1.Ameliorating effects of tetrahydrocurcumin and its nano-preparations on lipopolysaccharide-induced depression in mice
Hui Tan ; Yuanping Li ; Jingyuan Meng ; Tengteng Ma ; Yan Yang ; Zhengmao Yang ; Jiaqing Ma ; Jianping Xie ; Ying Guo
Acta Universitatis Medicinalis Anhui 2025;60(1):79-86
Objective :
To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN).
Methods :
Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays.
Results :
Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01).
Conclusion
Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.
2.Development and validation of a quality appraisal tool for case reports in traditional Chinese medicine using the Delphi method
Duoting TAN ; Hao LIANG ; Yipin YU ; Jin GUO ; Liqin ZHONG ; Zhixi HU
Digital Chinese Medicine 2025;8(2):137-146
Objective:
To develop a quality appraisal tool for case reports in traditional Chinese medicine (TCM) based on their characteristics.
[Methods]:
An extensive literature search was conducted in Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (CSTJ), focusing on expert consensus statements and checklists for TCM case reports. Relevant items were extracted, and a Delphi method involving 34 experts was used in two rounds to rate each item on a 5-point Likert scale. Items were screened based on measures of central tendency and coordination (including total score, mean score, percentage of items rated as unimportant, and coefficient of variation). The weighted average method was used to determine item weights and construct the appraisal tool. Internal consistency was assessed using Cronbach’s α coefficient. The finalized tool was pilot-tested by two reviewers independently appraising 20 case reports, with an additional four reviewers evaluating 5 of these cases to compare inter-rater consistency.
Results:
A total of 9 513 articles were retrieved, and 96 items from 25 articles were extracted. After two rounds of the Delphi method, 27 items across 10 domains were retained. The Cronbach’s α coefficient was 0.72 in the first round (acceptable range), and 0.96 in the second round, indicating strong internal consistency. The tool was piloted by six reviewers, achieving a kappa value of 0.663 and a Kendall’s coefficient of concordance of 0.845, demonstrating high consistency among reviewers.
Conclusion
The developed TCM case report quality appraisal tool, consisting of 27 items in 10 domains, offers a scientific and reliable means of assessing the quality of TCM case reports. The tool showed high consistency and practical utility, and its application is expected to enhance the standardization, scientific rigor, and evidence quality of TCM case reports, facilitating the integration of traditional medical knowledge with modern evidence-based standards.
3.Mechanism of Xiayuxue Tang in Inhibiting Hepatocellular Carcinoma Cells by Regulating YAP1/SIRT5 Signaling Axis to Mediate Succinate Metabolism and Succinylation
Linzhu LU ; Qianqian GUO ; Xuefei TIAN ; Bin CHEN ; Nianhua TAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):52-61
ObjectiveTo investigate the inhibitory effects and mechanisms of Xiayuxue Tang (XYXT) on hepatocellular carcinoma cells through the regulation of succinate metabolism and succinylation modification. MethodsXYXT-medicated serum was prepared. The effects of different concentrations of succinate on the proliferation of HepG2 and MHCC97H cells were observed using the cell counting kit-8 (CCK-8) assay, and the experimental concentrations for subsequent tests were determined. Further CCK-8 assays were performed to evaluate the effects of XYXT-medicated serum of different concentrations (5%, 10%, and 15%) on cell proliferation. Flow cytometry, scratch test, and Transwell assay were employed to analyze the effect of 10% XYXT-medicated serum on the cell cycle, migration, invasion, and apoptosis. The changes in succinate metabolism and succinylation modification were examined based on succinate content assays, succinate dehydrogenase (SDH) activity detection, and western blot. The expressions of Yes-associated protein 1 (YAP1) and sirtuin 5 (SIRT5) were detected via Real-time PCR and western blot. Molecular docking was applied to validate the binding between XYXT’s main components and target proteins. ResultsCompared with the control group, 1-2 mmol·L-¹ succinate significantly promoted HepG2 and MHCC97H cell proliferation (P<0.01). XYXT-medicated serum (5%, 10%, and 15%) markedly inhibited the proliferation of both cell lines compared with the blank group (P<0.05, P<0.01). Treatment with 10% XYXT-medicated serum arrested the cell cycle at the stage prior to DNA synthesis (G0/G1) (P<0.01), suppressed migration (P<0.01) and invasion (P<0.05, P<0.01), and promoted apoptosis of HepG2 and MHCC97H cells (P<0.01). Co-treatment with XYXT and succinate reversed the inhibitory effects of XYXT on proliferation, migration, and invasion of HepG2 and MHCC97H cells (P<0.05, P<0.01). The proportion of cells at G0/G1 phase decreased (P<0.01), and the apoptosis rate decreased (P<0.01). In terms of succinate metabolism, compared with the blank serum group, the 10% XYXT-medicated serum reduced succinate levels of HepG2 and MHCC97H cells (P<0.05, P<0.01), enhanced SDH activity (P<0.01), and downregulated succinylation modification. In terms of YAP1/SIRT5 pathway, compared with the blank serum group, the 10% XYXT-medicated serum significantly downregulated the mRNA and protein expressions of YAP1 in HepG2 and MHCC97H cells (P<0.05, P<0.01) while significantly upregulated the mRNA and protein expressions of SIRT5 (P<0.05, P<0.01). Molecular docking confirmed that there was a good binding ability between YAP1 and SIRT5, as well as between XYXT's main active components and YAP1 and SIRT5. ConclusionXYXT suppresses hepatocellular carcinoma cells by modulating the YAP1/SIRT5 signaling axis to intervene in succinate metabolism and succinylation modification.
4.Influencing factors of bladder management practices in patients with spinal cord injury
Zhirong LUO ; Xuyan GUO ; Qi XUE ; Xiao TAN ; Yunhua JI ; Fuxun ZHANG ; Yong JIAO ; Bo ZHANG
Journal of Modern Urology 2025;30(4):284-289
Objective: To explore the key factors affecting the selection and effectiveness of bladder management modalities in patients with spinal cord injury,so as to provide reference for the optimization of individualized bladder management strategies. Methods: The clinical and follow-up data of 78 patients with spinal cord injury treated in our hospital during Jan.1,2013 and Dec.31,2022 were retrospectively analyzed.The distribution of bladder management modalities among different grades of injuries was analyzed. Bowker symmetry test was used to evaluate the difference between bladder management modalities at discharge and at the end of follow-up. Multiple linear regression was used to explore the influencing factors of bladder management effects. Plotting Kaplan-Meier survival curves were adopted to calculate the median time of changes in bladder management. Results: At discharge,there were 9 cases of self-catheterization,19 cases of intermittent catheterization,22 cases of reflexive voiding,26 cases of long-term catheterization,and 2 cases using urinary collector.At the end of follow-up,there were 15 cases of self-catheterization,8 cases of intermittent catheterization,34 cases of reflexive voiding,14 cases of long-term catheterization,and 7 cases using urinary collector.There was a significant difference between the modalities of bladder management at discharge and at the end of follow-up (χ
=21.43,P=0.018).Multiple linear regression showed a significant decrease of 8.60 in the total neurogenic bladder symptom score (NBSS) for grade D injuries compared with grade A injuries (P=0.026). The median time to bladder management change was 7.93 months (95%CI:5.44-9.44), with approximately 50% of patients experiencing a change in bladder management within 8 months after discharge. Conclusion: The modalities of bladder management changed significantly after discharge.The grade of injury was a key factor affecting the effectiveness of bladder management.Higher grade was associated with worse effectiveness of bladder management.
5.Analysis of the causal relationship between gut microbiota and bladder cancer with Mendelian randomization
Xuyan GUO ; Zhirong LUO ; Qi XUE ; Yunhua JI ; Xiao TAN ; Yong JIAO
Journal of Modern Urology 2025;30(5):400-407
Objective: Previous observational studies have confirmed the correlation between gut microbiota and bladder cancer,but the causal relationship is still unclear.This study aimed to explore the causal relationship between them with Mendelian randomization. Methods: Genetic variation summary data of 211 gut microbiota and bladder cancer genome-wide association studies (GWAS) were obtained from the MiBioGen Consortium and Finngen database.Single nucleotide polymorphisms (SNPs) closely related to these studies were screened as instrumental variables.The causal relationship between gut microbiota and bladder cancer were analyzed with inverse variance weighting (IVW),MR-Egger,weighted median,maximum likelihood,robust adjustment feature score and MR-PRESSO,with IVW as the primary analysis method.Additionally,sensitivity analysis was used to test the heterogeneity (Cochran Q) and horizontal pleiotropy (MR-Egger intercept term and global test from MR-PRESSO estimator) to ensure the robustness of the results. Results: The IVW results indicated that Lachnospiraceae UCG004 (OR:1.42),Desulfovibrionales (Order) (OR:1.48),Eubacterium ruminantium group (OR:1.33),Olsenella (OR:1.24),Ruminococcaceae UCG002 (OR:1.39),Ruminococcaceae UCG005 (OR:1.42) and Ruminococcaceae UCG013 (OR:1.64) significantly increased the risk of bladder cancer.Conversely,Bacteroidetes (Phylum) (OR:0.61),Eubacterium brachy group (OR:0.80),Ruminococcaceae UCG004 (OR:0.73),Rikenellaceae (Family) (OR:0.67),Lachnospiraceae ND3007 group (OR:0.47), Adlercreutzia (OR:0.73) and an unknow genus (OR:0.75) were associated with a reduced risk of bladder cancer.Sensitivity analyses did not reveal any heterogeneity or horizontal pleiotropy. Conclusion: This study reveals the causal role of 14 gut microbiota in the pathogenesis of bladder cancer,among which Lachnospiraceae UCG004,Desulfovibrionales (Order),Eubacterium ruminantium group,Olsenella,Ruminococcaceae UCG002,Ruminococcaceae UCG005 and Ruminococcaceae UCG013 are risk factors for bladder cancer,while Bacteroidetes (Phylum),Eubacterium brachy group,Ruminococcaceae UCG004,Rikenellaceae (Family),Lachnospiraceae ND3007 group,Adlercreutzia and an unknown genus are the protective factors.
6.Early clinical outcomes of the domestic KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation: A single-arm, prospective, single-group target value clinical trial
Tong TAN ; Bingqi FU ; Peijian WEI ; Nianjin XIE ; Haozhong LIU ; Xiaoyi LI ; Shengwen WANG ; Haijiang GUO ; Jian LIU ; Jimei CHEN ; Jian ZHUANG ; Huiming GUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):269-275
Objective To summarize and analyze the preliminary clinical outcomes of the KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation (DMR). Methods This study was a single-arm, prospective, single-group target value clinical trial that enrolled patients who underwent the KokaclipTM transcatheter edge-to-edge repair (TEER) system for DMR in the Department of Heart Surgery of Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute from June 2022 to January 2023. Differences in the grade of mitral regurgitation (MR) during the perioperative and follow-up periods were compared, and the incidences of adverse events such as all-cause death, thoracotomy conversion, reoperation, and severe recurrence of MR during the study period were investigated. Results The enrolled patient population consisted of 14 (50.0%) females with a mean age of 70.9±5.4 years. Twenty-eight (100.0%) patients were preoperatively diagnosed with typeⅡ DMR, with a prolapse width of 12.5 (11.0, 16.1) mm, a degree of regurgitation 4+ leading to pulmonary venous reflux, and a New York Heart Association cardiac function class≥Ⅲ. All patients completed the TEER procedure successfully, with immediate postoperative improvement of MR to 0, 1+, and 2+ grade in 2 (7.1%), 21 (75.0%), and 5 (17.9%) patients, respectively. Mitral valve gradient was 2.5 (2.0, 3.0) mm Hg. Deaths, thoracotomy conversion, or device complications such as unileaflet clamping, clip dislodgement, or leaflet injury were negative. Twenty-eight (100.0%) patients completed at least 3-month postoperative follow-up with a median follow-up time of 5.9 (3.6, 6.8) months, during which patients had a mean MR grade of 1.0+ (1.0+, 2.0+) grade and a significant improvement from preoperative values (P<0.001). There was no recurrence of ≥3+ regurgitation, pulmonary venous reflux, reoperation, new-onset mitral stenosis, or major adverse cardiovascular events. Twenty-two (78.6%) patients’ cardiac function improved to classⅠorⅡ. Conclusion The domestic KokaclipTM TEER system has shown excellent preliminary clinical results in selected DMR patients with a high safety profile and significant improvement in MR. Additional large sample volume, prospective, multicenter studies, and long-term follow-up are expected to validate the effectiveness of this system in the future.
7.Modified Xiaoyaosan Alleviates Depression-like Behaviors by Regulating Activation of Hippocampal Microglia Cells in Rat Model of Juvenile Depression
Jiayi SHI ; Yun XIANG ; Ziyang ZHOU ; Dahua WU ; Feng QIU ; Chang LEI ; Hongyu ZENG ; Kaimei TAN ; Hongqing ZHAO ; Dong YANG ; Yuhong WANG ; Pengxiao GUO ; Xiuli ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):46-56
ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction (Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex) in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control, model, fluoxetine, and low-, medium-, and high-dose (5.36, 10.71, 21.42 g·kg-1, respectively) Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress (CUMS). The sucrose preference test (SPT) was carried out to examine the sucrose preference of rats. Forced swimming test (FST) was carried out to measure the immobility time of rats. The open field test (OFT) was conducted to measure the total distance, the central distance, the number of horizontal crossings, and the frequency of rearing. Morris water maze (MWM) was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase (iNOS, the polarization marker of M1 microglia) and CD206 (the polarization marker of M2 microglia). Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS, CD206, pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] and anti-inflammatory cytokines (IL-4 and IL-10) in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group, the model rats showed a reduction in sucrose preference (P<0.05), an increase in immobility time (P<0.05), decreased motor and exploratory behaviors (P<0.05), and weakened learning and spatial memory (P<0.05). In addition, the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β, IL-6, and TNF-α (P<0.05). Compared with the model group, Baihuan Xiaoyao decoction increased the sucrose preference value (P<0.05), shortened the immobility time (P<0.01), increased the motor and exploratory behaviors (P<0.05), and improved the learning and spatial memory (P<0.01). Furthermore, the decoction down-regulated the positive expression and protein level of iNOS, lowered the levels of TNF-α, IL-1β, and IL-6 (P<0.01), promoted the positive expression of CD206, and elevated the levels of IL-4 and IL-10 (P<0.01) in the hippocampus of the high dose group. Moreover, the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value (P<0.01), shorter immobility time (P<0.01), longer central distance (P<0.01), stronger learning and spatial memory (P<0.01), higher positive expression and protein level of iNOS (P<0.01), lower levels of TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), lower positive expression and mRNA level of iNOS (P<0.05), and higher levels of IL-4 and IL-10 (P<0.05, P<0.01) than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus.
9.Preparation and Application of Polypyrrole Conductive Hydrogels in Biomedical Field
Kun-Yu REN ; Ru-Min FU ; Yu TIAN ; Xin-Chang KANG ; Lei ZHOU ; Guo-Xin TAN
Chinese Journal of Analytical Chemistry 2024;52(1):1-12
Hydrogel is a kind of material with high water content,good biocompatibility and extracellular matrix-like property,among which polypyrrole(PPy)conductive hydrogels have both physical characteristics and excellent conductivity of hydrogels themselves.Its conductivity can be used to detect electrical signals generated in biological systems and provide electrical stimulation to regulate the activities and functions of cells and tissues.These characteristics make it widely used in the biomedical field.The recent progress of PPy conductive hydrogels in biomedical field was reviewed in this paper.In terms of classification,according to the cross-linking mechanism of PPy and hydrogel matrix,the non-covalent cross-linked PPy conductive hydrogels and covalent cross-linked PPy conductive hydrogels were divided.The applications of PPy conductive hydrogels in the biomedical field(Skin damage repair,nerve repair,myocardial repair and flexible sensing,etc.)were mainly introduced,and the development trend and challenges of PPy conductive hydrogels in the biomedical field were discussed.
10.Clinicopathological and prognostic characteristics of intestinal inflammatory myofibroblastic tumor in middle-aged and elderly patients
Minhua TAN ; Wei CHEN ; Jinhui GUO ; Yongjian ZHOU ; Weihua LEI ; Mushi LIU ; Dong SHEN ; Hong SHEN
The Journal of Practical Medicine 2024;40(4):503-507
Objective To investigate the clinicopathological and prognostic characteristics of intestinal inflammatory myofibroblastic tumours(IMT)in middle-aged and elderly patients.Methods The clinical,pathologi-cal morphology,immunophenotype and follow-up results of 5 cases of intestinal IMT in middle-aged and elderly patients were retrospectively analyzed.Results 4 cases of IMT occurred in the right half colon and 1 in the ileum.Most patients(3/5)had a history of intestinal injury,starting the digestive tract symptoms and increased leukocytes.The tumor tissue was composed of fusiform myofibroblasts and fibroblasts arranged in storiform pattern,with an infiltrative growth pattern,accompanied by a large number of lymphocytes and plasma cells infiltration,collagen formation and myxedema.One case was atypically large and deformed.Immunophenotype:vimentin(5cases),SMA(5 cases),desmin(3 cases),ALK(3 cases),CK(2 cases)were positive.Caldesmon,CD34,β-catenin,MC,CD117,DOG1,S-100,BCL-2,CD99,CD68 were negative,and Ki-67 proliferation index was 1.28%to 10.01%.All the 5 cases underwent complete tumor resection and were followed up for 48.5 to 133 months.Among them,1 patient aged 83 was considered to have tumor recurrence 27 months after surgery.The other patient survived 122 months without tumor and died of other causes.All the others survived without tumor and were in good condition.Conclusion(1)Intestinal IMT in the middle-aged and elderly people in this group was more common in the right half colon,and most of them had a history of intestinal injury,first gastrointestinal symptoms and elevated white blood cells;(2)Vimentin and SMA were positive at the same time,and ALK was more positive;(3)4/5 patients had good surgical resection,and 1/5 patients could relapse 2~3 years after surgery;old age,ALK-positive,Ki67 up to 10%,atypia may be an important risk factor for intestinal IMT recurrence in the elderly,of which ALK-positive patients may have a recurrence risk of 1/3.


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