expression (all P<0.05). In tumor tissues, the expression level of CCNA2 decreased with increased pathological and TNM stages (P<0.05). The expression level of CCNA2 in normal tissues was consistently lower than that in colon cancer tissues across all clinical stages (all P<0.001). GSEA suggested that Wnt/β-catenin, KRAS, and other signaling pathways were enriched when CCNA2 was lowly expressed. CIBERSORT analysis revealed an increase in the infiltration of immune cells such as regulatory T cells and macrophages M0 when CCNA2 expression was low. Conclusion CCNA2 is highly expressed in colon cancer and closely associated with grade of pathology and TNM stage. It may recruit regulatory T cells through the KRAS and Wnt/β-catenin pathways, thereby reducing immune-cell infiltration and promoting colon cancer progression, leading to poor prognosis.

Direct antiglobulin test (DAT), also known as Coomb's test, is a method used in blood immunology to detect whether the surface of red blood cells is sensitized by immunoglobulin or complement. It is mainly used in the diagnosis of autoimmune hemolytic anemia (AIHA), neonatal hemolytic anemia, hemolytic transfusion reaction and blood matching during blood transfusion. DAT positive has always been the focus of researchers, because it has an important impact on the efficacy of blood transfusion. In recent years, there has been extensive research on the identification of DAT positivity types and the distribution characteristics of diseases in clinical patients, and the study on hemolytic disease of the newborn has also been popular. However, the transfusion safety of DAT-positive blood donors has been a hot topic in the field of blood transfusion for many years. Moreover, there is no clear requirement from the state on the handling of DAT-positive blood and whether DAT-positive blood donors should be deferred from donation. Therefore, this article reviews the serological studies on DAT immunotyping and IgG subtype typing of voluntary blood donors, as well as the impact of DAT-positive blood on blood transfusion safety, in order to provide references for the blood issuance strategy of DAT-positive blood and whether DAT-positive blood donors should be deferred.

Cluster of differentiation 36 (CD36) is a highly glycosylated double transmembrane glycoprotein, which is involved in the inflammatory response and immune regulation of the body. It plays a key role in mediating the mechanism of immune-related blood transfusion reactions and regulating the function of immune cells. It has an important impact on blood transfusion safety and has become a current research hotspot. This article reviews and comprehensively analyzes the research progress of the specific role of CD36 in the immune response of blood transfusion and its regulatory mechanism at home and abroad. Combined with clinical cases and experimental data, the pathophysiological mechanism of CD36 in immune response and its immune-mediated blood transfusion safety issues are reviewed. It is expected to provide new theoretical support and practical guidance for the field of blood transfusion safety and promote the further development of blood transfusion medicine.

ObjectiveTo observe the antidepressant effect of Chaihu Shugansan combined with ferulic acid on the rat model of chronic unpredictable mild stress （CUMS） and explore the mechanism from the histomorphology of frontal cortex， expression of key molecules in the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrkB） signaling pathway， and changes in monoamine neurotransmitter levels. MethodsSixty adult male SD rats were randomized into six groups （n=10）： blank control， depression model， Chaihu Shugansan （3.3 g·kg^-1·d^-1）， ferulic acid （50 mg·kg^-1·d^-1）， Chaihu Shugansan （3.3 g·kg^-1·d^-1） + ferulic acid （50 mg·kg^-1·d^-1）， and fluoxetine （2.1 mg·kg^-1·d^-1）. Rats in other groups except the blank control group were subjected to a mild chronic unpredictable stress stimulus every day. Seven stimuli were used， including fasting with free access to water for 24 h， water deprivation with free access to food for 24 h， wetting the bedding with water in the cage， restraint for 3 h， tail clamping for 1 min， swimming in ice water at 4 ℃， and day and night reversal. Each stimulus was used 1 to 3 times， and the modeling lasted for a total of 21 days. At the same time of stimulation， rats in each medication group were treated with corresponding agents by gavage， while those in the blank control group and the depression model group received equal volumes of normal saline by gavage. The open field test， sucrose preference test， and forced swimming test were conducted before and after modeling. The rats were anesthetized by intraperitoneal injection of 3% pentobarbital sodium， and the frontal cortex was isolated on ice. The mRNA and protein levels of BDNF， TrkB， and cyclic adenosine monophosphate-responsive element-binding protein （CREB） in the frontal cortex were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The levels of monoamine neurotransmitters 5-hydroxytryptamine （5-HT）， dopamine （DA）， and norepinephrine （NE） in the frontal cortex were determined by enzyme-linked immunosorbent assay. Light microscopy was employed to observe the histopathological changes in the frontal cortex. ResultsCompared with the blank control group， the depression model group showed reduced body mass （P<0.05， P<0.01）， decreased number of crossings and rearings in the open field test and sucrose preference （P<0.01）， prolonged time of immobility in the forced swimming test （P<0.01）， reduced neuronal cells， increased necrotic cells， and darkening cell staining in the frontal cortex， down-regulated mRNA and protein levels of BDNF， TrkB， CREB， and lowered levels of 5-HT， NE， and DA in the frontal cortex （P<0.01）. Compared with the depression model group， each intervention group showed improved general state， increased body mass （P<0.05）， increased number of crossings （P<0.05）， shortened immobility time in the forced swimming test （P<0.01）， increased neuronal cells， reduced necrotic cells， and lightened cellular staining in the frontal cortex， up-regulated mRNA and protein levels of BDNF， TrkB and CREB， and elevated levels of 5-HT， NE， and DA in the frontal cortex （P<0.01）. Moreover， the Chaihu Shugansan + ferulic acid group outperformed the Chaihu Shugansan group and the ferulic acid group in increasing the body mass and the 5-HT content in the frontal cortex （P<0.05）. The combination group outperformed the Chaihu Shugansan group regarding the number of rearings and up-regulation in the mRNA level of BDNF in the frontal cortex （P<0.05）， and it was superior to the ferulic acid group in terms of shortening the immobility time in the forced swimming test， up-regulating the mRNA levels of BDNF， TrkB， and CREB and the protein levels of BDNF and CREB in the frontal cortex， and increasing the DA content in the frontal cortex （P<0.05）. ConclusionChaihu Shugansan combined with ferulic acid can exert antidepressant effect on the rat model of CUMS by regulating the BDNF/TrkB signaling pathway and monoamine neurotransmitter content in the frontal cortex. Moreover， the antidepressant effect of Chaihu Shugansan combined with ferulic acid was more significant than that of Chaihu Shugansan and ferulic acid used alone.

BACKGROUND: Lung adenocarcinoma (LUAD) is the predominant subtype of non-small cell lung cancer (NSCLC). Damage-specific DNA binding protein 1 (DDB1), as a core protein of the CUL4-DDB1 ubiquitin ligase complex, is involved in the regulation of DNA damage repair, epigenetic modification, and cell cycle checkpoint activation. While the involvement of DDB1 in tumour progression through DNA repair and RNA transcriptional regulation has been reported, its expression and role in LUAD remain to be elucidated. This study aims to investigate the expression and role of DDB1 in LUAD. METHODS: The expression, clinicopathological features and prognosis of DDB1 in LUAD were analysed using databases such as UALCAN, Kaplan-Meier Plotter and GEPIA; The interaction network and enriched functional pathways were constructed by GeneMANIA and Metascape; the correlation between DDB1 and immune cells by combining with TISIDB infiltration was evaluated, and the clustering results of cell subtypes and the expression of DDB1 in different immune cell subpopulations were analysed by single-cell sequencing; finally, tissue microarrays were used to further verify the expression and prognostic value of DDB1 in LUAD. RESULTS: The mRNA and protein expression of DDB1 in LUAD tissues were significantly higher than those in normal tissues (P<0.01), and the high expression correlated with later clinical stage (P<0.001), lymph node metastasis (P<0.001) and poor prognosis (P<0.001). Functional enrichment showed that DDB1 was involved in DNA repair and RNA transcriptional regulation, and TISIDB evaluation revealed that DDB1 was negatively correlated with the expression level of immune cells, suggesting the potential regulation of the immune microenvironment. Single cell analysis showed that DDB1 was mainly expressed in T cells, alveolar macrophages and dendritic cells. Tissue microarrays confirmed that overall survival was shorter in the DDB1 high expression group (P<0.001), and Cox multifactorial analysis showed that DDB1 was an independent predictor of LUAD prognosis. CONCLUSIONS DDB1 is highly expressed in LUAD, which is associated with poor prognosis, and is closely related to tumor immune cell infiltration, and is involved in tumourigenesis and development through DNA repair and RNA transcriptional regulation. DDB1 can be used as a potential prognostic marker and therapeutic target for LUAD.
Humans ; Adenocarcinoma of Lung/immunology* ; DNA-Binding Proteins/metabolism* ; Lung Neoplasms/diagnosis* ; Gene Expression Regulation, Neoplastic ; Prognosis ; Male ; Female ; Middle Aged

Allergen specific immunotherapy（AIT）, as an effective treatment for allergic rhinitis, asthma, and other allergic diseases, has received widespread attention in the field of health economic evaluation in recent years. This article reviews the current status and progress of economic research on AIT, mainly discussing the socioeconomic burden of allergic rhinitis, the results of health economic studies from different countries, and the primary methods used in health economic research on allergic rhinitis. Existing studies indicate that, although AIT involves high initial costs, it offers significant long-term economic benefits by reducing healthcare resource utilization, improving patient quality of life, and decreasing medication dependence. Moreover, reducing initial costs, applying standardized assessment tools, and conducting cross-national comparative analyses have become key directions for future research. Overall, AIT demonstrates strong potential in terms of long-term health benefits and cost savings, providing solid economic evidence for the management of allergic diseases.
Humans ; Desensitization, Immunologic/economics* ; Cost-Benefit Analysis ; Rhinitis, Allergic/economics* ; Economics, Medical

Objective:To investigate the efficacy of immune checkpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy for stage Ⅲ-ⅣA esophageal squamous cell carcinoma (ESCC) in the real world.Methods:The clinical data of 65 patients with stage Ⅲ-ⅣA ESCC treated by radical radiotherapy and chemotherapy from January 1, 2018 to December 31, 2022 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed. According to whether to undergo immune checkpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy, the patients were divided into a control group ( n=29) and an immune maintenance therapy group ( n=36) . The objective response rate (ORR) , progression-free survival (PFS) , and overall survival (OS) between the two groups were compared. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to conduct both univariate and multivariate analyses. Results:The ORR was 34.5% (10/29) in the control group and 61.1% (22/36) in the immune maintenance therapy group, with a statistically significant difference ( χ2=4.56, P=0.032) . The median PFS of control group and immune maintenance therapy group were 7.2 and 17.9 months, respectively, with a statistically significant difference ( χ2=7.86, P=0.005) . The median OS was 14.1 and 27.8 months, respectively, with a statistically significant difference ( χ2=5.40, P=0.020) . Univariate analysis showed that, objective response ( HR=0.09, 95% CI: 0.03-0.28, P<0.001) and immune maintenance therapy ( HR=0.38, 95% CI: 0.17-0.88, P=0.024) were the influential factors of OS in ESCC patients treaded by radical chemoradiotherapy in stage Ⅲ-ⅣA. Multivariate analysis showed that, objective response ( HR=0.09, 95% CI: 0.03-0.29, P<0.001) and immune maintenance therapy ( HR=0.40, 95% CI: 0.17-0.92, P=0.032) were the independent influencing factors for OS in ESCC patients treaded by radical chemoracial therapy in stage Ⅲ-ⅣA. The incidence of adverse reactions was 22.22% (8/36) in the immune maintenance therapy group and 10.34% (3/29) in the control group, with no statistically significant difference ( χ2=1.61, P=0.204) . All the adverse reactions were grade 1-2, and the symptoms were relieved after symptomatic treatment. Conclusion:Maintenance therapy with immune checkpoint inhibitors after radical chemoradiotherapy of stage Ⅲ-ⅣA ESCC can significantly improve the prognosis of patients with good safety.

ObjectiveTo investigate the effect and possible mechanism of Shenfu Injection （参附注射液） on rat cardiomyocyte injury induced by isoproterenol from the perspective of regulating the high mobility group protein B1 （HMGB1）/ Toll-like receptor 4 （TLR4）/nuclear factor κB （NF-κB） pathway through the deacetylation modification of silent information regulator 1 （SIRT1）. MethodsThe optimal concentration and intervention duration of isoproterenol hydrochloride and the optimal intervention concentration of Shenfu Injection were screened out by CCK-8 method. Logarithmically growing H9c2 rat cardiomyocytes were taken at 5×10⁴ cells/well and divided into normal group， model group， Shenfu Injection group， and SIRT1 inhibitor group， with 3 replicates in each group.Except for the normal group， the cells in the other groups were induced by isoproterenol hydrochloride to establish a chronic heart failure cell model. After modeling， the Shenfu Injection group was given Shenfu Injection at the optimal intervention concentration， and the SIRT1 inhibitor group was given 1 μmol/L of SIRT1 inhibitor EX-527， for optimal intervention duration.CCK-8 assay was used to detect the cell activity and calculate the inhibitory rate. ELISA assay was used to detect the nicotinamide adenine dinucleotide oxidation state/ nicotinamide adenine dinucleotide reduction state （NAD+/NADH） in cardiomyocytes. Immunofluorescence was used to detect the immunofluorescence localization of HMGB1 and SIRT1 in cardiomyocytes. Western blotting was used to detect the protein expression of acetylated HMGB1 in cardiomyocytes， HMGB1 in the nucleus and cytoplasm， and SIRT1， TLR4， myeloid differentiation factor 88 （MYD88） and NF-κB p65 in cardiomyocytes. RT-qPCR was used to detect the mRNA expression of SIRT1， HMGB1， TLR4， MYD88 and NF-κB p65 in cardiomyocytes. ResultsThe optimal intervention concentration of isoproterenol hydrochloride was 300 μmol/L， and the intervention duration was 48 hours； 8% was the optimal intervention concentration of Shenfu Injection. Compared to those in the normal group， the cell activity， NAD+/NADH value， nuclear HMGB1 protein expression， cardiomyocyte SIRT1 protein and mRNA expression in the model group decreased， while the cell inhibition rate， cardiomyocyte acetylated HMGB1 and cytoplasmic HMGB1 protein expression， cardiomyocyte TLR4， MYD88， NF-κB p65 protein and mRNA expression all increased （P＜0.05）； fluorescence localization showed that the content of HMGB1 in cardiomyocytes in the model group increased and was localized in both the nucleus and cytoplasm.Compared to the model group and the SIRT1 inhibitor group， the Shenfu Injection group showed significant improvements in all the above indicators （P＜0.05）； fluorescence localization showed that the SIRT1 content increased in the Shenfu injection group， while the HMGB1 content decreased， and was mainly located in the nucleus. ConclusionShenfu Injection can improve myocardial cell damage by increasing SIRT1 expression to reduce the acetylation level of HMGB1， regulating the HMGB1/TLR4/NF-κB pathway and inhibiting the nuclear translocation of HMGB1.