1.The Neurobiological Mechanisms of Runner’s High
Yun-Teng WANG ; Jia-Qi LIANG ; Wan-Tang SU ; Li ZHAO ; Yan LI
Progress in Biochemistry and Biophysics 2025;52(2):358-373
“Runner’s high” refers to a momentary sense of pleasure that suddenly appears during running or other exercise activities, characterized by anti-anxiety, pain relief, and other symptoms. The neurobiological mechanism of “runner’s high” is unclear. This review summarizes human and animal models for studying “runner’s high”, analyzes the neurotransmitters and neural circuits involved in runner’s high, and elucidates the evidence and shortcomings of researches related to “runner’s high”. This review also provides prospects for future research. Research has found that exercise lasting more than 30 min and with an intensity exceeding 70% of the maximum heart rate can reach a “runner’s high”. Human experiments on “runner’s high” mostly use treadmill exercise intervention, and evaluate it through questionnaire surveys, measurement of plasma AEA, miRNA and other indicators. Animal experiments often use voluntary wheel running intervention, and evaluate it through behavioral experiments such as conditional place preference, light dark box experiments (anxiety), hot plate experiments (pain sensitivity), and measurement of plasma AEA and other indicators. Dopamine, endogenous opioid peptides, endogenous cannabinoids, brain-derived neurotrophic factor, and other substances increase after exercise, which may be related to the “runner’s high”. However, attention should be paid to the functional differences of these substances in the central and peripheral regions, as well as in different brain regions. Moreover, current studies have not identified the targets of the neurotransmitters or neural factors mentioned above, and further in-depth researches are needed. The mesolimbic dopamine system, prefrontal cortex-nucleus accumbens projection, ventral hippocampus-nucleus accumbens projection, red nucleus-ventral tegmental area projection, cerebellar-ventral tegmental area projection, and brain-gut axis may be involved in the regulation of runner’s high, but there is a lack of direct evidence to prove their involvement. There are still many issues that need to be addressed in the research on the neurobiological mechanisms of “runner’s high”. (1) Most studies on “runner’s high” involve one-time exercise, and the characteristics of changes in “runner’s high” during long-term exercise still need to be explored. (2) The using of scales to evaluate subjects lead to the lacking of objective indicators. However, some potential biomarkers (such as endocannabinoids) have inconsistent characteristics of changes after one-time and long-term exercise. (3) The neurotransmitters involved in the formation of the “runner’s high” all increase in the peripheral and/or central nervous system after exercise. Attention should be paid to whether peripheral substances can enter the blood-brain barrier and the binding effects of neurotransmitters to different receptors are completely different in different brain regions. (4) Most of the current evidence show that some brain regions are activated after exercise. Is there a functional circuit mediating “runner’s high” between these brain regions? (5) Although training at a specific exercise intensity can lead to “runner’s high”, most runners have not experienced “runner’s high”. Can more scientific training methods or technological means be used to make it easier for people to experience the “runner’s high” and thus be more willing to engage in exercise? (6) The “runner’s high” and “addiction” behaviors are extremely similar, and there are evidences that exercise can reverse addictive behaviors. However, why is there still a considerable number of people in the sports population and even athletes who smoke or use addictive drugs instead of pursuing the “pleasure” brought by exercise? Solving the problems above is of great significance for enhancing the desire of exercise, improving the clinical application of neurological and psychiatric diseases through exercise, and enhancing the overall physical fitness of the population.
2.Differention and Treatment of Brain Metastasis from Lung Cancer Based on Theory of "Yang Qi Depletion and Latent Pathogens Transmitting to the Brain"
Huiying ZHAO ; Yanxia LIANG ; Guangsen LI ; Wenwen WANG ; Wenwen SU ; Fenggu LIU ; Hongfei XING ; Maorong FAN
Journal of Traditional Chinese Medicine 2025;66(9):968-972
3.Zuoguiwan Regulates Pdx1 Pathway to Improve Pancreas Development in Offspring of Gestational Diabetes Mellitus Model Rats
Wanqiu LIANG ; Rang CHEN ; Le ZHAO ; Xiaoyi REN ; Qianhui SU ; Yonghui WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):10-19
ObjectiveTo explore the mechanism by which Zuoguiwan improves the pancreas development in the gestational diabetes mellitus (GDM) model by observing the effects of Zuoguiwan on the expression of key regulatory factors in different stages of pancreas development. MethodsPregnant Wistar rats were randomly assigned into blank, model, insulin detemir (20 U·kg-1) and Zuoguiwan (1.89 g·kg-1) groups (n=18). GDM was induced by peritoneal injection of streptozotocin on day 6.5 (E6.5d) in the embryonic stage, and the blank group was given an equal volume of sodium citrate buffer. The modeling performance was assessed by measuring the blood glucose of pregnant rats. Except the blank group and model group, pregnant rats in other groups were administrated with corresponding drugs from E9.5d to delivery. The random blood glucose of pregnant rats was monitored, and the embryos and offspring rats were measured for the length and weighed on E12.5d, E18.5d and day 21 after birth (B21d). The Lee's index of rats on B21d was calculated. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the fasting insulin (FINS) levels of B22d rats and the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was calculated. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), total cholesterol (CHO), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) in E18.5d pregnant rats and B22d offspring were determined. The pathological changes in the pancreas of E12.5d, E18.5d and B22d rats were observed by hematoxylin-eosin (HE) staining. Western blot was used to determine the protein levels of pancreatic duodenal homeobox 1 (Pdx1), pancreas-specific transcription factor 1a (Ptf1a), and sex-determining region Y-box protein 9 (Sox9) in the pancreas of E12.5d embryos, Pdx1, Nkx2 homeobox 2 (Nkx2.2), and hairy and enhancer of split-1 (Hes1) in the pancreas of E18.5d embryos, and Pdx1, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa), and NK transcription factor-related homeobox gene family 6 locus 1 (Nkx6.1) in the pancreas of B22d rats. ResultsCompared with the blank group, the model group showed elevated blood glucose levels in pregnant rats on B0d, E9.5d, E12.5d, E15.5d, and E18.5d (P<0.05, P<0.01), decreased body weight and body length (P<0.01) and increased Lee's index in the offspring. In addition, the B22d offspring showed rising levels of FBG, FINS, HOMA-IR, AST, and TG (P<0.01), a declined level of HDL (P<0.01), and pancreatic acinous cells with edema and loose arrangement. The pregnant rats on E18.5d exhibited raised levels of ALT, AST, and TG (P<0.05, P<0.01) in the pancreas and a declined level of HDL (P<0.05). The E12.5d embryos showed up-regulated protein levels of Pdx1, Sox9, and Ptf1a in the pancreas (P<0.01) and the E18.5d embryos exhibited down-regulated protein levels of Pdx1, Nkx2.2, and Hes1 in the pancreas (P<0.01). The protein levels of Pdx1, Nkx6.1, and Mafa in the pancreas of B22d offspring were down-regulated (P<0.01). Compared with the model group, the insulin group exhibited lowered blood glucose in pregnant rats on B0d, E15.5d, and E18.5d (P<0.05, P<0.01). The offspring in all treatment groups showcased increased body weight and body length (P<0.01) and decreased Lee's index. The B22d offspring exhibited declined levels of FBG, FINS, and HOMA-IR in the insulin group (P<0.01) and lowered levels of FBG and HOMA-IR in the Zuoguiwan group (P<0.01). The B22d offspring in all the treatment groups showed reduced levels of ALT, AST, TBIL, CHO, TG, and LDL, a raised level of HDL, and alleviated edema of pancreatic acinous cells. The pregnant rats on E18.5d demonstrated declined levels of TG and ALT (P<0.05, P<0.01) and an elevated level of HDL (P<0.05). The pancreas of E12.5d embryos presented down-regulated protein levels of Pdx1 and Sox9 and an up-regulated protein level of Ptf1a in the insulin group (P<0.05). The pancreas of E12.5d embryos in the Zuoguiwan group presented down-regulated protein levels of Pdx1, Sox9, and Ptf1a (P<0.01). All the treatment groups showed up-regulated protein levels of Pdx1, Nkx2.2, and Hes1 in the pancreas of E18.5d embryos (P<0.01) and Pdx1, Nkx6.1, and Mafa in the pancreas of B22d embryos (P<0.05, P<0.01). ConclusionZuoguiwan can promote the growth and development and ameliorate the pathological changes in the pancreas of the offspring of GDM model by regulating the expression of Pdx1 pathway-related regulatory factors in different stages of pancreas development.
4.Improvement of quality standards for Zhuang medicine Yingbupu (Aralia armata)
Xiangpei ZHAO ; Jieying SU ; Tao XU ; Jing LIANG ; Yanjing LI ; Mei YANG
China Pharmacy 2025;36(21):2645-2650
OBJECTIVE To improve the quality standard of Zhuang medicine Yingbupu (Aralia armata). METHODS A total of 23 batches of Yingbupu (A. armata) were studied. Their macroscopic characteristics and powder microscopic features were observed. TLC was employed for the qualitative identification of oleanolic acid and araloside A. Items such as water content, total ash, acid-insoluble ash, and ethanol-soluble extract were determined according to the methods specified in the 2020 edition of the Chinese Pharmacopoeia (part Ⅳ). UPLC fingerprint was established for 23 batches of samples by using Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine (2012 edition), and the contents of oleanolic acid and araloside A were determined. RESULTS The powder microscopic characteristics of the medicinal material were distinctive. Oleanolic acid and araloside A were detected by TLC in all 23 batches. Among the 23 batches of samples, the content ranges of moisture, total ash, acid-insoluble ash, and ethanol-soluble extract were 6.9% to 10.4%, 1.8% to 6.8%, 0.1% to 1.9%, and 2.8% to 8.4%, respectively. Based on the UPLC fingerprint, a total of 15 common peaks were obtained, and 9 of these common peaks were identified. The content ranges of oleanolic acid and araloside A in the 23 batches of samples were 0.86% to 2.69% and 0.16% to 1.10%, respectively. CONCLUSIONS This study has added items such as moisture and total ash content fingerprint, TLC identification. A preliminary quality standard has been established for the medicinal material of Yingbupu (A. armata), stipulating that the moisture content should not exceed 11.0%, the total ash content should not exceed 5.0%, the acid-insoluble ash content should not exceed 2.5%, the ethanol-soluble extract(No. content should not be less than 4.0%, and the contents of zyyzdxk-2023165) oleanolic acid and araloside A should not be less than 1.00% and 0.45%( calculated by a dried basis), respectively.
5.Rapid characterization and identification of non-volatile components in Rhododendron tomentosum by UHPLC-Q-TOF-MS method.
Su-Ping XIAO ; Long-Mei LI ; Bin XIE ; Hong LIANG ; Qiong YIN ; Jian-Hui LI ; Jie DU ; Ji-Yong WANG ; Run-Huai ZHAO ; Yan-Qin XU ; Yun-Bo SUN ; Zong-Yuan LU ; Peng-Fei TU
China Journal of Chinese Materia Medica 2025;50(11):3054-3069
This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry*
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Chromatography, High Pressure Liquid/methods*
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Drugs, Chinese Herbal/chemistry*
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Mass Spectrometry/methods*
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Plant Leaves/chemistry*
6.Mechanism related to bile acids metabolism of liver injury induced by long-term administration of emodin.
Jing-Zhuo TIAN ; Lian-Mei WANG ; Yan YI ; Zhong XIAN ; Nuo DENG ; Yong ZHAO ; Chun-Ying LI ; Yu-Shi ZHANG ; Su-Yan LIU ; Jia-Yin HAN ; Chen PAN ; Chen-Yue LIU ; Jing MENG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(11):3079-3087
Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage*
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Bile Acids and Salts/metabolism*
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Animals
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Male
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Liver/injuries*
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Chemical and Drug Induced Liver Injury/genetics*
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Drugs, Chinese Herbal/adverse effects*
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Humans
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Rats, Sprague-Dawley
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Mice
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Rats
7.Establishment of different pneumonia mouse models suitable for traditional Chinese medicine screening.
Xing-Nan YUE ; Jia-Yin HAN ; Chen PAN ; Yu-Shi ZHANG ; Su-Yan LIU ; Yong ZHAO ; Xiao-Meng ZHANG ; Jing-Wen WU ; Xuan TANG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(15):4089-4099
In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals
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Disease Models, Animal
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Mice
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Pneumonia/genetics*
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Medicine, Chinese Traditional
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Male
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Humans
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Cytokines/immunology*
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Female
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Lipopolysaccharides/adverse effects*
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Lung/drug effects*
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Drugs, Chinese Herbal
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Ovalbumin
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Mice, Inbred BALB C
8.Primary intraosseous synovial sarcoma:a case report and literature review
Wen ZHAO ; Wei-Jun QIAN ; Li LI ; Yan-Min WANG ; Peng-Hui SU ; Chao-Xin ZHANG ; Liang XU ; Tie-Cheng WU ; Jun-Qi LIU ; Ya-Jun WANG
Medical Journal of Chinese People's Liberation Army 2025;50(11):1419-1425
Objective To report a case of tibial synovial sarcoma and review relevant literature to enhance understanding of this disease.Methods The clinical data of a patient with tibial synovial sarcoma treated at Kaifeng Central Hospital were retrospectively analyzed.A literature search was conducted in domestic and international databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,PubMed,Web of Science,and Embase,up to July 2024.Relevant literature was comprehensively reviewed to summarize the imaging and pathological characteristics,treatment,and prognosis of synovial sarcoma.Results A 29-year-old female patient was admitted with left lower extremity pain.X-ray examination revealed a proximal tibia space-occupying lesion suggestive of malignancy,and a mid-tibial space-occupying lesion considered benign.Contrast-enhanced computed tomography(CT)and plain magnetic resonance imaging(MRI)of the proximal tibial lesion also suggested malignancy.Ultrasound-guided biopsy of the proximal tibial tumor revealed a poorly differentiated malignant tumor.Immunohistochemistry results indicated monophasic synovial sarcoma,requiring genetic testing for definitive diagnosis.The patient underwent wide resection of the proximal left tibial malignancy with tumor-type artificial joint replacement,combined with curettage and bone cement filling for the left mid-tibial lesion under anesthesia.Postoperative pathology of space-occupying lesions in the proximal tibia confirmed monophasic synovial sarcoma,and fluorescence in situ hybridization(FISH)demonstrated a rupture of the synovial sarcoma translocation gene(SYT)(i.e.,SS18 positive).There was no recurrence or metastasis found in the patient during the reexamination 6 months after postoperative chemotherapy.As of July 2024,15 cases of genetically confirmed primary intraosseous synovial sarcoma have been reported internationally.Symptoms included pain and swelling,with a medical history of 1-2 years.The X-ray and CT findings showed osteolytic destruction with bone cortical discontinuity.In 13 cases,the intraosseous masses extended to the extraosseous area;in 2 cases,punctate calcifications were detected within the masses.Plain MRI scan showed iso-signal or hypo-signal on T1WI and hyper-signal,iso-signal,and hypo-signal on fat-suppressed T2WI,and enhanced MRI scan demonstrated heterogeneous enhancement.Pathological examination showed spindle-shaped cells under microscopy.Immunohistochemistry results showed positive epithelial membrane antigen(EMA),broad-spectrum cytokeratin(AE1/AE3),Ewing's sarcoma marker(CD99),and transducin-like enhancer of Split 1(TLE1).Twelve patients underwent surgical treatment;6 patients received adjuvant chemotherapy after surgery,of whom 4 developed local recurrence or distant metastasis at initial diagnosis,and 3 died during follow-up.Among the 6 patients who did not receive adjuvant chemotherapy,3 suffered from recurrence or distant metastasis.Conclusions Primary intraosseous synovial sarcoma is a rare malignant tumor with non-specific clinical manifestations.Imaging features typically include osteolytic destruction and intraosseous masses extending extraosseously,suggesting an intraosseous origin.Pathology and immunohistochemistry aid diagnosis,but definitive confirmation relies on further genetic testing.At present,the main treatment regimens for synovial sarcoma involve comprehensive therapies such as surgery and adjuvant chemotherapy,and the prognosis of patients is poor.
9.IL-17A collaborating with TGF-β1 in regulating benign tracheal stenosis after tracheal injury in experimental dogs
Chun ZHAO ; Yunfeng DENG ; Wei SU ; Hongyan DAI ; Lusheng LIANG ; Xueguang CAI ; Song XU ; Jun WANG ; Xin YANG ; Junren ZENG
Journal of Interventional Radiology 2025;34(5):487-492
Objective To discuss the effect of interleukin-17A(IL-17A)and transforming growth factor-β1(TGF-β1)on the benign tracheal stenosis after tracheal injury in experimental dogs.Methods The trachea stenosis model of healthy Beagle dogs was established by burning the middle part of trachea with electric snare under bronchoscopy guidance.A total of 21 dogs were divided into normal group(n=3,receiving normal feeding),molding group(n=12,after airway modeling every 3 dogs were sacrificed each week for 4 weeks),IL-17A suppression group(n=3,receiving Secukinumab after airway modeling),and IL-17A inhibitor+TGF-β1 inhibitor group(n=3,receiving Secukinumab and SB43154 after airway modeling).Bronchoscopy and CT scan were performed once a week,and the stenosis degree was calculated.RT-qPCR,immunohistochemistry,and HE staining of the obtained tracheal tissues were performed.Results Within 1-4 weeks after molding,in module-making dogs the degree of stenosis of the injured trachea gradually increased,and the expressions of ECM-related proteins,TGF-β1 and IL-17A were up-regulated.After treatment with IL-17A inhibitors,the inflammatory infiltration and granulation tissue hyperplasia were reduced and the early tracheal stenosis was improved(P<0.05).The combination use of IL-17A inhibitor and TGF-β1 inhibitor had a better remission effect(P<0.05).Conclusion IL-17A and TGF-β1 may synergistically affect the formation of tracheal stenosis.
10.Mechanism of Dahuang Tangluo Pills in Improving Renal Inflammatory Injury in Diabetic Kidkdey Disease by Regulating AGEs/RAGE/IKK/NF-κB Pathway
Pu ZHANG ; Jianqing LIANG ; Xia YANG ; Min BAI ; Xiangdong ZHU ; Chunxia XUE ; Beibei SU ; Yunhui ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):77-85
ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease (DKD) in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose (FBG). Mice with FBG ≥ 16.7 mmol·L-1, increased urine output, and persistent albuminuria were considered successful in model establishment. After successful modeling, they were randomly divided into a model group, a dapagliflozin group (1.5 mg·kg-1·d-1), and high, medium, and low dose groups of Dahuang Tangluo pills (3.6, 1.8, 0.9 g·kg-1·d-1, respectively), with eight mice in each group. All medication groups were administered orally, while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks, the survival status of the mice was observed, and their body weight, FBG, and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining, Masson staining, and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products (AGEs) and receptors for advanced glycation end products (RAGE) proteins. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were utilized to detect the gene and protein expression levels of AGEs, RAGE, inhibitor of nuclear factor-κB (NF-κB) kinase (IKK), and NF-κB in the renal tissues of mice in each group. ResultCompared with control group, the model group showed a significant increase in body weight, FBG, serum creatinine (SCr), urinary microalbumin/urine creatinine ratio (ACR), total cholesterol (TC), and triglycerides (TG) (P<0.05). The levels of intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in renal tissues were significantly elevated (P<0.05). Renal histopathological staining and electron microscopy revealed loose arrangement, gaps, structural disarray, mesangial proliferation, and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE, IKK, and NF-κB genes in renal tissues (P<0.05). Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues (P<0.05). Western blot results showed a significant increase in the expression of AGEs, RAGE, IKK, and NF-κB proteins in renal tissues (P<0.05). After drug intervention, compared with model group, the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight, FBG, SCr, and ACR (P<0.05), and a significant decrease in TC in mouse serum (P<0.05), while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum (P<0.05). All treatment groups showed a significant reduction in ICAM-1, IL-6, and TNF-α in renal tissues (P<0.05). Renal histopathological staining and electron microscopy showed improved kidney injury, decreased collagen fiber deposition, and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE, IKK, and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). Western blot results showed a significant decrease in the expression of AGEs, RAGE, IKK, and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups (P<0.05). ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice, possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

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