1.Exploring Intervention Mechanism of Changzhou Tongbian Formula on Functional Constipation Combined with Depressive-like Behaviors in Rats Based on TRPV4-mediated BDNF/TrkB/CREB Signaling Pathway
Ling YAO ; Longfang QUAN ; Zhennian XIE ; Jie DAI ; Qiuning LIU ; Yonghai LI ; Xiaoqiang JIA
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1289-1298
Objective To explore the intervention mechanism of Changzhou Tongbian Formula on functional constipation(FC)combined with depression in rats.Methods A rat model of FC combined with depressive-like behaviors was established by using gastric gavage of berberine hydrochloride and chronic unpredictable mild stress.The model rats were randomly divided into blank group,model group,lactulose group,and Changzhou Tongbian Formula high-,medium-,and low-dose groups,and the intervention was carried out for five weeks.The fecal water content was calculated before and after intervention.The small intestinal propulsion rate was calculated after intervention.The depressive-like behavior levels of rats were evaluated by forced swimming test and sucrose preference test before and after intervention.The colonic mucosal morphology was observed by HE staining.The morphology and number of pyramidal cells in the hippocampal CA1 and DG regions were observed by Nissl staining.The relative protein expression levels of the transient receptor potential vanilloid 4(TRPV4)in colonic tissue,as well as brain-derived neurotrophic factor(BDNF),tyrosine kinase receptor B(TrkB),mitogen-activated protein kinase(MAPK),and cAMP-response element binding protein(CREB)in the hippocampus of rats in each group were detected by Western Blot method.Results Compared with the blank group,the fecal water content of rats in the model group was significantly reduced(P<0.001),the small intestinal propulsion rate was significantly lower(P<0.01),the sucrose preference index was significantly decreased(P<0.001),the number of pyramidal cells in the CA1 and DG regions of the hippocampus was significantly reduced(P<0.001),and the TRPV4 in the colon and the BDNF,TrkB,MAPK,and CREB protein contents in the hippocampus were all significantly decreased(all P<0.001).Compared with the model group,the fecal water content of the Changzhou Tongbian Formula high-,midium-,low-dose groups and the lactulose group were significantly increased(P<0.001,P<0.01).The small intestinal propulsion rate of the Changzhou Tongbian Formula high-,low-dose groups and lactulose group were significantly increased(P<0.01,P<0.05).The sucrose preference indices of the Changzhou Tongbian Formula high-,midium-,low-dose groups and lactulose group were significantly increased(P<0.01,P<0.05).There was no abnormality in the colonic histology.The numbers of pyramidal cells in the CA1 and DG regions of the hippocampus of the Changzhou Tongbian Formula high-,midium-,low-dose groups and lactulose group were significantly increased(P<0.01,P<0.001).The TRPV4 content in the colon of the Changzhou Tongbian Formula high-,midium-,low-dose groups and lactulose group were significantly increased(P<0.001),and the BDNF,TrkB,MAPK,and CREB protein contents in the hippocampus were all significantly increased(P<0.05,P<0.01,P<0.001).Conclusion After intervention,Changzhou Tongbian Formula can significantly improve the TRPV4 content in the colon of model rats with the comorbidity of FC with depression,increase the moisture content of feces,promote intestinal peristalsis and improve constipation.Meanwhile,TRPV4 can activate the BDNF/TrkB/MAPK pathway,trigger an increase in downstream CREB,improve neuroplasticity and thus alleviate some depressive-like behavior.
2.Prognostic impact of different tumor invasion patterns in the surgical treatment of T3 glottic laryngeal cancer.
Zhiming LING ; Guohua HU ; Zhihai WANG ; Wei MA ; Xiaoqiang WANG ; Jiang ZHU ; Quan ZENG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(12):998-1004
Objective:To investigate the prognostic impact of different tumor invasion patterns in the surgical treatment of T3 glottic laryngeal cancer. Methods:A retrospective analysis was conducted on the clinical data of 91 patients with T3 glottic laryngeal cancer. Results:Among the 91 patients, 58 cases (63.7%) had anterior invasion and 33 cases (36.3%) had posterior invasion. The posterior invasion was significantly correlated with invasions of the dorsal plate of cricoid cartilage (P<0.001), arytenoid cartilage (P= 0.001), and subglottic region(P = 0.001). There was no statistical difference in survival outcomes between the total laryngectomy group and the partial laryngectomy group. But in the partial laryngectomy group, the 5-year disease-free survival(DFS) of patients with anterior invasive tumors was better than that of patients with posterior invasion tumors (HR: 4.681, 95%CI 1.337-16.393, P=0.016), and subglottic invasion was associated with worse loco-regional recurrence-free survival(LRRFS)(HR: 3.931, 95%CI 1.054-14.658, P=0.041). At the same time, we found that involvement of the dorsal plate of cricoid cartilage was an independent risk factor for postoperative laryngeal stenosis in partial laryngectomy patients (HR:11.67, 95%CI 1.89-71.98,P=0.008). Conclusion:Compared with total laryngectomy, selected partial laryngectomy can also achieve favorable oncological outcomes. Posterior invasion and subglottic extension are independent prognostic factors for recurrence of partial laryngectomy in T3 glottic laryngeal cancer, and the involvement of the dorsal plate of cricoid cartilage is associated with postoperative laryngeal stenosis. The tumor invasion pattern of laryngeal cancer should be further subdivided in order to select a more individualized treatment plan.
Humans
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Prognosis
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Laryngeal Neoplasms/pathology*
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Retrospective Studies
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Laryngostenosis/surgery*
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Carcinoma, Squamous Cell/pathology*
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Postoperative Complications/surgery*
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Laryngectomy
3.Cocktail Formula and Application Prospects for Oral and Maxillofacial Organoids
Mingyu OU ; Qing LI ; Xiaofang LING ; Jinguang YAO ; Xiaoqiang MO
Tissue Engineering and Regenerative Medicine 2022;19(5):913-925
Oral and maxillofacial organoids (OMOs), tiny tissues and organs derived from stem cells cultured through 3-d cell culture models, can fully summarize the cell tissue structure, physiological functions and biological characteristics of the source tissues in the body. OMOs are applied in areas such as disease modelling, developmental and regenerative medicine, drug screening, personalized treatment, etc. Although the construction of organoids in various parts of the oral and maxillofacial (OM) region has achieved considerable success, the existing cocktail formulae (construction strategies) are not widely applicable for tissues of various sources due to factors including the heterogeneity of the source tissues and the dependence on laboratory technology. Most of their formulae are based on growth factor niches containing expensive recombinant proteins with their efficiency remaining to be improved. In view of this, the cocktail formulae of various parts of the OM organs are reviewed with further discussion of the application and prospects for those OMOs to find some affordable cocktail formula with strong operability and high repeatability for various maxillofacial organs. The results may help improve the efficiency of organoid construction in the laboratory and accelerate the pace of the clinical use of organoid technology.
4.Effects of different negative pressure suction devices on collagen, MMP-1 and TGF-β secretion of skin
Ling ZHU ; Yanping ZHENG ; Chao WU ; Xiaoqiang XIAO
Chinese Journal of Medical Aesthetics and Cosmetology 2021;27(2):145-148
Objective:To compare the effects of circular arch device and dressing device on the secretion of collagen, matrix metalloproteinase (MMP-1), transforming growth factor (TGF-β) of fibroblasts in the treated skin, and to explore the changes and mechanisms.Methods:The animals were purchased from the Southern Medical University Laboratory Animal Center. Using the established animal model, 54 mice were randomly divided into three groups: 18 mice each group, including control group, dressing device group and and circular arch device group. At the first, third and fifth day after negative pressure suction treatment, dermal thickness and density of collagen levels were and eosin staining, collagen level in local skin was determined using spectrophotometry, and MMP-1 and TGF-β levels were determined using enzyme linked immunosorbent assay.Results:Dermal thickness level was increased significantly in negative suction treated groups [after 5 days of treatment, control group: (71±8) μm; circular arch device group: (351±9) μm; dressing device group: (267±12) μm, P< 0.05]. Compared with the control group, collagen level in the dermis was significantly higher in circular arch device groups [after 5 days of treatment, control group: (30.9±4.3) mg/g; circular arch device group: (72.7±3.6) mg/g, P< 0.05]. TGF-β level in circular arch device treated group was increasing gradually, and markedly higher than that in the dressing device group and the control group [after 5 days of treatment, control group: (0.24±0.1) ng/ml; circular arch device group: (0.78±0.08) ng/ml; dressing device group: (0.39±0.18) ng/ml, P< 0.05], while MMP-1 level was decreasing. In addition, TGF-β and MMP-1 levels in the dressing device treated group remained stable during the entire experiment. Conclusions:The interface of the circular arch negative pressure suction device can effectively activate the fibroblasts, promote the secretion of TGF-β and collagen, and thicken the skin tissue.
5.Clinical and prognostic significance of ABO promotor methylation level in adult leukemia and myelodydysplastic syndrome
Ming SHAO ; Ping TANG ; Xianping LYU ; Qiankun YANG ; Weitao ZHU ; Huifang JIN ; Li WANG ; Xiaoqiang ZHAO ; Xin LIU ; Ling SUN
Chinese Journal of Internal Medicine 2018;57(11):816-823
Objective To investigate the clinical and prognostic significance of ABO promotor methylation level in adult patients with leukemia and myelodydysplastic syndrome(MDS). Methods ABO promoter methylation level of 182 malignant hematological disease patients and 68 normal controls were detected by bisulfite sequencing PCR. Then clinical features and outcome were compared between hypermethylation group and hypomethylation group. Results The median methylation rate of ABO promoter in newly diagnosed acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) were 46.98% and 11.01% respectively, which were both higher than that in controls (2.30%, P<0.05). The methylation rates in remission AML and ALL were 1.58%and 2.30%respectively, which were comparable with that in normal group (P>0.05). As to relapse AML and ALL, methylation rates were 41.26% and 17.50%respectively, also significantly higher than that in controls (P<0.05).In patients with chronic myeloid leukemia (CML) chronic phase, the median methylation rate was 1.00%, which was similar to normal group. But a CML patient who transformed to ALL hadextremely high methylation rate 92.56%. The median methylation rate in patients with MDS significantly elevated as 5.81% compared with that in controls (P<0.05). The median overall survival (OS) of ALL and AML (non-M3) patients with hypermethylation were 12.5 months and 15.3 months, which were significantly shorter than those with hypomethylation (24.0 months and 20.0 months) (P<0.05). The median disease-free survival (DFS) of ALL and AML (non-M3) patients with hypermethylation were 9.9 months and 12.0 months, which were significantly shorter than those with hypomethylation (22.3 months and 18.5 months), (P<0.05). Multivariable analysis suggested that ABO promoter methylation level was an independent predictive factor of OS and DFS in ALL and AML (non-M3) patients. Conclusion ABO promoter hypermethylation is closely related to genesis, development and prognosis of leukemia and MDS. Hypermethylationis related to a clinical poor prognosis compare with hypomethylation.
6.Isolation and culture of bone marrow mesenchymal stem cells and their effects on immune regulation of CD8+T lymphocytes
Xiaoqiang ZHAO ; Ming SHAO ; Haiping YANG ; Ling SUN
Chinese Journal of Tissue Engineering Research 2017;38(5):682-686
BACKGROUND:Bone marrow mesenchymal stem cel s have immunomodulatory properties and have potential applications in immunosuppression. OBJECTIVE:To investigate the isolation and culture of bone marrow mesenchymal stem cel s and the immunoregulation of CD8+T lymphocytes. METHODS:Primary bone marrow mesenchymal stem cel s were isolated from Wistar rats by bone marrow adherence method. The primary cel s were purified by differential adherence and digestion, and col agen type I was added as extracel ular matrix to expand bone marrow mesenchymal stem cel s. Passage 2 bone marrow mesenchymal stem cel s at densities of 0, 1×103, 1×104 and 1×105/wel were co-cultured with CD8+T lymphocytes, fol owed by phytohemagglutinin stimulation for 68 hours. T lymphocyte aggregation and proliferation were detected by staining with staining with 5,6-carboxyfluorescein diacetate succinimidyl ester and MTT, respectively. RESULTS AND CONCLUSION:Different concentrations of bone marrow mesenchymal stem cel s had an inhibitory effect on T lymphocytes, but this effect was weakest for the cel s at the density of 1×103 per wel and strongest for the cel s at the density of 1×105 per wel . Obvious agglomeration was observed in the same media. The proliferation rates of CD8+T lymphocytes were (44.83±4.92)%, (31.94±6.28)%and (15.77±3.98)%, respectively, after co-culture with 1×103, 1×104, 1×105/wel bone marrow mesenchymal stem cel s. There were significant differences between groups (P<0.05). These results showed that primary rat bone marrow mesenchymal stem cel s could be obtained by direct adherence method of the whole bone marrow, and the cel s could be purified by differential adherence combined with digestion and control method. Bone marrow mesenchymal stem cel s could inhibit T lymphocyte proliferation in a concentration-dependent manner.
7.Effects and possible mechanisms of nerve growth factor on serum levels of VEGF and SDF-1 protein expression in rats with focal cerebral ischemia
Xiaoqiang LI ; Li LING ; Chuqiao LI ; Wenbin MA ; Yichen YIN
The Journal of Practical Medicine 2017;33(7):1021-1024
Objective To investigate the effects and the possible mechanisms of nerve growth factor (NGF) on serum levels of vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1) protein expression in rats with focal cerebral ischemia.Methods Male Sprague-Dawley rats weighting 200 ~ 250 g were subjected to middle cerebral occlusion (MCAO).MCAO rats were randomly divided into NGF group,saline control group and NGF+PI3K antagonist group (n =12).The neurological function was evaluated on the 4th,7th day after MCAO,and the serum levels of VEGF and SDF-1 protein were measured by ELISA.Results The neurological function was better in rats of the NGF group than those of the saline control group and NGF+PI3K antagonist on the 4th,7th day after MCAO (P < 0.05).The serum levels of VEGF and SDF-1 protein of the NGF group was significantly higher than that of the saline control group and NGF+PI3K antagonist group on the 4th day after MCAO (P < 0.05).Conclusions Treatment with NGF may improve neurological function of rats with focal cerebral ischemia,and upregulate serum levels of VEGF and SDF-1 protein expression.PI3K/AKT signal pathway may have attended the above regulation.
8.The change of large platelets and mean platelet volume in acute cerebral infarction patients with type 2 diabetes
Li LING ; Xiaoqiang LI ; Suping ZHANG ; Muzhen WANG ; Rui HE ; Wanqing DENG
The Journal of Practical Medicine 2015;(13):2127-2129
Objective To investigate the clinical value of large platelets (P-LCR) and mean platelet volume (MPV) in acute cerebral infarction patients with type 2 diabetes. Methods 627 patients with acute cerebral infarction from January 2012 to May 2015 were enrolled and divided into type 2 diabetes and non-type 2 diabetes groups. The hemocytometer was used to detect the changes of P-LCR and MPV. Results The levels of P-LCR and MPV in the type 2 diabetes group were significantly higher than those of non-type 2 group (P <0.05). Logistic regression analysis showed that there was a statistically significant association between P-LCR, hypertension and hyperlipemia and the cute cerebral infarction patients with type 2 diabetes. Conclusion The levels of P-LCR and MPV could be used as important indexes for prognosis and early diagnosis of acute cerebral infarction patients with type 2 diabetes.
9.Clinical features of the elderly patients over 80 years with cute cerebral infarction
Li LING ; Xiaoqiang LI ; Suping ZHANG ; Yichen YIN ; Muzhen WANG ; Rui HE ; Wanqing DENG
Clinical Medicine of China 2015;31(7):597-600
Objective To investigate the risk factors,severity and infarct site features and clinical characteristics of the elderly patients over 80 years with cute cerebral infarction.Methods One hundred and sixty-two patients with acute cerebral infarction in Red Cross Hospital of Guangzhou,The Forth Affiliated Hospital of Medical College of Jinan University from January 2012 to May 2015 were enrolled and randomly divided into the elderly patients (≥ 80 years old) and the middle aged patients (< 60 years old).The risk factors,national institutes of health stroke scale (NIHSS) scores and Oxfordshire community stroke project (OCSP) criteria were compared between the two groups.Results Coronary artery disease,atrial fibrillation and NIHSS in the elderly patients (25% (22/88),13.6% (12/88),7.74 ± 4.986) were significantly higher than those of the middle aged group (12.2% (9/47),4.1% (3/74),5.04± 4.305),and the differences were significant (x2 =4.281,4.393,t =-3.649;P< 0.05 or P< 0.001).The logistic regression analysis finally showed that smoking,hyperlipemia,NIHSS scores and gender(male) were the independent risk factors(OR=3.851,3.609,1.100 and 2.670;P<0.05).There were more LACI patients in the elderly group than he middle aged group ((40.9%,36/88) vs.(60.8%,45/74),x2 =6.369,P < 0.05).Conclusion Compare to the middle aged patients,occurrence of the elderly patients with acute cerebral infarction is more severe,and the clinical features and risk factors have its particularity.Secondary prevention strategy should be emphasized on the control of different risk factors based on the patients' age.
10.Three advantages of using traditional Chinese medicine to prevent and treat tumor.
Changquan LING ; Xiaoqiang YUE ; Chen LING
Journal of Integrative Medicine 2014;12(4):331-5
Traditional Chinese medicine (TCM), an important component of complementary and alternative medicine, has evolved over thousands of years with its own unique system of theories, diagnostics and therapies. TCM has been increasingly used in the last decades and become well known for its significant role in preventing and treating cancer. We believe that TCM possesses advantages over Western medicine in specific aspects at a certain stage of cancer treatment. Here we summarize the advantages of TCM from three aspects: preventing tumorigenesis; attenuating toxicity and enhancing the treatment effect; and reducing tumor recurrence and metastasis.


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