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.Clinical Analysis of Ixazomib-Based Chemotherapy Regimens in the Treatment of Newly Diagnosed Multiple Myeloma with 1q21 Amplification
Dan-Xia LIN ; Yan-Hong ZHUANG ; Jian TANG ; Jia-Sheng HU
Journal of Experimental Hematology 2025;33(6):1640-1649
Objective:To clarify the prognostic significance of 1q21 amplification in multiple myeloma(MM),and explore the efficacy and prognosis of ixazomib in the treatment of MM patients with 1q21 amplification.Methods:A retrospective analysis of clinical data was conducted on 77 patients with newly diagnosed MM who were hospitalized in Zhongshan Hospital,Xiamen University from January 2010 to December 2022.To analyze the clinical features of MM patients with 1q21 amplification,evaluate the mitigation rate and survival treated with ixazomib-based regimens.Results:Among the 77 newly diagnosed MM patients,40 patients had 1q21 amplification,while 37 didn't.Multivariate Cox regression analysis revealed that 1q21 amplification was an independent risk factor affecting the prognosis of MM patients(P<0.05).Compared to patients without 1q21 amplification,those with 1q21 amplification had poorer progression-free survival(PFS)and overall survival(OS)(both P<0.05).When the 1q21 amplification ratio exceeded 66.7%,both PFS and OS were worse(P<0.05).There were no statistical differences in the deep remission rate(≥VGPR),overall response rate and PFS between the 1 q21 amplification positive and negative groups treated with ixazomib-based regimens(P>0.05),but OS showed a significant difference(P<0.05).Among the patients who switched to ixazomib treatment from bortezomib,there was a statistically significant difference in the complete response rate(P<0.05).Compared to other treatment regimens,ixazomib-based regimens resulted in a significant reduction in adverse reactions such as peripheral neuropathy(P<0.05).Conclusion:Ixazomib-based chemotherapy regimens can overcome the poor prognosis associated with 1q21 amplification and improve mitigation rates and PFS in patients.Ixazomib has low incidence of adverse reactions,good safety profile and prolonged duration of therapy.
4.Dehydrocostus lactone ameliorates renal interstitial fibrosis in rats with unilateral ureteral obstruction by inhibiting the TGF-β1/Smad2/3 pathway
Zhongda LI ; Shuhong WANG ; Hongwei TAN ; Xiao WANG ; Jinyang ZHUANG ; Sheng SHEN ; Qipeng SUN
Organ Transplantation 2025;16(5):763-770
Objective To explore the action mechanism of dehydrocostus lactone(DHL)on renal interstitial fibrosis(RIF)in rats with unilateral ureteral obstruction(UUO).Methods Forty-four male SD rats were randomly divided into four groups:the sham surgery group(Sham group),the pure drug intervention group(Sham+DHL group),the experimental group(UUO+Vehicle group)and the DHL treatment group(UUO+DHL group),with 11 rats in each group.The rats underwent sham surgery,sham surgery+DHL[10 mg/(kg·d)],UUO modeling+the same volume of solvent and UUO modeling+DHL[10 mg/(kg·d)],respectively.After surgery,DHL or the same volume of solvent was administered by gavage for 14 days starting from day 2 post-surgery.Hematoxylin-eosin(HE)and Masson staining were used to observe the pathological changes in renal tissue.Immunohistochemical staining was performed to detect the expression levels of collagen I,collagen III and α-smooth muscle actin(α-SMA).Western blotting was used to detect the protein levels of the transforming growth factor(TGF)-β1/Smad2/3 pathway.Results Compared with the UUO+Vehicle group,DHL treatment alleviated renal interstitial pathological damage,reduced collagen fiber deposition,and decreased the expression of collagen I,collagen III and α-SMA.It also inhibited the expression of TGF-β1 and Smad2/3 proteins.Conclusions DHL mitigates RIF in rats by inhibiting the TGF-β1/Smad2/3 pathway,providing a new strategy for the treatment of chronic kidney disease.
5.Research progress on regulatory mechanism of AQP4 polarization distribution in glymphatic system
Xue-ling LIN ; Ying LI ; Jia-le REN ; Yan-jun ZHANG ; Peng-wei ZHUANG ; Qing-sheng YIN
Chinese Pharmacological Bulletin 2025;41(5):811-815
The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.
6.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.
7.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.
8.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.
9.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.
10.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.

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