1.Characteristic Analysis of Imprinting Template of Flavonoid Clusters in Four Chinese Medicines to Lung Meridian and Establishment of Experimental Approach of Meridian Tropism in Vitro
Qijun HE ; Dandan SHENG ; Yuxia CHEN ; Shaoqin OUYANG ; Kaiwen DENG ; Fuyuan HE ; Xinyu CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):141-147
ObjectiveTo study the characteristics of imprinting template of flavonoid clusters in four Chinese medicines attributed to the lung meridian, and to establish an in vitro experimental approach for the study of the attribution of Chinese medicines to the lung meridian. MethodBased on 13 Chinese medicines, including Xanthii Fructus, Houttuyniae Herba, Fagopyri Dibotryis Rhizoma, Belamcandae Rhizoma and so on, which only belong to the lung meridian in Chinese Materia Medica(the 13th Five-Year planning textbook of general higher education), we identified four representative Chinese medicines, namely Houttuyniae Herba, Fagopyri Dibotryis Rhizoma, Belamcandae Rhizoma and Mori Cortex, and set up their fingerprints by high performance liquid chromatography(HPLC) and calculated the molecular connectivity indices of various components in the four Chinese medicines, the similarity to their mean value was calculated by included angle cosine method, so as to establish the quantitative relationship of construction versus imprinting ability, and to determine the order of each component in the lung meridian. A total of 7 reference substances, including chlorogenic acid, rutin, quercetin, isoquercitrin, hyperoside, epicatechin, and iridin, were selected to validate the overall conformational relationships of flavonoids of the model, as well as its predictive ability. ResultHouttuyniae Herba, Fagopyri Dibotryis Rhizoma, Belamcandae Rhizoma and Mori Cortex contained a total of 437 chemical components with an average molecular connectivity index similarity of 0.995 6. The four Chinese medicines contained a total of 204 flavonoids with an average molecular connectivity index similarity of 0.978 0, which was second only to the alkaloids with 0.985 1. The retention time(tR) of the 7 reference substances showed a good conformational relationship with the similarity of the molecular connectivity index(tR=831.4×S-790.3, r=0.861 4, P<0.01), which was applicable to the in vitro attribution study of the position, similarity, and relative similarity with tR of the cluster of 98.04% of flavonoids. Accordingly, the 1st position was kuwanon D, with a similarity of molecular connectivity index of 0.987 7 and a tR of 30.88 min, the 200th position was chlorogenic acid, with a similarity of molecular connectivity index of 0.958 2 and a tR of 6.36 min. The total first-order moment of the four Chinese medicines calculated by total statistical moment method of fingerprint was 24.26 min, ranked 21, which could characterize 99.19% of the whole, and the total first-order moment of the total peak area of the 7 reference substances in the four Chinese medicines was 20.00 min, with a rank of 46, which could characterize 98.68% of the whole. ConclusionFlavonoid clusters are suitable probes for the characterization of imprinting template for the study of the lung meridian, which can be established a quantitative imprinting method for meridian tropism of Chinese medicines in vitro.
2.Research progress of novel opioid analgesics
Chunbo HE ; Dan WANG ; Shujia YANG ; Kaiwen ZHOU ; Yiping DENG ; Shouliang DONG
China Pharmacy 2024;35(17):2176-2180
Opioid analgesics are currently known as the best analgesics. However, toxicity and side effects such as constipation, tolerance and addiction severely limit their clinical application. With the in-depth understanding of the signal transduction mechanism of opioid receptors and the continuous advancement of drug design technology, researchers have managed to develop many promising new methods to get low-toxic and more efficient opioid analgesics, which are different from the traditional morphine skeleton structure modifications. This article focuses on three new research strategies of G-protein biased activation,“ one drug-multiple targets” and peripheral activation. The basic principles of relative separation of analgesic activity and adverse drug reaction by each strategy are introduced, and the latest research progress of representative drugs is briefly reviewed. Among them, the recently approved novel opioid analgesics oliceridine and tegileridine are G-protein biased μ-opioid receptor agonists, Cebranopadol is a typical “one drug-multiple targets” analgesic, and NFEPP is a representative drug of peripheral opioid receptor agonists. The above several strategies complement each other and provide reference for the development of new opioid analgesic drugs.
3.Theory and Analysis of Pharmacokinetic and Chromatokinetics Dose-time Characterization Methods in Traditional Chinese Medicine
Ru QIAO ; Peng HE ; Qijun HE ; Haiying LI ; Meifeng XIAO ; Kaiwen DENG ; Fuyuan HE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):178-186
ObjectiveTo establish a theoretical system of pharmacokinetic and spectrokinetic dose-time characterization of traditional Chinese medicine(TCM). By analyzing the pharmacokinetic and spectrokinetic behaviors of Lonicerae Flos, Houttuyniae Herba injection, Lonicerae Japonicae Flosand Buyang Huanwutang, this paper compared the similarities and differences of the three methods for characterizing the dose-time relationship, namely half-life, statistical moment and statistics, in order to find the most suitable method for characterizing the relationship. MethodTen mice were randomly selected from 100 Kunming mice as the blank group, and the remaining mice were coated with xylene in the auricle to establish the acute inflammation model of ear swelling. After successful modeling, the mice were gavaged with aqueous extract of Lonicerae Flos(30 g∙kg-1), and the blank group was gavaged with an equal volume of normal saline. The plasma of mice was collected at different time points to determine the content changes of components. At the same time, the pharmacokinetic results of Houttuyniae Herba injection, Lonicerae Japonicae Flos and Buyang Huanwutang were included, and the pharmacokinetic and spectrokinetic parameters were calculated. Then the difference in the time of calculating 95% total component content of metabolism by half-life method, statistical moment method and statistical method was compared. ResultOn the basis of the half-life method, the mathematical expressions of statistical moment method and statistical method suitable for the characterization of dose-time relationship of multi-component system of TCM were established. The results showed that the pharmacokinetic parameters of the individual components in Lonicerae Flos varied, with cryptochlorogenic acid and rutin showing a two-compartment model and the other components showing a one-compartment model. After calculation of spectrokinetic similarity, the metabolic patterns among the components contained in Houttuyniae Herba injection, Lonicerae Japonicae Flos, Lonicerae Flos and Buyang Huanwutang were different and varied greatly in vivo. The time to metabolize 95% of the total components of the four research subjects in vivo was calculated by the half-life method, statistical moment method and statistical method, and it was found that the difference between statistical moment method and half-life method was large, and the difference between statistical moment method and statistical method was small. ConclusionStatistical method not only reflects the characteristics of statistical moment method, characterizes the dispersion degree of each component, but also can be associated with fingerprint to form spectrokinetics, characterizing the dose-time relationship of 95% of drug components, which is a more desirable method to characterize the dose-time relationship of the component groups in TCM.
4.T 2-mapping and BOLD to evaluate the effect of swimming rehabilitation exercise on paraspinal muscles in rats model with discogenic low back pain
Jiyao MA ; Kaiwen YANG ; Baofa LUO ; Yilong HUANG ; Hongli ZHU ; Xinchen HUANG ; Bo HE
Chinese Journal of Radiology 2023;57(9):998-1005
Objective:To explore MRI T 2-mapping and blood oxygenation level dependent (BOLD) to evaluate the functional changes of paraspinal muscle in rats with discogenic low back pain (DLBP) after swimming. Methods:Totally 54 female 1-month-old SD rats were selected, which were divided into 3 groups by random number table method, sham operation (Sham) group, DLBP non-swimming group and DLBP swimming group, with 18 rats in each group. Under the guidance of X-ray fluoroscopy, the L4/5 and L5/6 intervertebral discs of the rats in the DLBP non-swimming group and DLBP swimming group were punctured by the posterior approach, and establishment of DLBP rat model by destroying nucleus pulposus, and only paraspinal muscles at the same level were punctured in the Sham group. After modeling, the DLBP swimming group received swimming exercise intervention for 5 consecutive days (30 min/d), while the DLBP non-swimming group and Sham group did not receive any rehabilitation exercise intervention. Each group was divided into 3 time point subgroups on average, the T 2-mapping and BOLD sequences were scanned at 30, 90 and 180 days after modeling to obtain the T 2 value, R 2* value of the paraspinal muscles, and the paraspinal muscles at the modeling level were taken for immunofluorescence staining, and the fluorescence intensity of myosin heavy chain (MYH)1 (type Ⅱ muscle fiber) and MYH7 (type I muscle fiber) was analyzed. One-way analysis of variance was used for comparison among the 3 groups, and the Bonferroni method was used for multiple comparisons, and Pearson correlation coefficient was used to evaluate the correlation between quantitative MRI parameters T 2 value, R 2* value and MYH1, MYH7 immunofluorescence intensity of rat paraspinal muscles at 180 days after modeling. Results:At 30 days after modeling, there was no significant difference in T 2 value and R 2* value among the 3 groups (all P>0.05). At 90 days after modeling, the T 2 value of the DLBP swimming group was higher than that of the DLBP non-swimming group, and the T 2 value of the DLBP non-swimming group was lower than that of the Sham group (all P<0.05), and there was no significant difference in the R 2* value among the 3 groups ( P>0.05). At 180 days after modeling, the T 2 value of the DLBP swimming group was higher than that of the DLBP non-swimming group, and the R 2* value was lower than that of the DLBP non-swimming group; the T 2 value of the DLBP non-swimming group was lower than that of the Sham group, and the R 2* value was higher than that of the Sham group (all P<0.05). At 30 and 90 days after modeling, there was no significant difference in the expressions of MYH1 and MYH7 among the 3 groups (all P>0.05). At 180 days after modeling, the expression of MYH1 decreased and the expression of MYH7 increased in the DLBP swimming group compared with the DLBP non-swimming group; the expression of MYH1 increased and the expression of MYH7 decreased in the DLBP non-swimming group compared with the Sham group (all P<0.05). At 180 days after modeling, the T 2 value had a moderate negative correlation with the fluorescence intensity of MYH1 ( r=-0.511, P=0.043), and a moderate positive correlation with the fluorescence intensity of MYH7 ( r=0.564, P=0.023); R 2* value was moderate positive correlated with the fluorescence intensity of MYH1 ( r=0.625, P=0.010), and moderate negative correlated with the fluorescence intensity of MYH7 ( r=-0.653, P=0.006). Conclusions:Swimming exercise can improve the reduction of water content and perfusion in the paraspinal muscles of DLBP rats, and reduce the transformation of muscle fibers from type Ⅰ to type Ⅱ, the changes of T 2 and R 2* value can reflect the transformation of paraspinal muscle fiber types to a certain extent.
5.Early clinical efficacy of ultrasound-guided platelet-rich plasma technology in the treatment of lumbodorsal myofascial pain syndrome after sports injury
Shaolong AI ; Qian WANG ; Kaiwen LI ; Xingzhen LIN ; Na LI ; Hongying JIANG ; Hongchen HE
Chinese Journal of Trauma 2023;39(9):786-792
Objective:To explore the early clinical efficacy of ultrasound visualized platelet-rich plasma (PRP) in the treatment of lower back myofascial pain syndrome (MPS) after sports injury.Methods:A prospective cohort study was conducted to analyze the clinical data of 32 patients with lower back MPS after sports injury, who were admitted to West China Hospital of Sichuan University from January 2023 to March 2023. Ultrasound-guided PRP injection into the erector spinalis or quadratus psoas muscles was used for treatment. Before treatment, at 24 hours, 2 weeks, and 4 weeks after treatment, pain and function were evaluated using visual analogue scale (VAS), McGill pain questionnaire (McGill), Roland Morris dysfunction questionnaire (RMDQ), and Oswestry dysfunction index (ODI). Before treatment and 4 weeks after treatment, the quality of life was evaluated using the short-form 36 item health survey questionnaire (SF-36). The adverse reactions were observed during treatment and follow-up.Results:A total of 32 patients with lower back MPS after sports injury were enrolled, including 10 males and 22 females; aged 12-68 years [(47.3±16.3)years]. All the patients were followed up for 4 weeks. Before and at 24 hours, 2 weeks, and 4 weeks after treatment, the VAS was 5.0(4.0, 6.0)points, 3.5(3.0, 4.8)points, 2.0(2.0, 3.0)points, and 2.0(1.3, 3.0)points, respectively; the McGill score was 9.0(7.0, 11.0)points, 7.0(5.0, 9.0)points, 4.0(3.0, 5.0)points, and 3.0(3.0, 5.0)points, respectively; the RMDQ score was 8.0(5.3, 10.8)points, 5.5(3.0, 8.0)points, 4.0(3.0, 5.8)points, and 3.0(2.0, 4.8)points, respectively; the ODI was 22.0(14.5, 30.0), 20.0(14.5, 25.5), 9.0(6.0, 16.0), and 8.0(4.5, 14.0), respectively. Compared with the values before treatment, the VAS, McGill score, and RMDQ score were significantly decreased at 24 hours, 2 weeks, and 4 weeks after treatment (all P<0.05); the ODI had no significant difference at 24 hours after treatment ( P>0.05), but it was significantly decreased at 2 and 4 weeks after treatment (all P<0.05). Compared with the values at 24 hours after treatment, the VAS, McGill score, RMDQ score and ODI further decreased at 2 weeks after treatment (all P<0.05). Compared with the values at 2 weeks after treatment, there was no significant difference in the VAS, McGill score, RMDQ score, or ODI at 4 weeks after treatment (all P>0.05). In the SF-36, the scores of physiological function [77.5(60.0, 93.8)points], physiological role [50.0(0.0, 100.0)points], body pain [64.0(44.5, 74.0)points], vitality [75.0(65.0, 78.8)points], social function [87.5(75.0, 100.0)points], emotional role [66.7(33.3, 100.0)points] and mental health [72.0(68.0, 83.0)points] before treatment were increased to 90.0(80.0, 98.8)points, 100.0(56.3, 100.0)points, 84.0(74.0, 84.0)points, 75.0(70.0, 80.0)points, 100.0(87.5, 112.5)points, 100.0(66.7, 100.0)points, and 76.0(68.0, 84.0)points after 4 weeks of treatment, respectively ( P<0.05 or 0.01). However, there was no significant difference in the general health status or health changes before and after treatment (all P>0.05). During treatment and follow-up, no adverse reactions such as redness, swelling, pain, or subcutaneous bleeding were observed. Conclusion:Ultrasound-guided PRP treatment can improve the early pain, lumbar mobility and quality of life of patients with lower back MPS after sports injury, with no presence of adverse reactions.
6.Research of SIRT1 on promoting the proliferation, migration and lipid metabolism of nasopharyngeal carcinoma
Haimeng YIN ; Xin HE ; Ying SHAN ; Hongxiang ZHAI ; Kaiwen ZHANG ; Tian XIA ; Siyu ZHANG ; Wenhui CHEN ; Yiwen YOU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2020;55(10):934-943
Objective:To analyze the differential expression of silent information regulator transcript-1 (SIRT1) in tissues and cells of nasopharyngeal carcinoma (NPC), to explore the effects of SIRT1 on the proliferation and migration of NPC cells, as well as the effects on and mechanisms of lipid metabolism in NPC cells.Methods:Experimental subjects: In this study, tissue specimens were obtained from patients who visited the Department of Otolaryngology and performed nasopharyngeal tissue biopsy in the Affiliated Hospital of Nantong University from 2019 to 2020. Among them, 6 cases were male, 6 cases were female, age range: 27-72 years old, including 7 cases of NPC diagnosed by pathology and 5 cases of normal nasopharyngeal mucosa. Experimental methods and outcome measures: Western Blot and quantitative real time polymerase chain reaction (qRT-PCR) were used to detect the protein and mRNA levels of SIRT1. CNE2 cell line was selected for subsequent experiments. Cell viability and migratory ability were evaluated by CCK8, wound healing and Transwell assays respectively. Animal xenograft tumor model was used to explore the role of SIRT1 inhibitor Ex527 on tumor growth in nude mice. Oil red and Bodipy were used to stain intracellular lipids. For the mechanical investigation, the interactions between SIRT1 and hypoxia inducible factor-1α (HIF-1α) were analyzed by immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP). Finally, statistical analysis was performed by SPSS 26.0 software, P<0.05 was considered statistically significant. Results:The levels of SIRT1 protein (1.005±0.168) and mRNA (5.829±2.395) in NPC tissues were higher than those in normal nasopharyngeal mucosa (0.181±0.042,1.995±1.605). Differences were statistically significant ( t values were 6.438 and 2.759, both P<0.05). The mRNA and protein levels of CNE1, CNE2, 5-8F and 6-10B cell lines were also higher than those in normal nasopharynx epithelial cell line NP69. Besides, overexpression of SIRT1 correlated with the proliferation and migration of NPC cells. The tumorigenesis ability of nude mice in the Ex527 group was lower than that in the control group. The low SIRT1 expression reduced the protein level of the key enzymes of liposynthesis in NPC cells, improved the expression of lipolysis enzymes, while HIF-1α overexpression promoted lipid synthesis enzymes in NPC cells. SIRT1 inhibited HIF-1α transcription by enhancing deacetylation levels. The binding ability of HIF-1α to SIRT1 promoter regions decreased when NPC cells were hypoxic. Conclusions:SIRT1 promotes the proliferation, migration and lipid metabolism of nasopharyngeal carcinoma cells, which might be expected to provide new theoretical basis for prognosis judgment and gene therapy.
7.An epidemiological investigation of oral lesions in HIV infected subjects aged 50 years and older in Yunnan China
Fei DU ; Rong LI ; Rui HE ; Jinsong BAI ; Jun LIU ; Kaiwen DUAN
Journal of Practical Stomatology 2019;35(1):41-45
Objective: To investigate the characteristics of oral lesions in HIV infected patients aged 50 years or older in Yunnan.Methods: 315 HIV infected patients aged 50 years and older from January 2013 to December 2016 were included in a cross-sectional survey at the Third People's Hospital of Kunming. The characteristics of oral mucosal lesions and the relationship between the oral lesions and CD4 count level were analyzed. Results: 13 kinds of oral mucosal lesion in 185 out of the 315 cases (58. 73%) were observed. 122 cases were with candidiasis (38. 73%), including 68 (21. 59%) of pseudomembranous type, 52 (16. 51%) of erythema and 18 (5. 71%) of stomatitis; 25 (7. 94%) were with Hairy leukoplakia, 20 (6. 35%) with recurrent oral ulcer, 17 (5. 40%) with fissured tongue, 11 (3. 49%) with herpes simplex. 2 and 3 lesions were detected in 41 cases (13. 02%) and 1 case (0. 32%), respectively. The rate of simultaneous detection of more than 2 lesions and the detection rate of oral candidiasis were related to the CD4 count level. Conclusion: Oral mucosal lesions are common in elderly patients with HIV infection, and oral candidiasis is the main type.
8. Anatomical hepatectomy combined with intraoperative choledochoscopy in treatment of complicated hepatolithiasis
Shaowu HE ; Bo WU ; Jie XU ; Junsheng KANG ; Feng QIAO ; Jie LIU ; Kaiwen LIU
Chinese Journal of Hepatobiliary Surgery 2019;25(9):681-684
Objective:
To study the clinical outcomes of anatomical hepatectomy combined with intraoperative choledochoscopy in treatment of complicated hepatolithiasis.
Methods:
The clinical data of 176 patients with complicated hepatolithiasis who underwent operation at the Department of General Surgery of No.960 Hospital of PLA from May 2005 to July 2015 were analyzed retrospectively. The data included general data, clinical manifestations, types of stones, operative methods, postoperative complications and follow-up.
Results:
There was no perioperative death. The postoperative complications which occurred in 31 patients (17.6%) included lung infection, intra-abdominal infection, bile leakage, and liver failure. Eighteen patients (10.2%) were found to have residual stones. After a follow-up which ranged from 1 to 3 years, 152 patients (94.4%) had good clinical outcomes. Recurrent stones were found in 12 patients (7.5%).
Conclusion
Anatomical hepatectomy combined with intraoperative choledochoscopy improved operative outcomes in patients with complicated hepatolithiasis and decreased residual stone and recurrence rates.
9.Analysis on property of meridian supramolecules by biological evolution path.
Kaiwen DENG ; Yeqin TAO ; Wenhan TANG ; Fuyuan HE ; Wenlong LIU ; Jilian SHI ; Yantao YANG ; Yiqun ZHOU ; Xiaorong CHANG
Chinese Acupuncture & Moxibustion 2017;37(3):325-330
With human placed in the whole nature, by following the biologic evolution path, the property of channel structure for "imprinting template" in meridian andwas explored with supramolecular chemistry. In the history of biologic evolution, each molecule in "molecule society" gradually developed into various highly-ordered supramolecular bodies based on self-identification, self-assembly, self-organization, self-replicating of"imprinting template", and thereby the original biochemical system was established, and finally evolved into human. In the forming process of supramolecular bodies, the channel structure of"imprinting template" in guest supramolecular bodies would be kept by host supramolecular bodies, and communicate with the outside to exchange materials, energy, information, otherwise life phenomenon could not continue, for which it was the chemical nature of biolo-gical supramolecular bodies for body to develop meridian. Therefore, the human was a gigantic and complicated supramolecules body in biological nature, and possessed the supramolecules "imprinting template" at each stage of evolution, for which the meridians were formed. When meridians converged, acupoints appeared; when acupointsconverged,appeared. With the promotion of the blood from heart, according to"imprinting template", the guest supramolecular bodies and host meridian produced-analysis, which was the-phenomenon of guest in meridian. It presented asimage of physiology and pathology as well as action regularities of medication and acupuncture tolerance, by which current various meridian viewpoints could be explained and propose the hypothesis of meridian supramolecular bodies. The meridian and its phenomenon was decide by its "imprinting template" of supramolecular bodies and self-reaction regularities, which abided through the living nature. This was the substance for meridian biology.
10.Study on Key Theoretical and Technological Issue of Combination Compatibility and Single Determinacy for Administration of Chinese Materia Medica Preparations
Fuyuan HE ; Kaiwen DENG ; Wenlong LIU ; Yantao YANG ; Jilian SHI
World Science and Technology-Modernization of Traditional Chinese Medicine 2013;(4):790-798
This study was aimed to analyze characteristics of Chinese Materia Medica ( CMM ) preparations in order to identify the long-term development direction of this discipline and suggest key questions and strategies to solve the problems. According to the development track of CMM preparation, traditional Chinese medicine (TCM) basic theories and modern new drug research techniques were combined with the author's experiences on modernization study of TCM. This article discussed key issues of CMM preparation development direction, characteristics and is-sues need to be solved and their countermeasures. The results showed that the development direction for CMM preparation discipline should entirety unify CMM preparation system. The medical resource should be convenient which include animal, plant and mineral products. The single determinacy (effectiveness, stability and controlled) and compatibility (prediction, optimization and lowest toxin) will be applied in the guidance of CMM preparation system. In order to achieve goals mentioned above, key issues need to be solved are efficiency categories for in-gredients, genetical stabilities and one sampling charge, emigration rules of properties among ingredients, the ki-netic and stable rules of ingredient extraction, controlled rules for integral models or for disorder and torrent, e-valuation rules in vivo and in vitro, microscopic and macroscopic qualities, determinacy for single administration and compatibility for combination applications. It was concluded that the CMM preparation is a series of integral unified effective ingredient preparations that behave the determinacy for single administration and compatibility for combination applications.

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