1.Differential Analysis on Chemical Composition and Pharmacodynamic Effect Between Combined Decoction and Single Decoction of Famous Classical Formula Huaganjian
Yang WANG ; Gaoju ZHANG ; Ling LI ; Liping CHEN ; Li ZHANG ; Xiao LIU ; Yuyu ZHANG ; Yuan CUI ; Minglong LI ; Chaomei FU ; Xin YAN ; Yuxin HE ; Qin DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):199-207
ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy, to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian, and meanwhile, the contents of four index components(geniposide, paeoniflorin, hesperidin and paeonol) were quantitatively analyzed by high performance liquid chromatography(HPLC). Nonalcoholic fatty liver disease(NAFLD) rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group, model group, lovastatin group(1.8 mg·kg-1), combined decoction group(1.26 g·kg-1) and single decoction group(1.18 g·kg-1). After successful modeling, lovastatin group, combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day, and the control group and model group were given equal amounts of normal saline by intragastric administration, after 4 weeks of administration, the serum and liver tissues were collected, and the contents of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) in serum of rats were detected, and the liver pathological examination was carried out by hematoxylin-eosin(HE) staining and oil red O staining, so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian, and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide, paeoniflorin, hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples(P<0.01). The pharmacodynamic results showed that compared with the model group, both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats, reduce the serum levels of AST, ALT, TC, TG and LDL-C, increase the serum level of HDL-C, and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However, there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition, but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.
2.Analysis of Animal Models of Autoimmune Thyroiditis Based on Clinical Characteristics of Traditional Chinese and Western Medicine
Sifeng JIA ; Zhuo ZHANG ; Yuyu DUAN ; Keqiu YAN ; Xinhe ZUO ; Yang LI ; Yong ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):235-243
ObjectiveAutoimmune thyroiditis (AIT) is a complex and immune-mediated disorder, with no established treatment protocol. Both Western and traditional Chinese medicine (TCM) focus on the pathogenesis and treatment of AIT. This study evaluated the clinical consistency of existing AIT animal models based on the diagnostic criteria of both Western and TCM, using a novel evaluation method. Additionally, it proposed recommendations and future prospects for improving these models. MethodsA comprehensive literature review was conducted on existing AIT animal models, using databases and the diagnostic criteria of both Western and TCM. Core and accompanying symptoms of these models were scored based on the diagnostic criteria of both Western and TCM, and clinical consistency was assessed. ResultsMice are the primary experimental animals used in AIT modeling. Modeling methods include vaccine immunization, iodine induction, heterologous thyroid antigen immunization, and a combination of high iodine water and antigen immunization. The average consistency of clinical syndromes based on TCM and Western medicine is 40%, 60%, 54%, and 63%, with the highest consistency observed in the combined high iodine water and antigen immunization model. Pathological models based on TCM are less common, with the liver-stagnation-spleen-deficiency rat model showing high clinical consistency. While most models are designed according to Western medical theory, meeting the surface and structural effectiveness criteria of Western medicine. However, there is a lack of fine-tuning and clear differentiation of TCM syndromes. ConclusionCurrent AIT syndrome-disease combination animal models primarily reflect the pathological features of Western medicine, with limited integration of TCM syndromes. Future research should aim to combine the syndrome characteristics of TCM with the pathological features of Western medicine, creating multi-factor and dynamic syndrome-disease models. Such models would better facilitate an experimental platform that conforms to the theories of TCM, providing more comprehensive support and guidance for the pathogenesis and treatment strategies of AIT.
3.Differences of clinical characteristics between temporal lobe epilepsy with bilateral hippocampal sclerosis and temporal lobe epilepsy with unilateral hippocampal sclerosis
Qi TAO ; Chenmin HE ; Jingjing QIU ; Yuyu YANG ; Sha XU ; Yi GUO ; Hong LI ; Yao DING ; Meiping DING ; Shuang WANG
Chinese Journal of Neuromedicine 2024;23(5):450-457
Objective:To compare the differences of clinical characteristics of temporal lobe epilepsy with bilateral hippocampal sclerosis (TLE-bHS) with those of temporal lobe epilepsy with unilateral hippocampal sclerosis (TLE-uHS).Methods:A retrospective analysis was performed. Forty-eight patients with confirmed TLE-bHS enrolled in Epilepsy Center, Department of Neurology, Second Affiliated Hospital, Medical School of Zhejiang University from January 2013 to January 2022 were chosen, and 101 patients with confirmed TLE-uHS admitted to our hospital at the same time period were selected as controls. Clinical data such as onset age, disease course, past medical history, seizure frequency, anti-seizure medications, video EEG and neuropsychological test results, and outcomes were analyzed.Results:Compared with the TLE-uHS group, the TLE-bHS group had higher male proportion, elder onset age, shorter disease course, higher seizure frequency, more types of past and currently used anti-seizure medications, lower proportion of autonomic nerve with aura, higher proportion of no aura at onset, higher proportion of slow head background movement in video EEG, and lower memory quotient, verbal memory scores and non-verbal memory scores, with significant differences ( P<0.05); the differences in ratio of past medical history and ratio of distributions of regions with interictal epileptiform abnormalities between the 2 groups were statistically significant ( P<0.05): the TLE-bHS group had significantly higher proportion of previous intracranial infection/encephalitis and higher ratio of bilateral temporal epileptiform abnormalities than the TLE-uHS group, while the TLE-uHS group had significantly higher proportion of patients with febrile convulsion history and higher ratio of unilateral temporal epileptiform abnormalities ( P<0.05). Only 10 patients (20.8%) in the TLE-bHS group received non-drug therapy, including anterior temporal lobectomy in 3 patients (Engel grading I in postoperative follow-up for 2 years), neuroregulatory therapy in 4, and ketogenic diet in 4; of the 55 patients (54.5%) in the TLE-uHS group who underwent anterior temporal lobectomy, 48 patients (87.3%) had Engel grading I, 1 patient (1.8%) had grading II, 4 (7.3%) had grading III, and 2 (3.6%) had grading IV after 2 years of follow-up. Conclusion:Differences in onset age, disease course, past medical history, seizure frequency, anti-seizure medications, and video EEG and neuropsychological test results can help to discriminate patients with TLE-bHS or with TLE-uHS.
4.An automatic evaluation study for anterior located ciliary body of primary angle-closure glaucoma based on deep learning
Yuyu CONG ; Weiyan JIANG ; Jian ZHU ; Biqing ZHENG ; Yanning YANG
Chinese Journal of Experimental Ophthalmology 2024;42(12):1134-1141
Objective:To explore the clinical application value of a deep learning algorithm-based ultrasound biomicroscopy (UBM) image analysis system for primary angles-closure glaucoma (PACG) anterior located ciliary body.Methods:A diagnostic test study was conducted.A total of 2 132 UBM images from 726 eyes of 378 PACG patients who underwent UBM examination were collected at Renmin Hospital of Wuhan University from August 2022 to December 2023.The dataset was divided into a training set of 1 599 images and a test set of 533 images, and a deep learning algorithm was employed to construct a model.An additional 334 UBM images from 101 eyes of 69 PACG patients treated at Huangshi Aier Eye Hospital were selected to conduct external testing.A separate set of another 110 UBM images were selected for a human-machine competition to compare the accuracy and speed between anterior located ciliary body evaluation system and three senior ophthalmologists.Furthermore, eight junior ophthalmologists assessed the 110 UBM images independently without and with the assistance of the model, and the differences between the two evaluations were analyzed to assess the assisstance effect of the model.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY-2022-K109).Results:The model achieved an accuracy of 93.43% for anterior located ciliary body identification in the internal test set, with a sensitivity of 84.30% and a specificity of 97.78%.The model also performed well on the external test set with an accuracy of 92.81%.In the human-machine competition, the model's accuracy was comparable to that of the senior ophthalmologists and outperformed two of the three senior ophthalmologists.The average total time of the three senior ophthalmologists was 726.73 seconds, approximately 12.47 times longer than the model's 58.30 seconds.With model assistance, the diagnostic accuracy of the eight junior ophthalmologists was 86.71%, which was significantly higher than 76.25% without model assistance ( χ2=-7.550, P<0.001).And the image evaluation time was (714.91±213.82)seconds, which was significantly lower than (987.90±238.56)seconds without model assistance ( t=2.774, P<0.05). Conclusions:The UBM image analysis system based on a deep learning algorithm demonstrates high accuracy in diagnosing anterior located ciliary body in PACG and provides a strong support for the UBM image recognition training of junior ophthalmologists.
5.Effects of targeting modification on intracellular transportation of PEG-PCL micelles in human cervical cancer cells
Jinjin YANG ; Qinghua YU ; Lingbo YU ; Yadong ZHANG ; Dongqin LIANG ; Yuyu SUN ; Huiyun WANG ; Yanan CUI
China Pharmacy 2024;35(12):1431-1436
OBJECTIVE To study the effects of transferrin-targeting peptide T7 (7pep) on intracellular transportation of polyethylene glycol-polycaprolactone (PEG-PCL) micelles in human cervical cancer HeLa cells. METHODS Using coumarin-6 (C6) as fluorescent indicator probe, both coumarin-6 (C6)-loaded PEG-PCL (PEG-PCL-C6) micelles and 7pep-modified PEG- PCL (7pep-PEG-PCL-C6) micelles were prepared by film-dispersion method. The particle size, polydispersity index and appearance morphology were compared between two types of micelles; the real-time uptake of two types of micelles by HeLa cells was compared, and the colocalization of two types of micelles with early endosomes (EE), endocytic recycling compartments (ERC) and late endosomes (LE) after entry into the cells was observed. RESULTS The particle sizes of PEG-PCL-C6 and 7pep-PEG-PCL- C6 micelles were(75.0±2.3)and(82.0±1.5)nm; the polymer dispersity indexes were 0.17±0.20 and 0.17±0.32, respectively, with a regular spherical appearance. The colocalization results showed that entry speed and amount of 7pep-PEG-PCL-C6 micelles were significantly faster/more than those of PEG-PCL-C6 micelles. 7pep-PEG-PCL-C6 micelles entered EE faster than PEG-PCL-C6 micelles, while PEG-PCL-C6 micelles entered ERC at a faster rate than 7pep-PEG-PCL-C6 micelles, and both PEG-PCL-C6 micelles and 7pep-PEG-PCL-C6 micelles tended to accumulate gradually in LE; Pearson coefficient, signal overlap ratio, and colocalization ratio of 7pep-PEG-PCL-C6 micelles with LE were significantly lower 60 minutes after entering the cell than those 30 minutes after entering the cell (P<0.05 or P<0.01). CONCLUSIONS Targeting 7pep modification can increase the entry speed and amount of PEG-PCL-C6 micelles, and also alter their intracellular transportation behavior.
6.Current Status of Outcome Indicators in Randomized Controlled Trials of Traditional Chinese Medicine for Treating Chronic Atrophic Gastritis
Jie ZHANG ; Yaxi SHANG ; Qingrui YANG ; Yuyu LEI ; Huan CHEN ; Cailing LI ; Yu KANG ; Xiaoquan DU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):193-202
ObjectiveThis paper aims to analyze the current status of outcome indicators in randomized controlled trials (RCT) of traditional Chinese medicine (TCM) for treating chronic atrophic gastritis (CAG), so as to provide references for constructing the core outcome set (COS) of TCM in the treatment of CAG. MethodChina National Knowledge Infrastructure (CNKI), Wanfang, VIP, SinoMed, PubMed, Embase, and Cochrane Library databases were searched for RCTs of TCM in the treatment of CAG in the last five years. The risk of bias of included studies was evaluated, and the selection status of outcome indicators was statistically analyzed. ResultA total of 150 RCTs were included, with a sample size of 44-398 cases. 164 outcome indicators were reported, with an application frequency of 1 229 times. The outcome indicators were classified into seven indicator domains according to functional attributes, followed by physical and chemical examination (69.41%), TCM syndrome (12.69%), symptoms and signs (11.15%), safety indicators (5.37%), quality of life (0.65%), long-term prognosis (0.65%), and economic evaluation (0.08%). According to the statistical analysis, there were problems in the selection of outcome indicators in RCTs of TCM for treating CAG, including various indicators, non-standard name reports, unclear primary and secondary indicators, random combination of subjective and objective indicators, neglected patient report outcome indicators, missing long-term prognosis and economic indicators, insufficient reporting of safety indicators, and inconsistent measurement tools and measurement time points. ConclusionIn the past five years, there have been many problems in the selection of outcome indicators in RCTs of TCM for treating CAG. It is necessary to actively promote the construction of the COS of TCM in the treatment of CAG and promote the high-quality development of clinical research of TCM.
7.Syndrome Differentiation-based Treatment of Diarrhea-predominant Irritable Bowel Syndrome with Chinese Medicine via 5-HT Signaling Pathway: A Review
Qingrui YANG ; Zeyu HU ; Yuyu LEI ; Xinzhu LI ; Huan CHEN ; Wei CUI ; Haitao LIU ; Xiaoquan DU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):250-259
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a chronic functional bowel disorder characterized by abdominal pain and diarrhea, with visceral hypersensitivity and abnormal gastrointestinal dynamics as the pathophysiological basis. The brain-gut interaction plays a role in pain-related functional gastrointestinal disorders, especially IBS-D. 5-Hydroxytryptamine (5-HT), as an important brain-gut peptide regulating gastrointestinal function, affects brain activity, gastrointestinal motility, pain perception, mucosal inflammation, and immune response through brain-gut interaction and is associated with the occurrence and development of IBS-D. In recent years, traditional Chinese medicine (TCM) has shown great potential to mitigate gastrointestinal symptoms and improve the quality of life with its holistic view and treatment based on syndrome differentiation. Studies have shown that TCM treats IBS-D by regulating the 5-HT signaling pathway. With a focus on syndrome differentiation in TCM, this paper systematically describes the efficacy and mechanism of TCM in treating different TCM syndromes of IBS-D via the 5-HT signaling pathway, aiming to provide a scientific basis for TCM treatment of this disease.
8.Coptidis Rhizoma Crude Polysaccharide and Berberine Synergistically Restore Intestinal Mucosal Barrier Damage in Ulcerative Colitis
Mingsong XUE ; Yuyu ZHENG ; Yufeng ZHANG ; Quan TAO ; Ye YANG ; Dengke YIN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(13):71-76
ObjectiveTo investigate the synergistic effect of Coptidis Rhizoma crude polysaccharide (CCP) and berberine (BBR) in treating ulcerative colitis (UC) model mice. MethodThirty male BALB/c mice were randomized into five groups. Except the 6 mice in the normal group, the rest were given 5% dextran sodium sulfate in their daily drinking water to establish the UC model. After modeling, the mice were administrated with corresponding agents by gavage once daily for 4 days: BBR (100 mg·kg-1) group, BBR (100 mg·kg-1) + low-dose (22.8 mg·kg-1) CCP group, BBR (100 mg·kg-1) + high-dose (45.6 mg·kg-1) CCP group. The mice in the model group and normal group were administrated with the same volume of normal saline. At the end of the experiment, the mice were sacrificed for the collection of colon, and the expression of tight junction proteins zonula occluden-1 (ZO-1), Claudin-1, and Occludin in colon tissue was detected by Western blot. With the normal group as the control, the disease activity index (DAI) score, colon length, colon histomorphology, and expression levels of tight junction proteins in other groups were evaluated. ResultCompared with the normal group, the modeling down-regulated the protein levels of ZO-1, Claudin-1, and Occludin (P<0.01). Compared with the model group, BBR did not significantly change the protein level of Claudin-1 and up-regulated those of ZO-1 and occludin (P<0.01). The expression levels of Claudin-1, ZO-1, and Occludin were up-regulated in BBR + CCP groups (P<0.01). The expression levels of tight junction proteins in BBR + CCP groups were significantly higher than those in the BBR group (P<0.05). ConclusionThe administration of CCP combined with BBR can effectively ameliorate intestinal mucosal barrier damage in the mice with UC.
9.New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.
Yuyu ZHU ; Zijun OUYANG ; Haojie DU ; Meijing WANG ; Jiaojiao WANG ; Haiyan SUN ; Lingdong KONG ; Qiang XU ; Hongyue MA ; Yang SUN
Acta Pharmaceutica Sinica B 2022;12(11):4011-4039
Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.
10.Celastrol targets adenylyl cyclase-associated protein 1 to reduce macrophages-mediated inflammation and ameliorates high fat diet-induced metabolic syndrome in mice.
Yuyu ZHU ; Ning WAN ; Xinni SHAN ; Guoliang DENG ; Qiang XU ; Hui YE ; Yang SUN
Acta Pharmaceutica Sinica B 2021;11(5):1200-1212
Metabolic syndrome is a clustering of metabolic disorder with unclear molecular mechanism. Increasing studies have found that the pathogenesis and progression of metabolic syndrome are closely related to inflammation. Here, we report celastrol, a traditional Chinese medicine, can improve high fat diet-induced metabolic syndrome through suppressing resistin-induced inflammation. Mechanistically, celastrol binds to adenylyl cyclase associated protein 1 (CAP1) and inhibits the interaction between CAP1 and resistin, which restrains the cyclic adenylate monophosphate (cAMP)-protein kinase A (PKA)-nuclear factor kappa-B (NF-

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