1.Herbal Textual Research on Houttuyniae Herba in Famous Classical Formulas
Dan ZHAO ; Changgui YANG ; Chuanzhi KANG ; Chenghong XIAO ; Zhikun WU ; Hongliang MA ; Jiwen WANG ; Xiufu WAN ; Sheng WANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):250-259
This article systematically analyzes the historical evolution of the name, medicinal parts, origin, harvesting, processing and other aspects of Houttuyniae Herba(HH) by referring to the medical books, prescription books and other documents of the past dynasties, combined with the research materials related to modern and contemporary times, in order to provide a basis for the development of famous classical formulas containing this herb. In ancient literature, HH was often referred to as "Ji" and "Jicai", the name of "Ji" was first recorded in Mingyi Bielu during the Han and Wei dynasties, and the name of Yuxingcao was first seen in Lyuchanyan Bencao during the southern Song dynasty and has continued to this day. The origin of HH used throughout history is consistent, all of which are the whole herb or aboveground parts of Houttuynia cordata in Saururaceae family. HH recorded throughout history has a wide range of production areas, mostly self-produced self-marketing. In ancient times, fresh HH was often used as medicine by pounding its juice without involving any processing steps. Both fresh and dried products can be used as medicine, the fresh products uses the whole plant, while the dried products uses the aboveground parts, which are cleaned, selected and processed before use. Fresh products are harvested regardless of season, while dried products are harvested in both summer and autumn, with summer as the best. In ancient times, there were no specific requirements for the quality of HH, while in modern times, "intact stems and leaves with a strong fishy smell" are preferred. In addition, the medicinal properties of HH have undergone significant changes from ancient to modern times. In the early period, it was believed that its medicinal property was slightly warm, until the 1977 edition of Chinese Pharmacopoeia officially changed it to slightly cold. Both ancient and modern literature states that HH can be used for the treatment of carbuncle and malignant sores, Lyuchanyan Bencao for the first time introduced HH fresh juice can relieve summer heat, since Diannan Bencao recorded that it can be used for lung carbuncle, and gradually developed into the first choice for the treatment of lung carbuncle. Based on the research results, it is suggested that fresh herb or dried aboveground parts of H. cordata are used as medicine when developing famous classical formulas.
2.Erratum: Author correction to "Generation of αGal-enhanced bifunctional tumor vaccine" Acta Pharm Sin B 12 (2022) 3177-3186.
Jian HE ; Yu HUO ; Zhikun ZHANG ; Yiqun LUO ; Xiuli LIU ; Qiaoying CHEN ; Pan WU ; Wei SHI ; Tao WU ; Chao TANG ; Huixue WANG ; Lan LI ; Xiyu LIU ; Yong HUANG ; Yongxiang ZHAO ; Lu GAN ; Bing WANG ; Liping ZHONG
Acta Pharmaceutica Sinica B 2025;15(2):1207-1207
[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].
3.Inhibition of WAC alleviates the chondrocyte proinflammatory secretory phenotype and cartilage degradation via H2BK120ub1 and H3K27me3 coregulation.
Peitao XU ; Guiwen YE ; Xiaojun XU ; Zhidong LIU ; Wenhui YU ; Guan ZHENG ; Zepeng SU ; Jiajie LIN ; Yunshu CHE ; Yipeng ZENG ; Zhikun LI ; Pei FENG ; Qian CAO ; Zhongyu XIE ; Yanfeng WU ; Huiyong SHEN ; Jinteng LI
Acta Pharmaceutica Sinica B 2025;15(8):4064-4077
Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.
4.Herbal Textual Research on Bletillae Rhizoma in Famous Classical Formulas
Dan ZHAO ; Tao ZHOU ; Chaolei LUO ; Dewei GAN ; Lingling LIU ; Chuanzhi KANG ; Zhikun WU ; Xu LI ; Yan FU ; Guoqiong CAO ; Yongping ZHANG ; Chenghong XIAO ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):77-88
In order to provide basic information for the utilization and development of famous classical formulas containing Bletillae Rhizoma, this article systematically analyzes the historical evolution of the name, origin, harvesting and processing of Bletillae Rhizoma by reviewing the ancient materia medica, prescription books, medical books and modern literature. The research results showed that Baiji(白及) was the main name, some scholars took Baiji(白芨) as its main name, and there were many other names such as Baiji(白给), Baigen(白根), Baiji(白苙). The mainstream source of Bletillae Rhizoma was the tubers of Bletilla striata, and drying, large, white, solid, root-free and skin removed completely were the good quality standards. With the promotion of wild to cultivated medicinal materials, there were certain differences between their traits, and the quality evaluation indexes should be adjusted accordingly. The origin of records in the past dynasties was widely distributed, with Guizhou and Sichuan having high production and good quality in modern times. The harvesting period is mostly in spring and autumn, and harvested in autumn was better. The processing and processing technology is relatively simple, and it was used fresh or powdered in past dynasties, while it is mainly sliced for raw use in modern times. Based on the results, it is suggested that the tubers of Bletilla striata of Orchidaceae should be used in the famous classical formulas, and it should be uniformly written as Baiji(白及). And if the original formula indicates the requirement of processing, it should be operated according to the requirement, if the requirement of processing is not indicated, it can be used in raw form as medicine.
5.Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma.
Zhikun LIU ; Yichao WU ; Abid Ali KHAN ; L U LUN ; Jianguo WANG ; Jun CHEN ; Ningyang JIA ; Shusen ZHENG ; Xiao XU
Journal of Zhejiang University. Science. B 2024;25(1):83-90
Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).
Humans
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Aged
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Sarcopenia/diagnostic imaging*
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Carcinoma, Hepatocellular/diagnostic imaging*
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Muscle, Skeletal/diagnostic imaging*
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Deep Learning
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Prognosis
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Radiomics
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Liver Neoplasms/diagnostic imaging*
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Retrospective Studies
6.Exploration and clinical validation of the repair mode of the sclerotic zone of steroid-induced osteonecrosis of the femoral head based on Tandem Mass Tags technology
Zhikun ZHUANG ; Mincong HE ; Tianye LIN ; Rongkai WU ; Jinhua GUO ; Zhaoke WU ; Qiushi WEI
Chinese Journal of Tissue Engineering Research 2024;28(14):2191-2196
BACKGROUND:The sclerotic zone in the femoral head is an important imaging feature in the progression of steroid-induced femoral head necrosis,which is associated with disease prognosis.Peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α)has been shown to possess biological activities such as osteogenesis,angiogenesis and anti-mitochondrial apoptosis,which may be closely related to bone repair of steroid-induced femoral head necrosis. OBJECTIVE:To screen for the differential proteins in the sclerotic zone of steroid-induced osteonecrosis of the femoral head versus the normal zone,to screen for hub proteins in the sclerotic zone,and to verify the differential expression of hub proteins in the femoral head specimens following steroid-induced femoral head necrosis,and to to explore the repair pattern of the sclerotic zone following steroid-induced femoral head necrosis. METHODS:Femoral head samples were collected from patients with steroid-induced osteonecrosis of the femoral head receiving total hip arthroplasty.The differentially expressed genes in the sclerotic zone and the normal zone were screened by Tandem Mass Tags and analyzed by GO and KEGG signaling pathways to construct a protein-protein interaction network and screen hub genes.In addition,the expression of hub genes in the sclerotic zone was verified by immunohistochemistry and western blot. RESULTS AND CONCLUSION:Quantitative protein profiling by Tandem Mass Tags revealed that 609 proteins were significantly differentially expressed(Log2FC>1.20,Log2FC<0.84 and P<0.05)in the sclerotic zone of the femoral head compared with the normal zone,of which 290 proteins were upregulated and 319 proteins were downregulated.The GO and KEGG pathway enrichment analyses revealed that among the top 10 enriched pathways,Wnt signaling pathway and life-cycle regulatory pathway were closely related to bone repair;in the life-cycle regulatory pathway,PGC-1α was one of the important proteins.In addition,western blot results verified the low expression of PGC-1α and NRF1 in the sclerotic zone and high expression of Cleaved Caspase-3 in the sclerotic zone compared with the normal zone of steroid-induced femoral head necrosis specimens.Light microscopic immunohistochemical results showed the distribution of PGC-1α,NRF1 and Cleaved Caspase-3 positive expression in the sclerotic and normal zones in the femoral head tissue specimens,indicating the presence of their expression in bone trabeculae,osteoblasts and bone marrow.In contrast,the brown area of the sclerotic zone of femoral head necrosis stained darker and showed more obvious expression of Cleaved Caspase-3.To conclude,in the sclerotic zone of steroid-induced femoral head necrosis,biological behaviors including activation of osteogenesis-related pathways such as Wnt and oxidative apoptosis characterized by low expression of PGC-1 are observed.Low expression of PGC-1α in the sclerotic zone of steroid-induced femoral head necrosis may be associated with the activation of oxidative apoptosis.
7.Study on gene mutation characteristics and its correlation with immunological markers in small cell lung cancer
Xuanpeng WU ; Zhikun JIA ; Tao JIANG ; Fei XUE ; Guangjian ZHANG ; Junke FU ; Xi LIU ; Qifei WU
Journal of Clinical Surgery 2024;32(11):1162-1165
Objective To investigate the relationship between gene mutation characteristics and immunological markers in patients with small cell lung cancer.Methods From January 2019 to 2020,155 patients with small cell lung cancer were admitted.Gene mutations were detected in these patients using target gene capture and sequencing method.Moreover,the tumor mutational burden(TMB)and expression of PD-L1 in some patients were detected.Results A total of 326 gene mutations were detected in the patients,the most significant of which were TP53 and RB1.Among the 8 genes with mutation frequency higher than 15%,patients with KMT2D,KMT2C,FAT1 and NOTCH1 mutations had higher TMB than those without mutation,and the difference was statistically significant(P<0.05).Conclusion The most common mutated genes in patients with small cell lung cancer are TP53 and RB1.KMT2D,KMT2C,FAT1 and NOTCH1 may be potential markers for the efficacy of immunotherapy in small cell lung cancer.
8.Establishment of MRI classification for traumatic osteonecrosis of the femoral head and its correlation with femoral head collapse
Zhikun ZHUANG ; Ziqi LI ; Shihua GAO ; Hanglin QIU ; Zhiqing XU ; Zhibing GONG ; Qingwen ZHANG ; Zhaoke WU ; Wei HE
Chinese Journal of Orthopaedics 2024;44(13):881-888
Objective:To establish a classification system for the repair band in the subchondral bone origination point in MRI for traumatic osteonecrosis of the femoral head (ONFH) and preliminarily explore the correlation between this classification and the progression of femoral head collapse.Methods:A retrospective analysis was conducted on 73 cases of traumatic ON-FH treated at the Quanzhou Orthopedic-traumatological hospital from January 2000 to December 2019. Among them, there were 46 males and 27 females with an average age of 34.9±8.3 years (range 19-55 years). Clinical and radiological data such as age, gender, side, fracture classification, reduction quality, JIC classification, and bone repair band (BRB) classification were recorded. The progression of traumatic ONFH was assessed using the ARCO staging system, with stages IIIA and IIIB defined as mild collapse and progressive collapse, respectively. The BRB classification was established based on MRI findings, and the inter- and intra-observer consistency of the BRB classification was analyzed using Kappa test. The correlation between the BRB classification and progressive femoral head collapse was analyzed using the Kaplan-Meier survival curve and binary variable Cox regression analysis.Results:According to the BRB classification, 73 cases were divided into type 1 with superficial lesion in 38.4%, type 2 with uncertain lesion in 21.9%, and type 3 with extensive lesion in 39.7%. The inter-observer consistency Kappa value for the BRB classification was 0.798, and the intra-observer consistency Kappa value was 0.896, indicating a high level of consistency. A follow-up of 73 cases (54.8±34.9 months, range 24-165 months) showed a significant correlation between the BRB classification and ARCO staging at the last follow-up (χ 2=37.556, P<0.001), with progression to stages IIIA and IIIB as follows: type 1 had 3 and 1 cases, type 2 had 4 and 1 cases, and type 3 had 14 and 12 cases, respectively. Using the occurrence of progressive collapse (stage IIIB) as the endpoint, the risk of progression to stage IIIB for type 2 was not statistically different from type 1 [ HR=1.766, 95% CI (0.465, 6.702), P=0.403]; the risk of progression to stage IIIB for type 3 was significantly higher than for type 1 [ HR=15.126, 95% CI (4.708, 48.592), P<0.001]. Conclusion:The BRB classification is closely related to the progression of traumatic ONFH and is an independent risk factor for predicting the occurrence of progressive collapse; this classification is helpful for early diagnosis and predicting the progression of collapse and treatment plan decision-making.
9.Analysis of influential factors for blood concentrations and adverse drug reaction in the treatment of lymphoma with high-dose methotrexate
Jiajun YE ; Zeyu LI ; Hanbiao WU ; Jia WANG ; Yanhui GE ; Zhikun QIU
China Pharmacy 2023;34(5):587-590
OBJECTIVE To discuss the factors affecting the blood concentration of high-dose methotrexate (HD-MTX) and the occurrence of adverse drug reactions (ADR) when treating lymphoma with HD-MTX. METHODS From July 2020 to November 2021, the information of HD-MTX patients who had been monitored for HD-MTX blood drug concentration in the First Affiliated Hospital of Guangdong Pharmaceutical University was collected by retrospective analysis, such as medical record number, age, sex, height, body mass, chemotherapy plan, dosage; test indexes such as alanine transaminase, aspartate transaminase, total bilirubin, creatinine clearance (CrCl), albumin (ALB) and other indexes were also collected before and after administration. The blood concentrations (c6 h, c24 h, c48 h) of HD-MTX were recorded, drug information of proton pump inhibitors (PPIs) was extracted and used, and ADR occurring within 48 h after administration were all evaluated. Single factor analysis, multiple linear regression and χ2 test were used to analyze the influential factors. RESULTS A total of 133 patients were included in this paper. The results of the single factor analysis of HD-MTX blood drug concentration showed that age, CrCl had an effect on c 6 h (P<0.05); age, CrCl and ALB had an effect on c24 h (P<0.05); age, body mass index (BMI), CrCl, combined use of PPIs and ALB had an effect on c48 h (P<0.05). The results of multiple linear regression analysis showed that age and CrCl had no effect on c 6 h (P>0.05), age was the main influential factor of c 24 h (P<0.05), and CrCl and combined use of PPIs were the main influential factors of c48 h (P<0.05); the coefficient of variance expansion was between 1 and 3.5, indicating that the analysis results were acceptable. The overall incidence of adverse reactions was 51.13%, of which the blood and lymphatic system reactions were the most common. The results of the influential factors of ADR showed that age, BMI, liver function and CrCl had effect on the incidence of ADR (P<0.05). CONCLUSIONS During the process of HD-MTX in the treatment of lymphoma, the patient’s age, CrCl and combined use of PPIs should be considered, and the patient’s blood concentration should be monitored; at the same time, the age of patients, BMI, liver function and CrCl have an impact on the incidence of ADR.
10.Generation of αGal-enhanced bifunctional tumor vaccine.
Jian HE ; Yu HUO ; Zhikun ZHANG ; Yiqun LUO ; Xiuli LIU ; Qiaoying CHEN ; Pan WU ; Wei SHI ; Tao WU ; Chao TANG ; Huixue WANG ; Lan LI ; Xiyu LIU ; Yong HUANG ; Yongxiang ZHAO ; Lu GAN ; Bing WANG ; Liping ZHONG
Acta Pharmaceutica Sinica B 2022;12(7):3177-3186
Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END+/Gal+-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.

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