1.Protective effect and mechanism of glycosides of cistanches on Parkinson's disease mouse via the Nrf2/HO-1 pathway
Zhipeng XU ; Xingyu WANG ; Shuqing YAO ; Jiayi ZHANG ; Chaoran XU ; Fengyan LIU ; Dongsheng HUO
Acta Universitatis Medicinalis Anhui 2026;61(9):1603-1610
ObjectiveTo investigate the neuroprotective effect of glycosides of cistanches (GCs) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) model mice and its potential mechanism. MethodsForty mice were randomly divided into control group, PD group, GCs group and levodopa (L-DOPA) group, with 10 mice in each group. The control group received intraperitoneal injection of normal saline, while the other groups were intraperitoneally injected with MPTP (30 mg/kg) once daily for 5 consecutive days. After model establishment, the control group and PD group were intragastrically administered normal saline, and the GCs group and L-DOPA group received intragastric administration once daily for 28 consecutive days, at doses of 100 mg/kg and 50 mg/kg, respectively. The open field test and rotarod test were used to evaluate motor function. Immunohistochemistry was performed to detect the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra of the midbrain. Transmission electron microscopy was adopted to observe the ultrastructure of mitochondria in the substantia nigra. Biochemical assays were used to determine the levels of glutathione (GSH), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and reactive oxygen species (ROS) in substantia nigra tissues. Western blot was applied to detect the protein expression of TH, nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap-1) and heme oxygenase-1 (HO-1) in substantia nigra tissues. ResultsCompared with the control group, mice in the PD group exhibited markedly impaired motor function, significantly decreased T-SOD activity, obvious reductions in the number of TH-positive neurons and GSH content, as well as elevated MDA and ROS levels in the substantia nigra (P<0.01). Compared with the PD group, mice in the GCs group showed improved motor function, increased T-SOD activity, higher number of TH-positive neurons and elevated GSH content, accompanied by decreased MDA and ROS levels (P<0.05). In the control group, mitochondria in the substantia nigra displayed normal morphology without obvious blurred membrane structures or vacuolar degeneration. The PD group presented mitochondrial swelling, disordered cristae and vacuolar changes, whereas these mitochondrial pathological alterations were alleviated in the GCs group. Compared with the control group, the protein levels of TH, Nrf2 and HO-1 were significantly downregulated, while Keap-1 protein expression was markedly upregulated in the PD group (P<0.01). Compared with the PD group, the GCs group showed significant upregulation of TH, Nrf2 and HO-1 protein levels and a notable reduction in Keap-1 protein level (P<0.05). ConclusionGCs ameliorate motor dysfunction and attenuate dopaminergic neuronal and mitochondrial damage in MPTP-induced PD model mice. These effects may be associated with modulation of Nrf2/HO-1 pathway-related protein expression, enhancement of antioxidant capacity, and alleviation of oxidative stress.
2.Clinical Efficacy of Modified Zhishi Daozhi Decoction on Metabolic Associated Fatty Liver Disease Due to Dampness-heat and Stasis Obstruction
Ya'nan QU ; Yijing LI ; Wenping ZHANG ; Chaoran BI ; Yanjing LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(22):189-197
ObjectiveTo evaluate the clinical efficacy of modified Zhishi Daozhi decoction in treating patients with metabolic associated fatty liver disease (MAFLD) due to dampness-heat and stasis obstruction. MethodsA randomized controlled trial design was adopted, with patients diagnosed with MAFLD due to dampness-heat and stasis obstruction treated in the Department of Endocrinology, Metabolism, and Gastroenterology at the Third Affiliated Hospital of Changchun University of Chinese Medicine between November 2023 and November 2024 as the study subjects. A total of 126 patients who met the inclusion criteria were randomized into an observation group and a control group, with 63 patients in each group. The observation group was administered the granule preparation of modified Zhishi Daozhi decoction, while the control group received Xuezhikang capsules orally. Both groups underwent a 12-week treatment course. The two groups before and after treatment were compared in terms of obesity indicators [body weight, body mass index (BMI), waist circumference (WC), weight-adjusted waist circumference index (WWI), and waist-to-hip ratio (WHR)], lipid indicators [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)], liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT)], liver ultrasound imaging, traditional Chinese medicine (TCM) symptom scores, and Patient-Reported Outcome (PRO) scale scores at follow-up. Results① After treatment, the body weight, BMI, and levels of TC, TG, and LDL-C declined in both groups (P<0.05, P<0.01), and the observation group demonstrated larger reductions in BMI, WC, LDL-C (P<0.05), and WHR (P<0.01). The levels of ALT, AST, and GGT declined in the observation group after treatment (P<0.05), whereas no statistically significant differences in the three indicators were observed in the control group before and after treatment. Subgroup analysis based on normal vs. abnormal liver function revealed intergroup differences only in the abnormal liver function cohort. After treatment, the observation group demonstrated greater reductions in ALT (P<0.01) and AST (P<0.05) than the control group. ② The total response rate of liver ultrasound imaging was 79.24% (42/53) in the observation group and 62% (31/50) in the control group. Post-treatment comparison showed that the observation group (χ2=21.311, P<0.01) achieved greater alleviation of fatty liver disease severity. ③ The total response rate of TCM syndrome was 94.34% (50/53) in the observation group and 66% (33/50) in the control group, with the observation group demonstrating superior efficacy (χ2=26.78, P<0.01). Compared with the control group post-treatment, the observation group showed enhanced reductions in the total TCM symptom score (P<0.01) and individual symptom scores of rib distension and pain, sticky and unsmooth stools, obesity with abdominal distension, sticky sensation in the mouth, and yellowish-red urine (P<0.01). ④ After treatment, the PRO score improved in both groups (P<0.01), and the increase was larger in the observation group (P<0.01), primarily reflected in the physiological dimension (P<0.01). ConclusionModified Zhishi Daozhi decoction shows definite efficacy in treating MAFLD patients with the syndrome of dampness-heat and stasis obstruction, with effects of alleviating abdominal obesity and regulating blood lipids. Additionally, it positively impacts patients quality of life, as evidenced by the changes in TCM symptom and PRO scores.
3.Mechanisms by Which Paraventricular Hypothalamic Nucleus Participates in the Acupuncture Treatment of Diseases
Ziyou BAI ; Chaoran ZHANG ; Yiqing RAO ; Qishun LIN ; Lingling YU ; Jiabao LIU ; Xianghong JING ; Man LI
Journal of Sichuan University (Medical Sciences) 2025;56(1):26-34
In recent years,a growing body of research has demonstrated that acupuncture can be used to effectively treat a diverse range of diseases,including functional gastrointestinal disorders,cardiovascular diseases,as well as anxiety and depression,through the modulation of the paraventricular hypothalamic nucleus(PVN).Acupuncture may exert its therapeutic effect either by modulating specific neurons within the PVN,such as corticotropin releasing hormone(CRH)neurons,or by regulating the release of hormones,such as oxytocin(OXT)and vasopressin(VP),and the activity of neural circuits associated with the PVN.This review summarizes the mechanisms by which PVN is involved in acupuncture treatment,including its regulatory mechanisms in gastrointestinal diseases,cardiovascular diseases,and negative emotions and pain.Future research should be conducted to further explore the precise mechanisms by which acupuncture regulates PVN to treat diseases,focusing on clarifying the specific processes of signaling pathway transduction,and exploring the specific effects of acupunture of different acupoint combinations and stimulation frequencies and intensity on PVN.
4.Co-culture with human umbilical cord-derived mesenchymal stem cells ameliorates allergic inflammation in mouse lung tissues
Yanghe HAO ; Xiuli LIU ; Chaoran ZHAO ; Chengshuo WANG ; Luo ZHANG ; Ming WANG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(5):299-303
OBJECTIVE To explore the therapeutic effect of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)in mouse model of allergic lung inflammation.METHODS hUC-MSCs were isolated and cultured from umbilical cord of healthy neonates.The expression of MSC cell surface markers were assessed by flow cytometry in the fifth generation of hUC-MSCs.Mice were sensitized by intraperitoneal injection of ovalbumin and challenged via inhalation of aerosolized ovalbumin to establish an allergic airway inflammation model.The same dose of normal saline was used in the control group.After 14 days of nebulization,lung tissues and bronchoalveolar lavage fluid(BALF)were collected from the mice.Hematoxylin and eosin staining and Luminex multiplex assay were performed to assess the levels of allergic inflammation.Lung tissues were minced,homogenized,and digested into single-cell suspensions for cell culture.hUC-MSCs or human nasal epithelial cells were co-cultured with mouse lung cells at a ratio of 1:5 or 1:10(cell number ratio).After 18 hours,the supernatants were collected,and Luminex multiplex assay was performed to assess the expression of inflammatory cytokines interleukin-5(IL-5)and IL-6.RESULTS Cultured hUC-MSCs showed an elongated spindle-shaped morphology.The positive markers CD105,CD73,and CD90 showed positive rates of>95%respectively,while the negative markers CD45,CD34,and CD11b exhibited positive rates of<2%respectively.Compared with the controls,the allergic mice showed significant infiltration of eosinophils in the peribronchial regions of lung tissues,and increased expression levels of IL-5(P<0.01)and IL-6(P<0.05)in BALF.Compared with the control group,mouse lung cells co-cultured with hUC-MSCs significantly decreased the levels of IL-5 and IL-6 in the supernatant(both P<0.05 in 1∶5 group and 1∶10 group).CONCLUSION Co-culture with hUC-MSCs can significantly ameliorate allergic inflammation in lung tissue of mouse model,indicating the therapeutic potential of hUC-MSCs in airway allergic inflammation.
5.Grey-scale Reversed T1-weighted MRI for Detecting Structural Lesions of the Sacroiliac Joint in Patients with Axial Spondyloarthritis
Ximeng LI ; Wenjuan LI ; Ke ZHANG ; Chaoran LIU ; Yunfei ZHU ; Yingying ZHAN ; Mingzhu LIANG ; Guobin HONG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(3):412-419
[Objective]To analyze the value of grey-scale reversed T1-weighted(rT1)MRI in the detection of structur-al lesions of the sacroiliac joint(SIJ)in patients with axial spondyloarthritis(ax-SpA).[Methods]Fifty-two ax-SpA pa-tients who underwent both MRI and CT in our hospital within a week from February 2020 to December 2022 were retrospec-tively included.Both sacral and iliac side of each SIJ on oblique coronal images were divided into anterior,middle and pos-terior portion.Two radiologists reviewed independently three groups of MRI including T1-weighted imaging(T1WI),rT1 and T1WI+rT1 images to evaluate the structural lesions like erosions,sclerosis and joint space changes in each of the 6 re-gions of the SIJ.One of the radiologist did the evaluation again one month later.CT images were scored for lesions by a third radiologist and served as the reference standard.Intra-class correlation coefficients(ICC)were calculated to test the inter-and intra-reader agreement for the assessment of SIJ lesions.A Friedman test was performed to compare the lesion results of MRI and CT image findings.We examined the diagnostic performance[accuracy,sensitivity(SE)and specifici-ty]of different groups of MRI in the detection of lesions by using diagnostic test.A McNemar test was used to compare the differences of three groups of MRI findings.[Results]CT showed erosions in 71 joints,sclerosis in 65 and joint space changes in 53.Good inter-and intra-reader agreements were found in three groups of MRI images for the assessment of le-sions,with the best agreement in T1WI+rT1.There were no difference between T1WI+rT1 and CT for the assessment of all lesions,nor between rT1 and CT for the assessment of erosions and joint space changes(P>0.05).T1WI+rT1 yielded better accuracy and SE than T1WI in detection of all lesions(Accuracy erosions:90.3%vs 76.9%;SE erosions:91.6%vs 76.1%;Accu-racy sclerosis:89.4%vs 80.8%;SE sclerosis:84.6%vs 73.9%;Accuracy joint space changes:86.5%vs 73.1%;SE joint space changes:84.9%vs 60.4%;P<0.05).rT1 yielded better accuracy and SE than T1WI in detection of erosions and joint space changes(Accuracy erosions:87.5%vs 76.9%;SE erosions:88.7%vs 76.1%;Accuracy joint space changes:85.6%vs 73.1%;SE joint space changes:83.0%vs 60.4%;P<0.05).[Conclusions]In the detection of SIJ structural lesions in ax-SpA,rT1 improves the diagnostic perfor-mance and T1WI+rT1 is more superior to others.
6.Research progress of integrated stress response in central nervous system diseases
Aili LAN ; Gang LIU ; Chaoran WU ; Hong LIAO
Journal of China Pharmaceutical University 2024;55(2):194-201
Abstract: Integrated stress response is an adaptive response produced by eukaryotic cells after intracellular and extracellular stimulation. The activation of integrated stress response inhibits the translation of most proteins, yet it can promote the translation of certain proteins to cope with complex cellular microenvironment changes. A large number of studies have found that in a variety of nervous system diseases, the integrated stress response can be activated by stress signals of disease-related cells and participates in the occurrence and progression of diseases through processes such as learning and memory consolidation, myelin regeneration and synaptic plasticity. This article summarizes the role, mechanism and possible drug targets of integrated stress response in central nervous system diseases and discusses the potential of pharmacological methods to regulate integrated stress response in the treatment of central nervous system diseases, in order to provide reference for pathological research on and drug development for central nervous system diseases.
7.The role of group Ⅰ mGluRs in acute brain injury and advances in drug research
Fengsheng Hou ; Chaoran Wu ; Gang Liu ; Hong Liao
Acta Universitatis Medicinalis Anhui 2024;59(11):2052-2058
Abstract
Glutamate receptors are widely distributed in the central nervous system(CNS) and participate in the delivery of excitatory neurotransmitters, including ionotropic glutamate receptors and metabotropic glutamate receptors. Metabotropic glutamate receptors(mGluRs) regulate neuronal excitability and synaptic plasticity, and are classified into group Ⅰ, Ⅱ and Ⅲ. The roles of group Ⅰ mGluRs in psychiatric and neurodegenerative diseases have been extensively studied, especially in the pathological progression of acute brain injury. Several studies have shown that group Ⅰ mGluRs can be involved in eliminating inflammatory damage, suppressing cell apoptosis, regulating neural network disorders, and promoting brain function recovery after acute brain injury. Therefore, group Ⅰ mGluRs have the potential to be effective targets for the treatment of acute brain injury. This paper reviews the distribution and function of group Ⅰ mGluRs in CNS, the pathological role in acute brain injury, and explore the potential of the development of drugs targeting group Ⅰ mGluRs.
8.Umbilical cord-derived mesenchymal stem cells inhibit macrophage M1 polarization
Xiaoxu WANG ; Chaoran LI ; Hui WANG ; Chunjuan YANG ; Fengxia LIU ; Donghua XU
Chinese Journal of Immunology 2024;40(4):673-679
Objective:To explore effect of human umbilical cord mesenchymal stem cells(hUC-MSCs)on macrophage M1/M2 polarization.Methods:hUC-MSCs were co-cultured with pTHP-1 cells which were macrophage-like cells induced by PMA and tran-scriptome sequencing data were analyzed.Differentially expressed genes were screened and analyzed by GO and KEGG enrichment analysis.Effect of hUC-MSCs on pTHP-1 cells proliferation was analyzed by cell proliferation assay(CCK-8 and EdU).Flow cytometry was used to verify influence of hUC-MSCs on relative contents of inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10 in pTHP-1 cells which were interaction with LPS.Effect of hUC-MSCs on M1/M2-related molecular phenotype of pTHP-1 cells was studied by qRT-PCR and flow cytometry.Results:Transcriptome sequencing data analysis showed that M1-related genes TNF-α(P<0.05)and HLA-DRA(P<0.01)decreased to a great extent and M2-related gene ARG1(P<0.05)increased to a great extent in pTHP-1 cells after co-culture with hUC-MSCs,suggesting that hUC-MSCs inhibited macrophage M1 polarization.GO and KEGG analysis showed that these dysregulated genes regulated inflammation and immune response.hUC-MSCs inhibited proliferation of pTHP-1 cells,reduced content of TNF-α and increased content of IL-10(P<0.001).qRT-PCR and flow cytometry showed mRNA expressions of HLA-DRA(P<0.05)and CD68(P<0.01)and CD14+CD11c+M1 macrophage percentage were down-regulated,while mRNA expressions of CD163(P<0.001),CD206(P<0.001)and CD14+CD163+M2 macrophage percentage were significantly up-regulated in pTHP-1 cells after co-culture with hUC-MSCs.Conclusion:hUC-MSCs inhibit macrophage polarization to M1 and promote polariza-tion to M2 in vitro.
9.Application of indocyanine green fluorescence imaging technology in laparoscopic radical resection of colorectal cancer
Jianzhan LIN ; Wei YAN ; Wenlong GUAN ; Linfeng YU ; Chaoran LIU ; Anlong ZHU
Chinese Journal of Digestive Surgery 2024;23(6):876-882
With the increasing maturity of laparoscopic surgery, laparoscopic radical resec-tion of colorectal cancer has been widely used in colorectal surgery. Accurate localization of colorectal tumors and surgical margins in the absence of tactile sensation during surgery, ensuring sufficient blood flow perfusion at the anastomotic site and effectively reducing the incidence of anastomotic leakage have become barriers to the development of laparoscopic radical resection of colorectal cancer. The application of indocyanine green fluorescence imaging (ICG-FI) technology is expected to provide feasible solutions to the above-mentioned problems. Through this technology, accurate localization of colorectal tumors, evaluation of blood supply to the anastomotic site, lymphatic system imaging, detection of colorectal liver metastases, and protection of pelvic autonomous nerves and ureters can be achieved during laparoscopic surgery, thereby further improving the surgical quality of laparoscopic radical resection of colorectal cancer. However, the clinical application of ICG-FI technology in colorectal surgery is relatively short, which is still in the stage of exploration and experience accumulation, and there are few guideline or consensus available for reference. Therefore, the authors aim to provide a reference for the clinical application of this technology by reviewing and summarizing relevant literature based on different application types of ICG in colo-rectal cancer surgery.
10.Myocarditis induced by the combination of disitamab vedotin and toripalimab
Chaojin LIN ; Guilin HE ; Nuan JIA ; Suichen CHEN ; Chaoran LIU
Adverse Drug Reactions Journal 2024;26(3):190-192
A 68-year-old female patient with invasive urothelial carcinoma received immune treatments with disitamab vedotin 120 mg and toripalimab 240 mg intravenously on the first day, and 14 days was a cycle. Nineteen days after the first medication, the patient complained of lower back muscle soreness. Laboratory tests showed creatine kinase (CK) 1 079 U/L and CK-MB 33 U/L. The 2nd cycle of immunotherapy was suspended and prednisone 20 mg orally once daily was given. Five days later, the patient felt chest tightness, and laboratory tests showed CK 3 366 U/L, CK-MB 91 U/L, lactic dehydrogenase 518 U/L, myoglobin 1 282 μg/L, high-sensitivity troponin T 0.068 μg/L, and N-terminal pro-brain natriuretic peptide 148 ng/L. Myocarditis caused by the combination of disitamab vedotin and toripalimab was considered, referring to the cardiac color Doppler ultrasound examination. Prednisone was switched to IV infusion of methylprednisolone 160 mg once daily. The above laboratory test indicators gradually decreased, but the electrocardiogram showed ectopic heart rhythm. Amiodarone was added. After 11 days of methylprednisolone treatment by IV infusion, methylprednisolone 20 mg orally once daily was given, which was gradually reduced and discontinued finally. Four days later, the patient′s laboratory indicators and electrocardiogram showed no abnormalities in the re-examination.


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