1.Xiaoyaosan Regulates HPT Axis in Rat Model with Syndrome of Liver Depression and Spleen Deficiency via CGA/GPX2/TSHβ Pathway for Thyroid Hormone Synthesis
Fang WANG ; Ruxin YUAN ; Lingjin FAN ; Zongli CHEN ; Huaye XIAO ; Liqiang YANG ; Xiaohong LI ; Chuncheng ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):1-10
ObjectiveTo explore the mechanism by which Xiaoyaosan regulates HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency by observing its effect on the glycoprotein hormone α-subunit (CGA)/glutathione peroxidase 2 (GPX2)/thyroid-stimulating hormone β-subunit (TSHβ) pathway for thyroid hormone synthesis. MethodsSeventy-two male SD rats were randomized into six groups: normal, model, high-dose (16.7 g·kg-1), medium-dose (8.35 g·kg-1), and low-dose (4.175 g·kg-1) Xiaoyaosan, and fluoxetine (0.001 8 g·kg-1) groups, with 12 rats in each group. The rat model of liver depression and spleen deficiency was induced by chronic restraint stress for 21 days. The intervention groups were treated with Xiaoyaosan decoctions or fluoxetine suspension, respectively. After modeling, hematoxylin-eosin staining was employed to observe morphological changes in the thyroid and pituitary tissue of the rats. Serum levels of triiodothyronine (T3), tetraiodothyronine (T4), and thyroid-stimulating hormone (TSH) were measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of TSH receptor (TSHR) in the thyroid tissue, thyrotropin-releasing hormone receptor (TRHR) and TSHβ in the pituitary tissue, and thyrotropin-releasing hormone (TRH), CGA, GPX2, and TSHβ in the hypothalamic tissue. ResultsCompared with the normal group, the model group showed significant atrophy and irregularity of thyroid follicles, a marked reduction in colloid secretion, extensive vacuolar degeneration of adenocytes in the anterior pituitary, lowered serum levels of T3, T4, and TSH (P<0.01), and down-regulated mRNA and protein levels of TSHR in the thyroid tissue, TRHR and TSHβ in the pituitary tissue, and TRH, CGA, GPX2, and TSHβ in the hypothalamic tissue (P<0.01). Compared with the model group, high- and medium-dose Xiaoyaosan and fluoxetine alleviated the pathological changes in the thyroid and pituitary tissue, outperforming the low-dose Xiaoyaosan group. Moreover, they elevated the serum levels of T3, T4, and TSH (P<0.05, P<0.01). The serum TSH level was also elevated in the low-dose Xiaoyaosan group (P<0.05). The mRNA and protein levels of TSHR in the thyroid, TRHR and TSHβ in the pituitary, and TRH, CGA, GPX2, and TSHβ in the hypothalamus were up-regulated in the high- and medium-dose Xiaoyaosan groups (P<0.05, P<0.01). Additionally, the mRNA and protein levels of TSHβ in the hypothalamus were up-regulated in the low-dose Xiaoyaosan group (P<0.01). In the fluoxetine group, the mRNA and protein levels of TSHR in the thyroid, TRHR in the pituitary, and TRH, CGA, and GPX2 in the hypothalamus were up-regulated (P<0.05, P<0.01). ConclusionThe downregulation of CGA/GPX2/TSHβ pathway may be one of the biological mechanisms underlying HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency. Xiaoyaosan may regulate the HPT axis dysfunction by up-regulating the CGA/GPX2/TSHβ pathway.
2.Terms Related to The Study of Biomacromolecular Condensates
Ke RUAN ; Xiao-Feng FANG ; Dan LI ; Pi-Long LI ; Yi LIN ; Zheng WANG ; Yun-Yu SHI ; Ming-Jie ZHANG ; Hong ZHANG ; Cong LIU
Progress in Biochemistry and Biophysics 2025;52(4):1027-1035
Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.
3.Review of chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex and prediction of its Q-markers.
Meng-Fan PENG ; Bao-Song LIU ; Pei-Pei YAN ; Cai-Xia LI ; Xiao-Fang ZHANG ; Yi ZHENG ; Ya-Gang SONG ; Tong LIU ; Lei YANG ; Ming-San MIAO
China Journal of Chinese Materia Medica 2025;50(4):946-958
Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry*
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Drugs, Chinese Herbal/pharmacology*
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Quality Control
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Humans
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Animals
4.Metabolomics combined with network pharmacology reveals mechanism of Jiaotai Pills in treating depression.
Guo-Liang DAI ; Ze-Yu CHEN ; Yan-Jun WANG ; Xin-Fang BIAN ; Yu-Jie CHEN ; Bing-Ting SUN ; Xiao-Yong WANG ; Wen-Zheng JU
China Journal of Chinese Materia Medica 2025;50(5):1340-1350
This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals
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Drugs, Chinese Herbal/chemistry*
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Depression/genetics*
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Mice
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Network Pharmacology
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Metabolomics
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Male
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Disease Models, Animal
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Humans
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Protein Interaction Maps/drug effects*
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Antidepressive Agents
5.Polarized light microscopic mineral phase authentication and health risk assessment of raw and calcined fossil mineral Chinese medicinal material Draconis Os.
Yan-Qiong PAN ; Zheng LIU ; Li-Wen ZHENG ; Ying ZHANG ; Liu ZHOU ; Xi-Long QIAN ; Fang FANG ; Xiao WU ; Sheng-Jin LIU
China Journal of Chinese Materia Medica 2025;50(15):4238-4247
This study aims to investigate the polarized microscopic mineral phase characteristics, inorganic element content, and potential health risks associated with the intake of raw and calcined fossil mineral Chinese medicinal material Draconis Os. Microscopy was employed to observe the mineralogical characteristics of Draconis Os and compare the microscopic features and phase composition of raw and calcined Draconis Os under monochromatic and orthogonal polarized light. Inductively coupled plasma mass spectrometry(ICP-MS) was employed to determine the content of 30 inorganic elements. Health risk assessment was conducted by calculating the single pollution index(P_i), average daily intake of elements for adults(ADI), target hazard quotient(THQ), non-carcinogenic assessment method-hazard quotient(HQ), and the carcinogenic risk of elements(CR). The results indicated that under monochromatic polarized light, the Draconis Os powder sections exhibited light gray-brown to gray-brown irregular fragments, some with undulating textures that were slightly curved. Under crossed polarized light, they appeared dark gray, grayish-white, and yellowish-white. Clear apatite was visible in the ground sections of Draconis Os under crossed polarized light. P_i results indicated that Draconis Os samples were free from contamination and were of good quality. According to the maximum allowable limits of heavy metals stipulated in ISO Traditional Chinese Medicine: Determination of heavy metals in herbal medicines used in Traditional Chinese Medicine, ADI, THQ, HQ, and CR were taken as assessment indicators. Only the THQ value for As(arsenic) in raw Draconis Os was greater than 1, while the THQ values for other heavy metal elements in the Draconis Os samples were all less than 1. The study demonstrates that the primary mineral phase of raw and calcined Draconis Os is apatite, with some samples co-existing with calcite, which can serve as one of the means for quality control of Draconis Os. The elemental analysis results from ICP-MS provide scientific evidence for the safety assessment of Draconis Os, indicating that Draconis Os is safe in clinical application.
Drugs, Chinese Herbal/analysis*
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Risk Assessment
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Minerals/chemistry*
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Fossils
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Humans
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Drug Contamination
;
Mass Spectrometry
6.Clinical characteristics and prognosis of chronic disseminated candidiasis in children with acute leukemia following chemotherapy: a multicenter clinical study.
Xin-Hong JIANG ; Pei-Jun LIU ; Chun-Ping WU ; Kai-Zhi WENG ; Shu-Quan ZHUANG ; Shu-Xian HUANG ; Xiao-Fang WANG ; Yong-Zhi ZHENG
Chinese Journal of Contemporary Pediatrics 2025;27(5):540-547
OBJECTIVES:
To investigate the clinical characteristics and prognosis of chronic disseminated candidiasis (CDC) in children with acute leukemia (AL) following chemotherapy.
METHODS:
A retrospective analysis was conducted on children diagnosed with CDC (including confirmed, clinically diagnosed, and suspected cases) after AL chemotherapy from January 2015 to December 2023 at Fujian Medical University Union Hospital, Zhangzhou Municipal Hospital, and Quanzhou First Hospital Affiliated to Fujian Medical University. Clinical characteristics and prognosis were analyzed.
RESULTS:
The incidence of CDC in children with AL following chemotherapy was 1.92% (32/1 668). Among the children with acute lymphoblastic leukemia, the incidence of CDC in the high-risk group was significantly higher than in the low-risk group (P=0.002). All patients presented with fever unresponsive to antibiotics during the neutropenic period, with 81% (26/32) involving the liver. C-reactive protein (CRP) levels were significantly elevated (≥50 mg/L) in 97% (31/32) of the patients. The efficacy of combined therapy with liposomal amphotericin B and caspofungin or posaconazole for CDC was 66% (19/29), higher than with caspofungin (9%, 2/22) or liposomal amphotericin B (18%, 2/11) monotherapy. The overall cure rate was 72% (23/32). The proportion of patients with CRP ≥50 mg/L and/or a positive β-D-glucan test for more than 2 weeks and breakthrough infections during caspofungin treatment was significantly higher in the treatment failure group compared to the successful treatment group (P<0.05).
CONCLUSIONS
CDC in children with AL after chemotherapy may be associated with prolonged neutropenia due to intensive chemotherapy. Combination antifungal regimens based on liposomal amphotericin B have a higher cure rate, while persistently high CRP levels and positive β-D-glucan tests may indicate poor prognosis.
Adolescent
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Child
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Child, Preschool
;
Female
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Humans
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Infant
;
Male
;
Antifungal Agents/therapeutic use*
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Candidiasis/diagnosis*
;
Chronic Disease
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Leukemia/complications*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*
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Prognosis
;
Retrospective Studies
7.Clinical efficacy of endocrinotherapy combined with Shenqi Pills on patients with hormone-sensitive prostate cancer.
Yu-Hong XIE ; Gang YI ; Xiao-Wen YI ; Tong-Lin SUN ; Qun-Fang LIN ; Jun ZHOU ; Xin-Jun LUO ; Fang-Zhi FU ; Biao WANG ; Qin-Zheng WANG ; Lie ZHANG ; Yang YANG ; Rui-Song GAO ; Qing ZHOU
National Journal of Andrology 2025;31(4):341-348
OBJECTIVE:
The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer (HSPC).
METHODS:
Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chinese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups. The patients in the control group were treated with androgen deprivation therapy (ADT). And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group. The baseline data of the two groups were analyzed. After 36 months of treatment, the differences between the two groups were compared in terms of overall survival (OS), prostate-specific antigen (PSA) level, PSA response rate, Functional Assessment Scale for Prostate Cancer Therapy (FACT-P), Chinese medicine evidence scores, testosterone level and safety.
RESULTS:
A total of 80 study subjects were included in this study, including 42 cases in the treatment group and 38 cases in the control group. There was no statistical difference in the baseline data between the two groups before treatment (P>0.05). At the end of the observation period, a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months (P<0.05). There was no statistically significant difference in PSA levels in the treatment group at 3 months (P>0.05). And the differences in the proportion of PSA50 (98.1% vs 91.4%), PSA90 (92.9% vs 84.6%) and the proportion of decrease in PSA (56.7% vs 33.8%) in the treatment group were found compared to those in the control group after 6 months of tre atment. After 12 months of treatment, the scores of FACT-4 and renal-yang deficiency in the treatment group were (95.28±7.93) and (15.73±5.70) respectively, compared to the scores in the control group ([85.46±10.12] and [18.20±4.27] (P<0.05). However, there was no significant difference in serum testosterone ([0.60±0.24] nmol/L vs [1.09±2.10] nmol/L) between the two groups (P>0.05). After 24 months of treatment, there were significant differences in in the FACT-4 total score ([97.95±7.54] vs [80.33±8.58]), renal-yang deficiency syndrome score ([14.64±5.15] vs [24.94±8.75]) between the treatment group and the control group (P<0.05). However, there was no significant difference in serum testosterone ( [0.73±1.01] nmol/L vs [0.59±0.25] nmol/L) between the two groups (P> 0.05). Better therapeutic results were showed in the treatment group in terms of total FACT-P score, physical situation score, social and family situation score, emotional state score, functional state score, additional score and renal-yang deficiency symptom score (P<0.05). After treatment, there was no serious adverse reaction in the course of treatment, and no obvious abnormality was found in the liver and kidney function of the patients from two groups.
CONCLUSION
Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients, and the earlier the intervention, the longer the overall survival of the patients. In addition, this treatment regimen can increase the PSA response rate, improve patients' quality of life, and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.
Humans
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Male
;
Drugs, Chinese Herbal/therapeutic use*
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Prostatic Neoplasms/drug therapy*
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Androgen Antagonists/therapeutic use*
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Prostate-Specific Antigen/blood*
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Aged
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Middle Aged
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Treatment Outcome
;
Testosterone
8.Effect of Hesperidin on Chronic Unpredictable Mild Stress-Related Depression in Rats through Gut-Brain Axis Pathway.
Hui-Qing LIANG ; Shao-Dong CHEN ; Yu-Jie WANG ; Xiao-Ting ZHENG ; Yao-Yu LIU ; Zhen-Ying GUO ; Chun-Fang ZHANG ; Hong-Li ZHUANG ; Si-Jie CHENG ; Xiao-Hong GU
Chinese journal of integrative medicine 2025;31(10):908-917
OBJECTIVES:
To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis.
METHODS:
Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats.
RESULTS:
Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05).
CONCLUSION
The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals
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Hesperidin/therapeutic use*
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Rats, Sprague-Dawley
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Depression/drug therapy*
;
Male
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Stress, Psychological/drug therapy*
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Brain/metabolism*
;
Brain-Derived Neurotrophic Factor/metabolism*
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Serotonin/metabolism*
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Gastrointestinal Microbiome/drug effects*
;
Behavior, Animal/drug effects*
;
Rats
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Brain-Gut Axis/drug effects*
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Chronic Disease
;
Colon/drug effects*
9.Sub-committee of Anesthesiology of Guangzhou Integrated Traditional Chinese and Western Medicine Society.
Yi LU ; Cunzhi LIU ; Wujun GENG ; Xiaozhen ZHENG ; Jingdun XIE ; Guangfang ZHANG ; Chao LIU ; Yun LI ; Yan QU ; Lei CHEN ; Xizhao HUANG ; Hang TIAN ; Yuhui LI ; Hongxin LI ; Heying ZHONG ; Ronggui TAO ; Jie ZHONG ; Yue ZHUANG ; Junyang MA ; Yan HU ; Jian FANG ; Gaofeng ZHAO ; Jianbin XIAO ; Weifeng TU ; Jiaze SUN ; Yuting DUAN ; Bao WANG
Journal of Southern Medical University 2025;45(8):1800-1808
OBJECTIVES:
To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and.
RESULTS:
Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.
CONCLUSIONS
The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans
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Medicine, Chinese Traditional
;
Cancer Pain/therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Drug Delivery Systems
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Pain Management/methods*
;
China
10.Interleukin-33 Knockout Promotes High Mobility Group Box 1 Release from Astrocytes by Acetylation Mediated by P300/CBP-Associated Factor in Experimental Autoimmune Encephalomyelitis.
Yifan XIAO ; Liyan HAO ; Xinyi CAO ; Yibo ZHANG ; Qingqing XU ; Luyao QIN ; Yixuan ZHANG ; Yangxingzi WU ; Hongyan ZHOU ; Mengjuan WU ; Mingshan PI ; Qi XIONG ; Youhua YANG ; Yuran GUI ; Wei LIU ; Fang ZHENG ; Xiji SHU ; Yiyuan XIA
Neuroscience Bulletin 2025;41(7):1181-1197
High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals
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Encephalomyelitis, Autoimmune, Experimental/metabolism*
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Astrocytes/metabolism*
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Interleukin-33/metabolism*
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HMGB1 Protein/metabolism*
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Acetylation
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Mice, Knockout
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Mice, Inbred C57BL
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p300-CBP Transcription Factors/metabolism*
;
Mice
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Spinal Cord/metabolism*
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Cells, Cultured
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Female
;
Signal Transduction

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