1.Mechanisms of Dihuang Yinzi in Treating Advanced Parkinson's Disease Based on Gut Microbiota-SCFAs-inflammation Axis
Renzhi MA ; Yasi LIN ; Tingyue JIANG ; Hongmei ZHU ; Jiayuan LI ; Yu WANG ; Ge ZHANG ; Wenxin FAN ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):11-21
ObjectiveTo observe the effects of Dihuang Yinzi (DY) on motor dysfunction in rats with advanced Parkinson's disease (PD) and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids (SCFAs)-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group, model group, positive drug group (levodopa, 50 mg·kg-1), and DY low-, medium-, and high-dose groups (5.2, 10.4, 20.8 g·kg-1). After 7 days of administration, motor function was evaluated using the open-field, pole-climbing, and inclined plate tests. Hematoxylin-eosin (HE) staining was used to observe pathological changes in the substantia nigra and colon, and immunohistochemistry was performed to detect α-Synuclein (α-Syn) and tyrosine hydroxylase (TH) expression in the substantia nigra. Enzyme-linked immunosorbent assay (ELISA) was used to measure levels of dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), Levodopa, homovanillic acid (HVA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Western blot analysis was used to detect the expression of zonula occludens-1 (ZO-1) and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing, and gas chromatography (GC) was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group, the model group showed significantly decreased movement speed and distance in the open-field test, prolonged pole-climbing time, and reduced retention angle on the inclined plate (P<0.01), accompanied by increased α-Syn expression (P<0.01) and decreased TH expression (P<0.01) in the brain. Compared with the model group, all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees (P<0.05, P<0.01) and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra (P<0.01) and increased TH expression (P<0.01). ELISA and Western blot results showed that, compared with the normal group, the model group exhibited decreased levels of DA, 5-HT, DOPAC, Levodopa, and HVA in the striatum (P<0.01), increased levels of TNF-α, IL-6, and IL-1β in the colon and striatum (P<0.01), and significantly reduced expression of ZO-1 (P<0.05) and occludin in the colon (P<0.01). Compared with the model group, all DY dose groups increased the levels of DA, 5-HT, DOPAC, Levodopa, and HVA in the striatum to varying degrees (P<0.05, P<0.01). In the high-dose DY group, the levels of TNF-α, IL-6, and IL-1β in the colon and striatum were reduced (P<0.01), while the expression of ZO-1 (P<0.05) and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota, Enterobacteriaceae, and Erysipelotrichaceae were increased in the model group, whereas the relative abundances of Bacteroidota, class Clostridia, Lachnospiraceae, and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased (P<0.05, P<0.01), while after high-dose DY intervention, the levels of acetate, propionate, isobutyrate, and butyrate were significantly increased (P<0.05, P<0.01). ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.
2.Fufang Kangjiaolv Capsules Treat Anxiety in Rat Model of Chronic Restraint Stress via Microbiota-gut-brain Axis
Wenxin FAN ; Tingyue JIANG ; Yu WANG ; Ge ZHANG ; Yifan LU ; Mengmeng LIU ; Jiayuan LI ; Renzhi MA ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):95-107
ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress (CRS) and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank, model, positive drug (diazepam, 1 mg·kg-1), and low-, medium-, and high-dose (0.75, 1.5, 3 g·kg-1, respectively) Fufang Kangjiaolv capsules groups. After 14 days of administration, the elevated plus maze test, open field test, light and dark box test, and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats, and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of zonula occludens-1 (ZO-1) and occludin in the colon of rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the colon, serum, and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1, occludin, nuclear factor-κB p65 (NF-κB p65) in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor (BDNF) in the hippocampal tissue. ResultsCompared with the blank group, the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze, the time and frequency of rats entering the central area of the open field, the time of entering the open box, the times of passing through the light and dark box, and the number of unburied beads (P<0.05, P<0.01). Compared with the model group, Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees, and the high-dose group had the best effect, with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze (P<0.05), the number of rats entering the central area in the open field (P<0.05), the time of entering the open box, the times of passing through the light and dark boxes, and the number of unburied beads (P<0.01). Moreover, the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes, Deferribacterota, Romboutsia, and Phascolarctobacterium, while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota, Bacteroides, norank f norank o Clostridia UCG-014, and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group, the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon (P<0.01), elevated levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated protein level of NF-κB p65 in the colon and hippocampus (P<0.01), and down-regulated protein level of BDNF in the hippocampus (P<0.05). Compared with the model group, high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon (P<0.01), lowered the levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated the protein levels of ZO-1 (P<0.01) and occludin (P<0.05) in the colon, down-regulated the protein level of NF-κB p65 in the colon and hippocampus (P<0.05), and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance, up-regulating the expression of tight junction proteins in the colon, repairing intestinal mucosal mechanical barrier, and down-regulating NF-κB/BDNF signaling pathway, thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis, providing a new idea for further research.
3.Targeted screening and profiling of massive components of colistimethate sodium by two-dimensional-liquid chromatography-mass spectrometry based on self-constructed compound database.
Xuan LI ; Minwen HUANG ; Yue-Mei ZHAO ; Wenxin LIU ; Nan HU ; Jie ZHOU ; Zi-Yi WANG ; Sheng TANG ; Jian-Bin PAN ; Hian Kee LEE ; Yao-Zuo YUAN ; Taijun HANG ; Hai-Wei SHI ; Hongyuan CHEN
Journal of Pharmaceutical Analysis 2025;15(2):101072-101072
In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.
4.Textual Analysis of Classical Prescription Yangweitang Based on Ancient Literature
Lyuyuan LIANG ; Jialei CAO ; Yiping WANG ; Mengmeng GENG ; Lujun ZHU ; Wenxin WEI ; Bingqi WEI ; Wenli SHI ; Bingxiang MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):147-157
The classical prescription Yangweitang, derived from Zhengzhi Zhunsheng, is specialized in treating syndromes of chill and fever due to exogenous pathogens, inner-cooling, and malaria, and it has been included in the Catalogue of Ancient Classical Formulas (the First Batch) published by the National Administration of Traditional Chinese Medicine (TCM) in 2018. Through bibliographical research, the relevant ancient books and modern documents were systematically sorted out, and it was found that there were many prescriptions related to the Yangweitang from Zhengzhi Zhunsheng. They were interwoven with Yangweitang from Zhengzhi Zhunsheng and widely used in clinical practice. In order to clarify their history and evolution, this paper combed the historical origin of Yangweitang and its related prescriptions and conducted textual analysis on key information such as semantic composition, herb origin, processing method, and efficacy. A total of 896 pieces of data on Yangweitang from Zhengzhi Zhunsheng were collected. 26 pieces of effective data were included after the screening, involving 17 ancient TCM books. Then, a total of 28 pieces of data on prescriptions related to the Yangweitang from Zhengzhi Zhunsheng were included, involving 23 ancient TCM books for reference. The textual analysis showed that Yangweitang originated from the Renshen Yangweitang recorded in Taiping Huimin Heji Jufang in the Song dynasty. Based on the original formula, medical experts from later generations have modified it into many different versions. A comparative analysis showed that Yangweitang from different generations had similar compositions, and the herb origin and processing method were basically clear. The recommended prescriptions are as follows: 37.3 g of Pinelliae Rhizoma Praeparatum Cum Alumine, Magnoliae Officinalis Cortex(fried with ginger juice), and frying with rice water Atractlodis Rhizoma, 27.98 g of Citri Exocarpium Rubrum, 18.65 g of Pogostemon cablin leaf, Tsaoko Fructus, Poria, and Ginseng Radix et Rhizoma, and 9.33 g of Glycyrrhizae Radix et Rhizoma. They could be ground into a coarse powder, with 14.92 g for every dose, and they could be orally taken after being decocted with 450 mL of water, 7 g of fresh ginger, and 2 g of Mume Fructus to 270 mL in warm conditions. Yangweitang from Zhengzhi Zhunsheng has the effect of warming the middle and releasing the external, and it can treat many syndromes including spleen and stomach disharmony caused by chill and fever due to exogenous pathogens and inner-cooling, as well as all kinds of malaria. Modern clinical applications mainly focus on chronic atrophic gastritis and other digestive system diseases.
5.Application of Quality Evaluation of Blind Method in Clinical Trials of Traditional Chinese Medicine
Zeyang SHI ; Yuan SUN ; Wenxin MA ; Yuyi WANG ; Zhijun BU ; Xuehui WANG ; Youyou ZHENG ; Jianping LIU ; Zhaolan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):75-80
The quality evaluation of the blind method is to evaluate the clinical blind data obtained from clinical trials adopting the blind method and judge the effectiveness of the blind method by investigating the blind effect of different blind objects. A successful blind method can avoid the influence of subjective factors on the test results of subjects and researchers to a certain extent. The quality evaluation of the blind method can reflect not only the effectiveness of the blind method but also the accuracy and credibility of clinical trial results. In recent years, randomized controlled trials have been widely used in the evaluation of the clinical efficacy of traditional Chinese medicine (TCM), but the quality of the implementation of blind methods is uneven, and the evaluation criteria have not yet been formed. In this paper, the data collection methods, calculation principles, advantages, and disadvantages of two quantitative quality evaluation methods of blind methods, namely James Blinding Index (JBI) and Bang Blinding Index (BBI), were introduced. The two indexes were analyzed in a randomized controlled trial of acupuncture and moxibustion to relieve postoperative oral pain. The calculation process of the results was demonstrated by R software and visualized by forest map. At the same time, a tool table was designed to facilitate the collection of evaluation data of blind methods in TCM clinical trials at different stages. Finally, the necessity and feasibility of quality evaluation of blind method in TCM research were discussed to provide a basis for evaluating and improving the quality of blind method implementation in TCM clinical trials.
6.Reconstruction and analysis of K-Clip surgery process based on finite element method
Hao SHI ; Wenbin OUYANG ; Shiguo LI ; Qi LI ; Fengwen ZHANG ; Yao LIU ; Wenxin LU ; Chang LIU ; Shaojie ZHANG ; Xiangbin PAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(01):44-50
Objective To investigate the effects of different types of tricuspid regurgitation, implantation positions, and device models on the treatment outcomes of K-Clip for tricuspid regurgitation using numerical simulations. Methods Three-dimensional reconstruction of the heart model was performed based on CT images. Two different regurgitation orifices were obtained by modifying the standard parameterized tricuspid valve leaflets and chordae tendineae. The effects of different K-Clip models at different implantation positions (posterior leaflet midpoint, anterior-posterior commissure, anterior leaflet midpoint, posterior septal commissure) were simulated using commercial explicit dynamics software Ls-Dyna. Conclusion For the two types of regurgitation in this study, clipping at the posterior leaflet midpoint resulted in a better reduction of the regurgitation orifice (up to 75% reduction in area). Higher clamping forces were required for implantation at the anterior leaflet midpoint and posterior septal commissure, which was unfavorable for the smooth closure of the clipping components. There was no statistical difference in the treatment outcomes between the 18T and 16T K-Clip components, and the 16T component required less clamping force. Therefore, the use of the 16T K-Clip component is recommended.
7.A Comparative Study on the Drugs in the Centralized Procurement List and the National Essential Medicine List of China
Xiaomei DENG ; Jin ZHANG ; Zhetao ZHANG ; Huiting LI ; Xiao LIU ; Yini MA ; Wenxin WU ; Tianlu SHI
Herald of Medicine 2024;43(7):1177-1180,后插1
Objective To compare and explore the differences between the eight batches of drugs in the centralized procurement list and the 2018 edition of the national essential medicine list,and to provide reference for updating and improving the national essential medicine list and the national centralized procurement list of drugs.Methods The category,generic name variety,specification,and other information of drugs included in the centralized drug procurement were collected and compared with the 2018 edition of the national essential medicine list,and the reasons for differences were analyzed.Results A proportion of 39%of centralized procurement drugs were listed in national essential medicines.Forty pharmacological classifications were not involved in the drugs of centralized procurement.Only anticoagulant and thrombolytic drugs with dual attributes accounted for a smaller variety proportion than the specification proportion.Conclusion There are some differences between the centralized procurement list and the 2018 edition of the national essential medicine list,which have some rationality,but also some problems to be solved.
8.Desktop-Stereolithography 3D Printing of a Decellularized Extracellular Matrix/Mesenchymal Stem Cell Exosome Bioink for Vaginal Reconstruction
Wenxin SHI ; Jiahua ZHENG ; Jingkun ZHANG ; Xiaoli DONG ; Zhongkang LI ; Yanlai XIAO ; Qian LI ; Xianghua HUANG ; Yanfang DU
Tissue Engineering and Regenerative Medicine 2024;21(6):943-957
BACKGROUND:
3D-printing is widely used in regenerative medicine and is expected to achieve vaginal morphological restoration and true functional reconstruction. Mesenchymal stem cells-derived exosomes (MSCs-Exos) were applyed in the regeneration of various tissues. The current study aimed to explore the effctive of MSCs-Exos in vaginal reconstruction.
METHODS:
In this work, hydrogel was designed using decellularized extracellular matrix (dECM) and gelatin methacrylate (GelMA) and silk fibroin (SF). The biological scaffolds were constructed using desktop-stereolithography.The physicochemical properties of the hydrogels were evaluated; Some experiments have been conducted to evaluate exosomes’ effect of promotion vaginal reconstruction and to explore the mechanism in this process.
RESULTS:
It was observed that the sustained release property of exosomes in the hydrogel both in vitro and in vitro.The results revealed that 3D scaffold encapsulating exosomes expressed significant effects on the vascularization and musule regeneration of the regenerative vagina tissue. Also, MSCs-Exos strongly promoted vascularization in the vaginal reconstruction of rats, which may through the PI3K/AKT signaling pathway.
CONCLUSION
The use of exosome-hydrogel composites improved the epithelial regeneration of vaginal tissue, increased angiogenesis, and promoted smooth muscle tissue regeneration. 3D-printed, lumenal scaffold encapsulating exosomes might be used as a cell-free alternative treatment strategy for vaginal reconstruction.
9.Survival analysis of liver cancer in Shanghai:a population-based study from 2002 to 2013
Linmeng ZHANG ; Chunxiao WU ; Hui WANG ; Kai GU ; Liang SHI ; Cun WANG ; Wenxin QIN ; Yan SHI
Tumor 2023;43(4):347-353
Objective:To investigate the survival rates of patients with liver cancer in Shanghai from 2002 to 2013. Methods:Data on new cases and deaths of liver cancer patients withfollow-up information from 2002 to 2013 were obtained from the Population-Based Cancer Registry and Vital Statistics System of the Shanghai Municipal Center for Disease Control and Prevention.Incidence and survival rates were stratified by year of diagnosis,gender,district,age-group and stage at diagnosis for analysis.Statistical indicators,such as case numbers,proportions,median age and mean age were calculated.The 1-to 5-year observed survival rates were calculated based on the life table method.The probabilities of surviving from 0 to 99 years old were estimated with the Elandt-Johnson model,and then cumulative expected survival rates were calculated using the Ederer Ⅱ method.Finally,the 1-to 5-year relative survival rates were calculated. Results:A total of 49 455 new cases of liver cancer were diagnosed from 2002 to 2013 in Shanghai,including 35 115 males and 14 340 females.The ratio of males to females was 2.45:1.The proportions of stage Ⅰ,stage Ⅳ and stage unknown were 3.32%,13.93%and 69.13%,respectively.The median survival time of patients with liver cancer diagnosed from 2002 to 2013 was 0.77 years,the 5-year observed survival rate was 13.23%,and the 5-year relative survival rate was 14.47%.According to the 5-year observed survival rate and 5-year relative survival rate of the cases,both survival indicators were higher in urban areas than in suburban areas,higher in males than in females,higher in cases under 45 years of age than in those over 75 years of age,higher in cases diagnosed from 2011 to 2013 than those diagnosed from 2002 to 2004.Additionally,the survival rate of cases decreased with increasing stage at diagnosis. Conclusion:With the continuous improvement of the diagnosis and treatment of liver cancer in Shanghai,the survival rate of patients with liver cancer has shown a significant upward trend over time.However,compared with various malignant tumors such as gastric cancer and breast cancer,the improvement effect of liver cancer survival rate is still not significant.Additionally,a high proportion of cases with unknown clinical stage at the time of diagnosis and a low survival rate of stage Ⅳ cases were observed.This study provides a basis for the prevention and research of liver cancer.
10.A machine learning-based predictive model of nonsuicidal self-injurious behavior among college students in Guizhou Province
PAN Chan, LIU Xiaorong, SHI Xiangzi, ZHAO Wenxin, TIAN Meng, CHEN Siyuan, ZHANG Wanzhu
Chinese Journal of School Health 2023;44(8):1198-1202
Objective:
To explore the effectiveness of machine learning algorithms in predicting non-suicidal self-injury (NSSI) behavior among college students, and to analyze the influencing factors of NSSI behavior, thus providing a reference for promoting psychological well-being.
Methods:
In December 2022, a stratified random cluster sampling method was used to select 835 college students from a university in Guizhou Province, China. The Adolescent Self-injury Scale, Family Function Assessment Scale, and Emotion Regulation Self-efficacy Scale were used to evaluate the participants. Demographic characteristics, family factors, and emotional factors were taken as independent variables, while the dependent variable was whether college students exhibited NSSI behavior. Machine learning algorithms, including Logistic regression, support vector machine (SVM), decision trees, algorithm gradient boosting trees, random forests, and AdaBoost, were used to construct predictive models.
Results:
The detection rate of NSSI behavior among the college students was 23.23% (194 individuals). The NSSI behavior group scored higher than the non-NSSI behavior group in total family function, emotional communication, egoism, and family rules ( t=3.02, 3.35 , 2.23,2.87, P <0.05). On the other hand, the non-NSSI behavior group scored higher than the NSSI behavior group in total emotion regulation selfefficacy, managing negative emotion self-efficacy, and expressing positive emotion self-efficacy ( t=-5.04, -5.48 , -2.43, P <0.05). The recall rates of random forests, SVM, Logistic regression, decision trees, algorithm gradient boosting trees, and AdaBoost were 84.3% , 90.6%, 73.4%, 87.5%, 95.3%, 89.0%, respectively. The F1 scores were 84.4%, 92.1%, 71.2 %, 79.4%, 91.7%, 89.1% , respectively. The respective precision rates were 84.4%, 93.5%, 69.1%, 72.7%, 88.4%, 89.1 %. The AUC scores were 0.845, 0.922, 0.706, 0.776, 0.915, and 0.891, respectively.
Conclusion
Compared to the algorithm gradient boosting tree, random forest, Logistic regression, and AdaBoost models, the SVM model has a better predictive effect on whether college students in Guizhou Province exhibits NSSI behavior. It is recommended to use an appropriate model to identify students at risk of NSSI behavior as early as possible and provide psychological crisis interventions to promote their mental health.


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