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.MiR-30e-5p overexpression promotes proliferation and migration of colorectal cancer cells by activating the CXCL12 axis via downregulating PTEN.
Ke WEI ; Jiwen SHI ; Yuhan XIAO ; Wenrui WANG ; Qingling YANG ; Changjie CHEN
Journal of Southern Medical University 2023;43(7):1081-1092
OBJECTIVE:
To investigate the regulatory effects of miR-30e-5p on biological behaviors of colorectal cancer cells and the role of PTEN/CXCL12 axis in mediating these effects.
METHODS:
Bioinformatic analysis was performed to explore the differential expression of miR-30e-5p between colorectal cancer tissues and normal tissues. RT-qPCR was used to detect the differential expression of miR-30e-5p in intestinal epithelial cells and colorectal cancer cells. Bioinformatics and dual luciferase assay were used to predict and validate the targeting relationship between miR-30e-5p and PTEN. Human and murine colorectal cancer cell lines were transfected with miR-30e-5p mimics, miR-30e-5p inhibitor, miR-30e-5p mimics+LV-PTEN, or miR-30e-5p inhibitor + si-PTEN. The changes in biological behaviors of the cells were detected using plate clone formation assay, CCK-8 assay, flow cytometry, scratch healing and Transwell assays. PTEN and CXCL12 expressions in the cancer cells were detected by Western blotting. The effects of miR-30e-5p inhibitor on colorectal carcinogenesis and development were observed in nude mice.
RESULTS:
Bioinformatic analysis showed that miR-30e-5p expression was significantly elevated in colorectal cancer tissues compared with the adjacent tissue (P < 0.01). Higher miR-30e-5p expression was detected in colorectal cancer cell lines than in intestinal epithelial cells (P < 0.01). Dual luciferase assay confirmed the targeting relationship between miR-30e-5p and PTEN (P < 0.05). Transfection with miR-30e-5p mimics significantly enhanced proliferation and metastasis and inhibited apoptosis of the colorectal cancer cells (P < 0.05), and co-transfection with LV-PTEN obviously reversed these changes (P < 0.05). MiR-30e-5p mimics significantly inhibited PTEN expression and enhanced CXCL12 expression in the cancer cells (P < 0.01), and miR-30e-5p inhibitor produced the opposite effect. Transfection with miR-30e-5p inhibitor caused cell cycle arrest in the cancer cells, which was reversed by co-transfection with si-PTEN (P < 0.05). In the in vivo experiments, the colorectal cancer cells transfected with miR-30e-5p inhibitor showed significantly lowered tumorigenesis.
CONCLUSION
Overexpression of miR-30e-5p promotes the malignant behaviors of colorectal cancer cells by downregulating PTEN to activate the CXCL12 axis.
Humans
;
Animals
;
Mice
;
MicroRNAs/metabolism*
;
Cell Line, Tumor
;
Cell Proliferation/physiology*
;
Mice, Nude
;
Cell Movement/physiology*
;
Colorectal Neoplasms/pathology*
;
Luciferases/metabolism*
;
Gene Expression Regulation, Neoplastic
;
PTEN Phosphohydrolase/metabolism*
;
Chemokine CXCL12/metabolism*
3.Bridging the structure gap between pellets in artificial dissolution media and in gastro-intestinal tract in rats.
Hongyu SUN ; Siyu HE ; Li WU ; Zeying CAO ; Xian SUN ; Mingwei XU ; Shan LU ; Mingdi XU ; Baoming NING ; Huimin SUN ; Tiqiao XIAO ; Peter YORK ; Xu XU ; Xianzhen YIN ; Jiwen ZHANG
Acta Pharmaceutica Sinica B 2022;12(1):326-338
Changes in structure of oral solid dosage forms (OSDF) elementally determine the drug release and its therapeutic effects. In this research, synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3D structure of enteric coated pellets recovered from the gastrointestinal tract of rats. The structures of pellets in solid state and in vitro compendium media were measured. Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media. Thus, optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media. The sphericity, pellet volume, pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for 2 h were recorded 0.47, 1.55 × 108 μm3, 0.44 × 108 μm3 and 27.6%, respectively. After adding pepsin and glass microspheres, the above parameters in vitro reached to 0.44, 1.64 × 108 μm3, 0.38 × 108 μm3 and 23.0%, respectively. Omeprazole magnesium pellets behaved similarly. The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3D structures to ensure better design, characterization and quality control of advanced OSDF.
4.Redefinition to bilayer osmotic pump tablets as subterranean river system within mini-earth via three-dimensional structure mechanism.
Abi MAHARJAN ; Hongyu SUN ; Zeying CAO ; Ke LI ; Jinping LIU ; Jun LIU ; Tiqiao XIAO ; Guanyun PENG ; Junqiu JI ; Peter YORK ; Balmukunda REGMI ; Xianzhen YIN ; Jiwen ZHANG ; Li WU
Acta Pharmaceutica Sinica B 2022;12(5):2568-2577
Defining and visualizing the three-dimensional (3D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography (SR-μCT). In situ formed 3D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral "roadways". Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed 3D microstructures, a "subterranean river model" for the drug release mechanism has been defined to explain the drug release mechanism.
5. Evaluation of spontaneous intracerebral hemorrhage by using CT image segmentation and volume assessment based on deep learning
Jiwen WANG ; Yu LIN ; Jianhua XIONG ; Shengping YU ; Wei WEI ; Xinyu YANG ; Fushun XIAO ; Yongli WANG ; Kongming LIANG ; Hao WANG ; Xiuli LI ; Bing LIU
Chinese Journal of Radiology 2019;53(11):941-945
Objective:
To evaluate the feasibility and accuracy of deep learning in CT image segmentation and further lesion-volume assessment of spontaneous intracerebral hemorrhage.
Methods:
A total of 1 223 cases of spontaneous intracerebral hemorrhage including parenchymal hemorrhage, ventricular hemorrhage, subarachnoid hemorrhage and mixture hemorrhage, from April 2016 to April 2018 in Tianjin Medical University General Hospital, were retrospectively enrolled and analyzed. The patients were randomly divided into training set (905 cases), validation set (156 cases) and test set (162 cases), among each group, the number of parenchymal hemorrhage was 498, 107 and 100, respectively. The bleeding area manually outlined by physician was served as the reference standard to build the segmentation model and to evaluate the performance of the validation set. Patients were divided into 3 groups according to the volume calculated by reference standard. The volume of hematoma in group 1 was less than 5 ml, while group 2 was 5-25 ml, and group 3 was more than 25 ml. Comparison of the hematoma volume calculated by segmentation model and that calculated by ABC/2 formula was conducted in 97 simple intraparenchymal hemorrhage cases.
Results:
In 162 cases of test set, the Dice coefficients of the segmentation model were 0.87, 0.85, 0.67 and 0.77 in parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage and mixture hemorrhage, respectively. The estimated hematoma volume in the 97 intraparenchymal hemorrhage cases calculated by the segmentation model was (29.55±37.69) ml, and that calculated by the ABC/2 formula was (24.04±31.22) ml. Compared with reference standard, the absolute errors of three segmentation model were (0.52±0.54), (1.53±1.22) and (7.93±8.49) ml in group 1, 2 and 3 respectively. The absolute errors of the ABC/2 formula were (0.68±0.60), (3.16±2.90) and (19.31±17.23) ml in group 1, 2 and 3.
Conclusion
Deep learning based segmentation model improved detection of intraparenchymal hematoma volume, compared with ABC/2 formula.
6.Study on Quality Standard of Flavone Extracts in Licorice Residue
Xiaoshuan LIU ; Xixiang LI ; Zhengguo XIAO ; Jiwen LI ; Yanyan LUO
Chinese Journal of Information on Traditional Chinese Medicine 2017;24(4):67-70
Objective To establish the quality standard of flavone extracts in licorice residue; To provide the methods and basis for the quality control of total flavonoids extracted from licorice residue.Methods TLC was applied to compare the extracts with liquiritin and licorice; UV-spectrophotometry was used to measure the content of total flavones; EDTA-2Na titration was used to determine the content of calciumion.Results In the chromatogram of the test product, the spots of the same color were displayed on the corresponding position of the control medicinal material, and the fluorescent spots of the same color were displayed on the corresponding position of the control product. UV-spectrophotometry showed glycyrrhizin had a good linear relationship in the range of 3.32–9.96 μg/mL (r=0.9997), the absorbance between 0.3 and 0.7. The average recovery rate was 102.41% (RSD=3.22%), and the average content of total flavonoids in three batches of flavonoids extract was 8.82%. The average content of calciumion was 0.107% (RSD=3.61%).Conclusion This method has good repeatability, high sensitivity and accurate results, and can be used for the quality control of flavonoids in licorice residue.
7.Synchrotron radiation-based Fourier-transform infrared spectromicroscopy for characterization of the protein/peptide distribution in single microspheres.
Manli WANG ; Xiaolong LU ; Xianzhen YIN ; Yajun TONG ; Weiwei PENG ; Li WU ; Haiyan LI ; Yan YANG ; Jingkai GU ; Tiqiao XIAO ; Min CHEN ; Jiwen ZHANG ;
Acta Pharmaceutica Sinica B 2015;5(3):270-276
The present study establishes a visualization method for the measurement of the distribution and localization of protein/peptide constituents within a single poly-lactide-co-glycolide (PLGA) microsphere using synchrotron radiation-based Fourier-transform infrared spectromicroscopy (SR-FTIR). The representative infrared wavenumbers specific for protein/peptide (Exenatide) and excipient (PLGA) were identified and chemical maps at the single microsphere level were generated by measuring and plotting the intensity of these specific bands. For quantitative analysis of the distribution within microspheres, Matlab software was used to transform the map file into a 3D matrix and the matrix values specific for the drug and excipient were extracted. Comparison of the normalized SR-FTIR maps of PLGA and Exenatide indicated that PLGA was uniformly distributed, while Exenatide was relatively non-uniformly distributed in the microspheres. In conclusion, SR-FTIR is a rapid, nondestructive and sensitive detection technology to provide the distribution of chemical constituents and functional groups in microparticles and microspheres.
8.Quantitative structure characteristics and fractal dimension of Chinese medicine granules measured by synchrotron radiation X-ray computed micro tomography.
Xiaolong LU ; Qin ZHENG ; Xianzhen YIN ; Guangqing XIAO ; Zuhua LIAO ; Ming YANG ; Jiwen ZHANG
Acta Pharmaceutica Sinica 2015;50(6):767-74
The shape and structure of granules are controlled by the granulation process, which is one of the main factors to determine the nature of the solid dosage forms. In this article, three kinds of granules of a traditional Chinese medicine for improving appetite and promoting digestion, namely, Jianwei Granules, were prepared using granulation technologies as pendular granulation, high speed stirring granulation, and fluidized bed granulation and the powder properties of them were investigated. Meanwhile, synchrotron radiation X-ray computed micro tomography (SR-µCT) was applied to quantitatively determine the irregular internal structures of the granules. The three-dimensional (3D) structure models were obtained by 3D reconstruction, which were more accurately to characterize the three-dimensional structures of the particles through the quantitative data. The models were also used to quantitatively compare the structural differences of granules prepared by different granulation processes with the same formula, so as to characterize how the production process plays a role in the pharmaceutical behaviors of the granules. To focus on the irregularity of the particle structure, the box counting method was used to calculate the fractal dimensions of the granules. The results showed that the fractal dimension is more sensitive to reflect the minor differences in the structure features than the conventional parameters, and capable to specifically distinct granules in structure. It is proved that the fractal dimension could quantitatively characterize the structural information of irregular granules. It is the first time suggested by our research that the fractal dimension difference (Df,c) between two fractal dimension parameters, namely, the volume matrix fractal dimension and the surface matrix fractal dimension, is a new index to characterize granules with irregular structures and evaluate the effects of production processes on the structures of granules as a new indicator for the granulating process control and optimization.
9.Reference significance of proximal fibula fractures for selecting surgical procedures for complex tibial plateau fractures involving posterior lateral spine
Yongfeng HUO ; Zhaoyang YIN ; Leiming LI ; Jiwen YU ; Guangxue GU ; Xiao SUN
Chongqing Medicine 2015;(14):1921-1923,1927
Objective To compare the effects of two surgical procedures via comparison on tibial fractures with/without proximal fibula fractures ,and to explore the reference importance of proximal fibula fractures in surgery for complex tibial plateau fracturesinvolvingposterior and lateral spine .Methods Totally 69 cases of patients with complex tibial plateau fracturesinvolving‐posterior and lateral spine (Schatzker Ⅴ and Ⅵ) were selected ,who accepted treatment between January 2008 and October 2012 . The patients were screed according to the quality of fracture reduction immediately after operation .39 cases were screened whose scores were excellent and the general condition was similar .The patients were divided into group A1 ,A2 and B1 and B2 according to the whether there was proximal fibula fractures and whether accepted posterior lateral support steel plate:group A1 (n=10):without proximal fibula fractures but with posterior lateral support steel plate;group A2 (n=11):without proximal fibula fractures and without posterior lateral support steel plate;group B1 (n=9):with proximal fibula fractures and with posterior lateral support steel plate;group B2 (n=9):with proximal fibula fractures but without posterior lateral support steel plate .According to the knee scoring system of American Hospital for Special Surgery (HSS) ,a total of 39 cases of patients were followed up for 12-14 months (average 12 .8 months) to evaluate the recovery condition of knee function .And correlations between the scores of the 4 groups were compared .Results There were statistically significant differences between group B1 and group B2 on HSS scores (P<0 .01) ,but there were not between group A1 and A2 (P>0 .05) .Conclusion For patients with complex tibial plateau fracturesin‐volvingposterior and lateral spine and with proximal fibula fractures ,posterior lateral support steel plate can achieve more satisfac‐tory rehabilitation function .
10.Treatment of malignant brain gliomas with the chemotherapy of intracerebral implantation of 5-Fu biodegradable polymer combined with radiotherapy of interstitial implantation of 125Ⅰ after microsurgery excision
Xueming Lü ; Shaoji YUAN ; Jiwen LI ; Rongwei ZHANG ; Xiyan SUN ; Yilei XIAO
Cancer Research and Clinic 2010;22(8):537-539
Objective To investigate the efficacy of treatment on malignant intracranial gliomas with the chemotherapy of intracerebral implantation of 5-Fu biodegradable polymers combined with radiotherapy of interstitial implantation of 125Ⅰ after microsurgery resection. Methods Sixty-five patients with malignant intracranial gliomas who had underwent craniotomy microsurgical resection were intraoperatively implanted in the tumor bed around with 5-Fu biodegradable polymers and 125Ⅰ seeds. After first implantation (3 months to 1 year), stereotactic guided implantation was carried out 1 or 2 times again. The patients were followed up for 6-36 months to observe the efficacy, edema and adverse reactions, compared with follow-up of 40 patients with malignant intracranial gliomas treated by conventional radiotherapy and chemotherapy after microsurgical total resection. Results Within 1 week after the implantation the patients had headache significantly, WBC of cerebrospinal fluid was increased to some degrees, and edema was obvious compared with surgery alone. All patients were treated and discharged. Forty-four patients were completely followed-up and the survival period was significantly longer. Within 6 months, 1 year, 2 years and 3 years, there were 4 cases (9.1 %) of recurrence and no case of death, 14 cases (31.8 %) of recurrence and no case of death, 20 cases (45.5 %) of recurrence and 12 cases (27.6 %) of death and 29 cases (65.9 %) of recurrence and 20 cases(45.5 %) of death, respectively. No obviously adverse reactions were found and the quality of life was significantly improved. Conclusion Microsurgical total resection is the key of the treatment. It is an alternative treatment of human malignant gliomas in the safe and effective way that the local chemotherapy of intracerebral implantation of 5-Fu biodegradable polymers combined with local sensitivity radiotherapy of interstitial implantation of 125Ⅰ after microsurgical resection.

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