1.Characteristics of STAT Family Association with Breast Cancer and Intervention Effect of Traditional Chinese Medicine
Lin GUO ; Xiaoran WANG ; Sizhe LIU ; Yuanxin ZHANG ; Shuo TIAN ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):225-233
As the pace of society increases and lifestyles change, the incidence and mortality rates of breast cancer continue to rise. Targeted therapies are now promising in the treatment of breast cancer, and a variety of protein targets have been identified to play an important role in the development of breast cancer. Among them, signal transducer and activator of transcription (STAT) proteins constitute a crucial group that serves as important targets for transducing cellular transcriptional information, which can regulate downstream cell proliferation, apoptosis, cell migration, invasion, angiogenic factors, etc. and then affect the progression of breast cancer. The STAT family is closely associated with the inflammatory response to tumors and plays a landmark role in tumor development as well as in diagnosis and prognosis. The "inflammation-cancer" transformation refers to the process in which the inflammatory microenvironment caused by uncontrolled inflammation promotes normal cells to become cancerous. According to the theory of Chinese medicine, "heat toxicity" in "cancer toxicity" corresponds to inflammation, which is closely related to tumor development. As a major link associated with the inflammatory response, the STAT family has a promising role in the development and treatment of a variety of tumors, but its relevance to breast cancer remains inadequately explored. Chinese medicine has been shown to have good efficacy in the prevention and treatment of breast cancer, and some current studies have shown that the active ingredients and compounds of Chinese medicine have certain intervention effects on breast cancer-related STAT proteins, but there has not been a systematic review. In order to better sort out and summarize the studies on the effects of Chinese herbal medicines based on the STAT family interventions in breast cancer, this paper reviewed the studies on Chinese herbal medicines acting on the STAT family in recent years, aiming to provide new ideas for clinical applications in breast cancer and to provide thoughts for the development of STAT protein-based drugs.
2.Effects of silver needle-thermal conduction therapy on skeletal muscle mitochondria and silent information regulator homolog 3 expression in a rat model of myofascial pain syndrome
Yue WANG ; Yuhan ZHANG ; Jiayi WANG ; Yuanxin HUANG ; Chunxin WO ; Caixia WANG ; Peiran ZHOU ; Lin WANG
Chinese Journal of Tissue Engineering Research 2024;28(14):2202-2208
BACKGROUND:Clinical studies have found good analgesic effects of silver needle-thermal conduction therapy in patients with myofascial pain syndrome,but the exact mechanism remains unclear. OBJECTIVE:To observe the effect of silver needle-thermal conduction therapy on silent information regulator homolog 3(SIRT3)changes and mitochondrial ultrastructure in a rat model of myofascial pain syndrome. METHODS:Twenty rats were randomly selected from 26 Sprague-Dawley rats and were subjected to percussion combined with motor fatigue for replicating the rat model of myofascial pain syndrome.Sixteen rats that were successfully modeled were randomly divided into model group and silver needle-thermal conduction therapy group(treatment group),with eight rats in each group.The remaining rats were used as controls(normal group).The treatment group was treated with silver needle-thermal conduction therapy.Mechanical withdrawal threshold and thermal withdrawal latency of rats were measured at 1 day before modeling,1 day after modeling and 14 days after treatment.Electromyographic activities of the right medial femoral muscle were measured at 14 days after treatment.The right medial femoral muscle tissue was taken for hematoxylin-eosin staining to observe the local morphology and for transmission electron microscopy to observe the mitochondrial ultrastructure.Western blot assay was performed to detect SIRT3 expression. RESULTS AND CONCLUSION:Pain threshold:The mechanical withdrawal threshold and thermal withdrawal latency of the model and treatment groups were significantly decreased compared with those in the normal group and before modeling(P<0.01).After treatment,the mechanical withdrawal threshold and thermal withdrawal latency of rats were significantly higher in the treatment group compared with the model group(P<0.01).Electromyography:The rats in the model group showed spontaneous electrical activity in the right medial femur,while the rats in the treatment group showed reduced spontaneous electrical activity,longer time frame(P<0.01)and lower wave amplitude(P<0.05)compared with the model group.Hematoxylin-eosin staining:In the normal group,rat muscle fibers arranged closely and regularly.In the model group,the muscle fibers of rats were atrophied,degenerated,and disordered in arrangement.In the treatment group,rat muscle structure disorder improved.Mitochondrial microstructure:Under the transmission electron microscope,mitochondrial structure in the normal group was normal;mitochondrial swelling with broken or disappeared cristae appeared in the model group;mitochondrial swelling in the treatment group was obviously relieved or tended to be normal.SIRT3 expression:SIRT3 expression was significantly downregulated in the model group compared with the normal group,but was significantly upregulated in the treatment group compared with the model group(P<0.05).To conclude,abnormalities in local muscle mitochondria and downregulation of SIRT3 expression suggest the presence of impaired energy metabolism in the rat model of myofascial pain syndrome.Mitochondrial changes recover and are close to normal after the silver needle-thermal conduction therapy,and the expression of SIRT3 is also upregulated close to the normal group,indicating the silver needle-thermal conduction therapy may play a therapeutic role by promoting mitochondrial repair and improving energy metabolism disorder.
3.Effects of different administration routes of chimeric antigen receptor T cells on arrhythmias in mice with myocardial infarction
Yuanxin ZHANG ; Puyuan YANG ; Penghan FU ; Xiangmeng KONG ; Xuanming YANG ; Qingyong ZHANG
Chinese Journal of Clinical Medicine 2024;31(4):612-618
Objective To investigate the therapeutic effect of chimeric antigen receptor(CAR)T cells on myocardial infarction(MI)and observe the impact of different administration routes on CAR-T cell cardiac toxicity.Methods Twenty-four SCID Beige immunodeficient mice,which successfully established a myocardial infarction model,were randomly divided into Hank's balanced salt solution(HBSS)group,CAR-TIM group,CAR-TIV group,and CAR-TIMIV group(n=6 for each group).In addition,a Sham group(n=6)was set up.The Sham group,HBSS group,CAR-TIM group,and CAR-TIMIV group were injected with HBSS or CAR-T cells via intramyocardial injection on the 7th day after modeling.The Sham group,HBSS group,CAR-TIV group,and CAR-TIMIV group were injected with HBSS or CAR-T cells via tail vein injection on the 7th day and 14th day after modeling.After 28 days of modeling,the electrical physiological indicators of the mice were observed,and the myocardial tissues were subjected to Masson staining to calculate the area of myocardial infarction.Results Compared with the Sham group,the HBSS group had significant increases in myocardial infarction size and incidence of arrhythmia(P<0.05).Compared with HBSS group,different routes of CAR-T cell therapy significantly reduced the area of myocardial infarction(all P<0.05)and significantly increased the incidence of arrhythmia(all P<0.05).There was no significant difference in the effect of CAR-TIV and CAR-TIM groups on the area of myocardial infarction and the incidence of arrhythmia.Compared with the CAR-TIV group,the area of myocardial infarction significantly reduced in the CAR-TIMIV group(P<0.05),with no significant difference in the incidence of arrhythmia between the two groups.Conclusions Intravenous and local myocardial injection of CAR-T cells can effectively reduce the myocardial infarction area but increase the incidence of arrhythmia.The mechanism needs further study.
4.Experience of home enteral nutritional support in the diagnosis and treatment of patients with high intestinal fistulae
Sijia LI ; Bingjun TANG ; Tianlei XU ; Zhuonan ZHUANG ; Qian ZHANG ; Feng WANG ; Yuanxin LI
Chinese Journal of General Surgery 2024;39(3):183-187
Objective:To explore the impact of home enteral nutrition (HEN) on the treatment strategy of patients with high position intestinal fistula.Methods:The clinical and follow-up data of 36 patients with high position intestinal fistula requiring HEN treated in Beijing Tsinghua Changgung Hospital from Jan 2021 to Sep 2023 was retrospectively analyzed.Results:Among the 36 cases, 2 had indwelling nasogastric tubes, 12 had indwelling nasojejunal nutritional tubes, and 22 had percutaneous jejunostomy. The incidence of HEN-related complications in patients was 13.9%, and there were no serious catheter complications.During HEN, high position intestinal fistula healed in 19 cases (52.8%), returned to the hospital for the next stage of intestinal fistula treatment in 11 cases (30.6%), needed to return to the hospital for nutritional support in 1 case (2.8%), and intestinal fistula aggravated to terminate HEN in 2 cases (5.6%).Conclusion:Under the management of professional team, HEN via nasogastric/jejunal nutritional tube or percutaneous jejunostomy is safe and feasible in patients with high intestinal fistula.
5.Silibinin inhibits lipogenic differentiation of 3T3-F442A adipocytes in murine through inhibition of MEK /ERK pathway and matrix metalloproteinase activity
Aiping Liu ; Tong Li ; Yaqing Cheng ; Renwen Zhang ; Yakun Ge ; Yuanxin Zhang
Acta Universitatis Medicinalis Anhui 2024;59(1):111-117
Objective :
To study the effect and mechanism of action of Silibinin on the differentiation of 3T3-F442A preadipocytes in murine.
Methods :
The effects of 0-400 μmol / L Silibinin on the proliferation of 3T3-F442A adi- pocytes at 24,48 and 72 h were detected by 3-(4,5-dimethylthiazol-2) -2,5-diphenyltetrazolium bromide ( MTT) assay,and the effects of Silibinin on the adipogenesis of 3T3-F442A adipocytes were visualized by Oil Red O stai- ning ; RT-qPCR , Western blot and ELISA assays were used to detect the effects of Silibinin on 3T3-F442A adipo- cyte differentiation-associated transcription factor CCAAT / enhancer binding protein ( C / EBP) α , C / EBP β , per- oxisome proliferator-activated receptor γ cular endothelial growth factor (VEGF) -α and VEGF receptor 2 (VEGFR-2) ,matrix metalloproteinase (MMP) -2 and MMP-9,mitogen-activated protein kinase (MEK) and phosphorylated MEK (p-MEK) ,and extracellular regu- lated protein kinase (ERK) and phosphorylated ERK (p-ERK) expression. (PPARγ) ,adipocyte protein 2 (aP2) ,adipose generation-associated vas
Results :
MTT assay showed that the cell proliferation rate of 3T3-F442A preadipocytes decreased after 100,200,and 400 μmol /L Silibinin treatment compared with the control group (P<0. 001) ; Oil Red O staining assay showed that the accumulation of red lipid droplets of the cells in the 160 μmol /L Silibinin assay group significantly decreased ; RT-qPCR assay showed that mRNA expression of C/EBPα , C/EBPβ , PPARγ , aP2,VEGF-α , VEGFR-2,MMP-2,and MMP-9 was down-reg- ulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin compared with the control group (P<0. 001) ; Western blot assay showed that protein expression of C /EBPα , C /EBPβ , PPARγ and aP2 was down-regulated in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin (P<0. 001) ,and the phosphorylation level of p-MEK/ MEK and p-ERK/ ERK proteins was down-regulated compared with the control group (P <0. 001) ; ELISA assay showed that the protein concentrations of MMP-2 and MMP-9 in the cell supernatant were down-regulated (P < 0. 001) in 3T3-F442A adipocytes treated with 160 μmol /L Silibinin.
Conclusion
Silibinin inhibited 3T3-F442A adipocyte differentiation and adipogenesis through inhibition of the MEK/ ERK pathway and matrix metalloproteinase activity.
6.Discussing the new implications of"toxins damaging brain collaterals"from the pathogenesis of acquired cerebral amyloid angiopathy
Fan ZHANG ; Jialin LIU ; Junchen JIANG ; Yuanxin ZHANG ; Junlong CHEN ; Jinmin LIU
Journal of Beijing University of Traditional Chinese Medicine 2024;47(5):598-602
Acquired cerebral amyloid angiopathy,as a cerebrovascular disease discovered in recent years,mainly spreads through iatrogenic factors.This paper focuses on acquired cerebral amyloid angiopathy and delves into the new applications and profound implications of the"toxins damaging brain collaterals"theory proposed by academician WANG Yongyan in stroke research.Starting from the perspective of"toxins damaging brain collaterals",it comprehensively analyzes the causes and pathological mechanisms of acquired cerebral amyloid angiopathy,emphasizing the importance of external toxins,latent toxins,and turbid toxins in understanding the pathogenesis of the disease.It reveals that"toxins damaging brain collaterals"is the core mechanism of acquired cerebral amyloid angiopathy.On this basis,it proposes a new connotation of"toxins damaging brain collaterals":first,"toxin"includes both internal and external toxins;second,the organic integration of"external wind theory"and"toxins damaging brain collaterals"guides the improvement of theoretical research,clinical treatment,and prevention strategies for stroke,and promotes a deeper understanding of the disease.This approach to understanding acquired cerebral amyloid angiopathy from the perspective of"toxins damaging brain collaterals"not only demonstrates the effective integration of traditional Chinese medicine theory and modern biomedical science,but also provides insights and references for the clinical diagnosis and treatment of the disease.
7.Application value of modified multivisceral transplantation in chronic intestinal pseudo-obs-truction secondary to autoimmune leiomyositis
Changzhen ZHU ; Yuanxin LI ; Zhidong ZHU ; Feng WANG ; Qian ZHANG ; Tianlei XU ; Huan LI ; Hongfang YIN
Chinese Journal of Digestive Surgery 2024;23(9):1178-1187
Objective:To investigate the application value of modified multivisceral trans-plantation (MMT) in chronic intestinal pseudo-obstruction (CIPO) secondary to autoimmune enteril leiomyositis (AEL).Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of a recipient who was admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University on February 2022 and underwent MTT for CIPO secondary to AEL were collected. The recipient was a male, aged 29 years old. Results of preoperative histopathological examination showed that there were muscle plexus and ganglion cells in the rectum, sigmoid colon, ascending colon, intrinsic muscle layer of ileum, and a small amount of submucosal layer. There was also a small amount of chronic inflammatory cell infiltration in the muscle, indicating a high possi-bility of diagnosis of neurogenic CIPO.Results:(1) Surgical situations. The operation time was 14 hours and 30 minutes, and the cold ischemia time was 9 hours and 30 minutes. The intra-operative blood product dosage included 14 U of red blood cells, 1 400 mL of fresh frozen plasma, and two therapeutic doses of platelets. (2) Postoperative histopathological examination. Results of postoperative histopathological examination showed chronic inflammation and local erosion of the small intestine and duodenal mucosa, with scattered disappearance of the focal mucosal muscle layer; There is a large infiltration of CD3 + and CD8 + lymphocytes in the lamina propria, especially in the muscularis propria. In severe lesions, there is infiltration of ribbon lymphocytes in the subserosal and muscular layers; Muscle fiber degeneration, reduction, and fibrosis. Deposition of pigment granules in the cytoplasm of smooth muscle cells; No abnormalities were found in the intermuscular, submu-cosal ganglia, and Cajal cells; Fibrosis of the serosal layer with local cellulose exudation; Chronic inflammation of the colonic mucosa, scattered and focal lymphocyte infiltration in the local muscle layer, and myositis related changes. Pathological diagnosis was secondary CIPO induced by AEL. (3) Postoperative immune rejection, recurrence and treatment. Results of colonoscopy and histopatholo-gical examination at postoperative 8 days showed acute cellular rejection. The cell count of reci-pient′s B lymphocytes, CD3 + lymphocytes, CD4 + lymphocytes, and CD8 + lymphocytes were 27.00×10 3, 373.00×10 3, 179.00×10 3 and 142.00×10 3 cell/mL, respectively. Anti-immune rejection treatment was performed using tacrolimus, rabbit anti-human thymocyte immunoglobulin, methylprednisolone mycophenolate mofetil, and monoclonal antibodies against basil. The cell count of recipient′s B lymphocytes, CD3 + lymphocytes, CD4 + lymphocytes, and CD8 + lymphocytes at postoperative 57 days were 0.72×10 3, 239.59×10 3, 89.28×10 3 and 91.53×10 3 cell/mL, respectively. Results of colonoscopy and histopathological examination at postoperative 79 days showed the recurrence of AEL. The cell count of recipient′s B lymphocytes, CD3 + lymphocytes, CD4 + lymphocytes, and CD8 + lymphocytes were 0.32×10 3, 264.92×10 3, 46.95×10 3 and 169.54×10 3 cell/mL, respectively. The tacrolimus and methylprednisolone were used for treatment. Results of colonoscopy and histopathological examina-tion at postoperative 89 days showed AEL recurrence without remission. The cell count of recipient′s B lymphocytes, CD3 + lymphocytes, CD4 + lympho-cytes, and CD8 + lymphocytes were 0.28×10 3, 187.00×10 3, 55.52×10 3 and 92.45×10 3 cell/mL, respec-tively. The tacrolimus and methylprednisolone were used for treatment. Results of colonoscopy and histopathological examination at postoperative 92 days showed the intestinal mucosa had returned to a normal state. (4) Postoperative oral feeding time and time to get rid of parenteral nutrition. The recipient began oral feeding at postoperative 28 days and eliminated parenteral nutrition at postoperative 35 days. (5) Follow-up. The recipient was discharged 114 days after surgery and as of the follow-up deadline, the graft function was good. The recipient maintained a low-fat, high sugar, and high protein diet, completely consumed orally, with a body mass index of 22 kg/m 2, and has returned to normal work. Conclusion:MMT can be used for the treatment of CIPO secondary to AEL.
8.Analysis of the Anastomosis between the Animal Model of Alopecia Areata and the Characteristics of Clinical Disease
Yuanxin ZHANG ; Xue WANG ; Lin GUO ; Shuo NAN ; Mingsan MIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(11):3744-3750
In this study,the existing animal models of alopecia areata were systematically summarized based on literature review and disease and syndrome characteristics assignment method,and the clinical anastomosis was analyzed.The results showed that cell induction and skin transplantation had a high anastomosis with the clinic,and the anastomosis was as high as 80%.The anastomosis between imiquimod cream and cyclophosphamide induced alopecia areata was 72%.C3H/HeJ mice and C57BL/6 mice were selected as the first choice in terms of the pathogenesis of alopecia areata disease,pathogenic factors,replicability,convenience and practicability of the model.Other SCID mice,B6.KM-AA mice,SD rats and BALB/c mice can be selected appropriately according to the content and period of the experimental study of alopecia areata.It is found that the existing models of alopecia areata mainly rely on Western medicine,lack of pathogenic factors of traditional Chinese medicine,and the model of combining disease and syndrome of alopecia areata is not widely used in practice.Based on this,it is suggested that the animal model of"combination of disease and syndrome"should be considered in the subsequent construction of alopecia areata model to make it more suitable for clinical characteristics of disease and syndrome.We can add the relevant indicators of different syndrome types of liver and kidney insufficiency,blood stasis and maoqiao,blood deficiency and blood heat and other pathogenic factors,and add the apparent indicators of animal mental state,diet and water intake,behavior,etc.,to improve the animal model of alopecia areata which is highly consistent with the clinical characteristics of traditional Chinese and western medicine.
9.Influence of exophthalmos on design of double eyelid incision
Zhaoyang SUI ; Cheng HUA ; Kaiping MAO ; Su LIU ; Yuanxin MIAO ; Zhenyu CHEN ; Weina ZHANG
Chinese Journal of Medical Aesthetics and Cosmetology 2023;29(2):104-108
Objective:To compare the postoperative effects of double eyelid surgery with different exophthalmos to find its influence on the surgery and necessary changes in preoperative design and during operation.Methods:A total of 50 female patients with single eyelid seeking beauty from June 2021 to March 2022 were selected from the Department of Plastic Surgery, Affiliated Hospital of Qingdao University. The ocular protrusion was measured by HETEL ophthalmostatometer before surgery. Both eyes at 12-15 mm were taken as normal group ( n=26), both eyes at 16-18 mm as mild protrusion group ( n=14) and both eyes at 19-22 mm as severe protrusion group ( n=10). All the patients were treated with double-eyelid surgery by orbital septum and unified postoperative nursing. Results:After six months of follow-up, there was no difference in eyelid width with closed eyes (all P>0.05). The width of double eyelid with open eyes in normal group was smaller than that in mild protrusion group ( F=23.23, all P<0.05), and the width of double eyelid with open eyes in mild protrusion group was smaller than that in severe protrusion group ( F=47.70, all P<0.05). There was no difference in the improvement rate of facial aesthetics among the three groups ( P>0.05). The " feeling of meet" and scar formation in the normal group were less than those in the mild protrusion group ( F=16.92, F=33.45, all P<0.05), and the " feeling of meet" and scar formation in the mild protrusion group were less than those in the severe protrusion group ( F=27.93, F=28.53, all P<0.05). The improvement rate of normal group was higher than that of mild and severe protrusion group (χ 2=7.25, 7.89, all P<0.05). There was no difference in the improvement rate between the mild and severe protrusion groups ( P>0.05). Conclusions:In clinical practice, it is necessary to make corresponding changes in the preoperative design and operation of double eyelid surgery for patients with high eyeball protrusion.
10.Influence of Inflammation on Tumor and Intervention of Chinese Medicine: Based on "Inflammation-tumor Transformation"
Mengfan PENG ; Ming LI ; Jinxin MIAO ; Shuo TIAN ; Yuanxin ZHANG ; Chenhui LI ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(22):196-204
With high incidence and lethality rate and certain disability rate, tumor has become a major global public health threat. It has been verified that the occurrence and development of tumor are resulted from the synergy of environment, heredity, and gene mutation, involving the abnormal activation or inhibition of a variety of related pathways such as oxidative stress, inflammation, autophagy, and mesenchymal transition of cells. Among them, the excessive activation of inflammatory signaling pathway is one of the main mechanisms of carcinogenesis and tumor progression, which enhances the proliferation, chemoradiotherapy resistance, invasion, and metastasis of cancer cells. At the moment, the correlation between long-term chronic uncontrollable inflammation and "inflammation-cancer transformation" has been widely recognized. Therefore, it is of great significance for the prevention and treatment, diagnosis, and prognosis evaluation of tumor to clarify the role of inflammation in the incidence of tumor. Blockers or activators have been developed to target the corresponding inflammatory pathways. However, tumor is accompanied by the abnormality of multiple inflammatory pathways, especially the advanced tumor with metastasis of cancer cells, and thus the efficacy of single pathway-targeting agents is non-ideal. Chinese medicine, featuring multiple components and multiple targets, can remarkably control the inflammatory response, delay tumor progression, enhance the sensitivity of tumor cells to radiotherapy and chemotherapy, and reduce postoperative infection and the adverse reactions caused by radiotherapy and chemotherapy, thereby exerting the anti-cancer effect. Nevertheless, a few reports on the anti-tumor effect of Chinese medicine from the perspective of inflammation are available. Therefore, this paper mainly expounds the influence of inflammation on the occurrence and development of tumor and summarizes the research on the intervention of tumor by Chinese medicine through inflammatory pathway, which is expected to provide a new mindset for the prevention and treatment of tumor.


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