Sangjuyin， as a pungent and cooling agent with precise therapeutic effect， is a classic pungent formula for cooling relief of the epidermis， which is highly respected by medical practitioners. This formula is from the Wenbing Tiaobian written by WU Jutong in the Qing dynasty， on the basis of which subsequent medical practitioners have made additions and subtractions to apply it. The authors used the bibliometric method to systematically organize the medical books from the Qing dynasty and the Republic of China and modern literature to analyze the composition， concoction， decoction， efficacy， and previous and modern application of Sangjuyin. After examination， the drug base of this formula is basically clear. Armeniacae Semen Amarum is the dried mature seeds of Armeniaca vulgaris， family Rosaceae. Forsythiae Fructus is the dried fruit of Forsythia suspensa， family Mulleinaceae. Menthae Haplocalycis Herba is the dried above-ground part of Mentha haplocalyx， family Labiatae. Mori Folium is the dried leaves of Morus alba， family Moraceae. Chrysanthemi Flos is the dried head of Chrysanthemum morifolium， family Asteraceae. Platycodonis Radix is the dried root of Eryngium grandiflorum， family Eryngium. Glycyrrhizae Radix et Rhizoma is the dried root and rhizome of Glycyrrhiza uralensis of the Leguminosae family， and Phragmitis Rhizoma is the fresh or dried rhizome of Phragmites communis of the Gramineae family. It is recommended that the eight drugs be used in raw form as medicine. The dosage and method of decoction were converted into a modern single dosage of 7.46 g Armeniacae Semen Amarum， 5.60 g Forsythiae Fructus， 2.98 g Menthae Haplocalycis Herba， 9.33 g Mori Folium， 3.73 g Chrysanthemi Flos， 7.46 g Platycodonis Radix， 2.98 g Glycyrrhizae Radix et Rhizoma， and 11.19 g Phragmitis Rhizoma， with 400 mL water added， and the solution was boiled to obtain 200 mL， taken twice a day. Sangjuyin has the efficacy of dispersing wind and clearing heat， promoting lung and relieving cough， and it is used for treating the initial onset of wind-warmth and the evidence of evil spirits in the lungs and collaterals. Modern research has shown that Sangjuyin is often used in the treatment of cough， pneumonia， rhinitis， and other respiratory diseases， and the results of this study provide a reference for the later development of Sangjuyin.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

Objective:To analyze the biological parameters of the anterior segment of age-related cataracts patients with or without zonular weakness with the new generation of sweep-source anterior optical coherence tomography (OCT) device CASIA2 to provide a basis for the diagnosis of zonular weakness.Methods:A case-control study was conducted.A total of 158 cases (186 eyes) of patients with age-related cataracts having zonular weakness as a zonular weakness group, and 80 cases (80 eyes) of cataract with age-related cataracts without zonular weakness as a normal zonule group were enroll from June 2022 to June 2023 at Beijing Tongren Hospital.All patients underwent routine preoperative ophthalmological examination including slit lamp microsopy, IOLMaster 700, ocular B-ultrasound and OCT.The anterior chamber depth (ACD), anterior chamber volume (ACV), lens thickness (LT), lens vault (LV), anterior chamber angle opening distance at 750 μm (AOD750), lens decentration and tilt, radius of curvature of the anterior lens surface (RAL), and radius of curvature of the posterior lens surface (RPL) of patients were measured with CASIA2 and compared between the two groups.The relationship between zonular weakness and anterior chamber parameters and lens parameters was evaluated by logistic regression analysis.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital (No.TRECKY2018-049), and all enrolled patients signed the informed consent form.Results:In the zonular weakness group, ACD, ACV, RAL, and AOD750 were (2.34±0.56)mm, (85.05±40.19)mm 3, 7.52 (7.13, 8.08)mm, and 0.27 (0.07, 0.30)mm, respectively, which were smaller than (3.13±0.38)mm, (127.75±38.15)mm 3, 9.28(8.51, 9.76)mm, and 0.52 (0.31, 0.65)mm in the normal zonule group, with statistically significant differences (all P<0.05).LT and LV in the zonular weakness group were (5.14±0.45)mm and (1.22±0.53)mm, respectively, which were larger than (4.27±0.52)mm and (0.32±0.30)mm in the normal zonule group, and the differences were statistically significant (both P<0.05).Magnitude of lens decentration and tilt in the zonular weakness were 0.34 (0.13, 0.45)mm and 6.44 (3.67, 7.32)°, respectively, which were significantly larger than 0.19 (0.12, 0.25)mm and 4.88 (3.85, 5.65)° in the normal zonule group (both P<0.05).No obvious pattern was found in the direction of decentration and tilt.Logistic regression analysis showed that LV and lens decentration were risk factors of zonular weakness (odds ratios [ OR]=706.170, 335.339; both P<0.05), and RAL was a protective factor of zonular weakness ( OR=0.239, P<0.05). Conclusions:Age-related cataract patients with zonular weakness often present with a decrease in ACV due to increased anterior convexity of the lens.Decreased RAL, increased lens decentration and elevated LV are risk factors for zonular weakness.

Purpose To investigate the clinicopathological features,molecular subtypes,and prognostic factors of diffuse midline glioma(DMG)with H3K27 alterations.Methods Clinical data from 19 patients from DMG were col-lected.The clinical manifestations,histopathological features,immunophenotypes,and molecular genetic characteris-tics were analyzed.Relevant literature was also reviewed.Results Among the 19 patients,12 cases had tumors loca-ted in the thalamus,while 7 cases had tumors in other midline regions(including 4 cases in the brainstem,1 case in the cerebellum,and 2 cases in the spinal cord).Clinical symptoms primarily included dizziness,gait instability,and blurred vision.Histological features were diverse,with 12 cases classified as high-grade gliomas and 7 cases as low-grade.Immunohistochemistry revealed a loss of H3K27me3 expression in all cases,with 18 cases showing diffuse H3K27M positivity and 1 case expressing EZHIP.Of the 16 cases that underwent next-generation sequencing(NGS),1 case showed EGFR mutation(1/16,6％),while the remaining 15 cases had H3F3A K27M mutations(15/16,94％).Among these,7 cases had ATRX mutations(7/15,46.6％),5 cases had MAPK pathway alterations(5/15,33.3％,including 2 cases FGFR1,2 cases NF1,1 case co-mutated with BRAF and NF1),5 cases had PDGFRA mis-sense mutations(5/15,33.3％),4 cases had p53 missense or frameshift deletions(4/15,26.6％).One case each had a DICER1 missense mutation and an IDH1-S202R frameshift deletion(1/15,6.6％).The prognosis was general-ly poor,with a median survival of 9.5 months.Conclusion DMG exhibits high tumor heterogeneity and an overall poor prognosis.The predominant molecular aleration was the H3F3A K27M mutation.Patients with co-altered MAPK pathway showed relatively better outcomes,providing new insights into the molecular genetic characteristics of DMG.

Objective To identify determinants of subtherapeutic voriconazole(VRCZ)concentrations in allogeneic hematopoietic stem cell transplantation(allo-HSCT)recipients and to develop/validate a nomogram-based risk prediction model.Methods This study retrospectively analyzed 310 VRCZ therapeutic drug monitoring(TDM)measurements from allo-HSCT recipients at 310 patients who under went allo-HSCT surgery at Hebei Yanda Ludaopei Hospital from October 2022 to October 2024 and received VRCZ for the prevention and treatment of invasive fungal infections before transplantion were selected as the study subjects.Cases were stratified into target-concentration group(0.5～5.0μg/ml)and subtherapeutic group(<0.5μg/ml).Through single factor and multiple factor Logistic regression analysis,indeipendent predictive factors forvecz plasma concentration non-compliance were screened,and a column chart prediction model(NPM)was constructed.The performance of the model was evaluateding area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow(H-L)goodness-of-fit test,and decision curve analysis(DCA).Results Among 310 VRCZ-TDM measurements,71.61%(222/310)achieved target concentrations.Multivariate analysis showed that CYP2C19 intermediate metabolite,daily dose of cyclosporine A(CSA),daily dose of VRCZ,creatinine(Cr)>97 μmol/L,albumin(Alb)and C-reactive protein(CRP)were independent influencing factors for VRCZ blood drug concentration non-compliance(Wald χ2=4.046～13.221,all P＜0.05).The nomogram demonstrated excellent discrimination,calibration(H-L goodness of fit test χ2=2.663,P=0.954),and clinical utility with net benefit across 0.05～0.96 risk thresholds.Conclusion The nomogram incorporating CYP2C19 gene phenotype,daily CSA dosing,daily VRCZ dosing,Cr levels,Alb and CRP provides a validated tool for optimizing VRCZ therapy in allo-HSCT recipients,enabling precision dosing strategies.

Objective·To explore the biological functions and underlying mechanisms of anaphase-promoting complex subunit 10(ANAPC10)in the development and progression of liver hepatocellular carcinoma(LIHC,often abbreviated as HCC).Methods·By integrating data from The Cancer Genome Atlas(TCGA)_LIHC,the hepatitis B virus-related subgroup(HBV)of the China Hepatocellular Carcinoma Genome Project(CHCC),and the Gene Expression Omnibus(GEO),the expression pattern of ANAPC10 in HCC was analyzed.Western blotting and quantitative real-time PCR(q-PCR)were used to verify the findings in HCC cell lines.shRNA-mediated knockdown of ANAPC10 was performed in MHCC-97H and SNU-398 cell lines to investigate the effect of ANAPC10 depletion on the in vitro proliferation of HCC cells.An orthotopic liver cancer model with Anapc10 knockout was constructed using the hydrodynamic tail-vein injection technique in mice to further confirm the impact of ANAPC10 deficiency in the liver on the development and progression of HCC.Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses were performed on the RNA-sequencing data from TCGA_LIHC and CHCC_HBV.Results·ANAPC10 was highly expressed in tumor tissues,and its expression level was closely related to patient survival.Downregulation of ANAPC10 in vitro and in vivo effectively inhibited HCC progression.ANAPC10 mainly reprogrammed the metabolism of tumors by affecting the PI3K-AKT-mTOR pathway.In the tumor tissues of the orthotopic liver cancer mouse model in the Anapc10 knockout group,the phosphorylation levels of Akt and S6k were decreased,and changes in the key downstream lipid metabolism proteins Fasn and Scd1 were verified.Conclusion·ANAPC10 is highly expressed in HCC and is positively correlated with poor prognosis.It promotes HCC occurrence and progression by activating the PI3K-AKT-mTOR signaling pathway and enhancing lipid metabolism reprogramming,thereby promoting tumor cell proliferation.These findings expand the understanding of ANAPC10 in tumor progression and suggest potential therapeutic targets for HCC.

Objective Based on the national drug sampling inspection program,this study aims to comprehensively and systematically evaluate the quality of Xuanmai Ganjie preparations,analyze existing quality issues,and provide references and suggestions for quality control of this variety.Methods A total of 237 batches of Xuanmai Ganjie preparations were tested using legal standards,and methods were established for detecting adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels,and determining the content of platycodin D in Xuanmai Ganjie preparations.These methods were applied to the quality control and evaluation of Xuanmai Ganjie preparations.Results Through statutory inspection,one batch of Xuanmai Ganjie granules was found non-compliant.Specific batches were identified to contain the following irregularities:adulteration of Ophiopogon japonicus with counterfeit varieties,paclobutrazol residue levels exceeding proposed limits,and platycodin D content below the established threshold.Conclusion The overall quality of Xuanmai Ganjie granules was average,while the overall quality of Xuanmai Ganjie capsules and lozenges was relatively good.Manufacturing enterprises should strengthen their sense of primary responsibility and enhance control over the entire drug production process.

Objective·To explore the function and potential mechanism of suppressor of zeste 12(SUZ12)in hepatocellular carcinoma(HCC).Methods·The expression of SUZ12 in HCC patients was analyzed using R language in liver cancer datasets,and relevant survival curves were drawn.Stable knockdown of SUZ12 was established in the liver cancer cell lines LM3 and Huh7.The knockdown efficiency of SUZ12 was assessed using quantitative real-time PCR(qPCR)and Western blotting.Cell proliferation ability was assessed using CCK-8 assay and colony formation assay.Using the hydrodynamic tail vein injection(HTVI)method,Suz12 was knocked out in the livers of fully immunocompetent mice to explore its tumorigenic function in vivo.The molecular mechanism of SUZ12 regulating HCC was explored using The Cancer Genome Atlas(TCGA)database.R language was used to analyze the relationship between SUZ12 and the expression of cancer stem cell(CSC)markers as well as key glycolysis-related genes.Findings were validated in liver cancer cell lines and mouse tumor tissues.Results·The expression of SUZ12 in liver cancer tissues was higher than in adjacent non-tumor tissues,and its expression increased with higher tumor stage.HCC patients with high SUZ12 expression had poorer prognoses.In LM3 and Huh7 liver cancer cell lines,stable knockdown of SUZ12 reduced cell proliferation ability.In the de novo MYC/Trp53-/-mouse liver cancer model,tumor nodule number and size,and tumor burden in liver tissue were reduced after endogenous knockout of Suz12.TCGA analysis showed that high SUZ12 expression in HCC was enriched in multiple tumor proliferation-and metabolism-related pathways.The expression of SUZ12 was positively correlated with CSC markers and key genes in glycolysis pathway.The mRNA levels of CSC markers and key genes in glycolysis pathway were decreased in liver cancer cell lines with stable SUZ12 knockdown and Suz12 knockout mouse HCC tissues.Conclusion·The expression of SUZ12 is significantly increased in HCC patients and is associated with poor prognosis.Stable knockdown of SUZ12 weakens the proliferative ability of liver cancer cells.Knockout of Suz12 in mice in vivo can suppress the occurrence and development of HCC.The high expression of SUZ12 maintains the CSC pool,induces metabolic reprogramming,and promotes the occurrence and progression of HCC.SUZ12 can serve as a potential biomarker for poor prognosis and a novel target for potential therapeutic intervention in HCC.