1.Impacts of remifentanil on proliferation,apoptosis and Wnt / β-catenin pathway of breast cancer MDA-MB-231 cells
Yang Zhang ; Wenwen Liu ; Huanhuan Miao ; Guang Yang
Acta Universitatis Medicinalis Anhui 2025;60(9):1606-1613
Objective:
To investigate the impacts of remifentanil on the proliferation,apoptosis and Wnt/β-catenin pathway of breast cancer MDA-MB-231 cells.
Methods:
Different concentrations of remifentanil(0,0. 5,2. 5,5. 0,10. 0,20. 0,40. 0 μg/mL) were used to treat human normal breast MCF-10A cells and breast cancer MDAMB-231 cells to screen for experimental concentrations of remifentanil. MDA-MB-231 cells were divided into control group,remifentanil low(5. 0 μg/mL),medium(10. 0 μg/mL),and high(20. 0 μg/mL) concentration groups,and remifentanil + SKL2001(Wnt/β-catenin pathway agonist) group. MTT assay and colony formation assay were applied to detect cell proliferation ability. Flow cytometry was applied to detect cell apoptosis and cell cycle changes. Western blot was applied to detect protein expression related to cell proliferation,apoptosis,and the Wnt/β-catenin signaling pathway.
Results:
Remifentanil at concentrations of 5. 0,10. 0,and 20. 0 μg/mL could reduce the viability of MDA-MB-231 cells and had no prominent toxicity to MCF-10A cells. Compared with the control group,the optical density value of cell proliferation,colony formation number,proportion of S-phase cells,and the protein levels of cellular myelocytomatosis(c-Myc),Cyclin D1,B lymphoblastoma 2(Bcl-2),precursor of cysteine aspartate protease-3(pro-caspase-3) and β-catenin were lower in the low,medium,and high concentration remifentanil groups(P 0/G1 phase cells,apoptosis rate,early apoptosis rate,the protein levels of Bcl-2 associated X protein(Bax) and cleaved cysteine aspartate protease-3(Cleaved caspase-3),and glycogen synthase kinase-3β(GSK-3β) were higher( P <0. 05) . SKL2001 could weaken the effects of remifentanil on the proliferation and apoptosis of MDA-MB-231 cells.
Conclusion
Remifentanil inhibits the proliferation of MDA-MB-231 cells,induces apoptosis and cell cycle arrest,and its mechanism may be related to the inhibition of Wnt / β-catenin signaling pathway activation.
2.Effects of transcranial alternating current stimulation combined with sertraline on cognitive function in patients with depressive disorder
Dan LI ; Zhong XIA ; Wenli ZHU ; Dandan LIANG ; Wenwen MIAO ; Chuanfu SONG
Sichuan Mental Health 2025;38(3):204-210
BackgroundCognitive function is closely related to an individual's quality of life and social functioning, with approximately 20%~35% of patients with depressive disorder experiencing some degree of cognitive impairment even after clinical symptom remission. Existing evidence suggests that tACS can improve specific cognitive domains, such as memory function, while its effects on other cognitive dimensions, such as executive functioning, attention, and information processing speed, remain unclear. ObjectiveTo explore the effects of tACS on the multidimensional cognitive functions and emotional problems of patients with depressive disorder, thus to provide references for the treatment of depressive disorder. MethodsForty-nine patients with depressive disorder who were hospitalized in the Fourth People's Hospital of Wuhu from November 2022 to October 2024 and met the diagnostic criteria for depressive disorder outlined in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), were selected as study participants. Subjects were randomly divided into study group (n=23) and control group (n=26) based on Microsoft Excel. Both groups received sertraline treatment. The initial dose was 50 mg/day, which gradually titrated upward based on individual variability, drug tolerance, and therapeutic response, with a maintenance dose ranging from 100 to 200 mg/day. In addition, the study group underwent tACS therapy for 4 weeks, with 5 sessions per week, each lasting 20 minutes. The control group received sham stimulation, in which the stimulus was interrupted after the first 30 seconds. At baseline, the 4th week, and the 12th week of treatment, patients were assessed using the Hamilton Depression Scale-17 item (HAMD-17), Hamilton Anxiety Scale (HAMA), and MATRICS Consensus Cognitive Battery (MCCB). ResultsRepeated measures analysis of variance indicated that both the time effect and the time×group interaction effect for HAMD-17 scores were statistically significant between the two groups (F=260.437, 25.309, P<0.01). At week 12 of treatment, the HAMD-17 score in the study group was lower than that in the control group (t=4.236, P<0.01). For HAMA scores, the time effect, group effect, and time×group interaction effect were all statistically significant between the two groups (F=248.082, 4.506, 9.500, P<0.05 or 0.01). At weeks 4 and 12, study group reported lower HAMA scores compared with control group (t=4.580, 2.608, P<0.05 or 0.01). Regarding the MCCB scores for attention/vigilance, verbal learning, and overall composite, the time effect, group effect, and time×group interaction effect were all statistically significant between the two groups (F=70.331, 27.882, 51.679, 5.560, 10.948, 7.860, 8.490, 3.874, 5.025, P<0.05 or 0.01). After intervention, the study group showed significantly higher MCCB scores for attention/vigilance, verbal learning, and overall composite at both week 4 (t=-2.149, -3.530, -2.740, P<0.05) and week 12 (t=-3.534, -3.576, -3.838, P<0.01) when compared to the control group. ConclusionThe combined tACS and sertraline therapy may demonstrate superior efficacy to pharmacotherapy alone in the short term for improving attention/vigilance, verbal learning, overall cognitive function, and anxiety symptoms in patients with depressive disorders. Based on the 12-week outcomes, the combined tACS and sertraline therapy not only sustaine its previously observed advantages in improving cognitive domains and anxiety symptoms, but also demonstrate potentially superior efficacy over monotherapy in alleviating depressive symptoms. [Fund by Clinical Medical Research Transformation Special Project of Anhui Province (number, 202204295107020065)]
3.Discussion on the Effects of Hedysarum Polybotrys Polysaccharide on Glucose Metabolism of Small Intestinal Smooth Muscle in Diabetic Gastroparesis Rats with Spleen Qi Deficiency Syndrome Based on AMPK/GLUT4 Signaling Pathway
Wenwen WANG ; Zihui ZHONG ; Shengfang WAN ; Xinxin MA ; Lei ZHANG ; Miao LIU ; Minqi XUN ; Jinyu LI ; Kang FENG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):91-97
Objective To observe the effects of Hedysarum Polybotrys polysaccharide(HPS)on the glucose metabolism of small intestinal smooth muscle in rats with diabetic gastroparesis(DGP)of spleen qi deficiency syndrome;To explore its mechanism based on AMPK/GLUT4 signaling pathway.Methods Totally 72 male Wistar rats were randomly divided into 12 in the blank group and the remaining 60 rats were assigned to the model group.The DGP spleen qi deficiency syndrome model was replicated by intraperitoneal injection of streptozotocin+irregular feeding with high-fat and high sugar feed combined with swimming exhaustion method.The model rats were randomly divided into model group,metformin group and HPS high-,medium-and low-dosage groups.The metformin group was given 100 mg/kg metformin hydrochloride by gavage,while the HPS high-,medium-and low-dosage groups were given 200,100 and 50 mg/kg HPS by gavage,respectively.The blank group and model group were given purified water by gavage once a day for 8 consecutive weeks.The gastric emptying rate and small intestine propulsion rate in rats were detected,HE staining was used to observe the smooth muscle morphology of gastric antrum and ileal tissue,immunofluorescence staining was used to detect the expression of glucagon like peptide-1(GLP-1)in ileal tissue,ELISA was used to detect the contents of adiponectin(APN),glucagon(Glu)and insulin(INS)in serum,Western blot was used to detect the protein expressions of glucose transporter(GLUT)4,GLUT1,AMP-activated protein kinase(AMPK)and p-AMPK in ileal tissue.Results Compared with the blank group,the model group rats showed significantly increased random blood glucose,significantly decreased body mass,gastric emptying rate and small intestinal propulsion rate(P<0.01);the edema in the submucosal layer,loose arrangement of connective tissue,infiltration of a small number of lymphocytes,granulocytes and macrophages,reduced number of goblet cells in the ileal tissue,shedding of intestinal villous epithelial cells and widening of the gap between the submucosal layer and the lamina propria;the expression of GLP-1 in ileal tissue was significantly decreased(P<0.05),the contents of serum APN and INS were significantly decreased,and the content of Glu significantly increased(P<0.01),the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue were significantly decreased,while the expression of GLUT1 protein significantly increased(P<0.01).Compared with the model group,rats in metformin group and HPS high-dosage group showed a random decrease in blood glucose,an increase in body mass,gastric emptying rate,and small intestine propulsion rate(P<0.05,P<0.01);a more regular arrangement of gastric antral tissue cells,a reduction of shedding cells and edema,the smooth muscle structure of the ileal tissue was relatively intact,with evenly distributed cells and reduced infiltration of inflammatory cells;the expression of GLP-1 in ileal tissue increased,the contents of serum APN and INS increased,and the content of Glu decreased,the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue increased,while the expression of GLUT1 protein decreased(P<0.05,P<0.01).Conclusion HPS may up-regulate GLUT4 and down-regulate GLUT1 expression through activates AMPK,promotes glucose uptake and utilization by small intestinal smooth muscle,and improves glucose metabolism of DGP rats with spleen qi deficiency syndrome.
4.Interpretation of the Nursing Principles Section in the 2024 EAUN Evidence-Based Guidelines for Best Practices in Adult Indwelling Catheterization
Wenwen JIA ; Beibei ZHANG ; Xiaoli ZHANG ; Feijie WANG ; Lijie HUANG ; Zhifeng WANG ; Jinpeng ZHANG ; Xiaohui MIAO
Chinese Journal of Practical Nursing 2025;41(32):2542-2547
Indwelling urinary catheterization is one of the most widely used invasive procedures in clinical practice, playing a critical role in disease diagnosis, treatment, and monitoring. In 2024, the European Association of Urology Nurses (EAUN) released the Best Practice Guidelines for Indwelling Urinary Catheterization in Adults-Transurethral and Suprapubic Catheterization (hereinafter referred to as the Guideline), aiming to provide evidence-based clinical guidance and health education information for healthcare professionals. This article interprets the section on "Nursing Principles" within the Guideline, which spans the entire process of catheter management. Key aspects covered include pre-insertion preparation, catheter insertion procedure, catheter maintenance and securement, observation of urine color, prevention of constipation, and catheter removal. The aim is to help urology nurses and related healthcare personnel gain an in-depth understanding of the recommendations in the Guideline, promote its standardized application in clinical practice, improve the quality of indwelling catheter care, and ensure patient safety.
5.Interpretation of the Nursing Principles Section in the 2024 EAUN Evidence-Based Guidelines for Best Practices in Adult Indwelling Catheterization
Wenwen JIA ; Beibei ZHANG ; Xiaoli ZHANG ; Feijie WANG ; Lijie HUANG ; Zhifeng WANG ; Jinpeng ZHANG ; Xiaohui MIAO
Chinese Journal of Practical Nursing 2025;41(32):2542-2547
Indwelling urinary catheterization is one of the most widely used invasive procedures in clinical practice, playing a critical role in disease diagnosis, treatment, and monitoring. In 2024, the European Association of Urology Nurses (EAUN) released the Best Practice Guidelines for Indwelling Urinary Catheterization in Adults-Transurethral and Suprapubic Catheterization (hereinafter referred to as the Guideline), aiming to provide evidence-based clinical guidance and health education information for healthcare professionals. This article interprets the section on "Nursing Principles" within the Guideline, which spans the entire process of catheter management. Key aspects covered include pre-insertion preparation, catheter insertion procedure, catheter maintenance and securement, observation of urine color, prevention of constipation, and catheter removal. The aim is to help urology nurses and related healthcare personnel gain an in-depth understanding of the recommendations in the Guideline, promote its standardized application in clinical practice, improve the quality of indwelling catheter care, and ensure patient safety.
6.Discussion on the Effects of Hedysarum Polybotrys Polysaccharide on Glucose Metabolism of Small Intestinal Smooth Muscle in Diabetic Gastroparesis Rats with Spleen Qi Deficiency Syndrome Based on AMPK/GLUT4 Signaling Pathway
Wenwen WANG ; Zihui ZHONG ; Shengfang WAN ; Xinxin MA ; Lei ZHANG ; Miao LIU ; Minqi XUN ; Jinyu LI ; Kang FENG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):91-97
Objective To observe the effects of Hedysarum Polybotrys polysaccharide(HPS)on the glucose metabolism of small intestinal smooth muscle in rats with diabetic gastroparesis(DGP)of spleen qi deficiency syndrome;To explore its mechanism based on AMPK/GLUT4 signaling pathway.Methods Totally 72 male Wistar rats were randomly divided into 12 in the blank group and the remaining 60 rats were assigned to the model group.The DGP spleen qi deficiency syndrome model was replicated by intraperitoneal injection of streptozotocin+irregular feeding with high-fat and high sugar feed combined with swimming exhaustion method.The model rats were randomly divided into model group,metformin group and HPS high-,medium-and low-dosage groups.The metformin group was given 100 mg/kg metformin hydrochloride by gavage,while the HPS high-,medium-and low-dosage groups were given 200,100 and 50 mg/kg HPS by gavage,respectively.The blank group and model group were given purified water by gavage once a day for 8 consecutive weeks.The gastric emptying rate and small intestine propulsion rate in rats were detected,HE staining was used to observe the smooth muscle morphology of gastric antrum and ileal tissue,immunofluorescence staining was used to detect the expression of glucagon like peptide-1(GLP-1)in ileal tissue,ELISA was used to detect the contents of adiponectin(APN),glucagon(Glu)and insulin(INS)in serum,Western blot was used to detect the protein expressions of glucose transporter(GLUT)4,GLUT1,AMP-activated protein kinase(AMPK)and p-AMPK in ileal tissue.Results Compared with the blank group,the model group rats showed significantly increased random blood glucose,significantly decreased body mass,gastric emptying rate and small intestinal propulsion rate(P<0.01);the edema in the submucosal layer,loose arrangement of connective tissue,infiltration of a small number of lymphocytes,granulocytes and macrophages,reduced number of goblet cells in the ileal tissue,shedding of intestinal villous epithelial cells and widening of the gap between the submucosal layer and the lamina propria;the expression of GLP-1 in ileal tissue was significantly decreased(P<0.05),the contents of serum APN and INS were significantly decreased,and the content of Glu significantly increased(P<0.01),the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue were significantly decreased,while the expression of GLUT1 protein significantly increased(P<0.01).Compared with the model group,rats in metformin group and HPS high-dosage group showed a random decrease in blood glucose,an increase in body mass,gastric emptying rate,and small intestine propulsion rate(P<0.05,P<0.01);a more regular arrangement of gastric antral tissue cells,a reduction of shedding cells and edema,the smooth muscle structure of the ileal tissue was relatively intact,with evenly distributed cells and reduced infiltration of inflammatory cells;the expression of GLP-1 in ileal tissue increased,the contents of serum APN and INS increased,and the content of Glu decreased,the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue increased,while the expression of GLUT1 protein decreased(P<0.05,P<0.01).Conclusion HPS may up-regulate GLUT4 and down-regulate GLUT1 expression through activates AMPK,promotes glucose uptake and utilization by small intestinal smooth muscle,and improves glucose metabolism of DGP rats with spleen qi deficiency syndrome.
7.Community pediatric services under the family physician team model
Wenwen WANG ; Feng XIAO ; Miao WANG ; Daoliang YANG ; Weifeng LU
Chinese Journal of General Practitioners 2024;23(2):176-180
Childhood is an important period for individual health. In order to provide community child health services, Zhoujiaqiao Community Health Service Center of Shanghai Changning District has opened a pediatric clinic since July 2017. Through equipping basic facilities, personnel training, extending service items and service time, allocating resources with cooperative hospitals, optimizing internal system management and other methods, the community pediatric service under the family physician team model has been initially constructed. The article summarizes experiences in the construction and operation of community pediatric services and child health care, to provide reference for the development of a replicable and promotable urban community pediatric service system under the contracted family physician team model.
8.Promotion effect of TGF-β-Zfp423-ApoD pathway on lip sensory recovery after nerve sacrifice caused by nerve collateral compensation.
Pingchuan MA ; Gaowei ZHANG ; Su CHEN ; Cheng MIAO ; Yubin CAO ; Meng WANG ; Wenwen LIU ; Jiefei SHEN ; Patrick Ming-Kuen TANG ; Yi MEN ; Li YE ; Chunjie LI
International Journal of Oral Science 2023;15(1):23-23
Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-β inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-β-Zfp423-ApoD pathway.
Mice
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Animals
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Lip/innervation*
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Prospective Studies
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Mandibular Nerve/pathology*
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Sensation/physiology*
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Trigeminal Nerve Injuries/pathology*
9.A redox-responsive self-assembling COA-4-arm PEG prodrug nanosystem for dual drug delivery suppresses cancer metastasis and drug resistance by downregulating hsp90 expression.
Yi ZHOU ; Yingling MIAO ; Qiudi HUANG ; Wenwen SHI ; Jiacui XIE ; Jiachang LIN ; Pei HUANG ; Chengfeng YUE ; Yuan QIN ; Xiyong YU ; He WANG ; Linghao QIN ; Jianhai CHEN
Acta Pharmaceutica Sinica B 2023;13(7):3153-3167
Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies. Heat shock protein 90 (Hsp90) as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance. Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance. In this study, a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX, and a COA-modified 4-arm PEG polymer (4PSC) was synthesized. COA, an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression, was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity. Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity. By blocking the Hsp90 signaling pathway, 4PSC significantly enhanced the antitumor effect of PTX, inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro. Remarkable results were further confirmed in vivo with two preclinical tumor models. These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.
10.Effects of aerobic exercise on cognitive function in male patients with chronic schizophrenia
Wenwen MIAO ; Wenli ZHU ; Yangying BU ; Wei REN ; Chenyang YU ; Jing CHEN ; Chuanfu SONG
Sichuan Mental Health 2023;36(6):521-526
BackgroundThe schizophrenia is majorly treated with drug and through physical therapy. However, both treatments would lead to adverse reactions, which could affect therapy adherence and treatment efficacy. Previous studies have shown that aerobic exercise can help alleviate cognitive function in patients with Alzheimer's disease and depressive disorder. At present, little research has been done on such alleviation in schizophrenia patients. ObjectiveTo explore the effect of aerobic exercise on cognitive function in male patients with chronic schizophrenia, so as to provide references for relevant treatments. MethodsA total of 76 male patients with chronic schizophrenia hospitalized in the Fourth People's Hospital of Wuhu between December 2022 and April 2023 were selected as the study subjects and, in accordance with random number table, divided into study group (n=36) and control group (n=40). Both groups received conventional drug treatment. On this basis, the study group received a 60-minute aerobic exercise 5 times a week for 8 weeks as intervention. Before and after intervention, assessment of cognitive function was performed by using MATRICS Consensus Cognitive Battery (MCCB) and Stroop Color Word Test (SCWT). ResultAfter intervention, compared with the control group, the study group spent less time on finishing the Trail Making Test and scored higher in both the spatial span test and maze test (Z=-2.070, -2.306, -2.375, P<0.05). Repeated measure ANOVA results showed that the time main effect of Hopkins Verbal Learning Test score was statistically significant in the two groups after intervention (F=39.067, P<0.05). So was the interaction effect between the time and group of the Brief Visuospatial Memory Test and Verbal Fluency Test scores (F=10.092, 9.252, P<0.05). After intervention, the scores of the Brief Visuospatial Memory Test and Verbal Fluency Test in the study group were higher than those in the control group (t=6.689, 4.249, P<0.05). As for the study group itself, the scores were higher than those before intervention (t=23.746, 23.842, P<0.05). After intervention, the numbers of correct reading in color test and word test in the study group were more than those in the control group (Z=-2.358, -2.771, P<0.05). The interaction effect between the time and group of the reaction time in color test, word test and color word interference test were statistically significant in both groups (F=23.383, 19.888, 19.662, P<0.05). After intervention, the reaction time in color test and color word interference test of the study group was shorter than those of the control group (t=4.895, 6.163, P<0.05). As for the study group itself, the reaction time were shorter than before intervention (t=54.318, 42.425, 42.141, P<0.01). ConclusionAerobic exercise may help alleviate the cognitive problems in male patients with chronic schizophrenia in terms of information processing speed, working memory, reasoning/problem solving ability, word learning and memorizing, visual learning and memorizing, and executive function. [Funded by Wuhu Science and Technology Plan Project (number, 2021jc2-3)]


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