1.Jiawei Chunze Decoction treats urinary retention after spinal cord injury in rats based on the regulation of endoplasmic reticulum stress apoptosis
Bochao ZHU ; Yanjie LI ; Hewei QIN ; Nannan ZHAO ; Haoyuan LIU ; Zhenhua XU ; Yupu WANG
Chinese Journal of Tissue Engineering Research 2025;29(2):371-378
BACKGROUND:Preliminary clinical observations found that Jiawei Chunze Decoction is an effective formula for clinical treatment of urinary retention after spinal cord injury.Animal experiments have found that the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway is closely related to the degree of bladder dysfunction. OBJECTIVE:To further investigate the effects of Jiawei Chunze Decoction on bladder function and PI3K/Akt signaling pathway in rats with urinary retention. METHODS:Sixty female Sprague-Dawley rats were randomly divided into sham operation group,model group,Jiawei Chunze Decoction low-dose group,Jiawei Chunze Decoction high-dose group and agonist group.In the sham operation group,the spinal cord was exposed but not transected.In the other groups,the modified Hassan Shaker spinal cord transection method was used to prepare the model of sacral medullary injury.At 24 hours after modeling,the sham operation group and model group were intragastrically given equal volume of normal saline,Jiawei Chunze Decoction low-dose and high-dose groups were given Jiawei Chunze Decoction granules containing 14.4 and 28.8 g/kg,respectively,via intragastric administration for 4 weeks,and the agonist group was treated with an intraperitoneal injection of PI3K/Akt signaling pathway agonist 740Y-P at a dose of 0.02 mg/kg.After 4 weeks of treatment,the maximum bladder capacity,leakage point pressure and bladder compliance of rats in each group were detected by urine flow dynamics.The minimum bladder contraction tension and frequency of rats in each group were detected by detrusor pull test.The pathological changes of the rat bladder in each group were observed by hematoxylin-eosin staining.The concentrations of GRP78,CHOP and Caspase-12 in serum were detected by ELISA,and the mRNA and protein expressions of PI3K,Akt,GRP78,CHOP and Caspase-12 in bladder tissues were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats in the model group were increased(P<0.05),and the leakage point pressure and bladder contraction frequency were decreased(P<0.05);serum GRP78,CHOP,and Caspase-12 levels were also increased(P<0.05).The arrangement of bladder epithelial cells in the model group was disordered,and there was monocyte infiltration between cells,tissue edema,and detrusor tract atrophy.The mRNA and protein expressions of PI3K and Akt in bladder tissues were significantly decreased in the model group compared with the sham operation group,while those of GRP78,CHOP and Caspase-12 were increased(P<0.05).Compared with the model group,the maximum bladder volume,bladder compliance and minimum systolic tension of rats were decreased in the Jiawei Chunze Decoction low-dose,high-dose and agonist groups after 4 weeks of intervention(P<0.05),while the leakage point pressure and bladder contraction frequency were increased(P<0.05);serum GRP78,CHOP,Caspase-12 levels were decreased(P<0.05).The bladder epithelial cells in the three intervention groups were distributed evenly,arranged neatly,with less inflammatory cell infiltration and fuller detrusor muscle bundle.Compared with the model group,the mRNA and protein expressions of PI3K and Akt were increased in the three intervention groups,while those of GRP78,CHOP and Caspase-12 were decreased(P<0.05).The Jiawei Chunze Decoction high-dose group was better than the Jiawei Chunze Decoction low-dose group and shared the similar results with the agonist group.To conclude,Jiawei Chunze Decoction can improve the bladder function of rats with urinary retention after spinal cord injury,and the mechanism may be related to reducing the occurrence of endoplasmic reticulum stress in bladder tissue through the PI3K/Akt signaling pathway,and then alleviating apoptosis.
2.Traditional Chinese medicine monomer in treatment of neuroinflammation after spinal cord injury:effects of nuclear transcription factor kappa B signaling pathway
Zhenhua XU ; Yanjie LI ; Hewei QIN ; Haoyuan LIU ; Bochao ZHU ; Yupu WANG
Chinese Journal of Tissue Engineering Research 2025;29(3):590-598
BACKGROUND:Targeted therapy based on nuclear transcription factor kappa B signaling pathway to explore neuroinflammation is increasingly worth exploring,and the advantages of Chinese medicine such as many targets,wide range,rich mechanisms,and few side effects have great potential in the treatment of various diseases. OBJECTIVE:Based on the nuclear transcription factor kappa B signaling pathway,this paper systematically expounded and summarized the research progress of kaempferol,safflower yellow,baicalin,and triptolide in the treatment of neuroinflammation after spinal cord injury. METHODS:Search terms"spinal cord injury,inflammation,anti-inflammatory,traditional Chinese medicine monomer,monomeric compound,NF-κB signaling pathway,flavonoids,glycosides,phenols,esters,alkaloids"were searched in CNKI and PubMed databases.Totally 67 articles were finally included. RESULTS AND CONCLUSION:(1)The role of nuclear transcription factor kappa B signaling pathway in the nervous system is complex and diverse,which can regulate neutrophils,microglia,astrocytes,and macrophages,and mediate the occurrence and development of inflammation after injury.(2)The effects of traditional Chinese medicine monomers such as baicalin on the degradation of nuclear transcription factor kappa B inhibitory protein,the inhibition of phosphorylation process by safflowerin on nuclear transcription factor kappa B signaling pathway,and the inhibition of kaempferol on nuclear transcription factor kappa B signaling pathway p65 nuclear translocation can reduce the impact of inflammatory response on the body,thereby promoting the recovery of neurological function.(3)The nuclear transcription factor kappa B signaling pathway can promote inflammation and immune cell migration and activation in the early stage of injury,and can promote the repair of injury site and the occurrence of fibrosis in the middle and late stages of injury.Appropriate activation of the nuclear transcription factor kappa B signaling pathway can promote the release of inflammatory factors,improve the antioxidant capacity of cells,and promote the activation of immune cells,but the over-activated nuclear transcription factor kappa B signaling pathway can easily lead to the occurrence and continuation of chronic inflammation and the inhibition of apoptosis.(4)Future research can further explore how to accurately regulate the activation level of nuclear transcription factor kappa B signaling pathway,how to achieve precise intervention for nervous system inflammation and injury,and can also focus on the preparation of traditional Chinese medicine monomers and the mechanism of action of traditional Chinese medicine monomers on signaling pathways,in order to provide more effective treatment strategies for the rehabilitation and functional recovery of neurological diseases.
3.Mechanistic of Modified Chunzetang in Treating Spinal Cord Injury-induced Urinary Retention in Rats Based on JNK/p38 MAPK Signaling Pathway
Yupu WANG ; Yanjie LI ; Hewei QIN ; Haoyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):30-38
ObjectiveTo investigate the effects of modified Chunzetang on urinary retention in rats with spinal cord injury (SCI) and the c-Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK) signaling pathway. MethodBefore modeling, 10 of the 70 female SD rats were randomly selected to assign to the blank group, and 10 to the sham group. The remaining 50 rats were used to prepare a SCI-induced urinary retention model using the spinal cord transection method. The model rats were randomly divided into model group, low-dose modified Chunzetang group, high-dose modified Chunzetang group, and inhibitor group. After modeling, the blank group, sham group, and inhibitor group were given 2 mL of saline by gavage. The high-dose and low-dose groups of modified Chunzetang were given modified Chunzetang at 28.8 g·kg-1 and 14.4 g·kg-1 by gavage, respectively. The inhibitor group was injected intraperitoneally with the JNK inhibitor SP600125 twice a week at a dose of 15 mg·kg-1. All rats were gavaged for a total of 28 days. Urodynamic and bladder muscle tension tests were conducted to evaluate bladder function. Hematoxylin-eosin (HE) staining was performed to observe the morphology of bladder smooth muscle tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of JNK, phosphorylated (p)-p38 MAPK, B cell lymphoma-2 (Bcl-2), and cysteinyl aspartate-specific proteinase-3 (Caspase-3). Western blot was used to detect the expression levels of p-JNK, p-p38 MAPK, ETS-like protein-1 (ELK-1), and activator protein-1 (AP1) in the detrusor muscle. Immunofluorescence was used to detect the expression levels of p-JNK, p-p38 MAPK, and AP1. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was conducted to measure cell apoptosis. ResultCompared with blank group and sham group, the model group showed a significant increase in maximum bladder capacity and bladder compliance, and a significant decrease in leak point pressure. The minimum contraction force was increased, and the contraction frequency was significantly decreased (P<0.01). The structure of bladder smooth muscle was disordered, with a large number of vacuolar cells, tissue edema, mononuclear cell infiltration, obvious hemorrhage, and a trend towards fibrosis in connective tissue. TUNEL positive cells increased significantly. The protein expression levels of p-JNK, p-p38 MAPK, AP1, and ELK-1 were significantly increased (P<0.01). Compared with model group, all intervention groups showed significant improvement in urodynamic and bladder muscle contraction tests. In the low-dose modified Chunzetang group, the levels of p-p38 MAPK and Caspase-3 was decreased (P<0.05,P<0.01). The levels of JNK, p-p38 MAPK and Caspase-3 in the high-dose group were significantly decreased (P<0.01), and the level of Bcl-2 was significantly increased (P<0.01). The expression levels of p-JNK, p-p38 MAPK, and AP1 proteins were significantly reduced (P<0.01), and ELK-1 protein expression was decreased (P<0.05). The positive rate of p-JNK and AP1 receptors was significantly decreased (P<0.01). The positive cell rate was significantly decreased (P<0.01). The high-dose modified Chunzetang group was positioned between the low-dose group and the inhibitor group, with no significant difference compared to the inhibitor group. ConclusionModified Chunzetang can improve urinary retention in SCI and enhance the contraction force of bladder smooth muscle. This effect is related to the inhibition of the JNK/p38 MAPK signaling pathway activation, thereby reducing apoptosis of bladder smooth muscle cells.
4.Clinical observation of Tuina plus Chinese medication hot compress for lumbar muscle strain
Ji MA ; Fei GU ; Yupu ZHANG ; Xingwei CHEN ; Yumin LIU ; Zhengcai YU ; Cheng WANG ; Jue HONG
Journal of Acupuncture and Tuina Science 2024;22(5):387-392
Objective:To discuss the clinical efficacy of treating lumbar muscle strain(LMS)with Tuina(Chinese therapeutic massage)plus Chinese medication hot compress. Methods:A total of 147 LMS patients were randomized into a Tuina group,a Chinese medication hot compress group,and a combined group,each consisting of 49 cases.The Tuina group received Tuina treatment;the Chinese medication hot compress group received Chinese medication hot compress treatment;and the combined group received the forementioned two therapies alternately.The three groups of patients were assessed using the visual analog scale(VAS)and Oswestry disability index(ODI)before treatment and after 2 weeks of treatment.A 2-month follow-up was also conducted to observe the relapse rate. Results:The VAS and ODI scores dropped significantly after treatment in all three groups compared with their baseline(P<0.05),and the combined group surpassed the other two groups in comparing the ODI score(P<0.05).The 2-month follow-up showed that the combined group had the lowest relapse rate among the three groups(P<0.05). Conclusion:Compared to each therapy used alone,Tuina plus Chinese medication hot compress can relieve pain,improve daily living function,and reduce the short-term relapse rate better in treating LMS patients.
5.Ten-year changes in clinical features of patients monitored by polysomnography in OSA diagnosis and treatment centers:Data analysis based on a large sample disease database
Jiaxin YANG ; Yupu LIU ; Lili MENG ; Huajun XU ; Huaming ZHU ; Jian GUAN ; Hongliang YI ; Sanlian HU ; Shankai YIN
Chinese Archives of Otolaryngology-Head and Neck Surgery 2023;30(12):794-799
OBJECTIVE Aimed to analyze the demographic,anthropometric,severity,and common comorbidities of individuals with suspected obstructive sleep apnea(OSA)referred to the OSA diagnosis and treatment center of the Sixth People's Hospital affiliated with Shanghai Jiao Tong University School of Medicine from 2012 to 2021.METHODS Data of subjects with suspected OSA who underwent polysomnography(PSG)from January 2012 to December 2021 were collected.Subjects were categorized into five groups based on the PSG study date with a two-year interval.Clinical characteristics trends were compared across groups,focusing on the comparison between 2020-2021 and 2018-2019 to explore changes after COVID-19 epidemic.RESULTS 1.A total of 5870 subjects were included from 2012 to 2019[age(43.2±12.7)years,21.7%females].OSA prevalence was 84.8%.Over the two-year intervals,age,female proportion,OSA severity,and other indicators showed no significant changes.Body mass index(median 26.8kg/m2 to 26.0kg/m2)and overweight rates(78.1%to 73.4%)decreased yearly,as did the proportions of subjects who smoked(38.1%to 27.8%)and consumed alcohol(13.5%to 6.4%).The prevalence of hypertension increased yearly(40.3%to 51.8%),while awareness rates gradually decreased(70.3%to 59.4%).Diabetes prevalence remained relatively stable(9.4%to 9.7%),with increased awareness(49.5%to 66.2%).Dyslipidemia prevalence remained high(76.7%to 78.3%),with low awareness rates(20.8%to 28.7%).2.A total of 805 subjects were included from 2020 to 2021.Compared with 2018-2019,the proportion of females decreased(14.9%vs.22.0%),and OSA severity increased(apnea-hypopnea index 40.4 times/h vs.29.2 times/h).Prevalence rates of hypertension,diabetes,dyslipidemia(47.1%,6.9%,62.1%)and awareness rates(52.4%,57.7%,17.8%)were lower than those from 2018-2019.3.Compared with subjects with known their comorbidities,unknown subjects had significantly higher levels of systolic blood pressure(141 mmHg vs.134 mmHg),diastolic blood pressure(93 mmHg vs.85 mmHg),fasting blood glucose(7.87 mmol/L vs.6.07 mmol/L),and low-density lipoprotein(3.08 mmol/L vs.2.91 mmol/L)(P<0.05).CONCLUSION From 2012 to 2021,individuals with suspected OSA referred for PSG test showed a tendency toward younger age,lower proportion of females,fewer comorbidities,but increased OSA severity.The awareness rate of comorbidities needs improvement,emphasizing the importance of a multidisciplinary approach to the diagnosis and treatment of OSA.
6.A review of animal models of post-traumatic stress disorder
Chang WANG ; Shuijin SHAO ; Yupu LIU ; Jing ZHU
Acta Laboratorium Animalis Scientia Sinica 2018;26(3):404-409
Post-traumatic stress disorder ( PTSD) is a serious psychiatric disorder when someone suffered from a major trauma, next followed by sleep disorder, emotional and cognitive disorder and other symptoms. Over the past few decades, many stress rodents models have been developed for searching the potential pathophysiological pathways of PTSD. All models showed PTSD-like symptoms, but none of them could manifestate all the symptoms and biological changes of PTSD completely. Thus, this article makes a brief summary about the PTSD models commonly used in recent years.
7.Mechanism of neural plasticity of acupuncture on chronic migraine.
Xiaobai XU ; Lu LIU ; Luopeng ZHAO ; Zhengyang QU ; Yupu ZHU ; Yajie ZHANG ; Linpeng WANG
Chinese Acupuncture & Moxibustion 2017;37(10):1134-1140
Chronic migraine is one of neurological disorders with high rate of disability, but sufficient attention has not been paid in this field. A large number of clinical studies have shown traditional Chinese acupuncture is a kind of effective treatment with less side effects. Through the analysis of literature regarding acupuncture and migraine published from 1981 to 2017 in CNKI and PubMed databases, the mechanism of neural plasticity of acupuncture on chronic migraine was explored. It was believed the progress of chronic migraine involved the changes of neural plasticity in neural structure and function, and the neural plasticity related with neural sensitization during the process of chronic migraine was discussed from three aspects of electrophysiology, molecular chemistry and radiography. Acupuncture could treat and prevent chronic migraine via the mechanism of neural plasticity, but there was no related literature, hindering the further spreading and development of acupuncture for chronic migraine.
8.Effects of Electroacupuncture on Brain Derived Neurotrophic Factor of Rats with Sciatic Nerve Injury
Xiaochun YE ; Shuijin SHAO ; Haidong GUO ; Xiaojing HAN ; Yupu LIU ; Pingping LU
Chinese Journal of Information on Traditional Chinese Medicine 2017;24(6):60-63
Objective To explore the effects of electroacupuncture on brain derived neurotrophic factor (BDNF) of rats with sciatic nerve injury (SNI); To discuss its biological mechanism for treatment of SNI. Methods Fifty adult male Wistar rats were chosen, and the sciatic nerves of rats were cut off and pulled on both sides of the cut ends into nerve regeneration chamber. The rats were randomly divided into normal group, sham-operation group, model group, and electroacupuncture group. In the electroacupuncture group, the rats were treated by electroacupuncture for 28 days. After the treatment, the nerve regeneration was observed through HE staining. Immunofluorescence was used to analyze the expression changes of BDNF in the nerve tissue and spinal cord. ELISA was used to observe the changes of expression of serum BDNF. Results The amount of axon regeneration in the electroacupuncture group was obviously more than that in the model group, and the outline of the tissue more clear. Electroacupuncture could promote the expression of BDNF in the nerve, spinal cord and serum of SNI of rats compared with model group (P<0.01). Conclusion Electroacupuncture can promote the repairment and regeneration of SNI in rats by upregulating the expression of BDNF.
10.The clinical and muscular pathological study of dermatomyositis with perifascicular atrophy changes
Zhi LIU ; Lin CHEN ; Yupu GUO ; Haitao REN ; Yanhuan ZHAO
Chinese Journal of Internal Medicine 2012;51(9):698-701
ObjectiveTo investigate the clinical and pathological characteristics of dermatomyositis with muscular perifascicular atrophy (PFA).MethodsA series of 104 consecutive patients clinically and pathologically diagnosed as dermatomyositis by muscle biopsy in our laboratory from December,2003 to August,2011,were enrolled in this study. Muscle biopsy of all the enrolled patients had shown PFA of muscle fibers.ResultsAmong the 104 patients,34 were males and 70 were females with a mean age of 45 years old.Among them,8 cases had normal electromyogram;42 had normal serum creatine kinase level;11 were diagnosed as carcinoma;75 were found to be combined with interstitial lung disease (ILD).Based on morphologic changes of muscle biopsy,they were divided into pure PFA group with 54 cases and PFA plus focal damage group with 50 cases.Compared with the pure PFA group,there was prominent mononuclear cell infiltration into perimysial intermediate sized vessels and membrane attack complement (MAC) deposition in the intramuscular capillaries in the PFA plus group.Skin biopsy had been taken in 12 cases together with muscle biopsy and had shown the border effectof both PFA and interface dermatitis in muscle and skin.ConclusionsOur study suggests that chronic immune vascular damage and insufficiency in dermatomyositis may cause ischemia and focal myofiber damage in watershed regions. The incidence of ILD in our dermatomyositis patients with PFA is high.

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