1.Transplantation of menstrual blood-derived endometrial stem cells allevi-ates chemotherapy-induced intestinal injury and flora imbalance in mice through immunomodulation
Qin LIU ; Mengyuan CHANG ; Haofeng SONG ; Chenxu DU ; Yonghai LI ; Shenghui ZHANG ; Yanli LIU ; Juntang LIN
Chinese Journal of Pathophysiology 2024;40(2):301-308
AIM:To investigate the therapeutic effect of menstrual blood-derived endometrial stem cells(MenSCs)on chemotherapy-induced intestinal mucositis and flora disorders in mice,and to explore the potential mecha-nism.METHODS:The mice were randomly divided into 3 groups including normal treatment,cisplatin(Cis)treatment and Cis+MenSC treatment,with 10 mice in each group.To induce intestinal mucositis,the mice were treated with Cis(2 mg·kg-1·d-1)by intraperitoneal injection for 5 consecutive days.Control mice for normal group were received equal vol-umes of normal saline.For Cis+MenSC treatment,MenSCs(1×106)was transplanted into the mice of Cis treated mice through tail vein.The performances and weight changes of mice were examined during the experiment.After the treat-ment,the small intestine and colon were isolated for subsequent HE staining,the ratio of F4/80 and IL-6 positive cells in small intestine were detected by immunohistochemical staining,and the expression of tight junction,inflammation and apoptosis related proteins was detected by Western blot.16S rDNA amplicon sequencing was performed to detect the diver-sity and richness of intestinal flora in mice.RESULTS:Compared to the Cis group,the MenSCs-treated mice showed sig-nificantly increased body weight,relieved intestinal lymphocytes infiltration,alleviated intestinal villous edema,and or-derly arranged glands in intestinal tissues.Further analysis indicated that MenSCs transplantation significantly up-regulat-ed the expression of intestinal tight junction related proteins ZO-1 and occludin in Cis-treated mice(P<0.05).Subse-quently,MenSCs transplantation significantly inhibited the macrophages infiltration in intestinal tissues(P<0.01),down-regulated the expression of pro-inflammatory factors IL-1 and IL-6 and pro-apoptotic protein Bax(P<0.01),while up-regu-lated anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2(P<0.01).Additionally,further microflora sequenc-ing indicated that MenSCs transplantation prevented mice from Cis-induced intestinal flora disorder,and significantly re-duced the abundance of harmful bacteria such as isenbergiella tayi and Anaerotruncus colihominis(P<0.01).At the same time,the abundance of beneficial bacteria Lactobacillus apodemi was increased(P<0.05),thereby restoring the composi-tion and function of healthy intestinal flora.CONCLUSION:MenSCs transplantation alleviates the chemotherapy-in-duced damage of intestinal structure,relieves the symptoms of chemotherapy-induced mucositis and restores the homeosta-sis of intestinal flora in mice.
2.Clinical Evaluation of New Chinese Herbal Medicines for Syndromes: A Preliminary Study on Target Design
Li ZHANG ; Mengyuan ZHONG ; Yongfa XING ; Duojing LI ; Zheying WU ; Yuhong HUANG
Journal of Traditional Chinese Medicine 2024;65(16):1730-1733
There are certain limitations in the current clinical evaluation methods and evaluation modes of new Chinese herbal medicines for syndromes, and there is a lack of a clinical evaluation system that meets the characteristics of traditional Chinese medicine (TCM). Based on the characteristics of TCM "syndrome differentiation and treatment" and "correspondence of formulas and syndromes", the target design model, hypothesis and its scope of application are proposed on the basis of the combination of diseases and syndromes. On the basis of fully considering the dual factors of diseases and syndromes, we distinguished the "centre of the target", "middle ring" and "outer ring" through the differences of different signs and symptoms in people with same syndrome, in order to determine the degree of conformity of the syndrome. Then, the population with same syndrome could be analysed according to the "centre of the target", "middle ring" and "outer ring", so as to achieve the precise positioning of new Chinese herbal medicines for syndromes, and try to provide research ideas and methods for syndrome differentiation and treatment of TCM and precise intervention.
3.Modified Xiaoyao powder for postpartum depression: A systematic review and meta-analysis
Mengyuan Hu ; Xiaowen Zhang ; Xuya Zhang ; Dan Cheng ; Yali Zhang ; Xinyu Zhang ; Lingling Li ; Xinjie Li ; Xue Li ; Yi Lu
Journal of Traditional Chinese Medical Sciences 2024;11(1):120-130
Objective:
To evaluate the effectiveness and safety of modified Xiaoyao powder for postpartum depression (PPD) by conducting a systematic review of randomized controlled trials (RCTs).
Methods:
The Chinese National Knowledge Infrastructure Databases (CNKI), the Chinese Scientific Journals Database (VIP), Wanfang, Google Scholar, the SinoMed, Embase, Cochrane Library, and PubMed databases were searched from their inception to April 25, 2023. The Cochrane Risk of Bias tool was used to assess the quality of the trials. We applied the risk ratio to present dichotomous data and the mean difference to present continuous data. Data with similar characteristics were pooled for meta-analysis and heterogeneity was assessed using I2.
Results:
This review included 35 trials involving 2848 participants. The quality of the included studies was low (unclear randomization processes and insufficient reporting of blinding). Participants treated with modified Xiaoyao powder plus Western medicine showed lower Hamilton Depression Scale (HAMD) depression score than those who used Western medicine alone (mean difference = −2.15; 95% confidence interval:−2.52 to 1.78; P < .00001), and higher effective rate (relative risk = 1.19; 95% confidence interval: 1.15 to 1.24; P < .00001), When comparing modified Xiaoyao alone with Western medicine, the HAMD depression score remained low, however, the efficacy rate was higher in the modified Xiaoyao group. Regarding adverse events, the modified Xiaoyao group reported weight gain, nausea, and diarrhea, but no severe adverse events were reported.
Conclusion
Modified Xiaoyao may help relieve depression in PPD when used alone or in combination with Western medicine, with minor side effects. Therefore, future high-quality, large-sample size RCTs are warranted.
4.Huaier alleviates acute pancreatitis in mice by reducing ROS-induced pyroptosis in acinar cells
Mengyuan GONG ; Bo ZHANG ; Ze’en ZHU ; Qingyong MA ; Zheng WU ; Zheng WANG ; Weikun QIAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(2):183-191
【Objective】 To investigate the therapeutic effect of Huaier on acute pancreatitis (AP) and its potential mechanism. 【Methods】 A mouse model of cerulean-induced AP was used to verify the therapeutic effect of Huaier in vivo. HE staining and immunohistochemical staining were used to evaluate the histopathological changes of the pancreas, and transmission electron microscopy was used to observe the pyroptosis morphology of the pancreas. In vitro, 266-6 cell line was used as the experimental carrier to verify the protective effect of Huaier on acinar cells. Electron microscopy and Western blotting were used to evaluate the pyroptosis level of acinar cells, and ROS fluorescence probe was used to detect the oxidative stress state of acinar cells. 【Results】 Huaier significantly alleviated the severity of AP in mice. HE staining of pancreas showed that necrosis and inflammatory cell infiltration were reduced, and the level of serum amylase was decreased. Immunohistochemical staining and Western blotting showed that Huaier effectively inhibited the expressions of pyroptosis-related molecules such as NLRP3 and GSDMD in pancreatic tissue. Electron microscopy showed that Huaier could reduce the pyroptosis level of pancreatic acinar cells under inflammatory state. In addition, the level of ROS in acinar cells was significantly reduced after the intervention of Huaier, and ROS-mediated pyroptosis of acinar cells could be effectively inhibited by Huaier. 【Conclusion】 Huaier can effectively reduce the severity of AP by inhibiting ROS-mediated pyroptosis of acinar cells.
5.Compatibility Mechanism of Mineral Medicine Os Draconis in Bupleuri Radix-containing Tri-herbal Medicines Based on Supramolecular Systems
Zi XING ; Junling HOU ; Yifan ZHAO ; Liman XIAO ; Mengjia WEI ; Mengyuan YANG ; Lu YUN ; Yuanfei NIU ; Zhijie ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):191-198
ObjectiveBy starting with the combination of Os Draconis, Bupleuri Radix, and Ostreae Concha, the role of mineral medicine Os Draconis in the combination of the Bupleuri Radix-containing tri-herbal medicines was preliminarily explored from the perspective of supramolecular system formation. Method① The appearance and Tyndall phenomenon of single decoction of Os Draconis, Bupleuri Radix, and Ostreae Concha, as well as co-decoction of Bupleuri Radix-Os Draconis, Bupleuri Radix-Os Draconis-Ostreae Concha, and Bupleuri Radix-Ostreae Concha were observed, and the average particle size, dispersion coefficient, and Zeta potential of suspension particles in each decoction were determined. The micromorphology of supramolecular structures was observed by scanning electron microscope (SEM). ② The pH of different compatibility systems, liquid viscosity coefficient, liquid surface tension, freeze-dried powder yield rate, and other physical properties were determined, and the interaction of different compatibility systems was detected by infrared absorption spectroscopy (FTIR) and UV-visible spectrophotometry (UV-Vis). ③ The composition and content difference of different compatible systems were determined by high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS). ResultCompared with the single decoction, the co-decoction had more obvious turbidity and Tyndall phenomenon. The particles in the co-decoction suspension were smaller and more evenly distributed, and the Zeta potential was reduced, indicating a more stable system. Under SEM, Bupleuri Radix was irregularly lamellar, and Bupleuri Radix-Os Draconis and Bupleuri Radix-Os Draconis-Ostreae Concha were mainly spherical nanoparticles. Bupleuri Radix-Ostreae Concha was irregularly lamellar, with a small number of spherical nanoparticles. The pH of the single decoction of Bupleuri Radix and co-decoction increased, and the viscosity coefficient increased. The liquid surface tension decreased. The freeze-dried powder yield rate of the Bupleuri Radix-Os Draconis co-decoction was the highest, followed by Bupleuri Radix-Ostreae Concha decoction and Bupleuri Radix-Os Draconis-Ostreae Concha decoction, and the yield rate of Bupleuri Radix single decoction was the lowest. The main change of FTIR was the stretching vibration of -OH, and the co-decoction moved to the low-frequency direction obviously. UV-Vis showed that the maximum absorption occurred at 295.8 nm for all groups, and the absorption intensity was different (Bupleuri Radix-Os Draconis>Bupleuri Radix-Os Draconis-Ostreae Concha>Bupleuri Radix-Ostreae Concha>Bupleuri Radix). The components of Bupleuri Radix were used as the indexes, and the content of methanol extract determined by HPLC was higher than that of water extract, and the components of Bupleuri Radix single decoction were mainly saikosaponin a (SSa) and saikosaponin c (SSc), which were slightly higher after co-decoction compatibility. UPLC-Q-TOF-MS could identify 37 compounds in both single decoction and co-decoction. ConclusionThe combination of Bupleuri Radix, Os Draconis, and Ostreae Concha can form a smaller, more uniform, and stable nano-sized supramolecular system, which is conducive to the dissolution of the main components of Bupleuri Radix, and the Os Draconis contributes the most in this process.
6.Effect of micellar curcumol on polarization of macrophages associated with ovarian cancer
Qin TANG ; Jing WANG ; Bing CHEN ; Sheng WANG ; Minmin ZHANG ; Mengyuan ZHANG ; Qiang WU
Acta Universitatis Medicinalis Anhui 2024;59(5):840-846
Objective To investigate the mechanism of micellar curcumol (MC) regulating the immune microenvi-ronment of ovarian cancer by promoting the polarization of M2-type macrophages to M1-type in ovarian cancer asci-tes.Methods ① After the mice were divided into groups, a mouse ovarian cancer ascites model was constructed by using the mouse ovarian cancer cell line ID8.Then weight changes were observed, tumor tissue and ascites were collected.The expression of CD86 and CD206 on macrophages of the tumor tissue and ascites was detected by flow cytometry.The expression of protein kinase B (PKB/Akt)/mammalian target of rapamycin (mTOR) was detected by Western blot.②A human monocytic leukemia cell line (THP-1) was induced to transform into M2 macrophage (THP-1 M2 macrophage) in vitro, and then treated with 10μg/ml MC.The apoptosis was detected by flow cytom-etry.The mRNA levels of macrophage mannose receptor (CD206), transforming growth factor-β(TGF-β), inter-leukin (IL)-1β and tumor necrosis factor-α (TNF-α) were detected by qRT-PCR.The expression of CD86 and CD206 was detected by flow cytometry, and Akt/mTOR expression and phosphorylation was detected by Western blot.Results ① In vitro study showed that the average body weight of the MC group was lower than that of the control group.Compared with the control group, CD206 expression of macrophages decreased in tumor tissue and ascites in the MC group, while the expression of CD86 increased.The Akt and mTOR phosphorylation level of mac-rophages in the MC group's ascites was lower than that in control group.②In vivo study showed that there was no difference in apoptosis rate among the groups detected by flow cytometry.The mRNA expression level of CD206, TGF-β and the protein expression level of CD206 in MC group were significantly lower than those in the control group, while the mRNA expression of IL-1β, TNF-α and the protein expression level of CD86 were significantly higher than those in the control group.Compared with the control group, the phosphorylation level of Akt and mTOR in the MC group decreased.Conclusion MC promotes M1 polarization of macrophages in ascites to regulate the immune microenvironment of ovarian cancer, which may be related to the Akt/mTOR pathway.
7.Researches related to pain in Parkinson's disease:a bibliometrics analysis
Mengyuan CHEN ; Qiuqin WANG ; Yuchen XU ; Jie LIU ; Xinyue ZHANG ; Juping CHEN ; Guihua XU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(7):797-803
Objective To analyze the hotspots and frontiers of researches related to pain in Parkinson's disease. Methods The literatures on pain in Parkinson's disease were retrieved from CNKI,VIP,Wanfang data,CBM and Web of Science Core Collection from inception to November,2023,and were analyzed with CiteSpace 6.1.R6. Results A total of 926 literatures were included with 293 in Chinese and 633 in English,respectively.Chinese high-fre-quency keywords were quality of life,sleep disorders and depression,while English high-frequency keywords were nonmotor symptom,quality of life and levodopa.The latest bursting word in Chinese was pathogenesis,while the latest bursting words in English were exercise and management. Conclusion Number of researches related to pain in Parkinson's disease is gradually rising,and the characteristics,patho-genesis,quality of life,rehabilitation interventions and clinical efficacy have become research hotspots.The mechanism of pain in Parkinson's disease and rehabilitation management program will be the main research top-ics in the future.
8.Effect of sling exercise with Tuina therapy on kinesiophobia in old patients with lumbar disc herniation:a ran-domized controlled trial based on concept of brain-bone axis
Yuqin DAN ; Jianing SU ; Yi DING ; Xueyan WANG ; Danghan XU ; Jinghua WANG ; Yujing WU ; Mengyuan ZHANG ; Meng YIN ; Haifeng LU ; Gongchang YU ; Li LI
Chinese Journal of Rehabilitation Theory and Practice 2024;30(7):861-868
Objective To explore the effect of sling exercise with Tuina therapy on kinesiophobia in old patients with lumbar disc herniation,and analyze the mechanism based on brain-bone axis. Methods A total of 56 old patients with chronic lumbar disc herniation and kinesiophobia were selected from the Reha-bilitation Hospital of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from September,2022 to December,2023;and randomly divided into control group(n=28)and experimental group(n=28).The control group accepted conventional exercise therapy,while the experimental group accepted sling exercise with Tuina therapy,for four weeks.They were assessed with simplified Chinese version of Tampa Scale of Kinesiophobia(TSK),Japanese Orthopaedic Association score(JOA)and Visual Analogue Scale for pain(VAS)before and after treatment,while the bone mineral density(BMD)was tested,the levels of osteoprote-gerin(OPG),norepinephrine(NE)and corticosteroids(Cor)in serum were measured,and the median frequency(MF)of weak-link erector spinae was detected with surface electromyography. Results Two cases dropped off in the control group,and one in the experimental group.The scores of all the assessment improved in both groups after treatment(|t|>14.168,P<0.001),as well as the serum levels of OPG,NE and Cor(|t|>2.103,P<0.05),BMD(|t|>2.726,P<0.05),and MF of erector spinae(|t|>14.736,P<0.001);all of them were better in the experimental group than in the control group(|t|>2.154,P<0.05). Conclusion Sling exercise with Tuina therapy can improve the pain and kinesiophobia of lumbar disc herniation in the old adults,which may promote the recovery of physical and mental function through regulating the levels of hor-mones and neurotransmitters related to the brain-bone axis.
9.Zhenwutang Ameliorates Diabetic Kidney Disease in Mice with Spleen-kidney Yang Deficiency via Nrf2/HO-1/GPX4 Signaling Pathway
Zhe ZHAO ; Guangshun CHEN ; Min BAI ; Yuqiu JIN ; Mengyuan TIAN ; Bing SONG ; Zhenhua LIU ; Yanying ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):29-37
ObjectiveTo investigate the effect and mechanism of Zhenwutang on renal oxidative damage in the mouse model of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency via the nuclear factor erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodTwenty-five 7-week-old SPF-grade male db/m mice and 95 7-week-old SPF-grade male db/db mice were adaptively fed for a week. A blank group was set with the db/m mice without treatment, and the other mice were administrated with Rhei Radix et Rhizoma decoction and hydrocortisone for the modeling of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency. The modeled mice were randomized into the model, irbesartan (25 mg·kg-1), and high-, medium-, low-dose (33.8, 16.9, 8.45 g·kg-1) Zhenwutang groups (n=15) and administrated with corresponding drugs for 8 weeks. The survival status of mice was observed, and the traditional Chinese medicine (TCM) syndrome score was recorded. The indicators related to spleen-kidney Yang deficiency, fasting blood glucose (FBG), and renal function indicators were determined. Hematoxylin-eosin staining was employed to observe the histopathological changes of the renal tissue in each group. Biochemical kits were used to determine the oxidative stress-related indicators in the renal tissue. Real-time polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels, respectively, of Nrf2, HO-1, glutamate-cysteine ligase catalytic subunit (GCLC), and GPX4 in the renal tissue of mice in each group. ResultCompared with the blank group, the modeling increased the TCM syndrome score (P<0.05), elevated the estradiol (E2) and FBG levels (P<0.05), lowered the testosterone (T), triiodothyronine (T3), and tetraiodothyronine (T4) levels (P<0.05), and weakened the renal function (P<0.05). In addition, the modeling led to glomerular hypertrophy and glomerular mesangial and basal thickening, decreased the catalase (CAT) activity, total antioxidant capacity (T-AOC), and glutathione (GSH) content (P<0.05), increased the malondialdehyde (MDA) content (P<0.05), and down-regulated the mRNA and protein levels of Nrf2, HO-1, GCLC, and GPX4 in the renal tissue (P<0.05). Compared with the model group, high and medium doses of Zhenwutang decreased the TCM syndrome score and E2 content (P<0.05), increased the T, T3, and T4 content (P<0.05), improved the renal function (P<0.05), alleviated the pathological changes in the renal tissue, increased CAT, T-AOC, and GSH (P<0.05), reduced MDA (P<0.05), and up-regulated the mRNA and protein levels of Nrf2, HO-1, GCLC, and GPX4 in the renal tissue (P<0.05). ConclusionZhenwutang can improve the general state and renal function and reduce the oxidative damage and pathological changes in the renal tissue of db/db mice with spleen-kidney Yang deficiency by regulating the Nrf2/HO-1/GPX4 signaling pathway.
10.Application value of MEX3A,CDX2,MUC2 and MUC5AC in judging cancerous gastric mucosal intestinal metaplasia
Mengyuan ZHANG ; Jiarui LIU ; Zhong ZHANG ; Lanlan JIAO ; Min ZHANG ; Wei BO ; Jiayu GOU ; Chengcheng WU ; Xudong YANG ; Xuguang WANG
China Modern Doctor 2024;62(10):1-5
Objective To investigate the correlation between MEX3A and differentiation characteristics of gastric cancer and intestinal metaplasia,and its combination with caudal-related homeobox transcription factor 2(CDX2)and mucin 2(MUC2)and mucin 5AC(MUC5AC)to determine the role of carcinogenic intestinal metaplasia.Methods From January 2010 to December 2014,a total of 410 cases of gastric cancer and paracarcinoma paraffin-embedded tissue samples were selected from the Central Hospital Affiliated to Shenyang Medical College and the Second Hospital Affiliated to Shenyang Medical College.According to pathological diagnosis,they were divided into control group(mild superficial gastritis,79 cases),intestinal metaplasia group(149 cases)and gastric cancer group(182 cases).The expressions of MEX3A,CDX2,MUC2 and MUC5AC were detected by immunohistochemistry.Results MEX3A was highly expressed in gastric cancer group and intestinal metaplasia group,especially diffuse gastric cancer,poorly differentiated gastric cancer and type Ⅲ intestinal metaplasia(P<0.05).CDX2 and MUC2 were highly expressed in gastric cancer group and intestinal metaplasia group,especially intestinal type gastric cancer,highly and moderately differentiated gastric cancer,type Ⅰ and type Ⅱ intestinal metaplasia(P<0.05).The expression of MUC5AC was high in control group and low in gastric cancer group and intestinal metaplasia group,especially in intestinal type gastric cancer,type Ⅰ and type Ⅲ intestinal metaplasia(P<0.05).Gastric cancer and intestinal metaplasia differentiation were negatively correlated with MEX3A and MUC5AC expression,but positively correlated with CDX2 and MUC2 expression(P<0.05).MEX3A was negatively correlated with the expression of CDX2 and MUC2,and positively correlated with the expression of MUC5AC in gastric cancer(P<0.05).MEX3A was negatively correlated with the expression of CDX2 and MUC2 in intestinal metaplasia(P<0.05),while CDX2 was positively correlated with the expression of MUC2(P<0.05).Conclusion MEX3A is negatively correlated with gastric cancer and intestinal metaplasia differentiation.Gastric cancer is characterized by high MEX3A expression and low CDX2 and MUC2 expression.


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