1.Anti-ulcerative Colitis Mechanism of Huaihuasan and Active Ingredients of Its Component Drugs: A Review
Xueli XU ; Jiacheng GU ; Zuowu XI ; Yanyan WANG ; Kexin DENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):295-305
Huaihuasan, first recorded in Experiential Prescriptions for Universal Relief (Pu Ji Ben Shi Fang), is a classic prescription for the treatment of ''hematochezia due to intestinal wind''. In 2018, it was included by the National Administration of Traditional Chinese Medicine as one of the first 100 classic prescriptions. This formula consists of four ingredients, i.e., Sophorae Flos, Platycladi Cacumen, Schizonepetae Spica, and Aurantii Fructus. It is known for its ability to clear the intestines, dispel wind, cool the blood, and stop bleeding. In modern clinical practice, Huaihuasan, often with modifications, is widely used to treat various digestive tract diseases, including ulcerative colitis (UC), with significant long-term effects. UC is a chronic, non-specific inflammatory bowel disease. Currently, Western medicine primarily treats UC with glucocorticoids, aminosalicylates, and immunosuppressants, which have good short-term efficacy but numerous adverse reactions, high recurrence rates, and the need for lifelong medication. Modern clinical studies have shown that Huaihuasan can significantly improve symptoms of UC, such as abdominal pain and diarrhea, reduce disease activity scores (Sutherland), promote intestinal mucosal healing, alleviate anxiety and depression, and significantly improve the quality of life of patients. Pharmacological studies have shown that the main active components of Huaihuasan include quercetin, rutin, kaempferol, naringenin, and volatile oils. These compounds exert their effects by inhibiting inflammatory responses and protecting the intestinal mucosal barrier. They also exhibit antioxidant properties and regulate various signaling pathways, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), nuclear factor-κB (NF-κB), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and the KRAS-regulated mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway. These multi-target pathways improve UC symptoms, inhibit inflammation-cancer transition, and help maintain intestinal homeostasis. However, the precise mechanism of action has not yet been systematically elucidated. This paper reviews the research progress on Huaihuasan and main ingredients from its component drugs, focusing on their effects against UC. It also discusses current research limitations and suggests strategies for improvement, aiming to provide a reference for further studies on Huaihuasan in the treatment of UC and the development of new drugs.
2.Improvement of Depression-like Behavior of Depression Model Mice by Sinisan via Regulating GSK-3β/A20/C/EBPβ to Inhibit Activation of Microglia
Hongyun CHEN ; Dongying YANG ; Huiqing LIAO ; Yanyan ZENG ; Linke PAN ; Shasha BAI ; Di DENG ; Yafei SHI ; Rong ZHANG ; Lei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):16-23
ObjectiveTo investigate the antidepressant effect of Sinisan (SNS) by regulating glycogen aynthase kinase-3β (GSK-3β)/tumor necrosis factor alpha-induced protein 3(A20)/CCAAT enhancer binding protein β(C/EBPβ) to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group, model group, fluoxetine group (5.0 mg·kg-1), low-dose Sinisan group (4.9 g·kg-1), medium-dose Sinisan group (9.8 g·kg-1), and high-dose Sinisan group (19.6 g·kg-1), with 12 mice in each group. After one week of adaptive feeding, chronic unpredictable mild stress (CUMS) was performed to establish the depression model. In the fifth week, drug treatment was conducted for four weeks. In the ninth week, behavioral tests were performed, including sucrose preference test (SPT), open field test (OPT), elevated plus maze (EPM) test, and forced swimming test (FST). Western blot was used to detect the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), nitric oxide synthase (iNOS), GSK-3β, A20, and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 (Iba1) and cluster of differentiation 68 (CD68) in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS, compared with the normal group, the mice in the model group had a significantly reduced sucrose preference rate (P<0.01), and the activity in the central area of the OPT was significantly reduced (P<0.01). The activity in the open arm area of the EPM test was significantly reduced (P<0.05), and the immobility time of FST was increased (P<0.01). The expression levels of inflammatory proteins IL-1β, IL-6, and iNOS were increased (P<0.01), and the fluorescence co-localization index of Iba1 and CD68 was increased (P<0.05). The protein expression levels of GSK-3β and C/EBPβ were significantly increased (P<0.05, P<0.01). After four weeks of SNS intervention, compared with the model group, the mice in the SNS group had significantly increased sucrose preference rate (P<0.01), significantly increased activities in the central area and the open arm area in the OPT and the EPM test (P<0.05), and significantly reduced immobility time in the FST (P< 0.01). The protein expression levels of IL-1β, IL-6, and iNOS were significantly decreased (P<0.05), and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group (P<0.05). The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased (P<0.01), and that of A20 was significantly increased (P<0.01). ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.
3.Experimental study to construct the three-dimensional scaffold of rabbit cartilage-shedding cells and evaluate their compatibility with stem cells
Juju XU ; Yanyan XIE ; Zhiyi GUO ; Yukai MA ; Linhong WANG ; Meirong YANG ; Zhaoling DENG ; Baolai HUA ; Zhenyu YAN
Acta Laboratorium Animalis Scientia Sinica 2024;32(8):1012-1022
Objective To prepare decellularized scaffolds from rabbit cartilage at various concentrations and assess their physicochemical properties and compatibility with stem cells to provide an experimental basis for cartilage repair.Methods Bone marrow mesenchymal stem cells(BMSCs)were cultured using the Percoll density gradient separation method,and this was followed by flow cytometric analysis and testing of their osteogenic and chondrogenic differentiation capabilities.Cartilage pieces were excised from rabbit knees and hip joints and subjected to physical crushing,repeated freeze-thaw cycles,and mixed enzymatic digestion for decellularization.To compare and observe the physicochemical properties of the decellularized scaffolds at different concentrations,three groups of scaffolds(labelwd A,B,and C)were designed with concentrations of 100%,50%and 30%,with three replicates each.Third-generation PKH26-labeled BMSCs were seeded onto optimally concentrated scaffolds and cultured for 1 week to observe cell growth.Results Flow cytometry detected BMSC surface antigens with positive expression of CD44 and CD90 and negative expression of CD45.Osteogenic induction stained with alizarin red showed red calcific nodules,and chondrogenic induction stained with alcian blue showed blue cartilaginous nodules.No apparent cell morphology was observed in the three groups of scaffolds stained with hematoxylin-eosin,and toluidine blue.There was a significant difference in DNA concentration between decellularized samples and non-decellularized scaffolds(P<0.05).The content of glycosaminoglycans was slightly lower than the normal values.Significant differences were observed between the three groups of scaffolds in terms of pore size,water absorption,porosity,tensile strength,and Young's modulus(P<0.05).After co-cultivation of stem cells with the scaffolds,cell adhesion was found to be good.Conclusions Percoll density gradient separation can obtain high-purity rabbit BMSCs,and the mixed decellularization method is superior.Group B scaffolds were the most suitable for tissue-engineered cartilage repair.BMSCs cultured in vitro grew well on Group B scaffolds.
4.Research progress in TACE-based combination therapy for primary hepatocellular carcinoma
Zhengfang XIAO ; Youbing ZHENG ; Feiyan DENG ; Siqian ZHENG ; Hongwei SUN ; Yanyan LIU ; Ligong LU
Journal of Interventional Radiology 2024;33(6):688-692
Liver cancer is a prevalent and highly malignant cancer worldwide,with 90%of cases being hepatocellular carcinoma,presenting a significant risk to human health.As early-stage liver cancer often lacks specific manifestations,most patients with liver cancer are already in the middle and late stage of the disease when liver cancer is diagnosed,thus,missing the opportunity for optimal radical treatment.However,the exploration of the treatment for middle and advanced primary hepatocellular carcinoma has never ceased.In recent years,transarterial chemoembolization(TACE)has been included in the standard treatment regimens for primary hepatocellular carcinoma.With the advancement of multidisciplinary comprehensive treatment,various treatment options to reduce the burden of liver cancer lesion with satisfactory therapeutic results have been reported and have been widely used in clinical practice,e.g.hepatic artery infusion chemotherapy(HAIC),targeted therapy,and immunotherapy in combination with TACE,which have significantly improved the overall survival of patients with liver cancer.This paper aims to make a comprehensive review about the latest progress of combination use of TACE and other therapies in reducing tumor burden and improving patient survival in the treatment of primary hepatocellular carcinoma,and to summarize the key issues in combination therapy that require more in-depth research.(J Intervent Radiol,2024,33:688-692)
5.Curative effect of wide pedicled double-vessel flap of posterolateral calf in repair of soft tissue defect in hind foot
Xiaowen DENG ; Lijun LYU ; Jie SHI ; Peng LIU ; Chuangbin LI ; Wenbo LI ; Wei WANG ; Yaqiang ZHANG ; Peisheng SHI ; Yun XUE ; Yanyan CHANG ; Qiuming GAO
Chinese Journal of Microsurgery 2023;46(1):32-38
Objective:To explore the curative effect of wide pedicled with double-vessel flap of posterior lateral calf in repair of soft tissue defect in hind foot.Methods:From January 2018 to June 2021, 12 patients with soft tissue defects on hind foot were reconstructed with double-vessel flaps pedicled perforator of peroneal artery and sural nerve nutrient vessels in the Department of Trauma Orthopaedics, No.940 Hospital of Chinese People's Liberation Army Joint Service Support Force. The patients were 8 males and 4 females, aged 9-45(27.17±12.14) years old. Time after injury to admission was 6-24(10.17±4.80) hours. Six patients were with simple soft tissue defects, 2 with tendon defects, 3 with bone defects and 1 with postoperative infection due to an open fracture. The sizes of soft tissue defect ranged from 4 cm×5 cm-8 cm×12 cm. Soft tissue defects were reconstructed by transfer of posterolateral calf flaps, and the bone defects were repaired by phase I or phase II bone grafts or antibiotic cement and membrane induction according to the wound surface. For larger bone defects, stage-II bone transport was carried out to restore the length of the hind foot. Defects of Achilles tendon were reconstructed by direct suture or tendon transposition. Foot functions were evaluated by American Orthopaedic Foot and Ankle Surgery(AOFAS) ankle-posterior sufficient scale, visual analogue scale(VSA) score and flap healing. All patients were included in postoperative follow-up regularly through outpatient clinic or via WeChat.Results:All 12 patients had postoperative follow-up that lasted for 6-24(12.92±6.22) months. One flap developed dark purple colour with swelling at the distal end of the flap 3 days after surgery. It eventually healed after removed some sutures from the pedicle together with blood-letting on the flap surface. Three flaps developed local infection, and they were cured after debridement, dressing change and the use of sensitive antibiotics. The remaining 8 patients had achieved good appearance of flaps and normal ankle function. According to AOFAS, scores of ankle-posterior sufficiency scale increased from 14-45(25.25±5.42) before surgery up to 65-96(75.92±7.73) at the final follow-up. Of the 12 patients, 8 were in excellent, 2 in good and 2 in fair. The VAS scores decreased from 5-8(6.55±1.13) before surgery down to 0-4(1.55±1.37) at the final follow-up. The difference had statistics significance( P<0.01). All patients had satisfactory recovery of ankle function, with the extension at 15-20 degrees and plantar flexion of 30-40 degrees. The donor site healed well and all skin grafts survived. Conclusion:The double-vessel flap pedicled with perforating branch of peroneal artery and nutrient vessels of sural nerve can be used for reconstruction of soft tissue defect of hind foot. It achieved good surgical effects with reliable blood supply, smooth venous return, strong anti-infection ability, satisfactory appearance at donor site and flap itself, as well as a good recovery of foot function.
6.A deep learning prediction model for early evaluation of treatment response to neoadjuvant chemotherapy based on ultrasound images of breast cancer patients
Feihong YU ; Yanyan ZHANG ; Shumei MIAO ; Cuiying LI ; Jing DENG ; Bin YANG ; Xinhua YE ; Yun LIU ; Hui WANG
Chinese Journal of Ultrasonography 2023;32(7):614-620
Objective:To investigate the feasibility of deep learning radiomics model in the prediction of neoadjuvant chemotherapy (NAC) response in breast cancer based on ultrasound images at an early stage.Methods:Between January 2018 and June 2021, 218 patients with breast cancer who underwent NAC were enrolled in the retrospective study. All patients received a full cycle of NAC before surgery and underwent standard ultrasound examination before NAC and after the second cycles of NAC. Of all the patients, 166 patients came from institution 1 (the First Affiliated Hospital of Nanjing Medical University) were allocated into a primary cohort.Based on the architecture of Resnet 50 convolutional neural, a deep learning prediction model was built.Further validation was performed in an external testing cohort ( n=52) from institution 2 (General Hospital of Eastern Theater Command, PLA). The clinical model was constructed using independent clinical variables. To evaluate the predictive performance, areas under the curve (AUCs) of these models and two radiologists were compared by using the DeLong method. Results:The Resnet 50 model predicted the response of NAC with accuracy. The deep learning model, achieving an AUC of 0.923 (95% CI=0.884-0.962) in the primary cohort and an AUC of 0.896 (95% CI=0.807-0.980) in the test cohort, outperformed the clinical model and also performed better than two radiologists′ prediction (all P<0.05). Furthermore, the two radiologists achieved a better predictive efficacy (AUC 0.832 and 0.808 for radiologists 1 and 2, respectively) when assisted by the DL model (all P<0.01). Conclusions:The deep learning radiomics model is able to predict therapy response in the early-stage of NAC for breast cancer patients, which could guide clinicians and provide benefit for timely treatment strategy adjustment.
7.Recommendations for prescription review of commonly used anti-seizure medications in treatment of children with epilepsy
Qianqian QIN ; Qian DING ; Xiaoling LIU ; Heping CAI ; Zebin CHEN ; Lina HAO ; Liang HUANG ; Yuntao JIA ; Lingyan JIAN ; Zhong LI ; Hua LIANG ; Maochang LIU ; Qinghong LU ; Xiaolan MO ; Jing MIAO ; Yanli REN ; Huajun SUN ; Yanyan SUN ; Jing XU ; Meixing YAN ; Li YANG ; Shengnan ZHANG ; Shunguo ZHANG ; Xin ZHAO ; Jie DENG ; Fang FANG ; Li GAO ; Hong HAN ; Shaoping HUANG ; Li JIANG ; Baomin LI ; Jianmin LIANG ; Jianxiang LIAO ; Zhisheng LIU ; Rong LUO ; Jing PENG ; Dan SUN ; Hua WANG ; Ye WU ; Jian YANG ; Yuqin ZHANG ; Jianmin ZHONG ; Shuizhen ZHOU ; Liping ZOU ; Yuwu JIANG ; Xiaoling WANG
Chinese Journal of Applied Clinical Pediatrics 2023;38(10):740-748
Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.
8.Characteristics of ocular involvement in Chinese patients with hereditary transthyretin amyloidosis
Yanbing FENG ; Wenqing WENG ; Yanyan HE ; Yibo WU ; Yixing ZHU ; Chao DENG ; Yongwei ZHU
Chinese Journal of Ocular Fundus Diseases 2023;39(9):792-798
Hereditary thyroxine protein amyloidosis (ATTRv) is one of the most common forms of systemic and ocular amyloidosis, characterized by autosomal dominant inheritance, incomplete penetrance, and diverse manifestations. ATTRv deposition leads to visual impairment and even irreversible visual loss, which has a negative impact on the quality of life of patients. The diagnostic rate of pathological examination and genetic testing in ATTRv patients is low, and the detection rate of systemic amyloid lesions is low. We need to increase our awareness of this disease and gain a deeper understanding of its systemic manifestations and corresponding examination methods; genetic testing is conducted on the proband's family to investigate the relationship between different gene mutations and eye manifestations. In the future, multidisciplinary consultations can be conducted to jointly diagnose and treat patients with ATTRv eye involvement, conducting large-scale and long-term follow-up studies on the early clinical characteristics, treatment plans, efficacy, possible complications, and early prevention, in order to improve clinical diagnosis rate, reduce misdiagnosis rate, and improve patient prognosis.
9.Effect of ultra-early nursing intervention on postoperative cognitive impairment in patients with cerebral hemorrhage
Junfang MA ; Yanyan MENG ; Haihong LIU ; Hua DENG ; Xiaohong CHEN ; Yixuan ZHAI
Chinese Journal of Modern Nursing 2022;28(21):2921-2925
Objective:To explore the effect of ultra-early nursing intervention on postoperative cognitive behavior and prognosis of patients with cerebral hemorrhage.Methods:Using the convenient sampling method, a total of 82 patients with cerebral hemorrhage who were admitted to the First Affiliated Hospital of Zhengzhou University from March 2019 to January 2021 were selected as the research objects. According to the random number table method, they were divided into the control group and the observation group, with 41 cases in each group. Both groups received surgical treatment. The control group received routine nursing, while the observation group received ultra-early nursing intervention on the basis of routine nursing when vital signs were stable 48 hours after operation. The differences in neurological function (National Institutes of Health Stroke Scale, NIHSS) , cognitive function (Loewenstein Occupational Therapy Cognitive Assessment, LOTCA) and activity of daily living scores were compared between the two groups at 48 hours and 1 month after operation.Results:The NIHSS score at 1 month after surgery in both groups was lower than that at 48 hours after surgery and the NIHSS score at 1 month after surgery in observation group was lower than that in control group ( P<0.05) . The LOTCA dimension scores of the two groups at 1 month after operation were higher than those at 48 hours after operation and the LOTCA dimension scores of the observation group at 1 month after operation were higher than those of the control group ( P<0.05) . The activity of daily living scores of the two groups at 1 month after operation were higher than those at 48 hours after operation and the activity of daily living score of the observation group at 1 month after operation was higher than that of the control group , the differences were statistically significant ( P<0.05) . Conclusions:Ultra-early nursing intervention can effectively promote the recovery of postoperative neurological function and cognitive function in patients with cerebral hemorrhage and improve the activity of daily living of patients.
10.Role and mechanism of microRNA-92b-3p in esophageal squamous cell carcinoma analyzed by weighted gene co-expression network analysis
Wanpeng WANG ; Chenghong FU ; Qidi ZHANG ; Chengshi WANG ; Zhongxiang HE ; Yun GU ; Yanyan ZHANG ; Weijun DENG ; Juan PU
Chinese Journal of Digestion 2019;39(6):390-396
Objective To screen the critical genes related to the development of esophageal squamous cell carcinoma ( ESCC ) by weighted gene co-expression network analysis ( WGCNA ) and to verify by experiments.Methods Gene expression data of ESCC were downloaded from gene expression omnibus (GEO) database based on gene chip platform ( GPL) 570, GPL571, GPL96/97 or GPL14613 platform, respectively. Meanwhile, the obtained differentially expressed genes together with gene expression data of 81 ESCC patients from the cancer genome atlas ( TCGA ) and clinical data were analyzed by WGCNA to set up co-expression networks including mRNA and microRNA ( miRNA ) . The expression of miRNA in ESCC tissues and paracancerous tissues was examined by quantitative real-time polymerase chain reaction ( RT-PCR ) .And the expression of target protein Kruppel like factor 4 ( KLF4 ) and desmocollin 2 ( DSC2 ) were detected by immunohistochemistry .After ESCC cell line ECA-109 cells were transfected with miRNA-92b-3p mimic, cell cycle was tested by flow cytometry ,the cell invasion and migration ability was measured by Transwell chamber assay and scratch-wound assay.The expression of KLF4 and DSC2 was observed by confocal laser scanning microscopy and Western blotting .The target genes were verified by luciferase assay .T-test, rank sum test, chi-square test and Pearson correlation analysis were performed for statistical analysis .Results A total of 4023 differential expression gene ( DEG) and 328 differential expression miRNA ( DEM) were screened and 11 gene modules were set up by WGCNA .Among them, the brown modules were negatively associated with tumor grade and T stage (r=-0.340 and -0.268, P=0.002 and 0.016).Meanwhile, has-miR-92b and the potential target genes KLF4 and DSC2 were all in the brown module .Furthermore, the results of RT-PCR showed the expression of miRNA-92b-3p in ESCC tissues was higher than that in paracancerous tissues (3.052(1.652, 5.371) vs.0.985(0.558, 2.032)), and the difference was statistically significant (Z=-4.021,P<0.01). The results of immunohistochemistry demonstrated that the positive rates of KLF 4 and DSC2 in ESCC tissues were 43.3%(13/30) and 20.0%(6/30), respectively, which were lower than those of paracancerous tissues (70.0%(21/30) and 63.3%(19/30)), and the differences were statistically significant (χ2 =4.344 and 1.589, both P<0.05).After ECA-109 cells were transfected with miRNA-92b-3p mimics, the percentage of cells at G0/G1 phase decreased ((63.71 ±2.83)%vs.(54.62 ±4.00)%) and the percentage of cells at the S phase and G2/M phase increased ((31.81 ±2.88)%vs.(41.20%±2.87)%, and (3.87 ±1.75)%vs. (8.10 ±1.71)%, respectively), and the differences were statistically significant (t =3.215, 4.000 and 2.998;P=0.032, 0.016 and 0.040).The invasion and migration ability of the cells were significantly improved (79.67 ±27.54 vs.280.33 ±46.18, (69.72 ±3.91)% vs.(84.90 ±5.25)%), and the differences were statistically significant (t=6.465 and 4.019, P=0.003 and 0.016).The results of Western blotting indicated that, compared with control mimic group , the expression of KLF4 and DSC2 was both dramatically downregulated after transfected with miRNA-92b-3p mimics transfected (1.00 ±0.23 vs.0.42 ±0.03, 1.00 ±0.20 vs.0.55 ± 0.21), and differences were statistically significant (t=4.470 and 5.493, P=0.042 and 0.032).The results of luciferase assay demonstrated that miRNA-92b-3p could directly bind KLF4 and DSC2. Conclusion WGCNA is an efficient systemic biological approach by which miRNA-92b-3p is identified as a new cancer-promoting gene .

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