1.VEGF Inhibitor–Associated Side Effects in Antitumor Therapy and Intervention Strategies
Lu LIU ; Wanting SUN ; Shuning YAO ; Zhenyu CHEN ; Yuefei WANG ; Jing YANG
Cancer Research on Prevention and Treatment 2026;53(4):289-300
Vascular endothelial growth factor (VEGF) inhibitors are drugs that target and inhibit tumor angiogenesis. By blocking the signaling pathway of VEGF and its receptor, they suppress tumor proliferation and play a crucial role in tumor treatment. However, their side effects, such as hypertension, proteinuria, hand-foot skin reactions, and myelosuppression, during treatment seriously affect patients' treatment compliance and quality of life. The development of intervention strategies for the side effects of VEGF inhibitors is of great importance for tumor treatment. This article reviews the clinical characteristics and toxic mechanisms of common side effects caused by VEGF inhibitors during tumor treatment and summarizes intervention strategies that combine traditional Chinese and Western medicines. Drug dosages were precisely monitored and adjusted to achieve antitumor treatment. Patients' discomfort symptoms are improved through prescriptions that act by tonifying qi and promoting blood circulation, strengthening the spleen, and tonifying the kidney. The combination of traditional Chinese and Western medicines is used to treat patients, thus providing a safe and effective treatment plan for patients with cancer.
2.Targeting SARS-CoV-2 main protease for the discovery of a broad-spectrum COVID-19 inhibitor by intensive multi-tiered validation.
Min ZHANG ; Changjian WANG ; Lu FENG ; Qi YANG ; Yipeng CAO ; Yao ZHAO ; Junhua ZHANG ; Yuefei WANG ; Zihe RAO ; Boli ZHANG
Acta Pharmaceutica Sinica B 2025;15(11):5789-5802
SARS-CoV-2 and its emerging variants continue to pose a significant global public health threat. The SARS-CoV-2 main protease (Mpro) is a critical target for the development of antiviral agents that can inhibit viral replication and transcription. In this study, we identified chebulagic acid (CHLA), isolated from Terminalia chebula Retz., as a potent non-peptidomimetic and non-covalent Mpro inhibitor. CHLA exhibited intermolecular interactions and provided significant protection to Vero E6 cells against a range of SARS-CoV-2 variants, including the wild-type, Delta, Omicron BA.1.1, BA.2.3, BA.4, and BA.5, with EC50 values below 2 μmol/L. Moreover, in vivo studies confirmed the antiviral efficacy of CHLA in K18-hACE2 mice. Notably, CHLA bound to a unique groove at the interface between Mpro domains I and II, which was revealed by the high-resolution crystal structure (1.4 Å) of the Mpro-CHLA complex, shrinking the substrate binding pocket of Mpro and inducing Mpro aggregation. CHLA was proposed to act as an allosteric inhibitor. Pharmacokinetic profiling and safety assessments underscore CHLA's potential as a promising broad-spectrum antiviral candidate. These findings report a novel binding site on Mpro and identify antiviral activity of CHLA, providing a robust framework for lead compounds discovery and elucidating the underlying molecular mechanisms of inhibition.
3.Adaptive multi-view learning method for enhanced drug repurposing using chemical-induced transcriptional profiles, knowledge graphs, and large language models.
Yudong YAN ; Yinqi YANG ; Zhuohao TONG ; Yu WANG ; Fan YANG ; Zupeng PAN ; Chuan LIU ; Mingze BAI ; Yongfang XIE ; Yuefei LI ; Kunxian SHU ; Yinghong LI
Journal of Pharmaceutical Analysis 2025;15(6):101275-101275
Drug repurposing offers a promising alternative to traditional drug development and significantly reduces costs and timelines by identifying new therapeutic uses for existing drugs. However, the current approaches often rely on limited data sources and simplistic hypotheses, which restrict their ability to capture the multi-faceted nature of biological systems. This study introduces adaptive multi-view learning (AMVL), a novel methodology that integrates chemical-induced transcriptional profiles (CTPs), knowledge graph (KG) embeddings, and large language model (LLM) representations, to enhance drug repurposing predictions. AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning (MVL), matrix factorization, and ensemble optimization techniques to integrate heterogeneous multi-source data. Comprehensive evaluations on benchmark datasets (Fdataset, Cdataset, and Ydataset) and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art (SOTA) methods, achieving superior accuracy in predicting drug-disease associations across multiple metrics. Literature-based validation further confirmed the model's predictive capabilities, with seven out of the top ten predictions corroborated by post-2011 evidence. To promote transparency and reproducibility, all data and codes used in this study were open-sourced, providing resources for processing CTPs, KG, and LLM-based similarity calculations, along with the complete AMVL algorithm and benchmarking procedures. By unifying diverse data modalities, AMVL offers a robust and scalable solution for accelerating drug discovery, fostering advancements in translational medicine and integrating multi-omics data. We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.
4.Adaptive multi-view learning method for enhanced drug repurposing using chemical-induced transcriptional profiles,knowledge graphs,and large language models
Yudong YAN ; Yinqi YANG ; Zhuohao TONG ; Yu WANG ; Fan YANG ; Zupeng PAN ; Chuan LIU ; Mingze BAI ; Yongfang XIE ; Yuefei LI ; Kunxian SHU ; Yinghong LI
Journal of Pharmaceutical Analysis 2025;15(6):1354-1369
Drug repurposing offers a promising alternative to traditional drug development and significantly re-duces costs and timelines by identifying new therapeutic uses for existing drugs.However,the current approaches often rely on limited data sources and simplistic hypotheses,which restrict their ability to capture the multi-faceted nature of biological systems.This study introduces adaptive multi-view learning(AMVL),a novel methodology that integrates chemical-induced transcriptional profiles(CTPs),knowledge graph(KG)embeddings,and large language model(LLM)representations,to enhance drug repurposing predictions.AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning(MVL),matrix factorization,and ensemble optimization techniques to integrate heterogeneous multi-source data.Comprehensive evaluations on benchmark datasets(Fdata-set,Cdataset,and Ydataset)and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art(SOTA)methods,achieving superior accuracy in predicting drug-disease associations across multiple metrics.Literature-based validation further confirmed the model's predictive capabilities,with seven out of the top ten predictions corroborated by post-2011 evidence.To promote transparency and reproducibility,all data and codes used in this study were open-sourced,providing resources for pro-cessing CTPs,KG,and LLM-based similarity calculations,along with the complete AMVL algorithm and benchmarking procedures.By unifying diverse data modalities,AMVL offers a robust and scalable so-lution for accelerating drug discovery,fostering advancements in translational medicine and integrating multi-omics data.We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.
5.Imaging landmarks of one-hole split endoscope in the treatment of upper lumbar intervertebral disc herniation under the guidance of three-dimensional reconstruction
Changzhen LIU ; Xin LIU ; Yuefei LI ; Jianye WANG ; Zhimeng FENG ; Zhaozhong SUN
Chinese Journal of Tissue Engineering Research 2024;28(6):939-944
BACKGROUND:One-hole split endoscope technique has been widely used in the treatment of lumbar degenerative diseases,but there is no relevant literature on the safety analysis of this technique in the treatment of upper lumbar disc herniation. OBJECTIVE:To observe the position relationship of nerve roots,intervertebral space and bone landmarks in the upper lumbar spine by three-dimensional lumbar CT reconstruction technology,and to provide a basis for the clinical operation of one-hole split endoscope surgery. METHODS:Twenty-six patients with upper lumbar disc herniation underwent a lumbar CT scan.Mimics 17.0 software was imported to measure the related imaging parameters of L1/2 to L3/4 segments:(1)Measurement of vertical distance:In coronal view,the distance(a)from the intersection point of the medial facet of the superior articular process and the superior endplate(N)to the apex of the articular process(S);in the coronal view,the distance(b)from the sagittal intersection(M)of N and the inferior endplate to the apex of the inferior articular process(X).(2)Measured horizontal distance:the distance(c)between the cross-section of N and the lower edge of the outlet nerve root(N2);distance(d)between the cross-section of N and the intersection point of neural tissue(N1);N1 to N2 distance(e);distance(f)between the cross-section of M and the lateral edge of the nerve tissue(M1);M to M cross-section and exit nerve root intersection(M2)distance(g);distance(h)from M1 to M2;distance(i)from M2 to N1;distance(j)from the posterior edge of the articular surface(R)to M2 in sagittal view of the superior articular process. RESULTS AND CONCLUSION:(1)With the decrease of the segment,the distances a and b gradually increased,and the distance j gradually decreased.There was no significant difference between L1/2 and L2/3 segments(P>0.05).(2)With the decrease of the segment,distance d first decreased and then increased;distance f gradually decreased;distances c,e,g,h and i gradually increased;and there was no significant difference between L2/3 and L3/4 segments(P>0.05).(3)Distance i was the shortest distance without pulling nerve roots in the natural state,and the area of the safety zone was between four points M1,M2,N1,and N2.The bone was removed to the upper and lower endplates by biting the bone downward and upward through S and X,respectively,to expose the intervertebral space,and the window of distance g to M2 could be opened outward to avoid injury of the outlet nerve roots.(4)In conclusion,the upper lumbar vertebrae have unique anatomical characteristics.Based on the relevant measurements of nerve roots,spinal dura and intervertebral space,the parameters of the one-hole split endoscope technique are more accurate and safe during operation.
6.Epidemiological characteristic of viral encephalitis in children and adolescents in Henan Province, 2012-2023
Shujie HAN ; Shouhang CHEN ; Bowen DAI ; Yu CHEN ; Shujuan HAN ; Ruyu ZHANG ; Chenyu WANG ; Qingmei WANG ; Jiaying ZHENG ; Guangcai DUAN ; Fang WANG ; Yuefei JIN
Chinese Journal of Epidemiology 2024;45(6):852-856
Objective:To understand the epidemiological characteristics and spatiotemporal distribution of viral encephalitis in children and adolescents in Henan Province from 2012 to 2023.Methods:The information about viral encephalitis cases from October 1, 2012 to July 26, 2023 were collected from Zhengzhou Children's Hospital (National Children's Regional Medical Center),Henan Provincial Children's Hospital for the analyses on temporal distribution the cases, the severe illness rate, age distribution, pathogen type and imaging findings of the cases.Results:A total of 6 276 cases of viral encephalitis were included in this study after excluding cases with incomplete information. The cases mainly originated from Zhengzhou (38.96%), followed by Zhoukou (9.93%), Xuchang (8.68%), Zhumadian (7.90%) and Pingdingshan (7.39%). The cases in boys accounted for 62.13% and the cases in girls accounted for 37.87%. Most cases (72.45%) occurred in age group 7-13 years. The overall rate of severe illness cases was 4.51% from 2012 to 2023. There were significant differences in severe illness cases among different areas and years ( χ2=5.33, P=0.021; χ2=48.14, P<0.001). Enteroviruses were mainly detected (31.57%), in which Coxsackie virus was predominant (58.37%). Imaging findings showed that cerebral hemisphere damage was most common in children and adolescents with viral encephalitis (54.93%). Conclusions:From 2012 to 2023, more cases of viral encephalitis occurred in boys in Henan. Children and adolescents aged 7-13 years were the main affected group. The prevention of enteroviruses infection, especially Coxsackie virus, needs to be strengthened. Special attention should be paid to the prevention of cerebral hemisphere damage after viral encephalitis diagnosis.
7.Investigation of oligomeric proanthocyanidins extracted from Rhodiolae Crenulatae Radix et Rhizomes using deep eutectic solvents and identified via data-dependent acquisition mass-spectroscopy.
Li JIA ; Liming WANG ; Xiaoxiao ZHANG ; Qingrui ZHANG ; Peng LEI ; Yanxu CHANG ; Lifeng HAN ; Xin CHAI ; Wenzhi YANG ; Yuefei WANG ; Miaomiao JIANG
Journal of Pharmaceutical Analysis 2024;14(11):101002-101002
In this study, 34 deep eutectic solvents (DESs) were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes. The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis. The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30% (V/V) in DESs. AB-8 macroporous resin and ethyl acetate were used for separation and refining, and the oligomer-rich proanthocyanidin components were eventually obtained. The ultraviolet (UV) and infrared (IR) spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin. To further clarify the chemical composition of proanthocyanidin, an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins structural library and mass defect filtering (MDF) algorithm, combined with the full mass spectrometry (MS)/dd-MS2 scan mode that turns on the "if idle pick others" function. By using ultra-high performance liquid chromatography and high-resolution MS (UHPLC/HRMS), the analysis used both targeted and non-targeted methods to detect proanthocyanidins. Finally, 50 oligomeric proanthocyanidin (OPC) compounds were identified, including 7 monomers, 22 dimers, 20 trimers, and 1 tetramer, most of which were procyanidins of proanthocyanidins (84%), and a small amount of prodelphinidin (14%) and other types of proanthocyanidins (2%), which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes. Meanwhile, the comparison with the grape seeds OPCs standard (United States Pharmacopeia) revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant, suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.
8.Formulation, characterization, and evaluation of curcumin-loaded ginger-derived nanovesicles for anti-colitis activity.
Shengjie HUANG ; Min ZHANG ; Xiaoge LI ; Jierong PEI ; Zhirong ZHOU ; Peng LEI ; Meng WANG ; Peng ZHANG ; Heshui YU ; Guanwei FAN ; Lifeng HAN ; Haiyang YU ; Yuefei WANG ; Miaomiao JIANG
Journal of Pharmaceutical Analysis 2024;14(12):101014-101014
Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.
9.Investigation of oligomeric proanthocyanidins extracted from Rhodiolae Crenulatae Radix et Rhizomes using deep eutectic solvents and identified via data-dependent acquisition mass-spectroscopy
Li JIA ; Liming WANG ; Xiaoxiao ZHANG ; Qingrui ZHANG ; Peng LEI ; Yanxu CHANG ; Lifeng HAN ; Xin CHAI ; Wenzhi YANG ; Yuefei WANG ; Miaomiao JIANG
Journal of Pharmaceutical Analysis 2024;14(11):1695-1706
In this study,34 deep eutectic solvents(DESs)were successfully prepared for the extraction of proan-thocyanidin from Rhodiolae Crenulatae Radix et Rhizomes.The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis.The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30%(V/V)in DESs.AB-8 macroporous resin and ethyl acetate were used for separation and refining,and the oligomer-rich proanthocyanidin components were eventually obtained.The ultra-violet(UV)and infrared(IR)spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin.To further clarify the chemical composition of proanthocyanidin,an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins struc-tural library and mass defect filtering(MDF)algorithm,combined with the full mass spectrometry(MS)/dd-MS2 scan mode that turns on the"if idle pick others"function.By using ultra-high performance liquid chromatography and high-resolution MS(UHPLC/HRMS),the analysis used both targeted and non-targeted methods to detect proanthocyanidins.Finally,50 oligomeric proanthocyanidin(OPC)com-pounds were identified,including 7 monomers,22 dimers,20 trimers,and 1 tetramer,most of which were procyanidins of proanthocyanidins(84%),and a small amount of prodelphinidin(14%)and other types of proanthocyanidins(2%),which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes.Meanwhile,the comparison with the grape seeds OPCs standard(United States Pharmacopeia)revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant,suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.
10.Formulation,characterization,and evaluation of curcumin-loaded ginger-derived nanovesicles for anti-colitis activity
Shengjie HUANG ; Min ZHANG ; Xiaoge LI ; Jierong PEI ; Zhirong ZHOU ; Peng LEI ; Meng WANG ; Peng ZHANG ; Heshui YU ; Guanwei FAN ; Lifeng HAN ; Haiyang YU ; Yuefei WANG ; Miaomiao JIANG
Journal of Pharmaceutical Analysis 2024;14(12):1879-1890
Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost,sustainability,and tissue targeting.Thus,they hold promise for disease treatment and drug delivery.In this study,we proposed a time-efficient method,PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles(GDNVs).Subse-quently,curcumin(CUR)was loaded onto GDNV by ultrasonic incubation.The optimum conditions for ginger-derived nanovesicles loaded with curcumin(CG)were ultrasound time of 3 min,a carrier-to-drug ratio(GDNV:CUR)of 1∶1.The study achieved a high loading capacity(94.027%±0.094%)and encapsu-lation efficiency(89.300%±0.344%).Finally,the drugs'in vivo distribution and anti-colitis activity were investigated in mice.CG was primarily distributed in the colon after oral administration.Compared to CUR and GDNV,CG was superior in improving disease activity,colon length,liver and spleen coefficients,myeloperoxidase activity,and biochemical factor levels in ulcerative colitis(UC)mice.In addition,CG plays a protective role against UC by modulating serum metabolite levels and gut flora.In summary,our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

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