1.Synergistic Effect and Mechanism of FUT8 Inhibitor 2FF With DOX for Cancer Treatment
Zhi-Dong XIE ; Xiao-Lian ZHANG
Progress in Biochemistry and Biophysics 2025;52(2):478-486
ObjectiveChemotherapy is one of the important therapeutic approaches for cancer treatment. However, the emergence of multidrug resistance and side effects significantly limit its application. To address these challenges, chemotherapy is often combined with other drugs or therapies. Among the 13 human fucosyltransferases (FUTs) identified, FUT8 (alpha-(1,6)-fucosyltransferase) is the only enzyme responsible for core fucosylation. Core fucosylation plays an important role in cancer occurrence, metastasis and chemotherapy resistance, making the suppression of FUT8 a potential strategy for reversing multidrug resistance. This study aims to evaluate the feasibility of combining the small molecule FUT8 inhibitor 2FF (2-deoxy-2-fluoro-L-fucose) with the clinical chemotherapeutic drug doxorubicin (DOX) for treating malignant tumors. MethodsThe human hepatocellular carcinoma cell line HepG2 and mouse colon cancer cell line CT26 cells were treated with 2FF, DOX or their combination and core fucosylation levels were assessed using Lectin blot. HepG2 and CT26 cells were exposed to 50 μmol/L 2FF for 72 h, followed by treatment with a gradient concentration of DOX for 24 h. Cell viability and IC50 values were determined via the CCK-8 assay. Transwell invasion assays were conducted to evaluate the combined effect of 2FF and DOX on the invasion ability of HepG2 cells. Flow cytometry was performed to analyze the impact of 2FF, DOX and their combination on membrane PD-L1 expression of HepG2 cells. To assess the in vivo effect, 6- to 8-week-old female BALB/c mice (20-25 g), were subcutaneously injected with 1×106 CT26 cells into the right axilla (four groups, six mice in each group). After the average tumor volume reached 100 mm3, mice were treated with DOX, 2FF, their combination, or saline (mock group) every other day. DOX was administrated intraperitoneally (2 mg/kg), 2FF intravenously (5 mg/kg), and the combination group, received the both treatment. Tumor size was measured every other day using a vernier caliper. ResultsThis study demonstrated that DOX upregulates the core fucosylation levels in HepG2 and CT26 cells,while 2FF effectively inhibits this DOX-induced effect. Furthermone, 2FF enhanced the sensitivity of HepG2 and CT26 cells to DOX. The combination of 2FF and DOX synergistically inhibited the invasion ability of HepG2 cells, and enhanced the anti-tumor efficacy of CT26 subcutaneous tumor model in BALB/c mice. However the combination treatment led to weight loss in mice. In addition, DOX increased the cell surface PD-L1 expression in HepG2 cells, which was effectively suppressed by 2FF. ConclusionThe FUT8 inhibitor 2FF effectively suppresses DOX-induced upregulation of core fucosylation and PD-L1 levels in tumor cells, and 2FF synergistically enhances the anticancer efficacy of DOX.
2.Research progress on the application of visual electrophysiological examination in early diagnosis of glaucoma
Chang SUN ; Rong ZHANG ; Xiaolin XIAO ; Minpeng XU ; Dong MING ; Xia HUA
International Eye Science 2025;25(7):1073-1078
Glaucoma is a group of optic nerve disorders characterized by progressive optic nerve atrophy and visual field defects, which can lead to irreversible blindness. Early diagnosis of glaucoma is essential for preventing visual loss. However, due to the absence of obvious early symptoms, the diagnosis of glaucoma remains challenging. Visual electrophysiological examinations, an objective approach for evaluating visual function, have the potential to be used in the early diagnosis of glaucoma. This review integrates the latest publications to introduce visual electrophysiological examination techniques, including electroretinography(ERG)and visual evoked potential(VEP). It also explores the mechanisms underlying these techniques and their application value in the early diagnosis of glaucoma. In addition, this review summarizes the advantages, limitations, and applicable scenarios of different visual electrophysiological techniques. Finally, the review provides an outlook on the development prospects of visual electrophysiological techniques in the early diagnosis of glaucoma. The findings of this review can assist clinicians in selecting appropriate diagnostic methods, promote the innovation and development of early visual electrophysiological diagnostic techniques for glaucoma, and contribute to reducing the risk of blindness caused by glaucoma.
3.Differential Analysis on Chemical Composition and Pharmacodynamic Effect Between Combined Decoction and Single Decoction of Famous Classical Formula Huaganjian
Yang WANG ; Gaoju ZHANG ; Ling LI ; Liping CHEN ; Li ZHANG ; Xiao LIU ; Yuyu ZHANG ; Yuan CUI ; Minglong LI ; Chaomei FU ; Xin YAN ; Yuxin HE ; Qin DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):199-207
ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy, to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian, and meanwhile, the contents of four index components(geniposide, paeoniflorin, hesperidin and paeonol) were quantitatively analyzed by high performance liquid chromatography(HPLC). Nonalcoholic fatty liver disease(NAFLD) rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group, model group, lovastatin group(1.8 mg·kg-1), combined decoction group(1.26 g·kg-1) and single decoction group(1.18 g·kg-1). After successful modeling, lovastatin group, combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day, and the control group and model group were given equal amounts of normal saline by intragastric administration, after 4 weeks of administration, the serum and liver tissues were collected, and the contents of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) in serum of rats were detected, and the liver pathological examination was carried out by hematoxylin-eosin(HE) staining and oil red O staining, so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian, and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide, paeoniflorin, hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples(P<0.01). The pharmacodynamic results showed that compared with the model group, both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats, reduce the serum levels of AST, ALT, TC, TG and LDL-C, increase the serum level of HDL-C, and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However, there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition, but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.
4.Expression of indoleamin 2, 3-dioxygenase 1 in different types of breast cancer and its relationship with patient prognosis and immune cell infiltration
LI Xiaopiao1 ; LI Jie1 ; XIAO Jun2 ; DONG Yuhua2 ; HE Xun1 ; ZHANG Jinjuan2,3
Chinese Journal of Cancer Biotherapy 2025;32(6):620-627
[摘 要] 目的:探究吲哚胺2,3-双加氧酶1(IDO1)在不同类型乳腺癌组织中的表达及其与患者预后和免疫细胞浸润的关系。方法:收集 TCGA 数据库中乳腺癌RNA测序数据和相应临床资料,分析IDO1 mRNA在不同亚型、不同分期、不同绝经阶段及不同年龄等各类型乳腺癌组织与癌旁组织中的表达差异。将IDO1 mRNA表达有明显差异的乳腺癌类型的患者分为IDO1高、低表达组,比较3组间的疾病特异性生存率(DSS),分析IDO1 mRNA在DSS有明显差异的癌组织中的表达水平与免疫细胞浸润的关系。采用免疫组化法检测IDO1蛋白在ER阴性、PR阴性、HER2阳性及Ⅱ期乳腺癌组织中的表达情况,对数据库数据进行验证。结果:IDO1 mRNA在乳腺癌组织中呈高表达,但在不同类型乳腺癌中的表达不同。IDO1 mRNA在ER阴性、PR阴性、HER2阳性、HER2阴性亚型、Ⅱ期、T2期、N0期和M0期分期、绝经前、绝经后和年龄≤ 60岁患者的乳腺癌组织中呈高表达(P < 0.05或P < 0.01或P < 0.001)。ER阴性、PR阴性、HER2阳性和Ⅱ期亚组中,IDO1 mRNA高表达患者的DSS明显高于低表达患者(P < 0.05或P < 0.01)。ER阴性、PR阴性、HER2阳性和Ⅱ期乳腺癌组织中IDO1 mRNA表达与活化的树突状细胞(aDC)、Th1细胞、T细胞、CD56dim NK细胞、CTL和Treg细胞等免疫细胞浸润有关联(均P < 0.001)。IDO1蛋白在ER阴性、PR阴性、HER2阳性及Ⅱ期乳腺癌组织中均呈高表达(均P < 0.001),与数据库数据分析结果一致。结论:IDO1在不同类型的乳腺癌组织中的表达不同,IDO1表达与ER阴性、PR阴性、HER2阳性和Ⅱ期乳腺癌患者的预后和免疫细胞浸润有关联。
5.The Near-infrared II Emission of Gold Clusters and Their Applications in Biomedicine
Zhen-Hua LI ; Hui-Zhen MA ; Hao WANG ; Chang-Long LIU ; Xiao-Dong ZHANG
Progress in Biochemistry and Biophysics 2025;52(8):2068-2086
Optical imaging is highly valued for its superior temporal and spatial resolution. This is particularly important in near-infrared II (NIR-II, 1 000-3 000 nm) imaging, which offers advantages such as reduced tissue absorption, minimal scattering, and low autofluorescence. These characteristics make NIR-II imaging especially suitable for deep tissue visualization, where high contrast and minimal background interference are critical for accurate diagnosis and monitoring. Currently, inorganic fluorescent probes—such as carbon nanotubes, rare earth nanoparticles, and quantum dots—offer high brightness and stability. However, they are hindered by ambiguous structures, larger sizes, and potential accumulation toxicity in vivo. In contrast, organic fluorescent probes, including small molecules and polymers, demonstrate higher biocompatibility but are limited by shorter emission wavelengths, lower quantum yields, and reduced stability. Recently, gold clusters have emerged as a promising class of nanomaterials with potential applications in biocatalysis, fluorescence sensing, biological imaging, and more. Water-soluble gold clusters are particularly attractive as fluorescent probes due to their remarkable optical properties, including strong photoluminescence, large Stokes shifts, and excellent photostability. Furthermore, their outstanding biocompatibility—attributed to good aqueous stability, ultra-small hydrodynamic size, and high renal clearance efficiency—makes them especially suitable for biomedical applications. Gold clusters hold significant potential for NIR-II fluorescence imaging. Atomic-precision gold clusters, typically composed of tens to hundreds of gold atoms and measuring only a few nanometers in diameter, possess well-defined three-dimensional structures and clear spatial coordination. This atomic-level precision enables fine-tuned structural regulation, further enhancing their fluorescence properties. Variations in cluster size, surface ligands, and alloying elements can result in distinct physicochemical characteristics. The incorporation of different atoms can modulate the atomic and electronic structures of gold clusters, while diverse ligands can influence surface polarity and steric hindrance. As such, strategies like alloying and ligand engineering are effective in enhancing both fluorescence and catalytic performance, thereby meeting a broader range of clinical needs. In recent years, gold clusters have attracted growing attention in the biomedical field. Their application in NIR-II imaging has led to significant progress in vascular, organ, and tumor imaging. The resulting high-resolution, high signal-to-noise imaging provides powerful tools for clinical diagnostics. Moreover, biologically active gold clusters can aid in drug delivery and disease diagnosis and treatment, offering new opportunities for clinical therapeutics. Despite the notable achievements in fundamental research and clinical translation, further studies are required to address challenges related to the standardized synthesis and complex metabolic behavior of gold clusters. Resolving these issues will help accelerate their clinical adoption and broaden their biomedical applications.
6.Evaluation of drug local tolerance testing and analysis of common problems
Mei-Ling CHEN ; Qing-Li WANG ; Hong-Mei GUANG ; Lan CUI ; Xiao-Dong ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(1):139-143
Conducting local tolerance testing on parentaral drugs is of great significance for evaluating the clinical medication risks of drugs.Although relevant domestic and international guidelines provide detailed instructions on how to conduct local tolerance testing,it was found that some products still provide non-standard application materials,which affects the efficiency of drug development.This article summarizes the information on domestic and international guidance related to the local tolerance testing and elaborates on common problems based on specific application cases,with the aim of of providing reference for related work.
7.Research progress on Buyang Huanwu Decoction in preventing and treating vascular dementia by regulating inflammatory factors
Yan-Hong LIU ; Shu-Yuan CONG ; Feng WU ; Ke-Wu ZHAO ; Xiao-Hong DONG ; Ning ZHANG ; Bin LIU
The Chinese Journal of Clinical Pharmacology 2024;40(5):749-753
Objective Vascular dementia(VD)is a clinical syndrome caused by various cerebrovascular diseases,including ischemic,hemorrhagic,and acute and chronic hypoxic cerebrovascular diseases,leading to impaired brain function and affecting patients'cognitive ability,daily life,and work abilities.Vascular dementia is a preventable and reversible form of dementia,second only to Alzheimer's disease as the second common cause of dementia.At present,the relevant pathogenesis of vascular dementia is not clear,and there is no clear treatment method.However,its pathogenesis may be related to neuroinflammation,oxidative stress,neuronal damage and white matter lesions.Its main risk factors include genetic factors,hypercholesterolemia,diabetes,hypertension,etc.Neuroinflammatory response plays a major role in the process of secondary brain injury caused by cerebral ischemia,and inflammatory factors lead to an inflammatory cascade reaction that exacerbates damage to the nervous system.Inhibiting the inflammatory pathway and reducing the expression of inflammatory factors can improve the symptoms of vascular dementia patients and animal models,indicating that neuroinflammation may play an important role in the pathogenesis of vascular dementia.This article explores the effects of Buyang Huanwu Decoction on inflammatory factors from the perspective of summarizing relevant literature in recent years.It mainly reviews the pharmacological effects of Buyang Huanwu Decoction on treating vascular dementia,the relationship between inflammatory factor levels and vascular dementia,and the prevention and treatment of vascular dementia by regulating inflammatory factor levels.
8.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
9.Protective effect of vitamin D on mice with atopic dermatitis
Zhang-Jun DING ; Zhi-Peng WU ; Xiao-Dong CHEN
The Chinese Journal of Clinical Pharmacology 2024;40(6):884-888
Objective To investigate the protective effect of vitamin D on atopic dermatitis mice,and its mechanism.Methods Fifty male BALB/c mice in clean grade were randomly divided into blank group,model group,control group and experimental-L group,experimental-H group,10 rats in each group.Except for the blank group,mice in the other groups were modeled with 2,4-dinitrofluorobenzene(DNCB).After modeling,mice in experimental-L and experimental-H groups were evenly smeared with 5 and 10 μg·kg-11,25(OH)2D3 on their backs every day,respectively;control group were evenly coated with hydrocortisone solution(1 mg·cm-2)twice a day for 10 days,and the mice in blank group and model group were coated with the same amount of 0.9%NaCl every day.After the administration,the skin lesions were evaluated,and orbital blood was collected and the back skin tissues were collected for use.The epidermal thickness was observed by hematoxylin-eosin staining,and the number of mast cells was detected by toluidine blue staining.The expression levels of serum immunoglobulin E(IgE),interleukin(IL)-13,IL-4,IL-17 were detected by enzyme-linked immunosorbent assay(ELISA),and the proportion of serum Th1 and Th2 cells were detected by flow cytometry.The expression of histamine type 1 receptor(HIR),protease activating receptor 2(PAR2),transient receptor potential vanillin 1(TRPV1)in back skin was detected by immunohistochemistry.Results The symptom scores of mice in blank group,model group,experimental-L group,experimental-H group and control group were 0,(8.50±1.12),(6.34±0.54),(3.91±0.29)and(3.79±0.53)points;the epidermal thickness of the back skin were(42.05±4.14),(77.65±7.02),(61.12±5.02),(55.34±4.13)and(52.19±3.08)μm;the number of mast cells in back tissue were(4.67±0.27),(32.16±2.49),(25.23±2.07),(18.13±1.46)and(15.37±1.29)number·mm-2;Th1/Th2 cell ratios were 2.76±0.28,0.36±0.06,1.02±0.18,2.05±0.14 and 2.07±0.29,respectively;HIR expression levels were 0.05±0.00,0.21±0.02,0.16±0.02,0.10±0.01 and 0.08±0.01;the expression levels of PAR2 were 0.05±0.01,0.19±0.01,0.12±0.01,0.09±0.01 and 0.07±0.01;the expression levels of TRPV1 were 0.05±0.01,0.25±0.03,0.15±0.01,0.10±0.01 and 0.09±0.00,respectively.The above indicators,experimental-L group,experimental-H group and control group were compared with model group;experimental-H group compared with experimental-L group,the differences were all statistically significant(all P<0.05).Conclusion Vitamin D can reduce DNCB induced atopic dermatitis by regulating Th1/Th2 cell balance,which may be related to the TRPV1 oxygen signaling pathway mediated by HIR and PAR2.
10.Automatic monitoring of adverse drug reaction of anti-tuberculosis and analysis of influencing factors
Kai ZHANG ; Xiao-Qin LU ; Zhi DONG
The Chinese Journal of Clinical Pharmacology 2024;40(7):1059-1062
Objective To provide reference for clinical rational drug use,the adverse drug reaction(ADR)automatic monitoring system was used to monitor ADR in patients treated with first-line anti-tuberculosis drugs.Methods A total of 1 147 tuberculosis patients hospitalized in the infection department of our hospital from 2019 to 2022 were selected to monitor the occurrence of ADR during the hospitalization.Univariate and multivariate analysis were used to study the risk factors affecting the incidence of ADR.Results After systematic screening and pharmacist review,a total of 598 cases of ADR related to first-line anti-tuberculosis drugs were found,with an incidence of 52.14%.ADR mainly affects the endocrine system,digestive system,and hepatobiliary system.The incidence of ADR in oral isoniazid is higher than that in intravenous drip and nebulization routes.The results of multivariate regression analysis showed that women and a history of hepatitis were independent risk factors for the occurrence of ADR(all P<0.05).Conclusion The incidence of ADR with anti-tuberculosis drugs is high.Women and patients with a history of hepatitis are high-risk groups for adverse drug reactions to anti-tuberculosis drugs.In clinical,safer drugs should be selected for such patients,and the occurrence of ADR should be closely monitored to reduce the impact of ADR on the treatment process.

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