1.Study on the mechanism of Jiawei xiaochaihu decoction inhibiting hippocampal neuronal apoptosis in epileptic mice via regulating AKT/Bcl-xL/Bax/Caspase-3 signaling axis
Ling LU ; Sheng ZHUANG ; Yijue QIN ; Haishun QU ; Yanwei YANG ; Weicheng XU
China Pharmacy 2026;37(13):1728-1734
OBJECTIVE To explore the mechanism of Jiawei xiaochaihu decoction against hippocampal neuronal apoptosis in acute epileptic model mice. METHODS Thirty-six male KM mice were randomly divided into four groups with 9 mice in each group: normal control group (normal saline), epilepsy model group (normal saline), Jiawei xiaochaihu decoction group [7 g/(kg·d)] and carbamazepine group [positive control, 30 mg/(kg·d)]. Except for the normal control group, the acute epilepsy model was established in the other groups. After successful modeling, mice in each group were given corresponding drugs or normal saline by intragastric administration once a day for 2 consecutive weeks. After drug intervention, the ultrastructure and pathological morphology of hippocampal CA1 region were observed. The number of TUNEL-positive cells in hippocampus was detected, and the expression levels of protein kinase B (AKT), Caspase-3, B-cell lymphoma-extra large (Bcl-xL), Bcl-2-associated X protein (Bax), as well as the ratio of phosphorylated AKT(p-AKT) to AKT were determined. RESULTS Compared with the normal control group, severe ultrastructural and pathological damages were observed in the hippocampal CA1 region of epilepsy model group; the number of TUNEL-positive cells was significantly increased ( P <0.05). The expression levels of p-AKT and Bcl-xL were significantly down-regulated ( P <0.05), while the Bax and Caspase-3 were significantly up-regulated ( P <0.05),accompanied by a remarkable decrease of p-AKT/AKT ratio ( P <0.05). Compared with the epilepsy model group, hippocampal tissue ultrastructure, pathological damage, and the aforementioned indicators were significantly improved in Jiawei xiaochaihu decoction group ( P <0.05). CONCLUSIONS Jiawei xiaochaihu decoction can inhibit hippocampal neuronal apoptosis in acute epileptic mice, and its mechanism may be related to activating AKT phosphorylation, increasing p-AKT/AKT ratio, up-regulating Bcl-xL expression and down-regulating the expression of Bax and Caspase-3.
2.Study on the mechanism of Jiawei xiaochaihu decoction inhibiting hippocampal neuronal apoptosis in epileptic mice via regulating AKT/Bcl-xL/Bax/Caspase-3 signaling axis
Ling LU ; Sheng ZHUANG ; Yijue QIN ; Haishun QU ; Yanwei YANG ; Weicheng XU
China Pharmacy 2026;37(13):1728-1734
OBJECTIVE To explore the mechanism of Jiawei xiaochaihu decoction against hippocampal neuronal apoptosis in acute epileptic model mice. METHODS Thirty-six male KM mice were randomly divided into four groups with 9 mice in each group: normal control group (normal saline), epilepsy model group (normal saline), Jiawei xiaochaihu decoction group [7 g/(kg·d)] and carbamazepine group [positive control, 30 mg/(kg·d)]. Except for the normal control group, the acute epilepsy model was established in the other groups. After successful modeling, mice in each group were given corresponding drugs or normal saline by intragastric administration once a day for 2 consecutive weeks. After drug intervention, the ultrastructure and pathological morphology of hippocampal CA1 region were observed. The number of TUNEL-positive cells in hippocampus was detected, and the expression levels of protein kinase B (AKT), Caspase-3, B-cell lymphoma-extra large (Bcl-xL), Bcl-2-associated X protein (Bax), as well as the ratio of phosphorylated AKT(p-AKT) to AKT were determined. RESULTS Compared with the normal control group, severe ultrastructural and pathological damages were observed in the hippocampal CA1 region of epilepsy model group; the number of TUNEL-positive cells was significantly increased ( P <0.05). The expression levels of p-AKT and Bcl-xL were significantly down-regulated ( P <0.05), while the Bax and Caspase-3 were significantly up-regulated ( P <0.05),accompanied by a remarkable decrease of p-AKT/AKT ratio ( P <0.05). Compared with the epilepsy model group, hippocampal tissue ultrastructure, pathological damage, and the aforementioned indicators were significantly improved in Jiawei xiaochaihu decoction group ( P <0.05). CONCLUSIONS Jiawei xiaochaihu decoction can inhibit hippocampal neuronal apoptosis in acute epileptic mice, and its mechanism may be related to activating AKT phosphorylation, increasing p-AKT/AKT ratio, up-regulating Bcl-xL expression and down-regulating the expression of Bax and Caspase-3.
3.Immunoregulatory mechanisms in the aging microenvironment: Targeting the senescence-associated secretory phenotype for cancer immunotherapy.
Haojun WANG ; Yang YU ; Runze LI ; Huiru ZHANG ; Zhe-Sheng CHEN ; Changgang SUN ; Jing ZHUANG
Acta Pharmaceutica Sinica B 2025;15(9):4476-4496
The aging microenvironment, as a key driver of tumorigenesis and progression, plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype (SASP). SASP consists of a variety of interleukins, chemokines, proteases, and growth factors. It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms, thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment. Furthermore, these secreted factors activate key signaling pathways such as NF-κB, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.
4.International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025).
Sheng-Sheng ZHANG ; Lu-Qing ZHAO ; Xiao-Hua HOU ; Zhao-Xiang BIAN ; Jian-Hua ZHENG ; Hai-He TIAN ; Guan-Hu YANG ; Won-Sook HONG ; Yu-Ying HE ; Li LIU ; Hong SHEN ; Yan-Ping LI ; Sheng XIE ; Jin SHU ; Bin-Fang ZENG ; Jun-Xiang LI ; Zhen LIU ; Zheng-Hua XIAO ; Jing-Dong XIAO ; Pei-Yong ZHENG ; Shao-Gang HUANG ; Sheng-Liang CHEN ; Gui-Jun FEI
Journal of Integrative Medicine 2025;23(5):502-518
Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy*
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Humans
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Medicine, Chinese Traditional/methods*
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Practice Guidelines as Topic
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Drugs, Chinese Herbal/therapeutic use*
5.A case report of acute ischemic stroke with middle cerebral artery occlusion caused by Takotsubo syndrome
Shiya ZHANG ; Suqiu HUAN ; Sheng ZHUANG ; Guodong XIAO ; Yongjun CAO ; Shoujiang YOU
Chinese Journal of Neurology 2025;58(8):869-873
Takotsubo syndrome is a transient, reversible syndrome characterized by acute regional dysfunction of the left ventricle, with symptoms resembling those of acute coronary syndrome. Takotsubo syndrome can lead to left ventricular thrombus formation, which may embolize and cause ischemic stroke. However, such cases are relatively rare. A case of acute ischemic stroke with middle cerebral artery occlusion caused by Takotsubo syndrome is reported in this article. The patient presented primarily with left-sided limb weakness. Cerebral angiography indicated occlusion of the right middle cerebral artery, and complete vascular recanalization was achieved after endovascular thrombectomy. Cranial magnetic resonance imaging indicated multiple infarctions in both the anterior and posterior circulations. Transthoracic echocardiography showed apical thrombus formation in the left ventricle and significantly reduced left ventricular systolic function. After a short course of anticoagulation combined with antiplatelet therapy, the apical thrombus resolved, and left ventricular systolic function significantly improved. This case indicates that although large-vessel occlusion acute ischemic stroke caused by Takotsubo syndrome is relatively rare, comprehensive etiological evaluation should be emphasized in patients with suspected cardioembolic stroke. Dynamic monitoring of echocardiographic changes is important for accurate diagnosis of the underlying cause.
6.Glial fibrillary acidic protein astrocytopathy presenting as progressive encephalomyelitis with rigidity and myoclonus: 1 case report
Sheng ZHUANG ; Hanying GU ; Jinru ZHANG ; Huihui LIU ; Weidong HU
Chinese Journal of Neurology 2025;58(8):873-876
Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is an immune-mediated inflammatory disease of the central nervous system. However, GFAP-A characterized by progressive encephalomyelitis with rigidity and myoclonus as its predominant clinical phenotype is rare. This article described a case, supplemented with clinical video, of a young male patient who developed fever and neck pain at disease onset. Over the course of the illness, the patient experienced progressively worsening painful muscle spasms, muscle rigidity, and stimulus-sensitive myoclonus, accompanied by autonomic dysfunction. Cerebrospinal fluid analysis revealed positive GFAP-IgG antibodies. The patient showed significant improvement with treatment of high-dose corticosteroids, intravenous immunoglobulin, and mycophenolate mofetil.
7.Berberine promotes expression of AQP4 in astrocytes by regulating production of miR-383-5p in HepG2 cell-derived exosomes under insulin resistance.
Xue-Ling LIN ; Ying LI ; Meng-Qing GUO ; Yan-Jun ZHANG ; Qing-Sheng YIN ; Peng-Wei ZHUANG
China Journal of Chinese Materia Medica 2025;50(3):768-775
This study aims to explore the role and mechanism of berberine in promoting the expression of aquaporin 4(AQP4) in astrocytes by regulating the expression of miR-383-5p in HepG2 cell-derived exosomes under insulin resistance(IR). The IR-HepG2 cell model was established with 1×10~(-6) mol·L~(-1) insulin. With metformin as the positive control, the safe concentrations of berberine and metformin were screened by cell counting kit-8(CCK-8) and lactate dehydrogenase(LDH) leakage assays, and the effect of berberine on the IR of HepG2 cells was evaluated by glucose consumption. NanoSight was used to measure the particle size and concentration of exosomes secreted by HepG2 cells in each group. HepG2 cell-derived exosomes in each group were incubated with astrocytes for 24 h, and the protein and mRNA levels of AQP4 in HA1800 cells were determined by Western blot and qRT-PCR, respectively. qRT-PCR was performed to determine the expression of miR-383-5p in HepG2 cell-derived exosomes and HA1800 cells after co-incubation. Western blotting was employed to determine the expression levels of miRNAs and proteins associated with exosome production and release in HepG2 cells. The results showed that 10 μmol·L~(-1) berberine and 1 mmol·L~(-1) metformin significantly alleviated the IR of HepG2 cells and reduced the concentration of exosomes in HepG2 cells. The exosomes of HepG2 cells treated with berberine and metformin significantly up-regulated the protein and mRNA levels of AQP4 in HA1800 cells. The mRNA level of miR-383-5p in HepG2 cell exosomes and HA1800 cells co-incubated with berberine and metformin decreased significantly. The intervention with berberine and metformin significantly down-regulated the expression of proteins associated with the production of miRNAs(Dicer, Drosha) as well as the production(Alix, Vps4A) and release(Rab35, VAMP3) of exosomes in IR-HepG2 cells. In conclusion, berberine can promote the expression of AQP4 in astrocytes by inhibiting the production and release of miR-383-5p in HepG2-derived exosomes under IR.
Humans
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MicroRNAs/metabolism*
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Berberine/pharmacology*
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Hep G2 Cells
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Exosomes/genetics*
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Aquaporin 4/metabolism*
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Insulin Resistance
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Astrocytes/drug effects*
8.Evolution of grading for solitary fibrous tumors of the central nervous system: a clinical pathological and prognostic analysis
Xiaoling LI ; Hua ZHANG ; Chengcong HU ; Jianfeng ZHOU ; Mengyi ZHUANG ; Xinxin FAN ; Liwen HU ; Yupeng CHEN ; Qian HUANG ; Sheng ZHANG ; Xingfu WANG
Chinese Journal of Oncology 2025;47(3):275-282
Objective:The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis.Methods:This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data.Results:The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients ( P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis ( P<0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients ( P=0.017). Conclusions:The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.
9.Research progress in regulation of exosomes on diabetes encephalopathy and intervention of traditional Chinese medicine
Jie BU ; Ying LI ; Xue-ling LIN ; Peng-wei ZHUANG ; Yan-jun ZHANG ; Qing-sheng YIN
Chinese Pharmacological Bulletin 2025;41(8):1431-1435
Diabetic encephalopathy(DE)is a complication of the central nervous system induced by diabetes,characterized by insidious onset and complex pathological mechanisms.Recent research has revealed that the pathological mechanisms of DE are closely associated with the imbalance of intercellular communica-tion across multiple organs.Exosomes,serving as vital media-tors of intercellular communication,are involved in the patholog-ical progression of DE and hold promise as diagnostic biomarkers and therapeutic targets for DE.Traditional Chinese medicine(TCM)can improve communication between brain cells and be-tween peripheral and brain tissues by regulating exosomes and their contents,thereby preventing and treating DE.Meanwhile,exosomes,as targeted delivery carriers of active molecules,can carry TCM monomers more easily across the blood-brain barrier to prevent and treat DE.In light of this,this review summarizes the regulatory role of exosomes in the pathological progression of DE and explores the enormous potential of TCM in the preven-tion and treatment of DE by regulating exosomes and using exo-somes as traditional Chinese medicine carriers,aiming to pro-vide new evidence for the prevention and treatment of DE with TCM.
10.Clinicopathological features and molecular phenotypes of pleomorphic xanthoas-trocytoma:an analysis of 79 cases
Yu ZHANG ; Weiwei FU ; Yupeng CHEN ; Hong LI ; Weiping SHI ; Jianfeng ZHOU ; Mengyi ZHUANG ; Xinxin FAN ; Sheng ZHANG ; Xingfu WANG
Chinese Journal of Clinical and Experimental Pathology 2025;41(2):221-227,232
Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1%),and CDKN2A homozygous deletion(36.8%)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.

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