Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

{"title":"Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases.","authors":"Abudurousuli Adili, Aerken Dilihumaer, Huhu Zhu, Huifang Tang","doi":"10.3724/zdxbyxb-2024-0023","DOIUrl":"10.3724/zdxbyxb-2024-0023","url":null,"abstract":"<p><p>Phosphodiesterases (PDE) are involved in the regulation of cellular physiological processes and neurological functions, including neuronal plasticity, synapto-genesis, synaptic transmission, memory formation and cognitive functions by catalyzing the hydrolysis of intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Many basic and clinical studies have shown that PDE4 inhibitors block or ameliorate the occurrence and development of central nervous system (CNS) diseases by inhibiting cAMP hydrolysis, increasing cAMP content and enhancing its downstream effects. PDE4 inhibitors have long-term potentiation effect, which can enhance phosphorylation of cAMP response element binding protein (CREB) and upregulate expression of memory related Arc genes in hippocampal neurons, thereby improving cognitive impairment and Alzheimer's disease-like symptoms. They can also delay the occurrence and development of Parkinson's disease by reducing the cytotoxicity induced by α-syn and increasing the effect of miR-124-3p on cell functions. Alteration of PDE4 activity is the molecular basis for psychosis and some cognitive disorders, therefore it is considered as a therapeutic target for schizophrenia. PDE4 inhibitors play a role in depression by inhibiting the advanced glycation end product receptor (RAGE), TLR4 and NLRP3 pathways in the hippocampus, reducing the activation of microglia and the production of IL-1β, down-regulating HMGB1/RAGE signaling pathway and inhibiting inflammatory factors. PDE4 inhibitor plays a role in the treatment of autism spectrum disorder by reducing the damage of cerebellar glial cells, increasing nociceptive threshold, and improving mutual learning and memory deficits. PDE4 inhibitors might be used in the treatment of fragile X syndrome by regulating the level of cAMP and affecting the expression of fragile X mental retardation protein (FMRP). PDE4 inhibitors can also promote the differentiation of oligodendrocyte progenitor cells and enhance myelination, which has potential in the treatment of multiple sclerosis. PDE4 is also related to bipolar disorder, which may be one of the therapeutic targets. At present, several PDE4 inhibitors are in clinical trials for the treatment of CNS diseases. This article reviews and discusses the progress on basic research and clinical trials of PDE4 inhibitors in CNS diseases, providing a reference for the prevention and treatment of CNS diseases and the development of new drugs.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"390-398"},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnancy outcomes of patients with positive anticentromere antibodies receiving <i>in vitro</i> fertilization-embryo transfer.","authors":"Yuqing Tian, Yi'er Zhou, Yuhang Fan, Sufeng Chen, Xiaoyan Guo, Yiqi Yu, Xiangli Wu, Weihai Xu, Jing Shu","doi":"10.3724/zdxbyxb-2023-0559","DOIUrl":"10.3724/zdxbyxb-2023-0559","url":null,"abstract":"<p><strong>Objectives: </strong>To analyze the pregnancy outcomes in patients with positive anti-centromere antibodies (ACA) receiving <i>in vitro</i> fertilization (IVF)-embryo transfer (ET) and natural conception.</p><p><strong>Methods: </strong>A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received IVF-ET therapy and had the results of antinuclear antibody (ANA) spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023. Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching. Embryo outcomes of IVF were compared between the two groups, and the impact of different fertilization methods and the use of immunosuppressants on pregnancy outcomes were analyzed using self-matching. The natural conception and disease progress were followed up for ACA-positive patients after IVF failure.</p><p><strong>Results: </strong>The ACA-positive patients accounted for 0.86% of all IVF patients (34/3955) and 2.51% of total ANA-positive IVF patients. Regardless of whether patients received conventional IVF (c-IVF) or intracytoplasmic sperm injection (ICSI), the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group (both <i>P</i><0.01). Moreover, the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos (both <i>P</i><0.05). In 5 cases of ACA-positive patients who underwent ICSI cycles, the two pronucleus (2PN) rate did not increase compared to c-IVF cycles (<i>P</i>>0.05), and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos (both <i>P</i><0.05). After 1-2 months of immuno-suppressant treatment, 12 ACA-positive patients underwent c-IVF/ICSI again, and there were no changes in egg retrieval and fertilization before and after medication (both <i>P</i>>0.05), but there was an improvement in the 2PN embryo cleavage rate (<i>P</i><0.05). The number of embryos transferred was similar between the ACA-positive and negative groups, but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group (both <i>P</i><0.05), with no significant differences in the miscarriage rate between the two groups (<i>P</i>>0.05). Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure, resulting in a total of 7 cases of clinical pregnancy.</p><p><strong>Conclusions: </strong>Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes, with no improvement observed with ICSI and immunosuppressant use. However, ACA-positive patients may still achieve natural pregnancy.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"342-350"},"PeriodicalIF":0.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subacute exposure to DEHP leads to impaired decidual reaction and exacerbates the risk of early miscarriage in mice.","authors":"Qiuju Liu, Liping Tan, Liu Yuan, Xuemei Chen, Fangfang Li, Junlin He, Rufei Gao","doi":"10.3724/zdxbyxb-2023-0583","DOIUrl":"10.3724/zdxbyxb-2023-0583","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect of subacute exposure of Di (2-ethylhexyl) phthalate (DEHP) on endometrial decidualization and early pregnancy miscarriage in mice.</p><p><strong>Methods: </strong>CD1 mice were orally administrated with 300 (low-dose group), 1000 (medium-dose group), or 3000 mg·kg^－1·d^－1 DEHP (1/10 LD₅₀, high-dose group) for 28 days, respectively. An early natural pregnancy model and an artificially induced decidualization model were established. The uterine tissues were collected on D7 of natural pregnancy and D8 of artificially induced decidualization, respectively. The effects of a subacute exposure to DEHP on the decidualization of mice were detected by HE staining, Masson staining, TUNEL assay, and Western blotting. A model of spontaneous abortion was constructed in mice after subacute exposure to 300 mg·kg^－1·d^－1 DEHP, and the effect of impaired decidualization on pregnancy was investigated by observing the pregnancy outcome on the 10th day of gestation.</p><p><strong>Results: </strong>Compared with the control group, the conception rate was significantly decreased in the high-dose DEHP subacute exposure group (<i>P</i><0.05). HE staining showed that, compared with the control group, the decidual stromal cells in the low- and medium-dose exposure groups were disorganized, the nuclei of the cells were irregular, the cytoplasmic staining was uneven, and the number of polymorphonuclear cells was significantly reduced. Masson staining showed that compared with the control group, the collagen fibers in the decidua region of the DEHP low-dose group and the medium-dose group were more distributed, more abundant and more disorderly. TUNEL assay showed increased apoptosis in the decidua area compared to the control group. Western blotting showed that the expression of BMP2, a marker molecule for endometrial decidualization, was significantly reduced (<i>P</i><0.05 or <i>P</i><0.01). The abortion rate and embryo resorption rate were increased, and the number of embryos, uterine wet weight, uterine area and placenta wet weight were decreased in DEHP low-dose group compared to the control group stimulated by mifepristone, an abortifacient drug (<i>P</i><0.05 or <i>P</i><0.01).</p><p><strong>Conclusions: </strong>Subacute exposure to DEHP leads to impaired endometrial decidualization during early pregnancy and exacerbates the risk of adverse pregnancy outcomes in mice.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"331-341"},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benefit from luteal phase progestin primed ovarian stimulation with clomiphene citrate supplementation in young women with diminished ovarian reserve: a retrospective study.","authors":"Qianqian Chen, Xuefeng Huang, Haiyan Yang, Yue Lin","doi":"10.3724/zdxbyxb-2023-0533","DOIUrl":"10.3724/zdxbyxb-2023-0533","url":null,"abstract":"<p><strong>Objectives: </strong>To compare the pregnancy outcomes of luteal phase and follicular phase progestin-primed ovarian stimulation protocol with clomiphene citrate supplementation (LPPOS+CC and FPPOS+CC) in young women with diminished ovarian reserve (DOR).</p><p><strong>Methods: </strong>A total of 483 women aged ≤35 years with DOR, who underwent <i>in vitro</i> fertilization (IVF)/intracytoplasmic sperm injection (ICSI)/embryo transfer (ET) with controlled ovarian stimulation using LPPOS+CC (<i>n</i>=257) or FPPOS+CC (<i>n</i>=226) protocols during June 2018 and December 2021 at the First Affiliated Hospital of Wenzhou Medical University, were included in this retrospective study. The baseline characteristics, superovulation results, laboratory related indicators between the two groups, and the pregnancy outcomes of women who achieved at least one high-quality cleavage-stage embryo or good-morphology blastocyst were compared between the two groups.</p><p><strong>Results: </strong>No statistically significant differences were identified between the groups with respect to age, duration of infertility, proportion of secondary infertility, previous failed cycles, body mass index, anti-Müllerian hormone, antral follicle count, basal luteinizing hormone level, basal progesterone level, number of oocytes retrieved, oocyte maturation rate, high-quality cleavage-stage embryo cycle rate, the percentage of women with profound pituitary suppression, live birth rate and preterm birth rate (all <i>P</i>>0.05). The LH levels on the day of trigger [4.0 (2.7, 5.3) <i>vs.</i> 5.1 (3.2, 7.2) IU/L], the percentage of women with LH levels of >10 IU/L on the trigger day (3.13% <i>vs.</i> 10.67%), and the two pronucleus (2PN) rate of ICSI oocytes (72.16% <i>vs.</i> 79.56%) were significantly lower in the LPPOS+CC group than those in the FPPOS+CC group (<i>P</i><0.05 or <i>P</i><0.01). The duration of stimulation [11 (9, 12) <i>vs.</i> 9 (8, 11) d], the consumption of total gonadotropin [2213 (1650, 2700) <i>vs.</i> 2000 (1575, 2325) IU], the progesterone levels on the day of trigger [1.3 (0.8, 2.9) <i>vs.</i> 0.9 (0.6, 1.2) ng/mL], the clinical pregnancy rate [61.88% <i>vs.</i> 46.84%], and implantation rate [42.20% <i>vs</i>. 31.07%] in the LPPOS+CC group were significantly higher than those in the FPPOS+CC group (all <i>P</i><0.01).</p><p><strong>Conclusions: </strong>Compared to FPPOS+CC, the LPPOS+CC protocol appears to have better pregnancy outcomes for young women with DOR undergoing IVF/ICSI-ET.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"297-305"},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chinese medicine Jianpi Antai formula improves pregnancy outcomes of <i>in vitro</i> fertilization-embryo transfer in infertile women.","authors":"Qing Liu, Fangxuan Lin, Chenyun Miao, Chao Li, Guofen Wen, Songying Zhang, Qin Zhang","doi":"10.3724/zdxbyxb-2023-0536","DOIUrl":"10.3724/zdxbyxb-2023-0536","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the efficacy and safety of Chinese medicine Jianpi Antai formula in infertile women undergoing <i>in vitro</i> fertilization-embryo transfer (IVF-ET).</p><p><strong>Methods: </strong>A total of 300 infertile women who underwent 2 frozen embryo transfer procedures at the Reproductive Medicine Center, Sir Run Run Shaw Hospital were included in the study. The participants were randomly divided into study group and control group. The study group received routine medication plus the Jianpi Antai formula during the period of embryo transfer, while the control group received routine medication only. The general condition, embryo implantation rate, clinical pregnancy rate, live birth rate, and the blood routine and liver and kidney function were evaluated and compared between two groups.</p><p><strong>Results: </strong>There were 277 cases who completed the study, including 134 in the study group and 143 in the control group. The embryo implantation rate (68.7% <i>vs</i>. 55.9%), the clinical pregnancy rate (56.7% <i>vs</i>. 44.8%) and the live birth rate (50.7% <i>vs</i>. 37.8%) in the study group were all higher than those in the control group (all <i>P</i><0.05). Subgroup analysis revealed that in patients of advanced age (≥35 years) and those with decreased ovarian reserve function (anti-Müllerian hormone <1.68 ng/mL), the embryo implantation rate, clinical pregnancy rate, and live birth rate in the study group were all higher than those in the control group (all <i>P</i><0.05). During the follow-up period, there were no abnormalities in the basic vital signs of both groups, and no adverse events were reported.</p><p><strong>Conclusions: </strong>Jianpi Antai formula can safely improve the embryo implantation rate in infertile women undergoing IVF-ET, reduce the embryo miscarriage rate, increase the live birth rate as well as improve the clinical outcomes.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"306-312"},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on the prevention and treatment of chemotherapy-induced ovarian damage.","authors":"Yuxin Zha, Yang Li, Weiguo Lyu","doi":"10.3724/zdxbyxb-2023-0495","DOIUrl":"10.3724/zdxbyxb-2023-0495","url":null,"abstract":"<p><p>Chemotherapy is a main treatment option for malignant tumors, but it may cause various adverse effects, including dysfunction of female endocrine system and fertility. Chemotherapy-induced ovarian damage has been concerned with ovarian preservation but also the prevention and treatment of ovarian dysfunction. In this article, the mechanisms of ovarian injury caused by chemotherapy, including apoptosis of the follicle and supporting cells, follicle \"burn out\", ovarian stromal and microvascular damage; and influencing factors, including age at diagnosis, initial low pre-treatment anti-Müllerian hormone levels, toxicity, dose and regimen of chemotherapy drugs are reviewed based on the latest research results and clinical practice. The article also discusses measures and frontier therapies for the prevention and treatment of ovarian injury, including the application of gonadotropin releasing hormone agonists or antagonists, tyrosine kinase inhibitors, antioxidants, sphingosine-1-phosphate, ceramide-1-phosphate, mammalian target of rapamycin inhibitors, granulocyte-colony stimulating factor, stem cell therapy and artificial ovaries.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"288-296"},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influencing factors of futile recanalization after endovascular intervention in patients with acute basilar artery occlusion.","authors":"Yi Yan, Kemeng Zhang, Wansi Zhong, Shenqiang Yan, Bing Zhang, Jianhua Cheng, Min Lou","doi":"10.3724/zdxbyxb-2023-0425","DOIUrl":"10.3724/zdxbyxb-2023-0425","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the influence factors for futile recanalization following endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO).</p><p><strong>Methods: </strong>Clinical data of patients with acute BAO, who underwent endovascular treatment within 24 h of onset from January 2017 to November 2022, were retrospectively analyzed. The futile recanalization was defined as modified thrombolysis in cerebral infarction (mTICI) grade ≥2b or 3 after successful reperfusion, but the modified Rankin Scale score >2 at 3 months after EVT. Binary logistic regression model was used to analyze the influencing factors of futile recanalization.</p><p><strong>Results: </strong>A total of 471 patients with a median age of 68 (57, 74) years were included and 68.9% were males, among whom 298 (63.27%) experienced futile recanalization. Multivariate analysis revealed that concomitant atrial fibrillation (<i>OR</i>=0.456, 95%<i>CI</i>: 0.282-0.737, <i>P</i><0.01), bridging thrombolysis (<i>OR</i>=0.640, 95%<i>CI</i>: 0.416-0.985, <i>P</i><0.05), achieving mTICI grade 3 (<i>OR</i>=0.554, 95%<i>CI</i>: 0.334-0.918, <i>P</i><0.05), arterial occlusive lesion (AOL) grade 3 (<i>OR</i>=0.521, 95%<i>CI</i>: 0.326-0.834, <i>P</i><0.01), and early postoperative statin therapy (<i>OR</i>=0.509, 95%<i>CI</i>: 0.273-0.948, <i>P</i><0.05) were protective factors for futile recanalization after EVT in acute BAO patients. High baseline National Institutes of Health Stroke Scale (NIHSS) score (<i>OR</i>=1.068, 95%<i>CI</i>: 1.049-1.087, <i>P</i><0.01), coexisting hypertension (<i>OR</i>=1.571, 95%<i>CI</i>: 1.017-2.427, <i>P</i><0.05), multiple retrieval attempts (<i>OR</i>=1.237, 95%<i>CI</i>: 1.029-1.488, <i>P</i><0.05) and postoperative hemorrhagic transformation (<i>OR</i>=8.497, 95%<i>CI</i>: 2.879-25.076, <i>P</i><0.01) were risk factors. For trial of ORG 10172 in acute stroke treatment (TOAST) classification, cardiogenic embolism (<i>OR</i>=0.321, 95%<i>CI</i>: 0.193-0.534, <i>P</i><0.01) and other types (<i>OR</i>=0.499, 95%<i>CI</i>: 0.260-0.961, <i>P</i><0.05) were related to lower incidence of futile recanalization.</p><p><strong>Conclusions: </strong>The incidence of futile recanalization after EVT in patients with acute BAO is high. Bridging venous thrombolysis before operation and an early postoperative statin therapy may reduce the incidence of futile recanalization.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"141-150"},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress on functions of intracellular domain <b>of</b> trimeric ligand-gated ion channels.","authors":"Yan Lu, Yiyu Lin, Jin Wang","doi":"10.3724/zdxbyxb-2023-0472","DOIUrl":"10.3724/zdxbyxb-2023-0472","url":null,"abstract":"<p><p>Ligand-gated ion channels are a large category of essential ion channels, modulating their state by binding to specific ligands to allow ions to pass through the cell membrane. Purinergic ligand-gated ion channel receptors (P2XRs) and acid-sensitive ion channels (ASICs) are representative members of trimeric ligand-gated ion channel. Recent studies have shown that structural differences in the intracellular domain of P2XRs may determine the desensitization process. The lateral fenestrations of P2XRs potentially serve as a pathway for ion conductance and play a decisive role in ion selectivity. Phosphorylation of numerous amino acid residues in the P2XRs are involved in regulating the activity of ion channels. Additionally, the P2XRs interact with other ligand-gated ion channels including <i>N</i>-methyl-<i>D</i>-aspartate receptors, γ-aminobutyric acid receptors, 5-hydroxytryptamin receptors and nicotinic acetylcholine receptors, mediating physiological processes such as synaptic plasticity. Conformational changes in the intracellular domain of the ASICs expose binding sites of intracellular signal partners, facilitating metabolic signal transduction. Amino acids such as Val16, Ser17, Ile18, Gln19 and Ala20 in the ASICs participate in channel opening and membrane expression. ASICs can also bind to intracellular proteins, such as CIPP and p11, to regulate channel function. Many phosphorylation sites at the C-terminus and N-terminus of ASICs are involved in the regulation of receptors. Furthermore, ASICs are involved in various physiological and pathophysiological processes, which include pain, ischemic stroke, psychiatric disorders, and neurodegenerative disease. In this article, we review the roles of the intracellular domains of these trimeric ligand-gated ion channels in channel gating as well as their physiological and pathological functions, in order to provide new insights into the discovery of related drugs.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"221-230"},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.","authors":"Dongjuan Xu, Huan Zhou, Mengmeng Hu, Yilei Shen, Hongfei Li, Lianyan Wei, Jing Xu, Zhuangzhuang Jiang, Xiaoli Shao, Zhenhua Xi, Songbin He, Min Lou, Shaofa Ke","doi":"10.3724/zdxbyxb-2023-0423","DOIUrl":"10.3724/zdxbyxb-2023-0423","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.</p><p><strong>Methods: </strong>Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale (NIHSS) score ≤3 and a platelet count <100×10⁹/L were obtained from a multicenter register. Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded. Short-term safety outcomes were in-hospital bleeding events, while the long-term safety outcome was a 1-year all-cause death. The short-term neurological outcomes were evaluated by modified Rankin scale (mRS) score at discharge.</p><p><strong>Results: </strong>A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled. Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge (<i>OR</i>=1.657, 95%<i>CI</i>: 1.253-2.192, <i>P</i><0.01) and did not increase the risk of intracranial hemorrhage (<i>OR</i>=2.359, 95%<i>CI</i>: 0.301-18.503, <i>P</i>>0.05), compared with those without antiplatelet therapy. However, dual-antiplatelet therapy did not bring more neurological benefits (<i>OR</i>=0.923, 95%<i>CI</i>: 0.690-1.234, <i>P</i>>0.05), but increased the risk of gastrointestinal bleeding (<i>OR</i>=2.837, 95%<i>CI</i>: 1.311-6.136, <i>P</i><0.01) compared with those with mono-antiplatelet therapy. For patients with platelet counts ≤75×10⁹/L and >90×10⁹/L, antiplatelet therapy significantly improved neurological functional outcomes (both <i>P</i><0.05). For those with platelet counts (>75-90)×10⁹/L, antiplatelet therapy resulted in a significant improvement of 1-year survival (<i>P</i><0.05). For patients even with concurrent coagulation abnormalities, mono-antiplatelet therapy did not increase the risk of various types of bleeding (all <i>P</i>>0.05) but improved neurological functional outcomes (all <i>P</i><0.01). There was no significant difference in the occurrence of bleeding events, 1-year all-cause mortality risk, and neurological functional outcomes between aspirin and clopidogrel (all <i>P</i>>0.05).</p><p><strong>Conclusions: </strong>For non-cardioembolic mild stroke patients with thrombocytopenia, antiplatelet therapy remains a reasonable choice. Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"175-183"},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and genetic analysis of essential hypertension with mitochondrial tRNA^Met 4435A>G and <i>YARS2</i> mutation.","authors":"Meili Guo, Yunfan He, Ade Chen, Zaishou Zhuang, Xiaoyong Pan, Minxin Guan","doi":"10.3724/zdxbyxb-2023-0571","DOIUrl":"10.3724/zdxbyxb-2023-0571","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the role of m.4435A>G and <i>YARS2</i> c.572G>T (p.G191V) mutations in the development of essential hypertension.</p><p><strong>Methods: </strong>A hypertensive patient with m.4435A>G and <i>YARS2</i> p.G191V mutations was identified from previously collected mitochondrial genome and exon sequencing data. Clinical data were collected, and a molecular genetic study was conducted in the proband and his family members. Peripheral venous blood was collected, and immortalized lymphocyte lines constructed. The mitochondrial transfer RNA (tRNA), mitochondrial protein, adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) in the constructed lymphocyte cell lines were measured.</p><p><strong>Results: </strong>Mitochondrial genome sequencing showed that all maternal members carried a highly conserved m.4435A>G mutation. The m.4435A>G mutation might affect the secondary structure and folding free energy of mitochondrial tRNA and change its stability, which may influence the anticodon ring structure. Compared with the control group, the cell lines carrying m.4435A>G and <i>YARS2</i> p.G191V mutations had decreased mitochondrial tRNA homeostasis, mitochondrial protein expression, ATP production and MMP levels, as well as increased ROS levels (all <i>P</i><0.05).</p><p><strong>Conclusions: </strong>The <i>YARS2</i> p.G191V mutation aggravates the changes in mitochondrial translation and mitochondrial function caused by m.4435A>G through affecting the steady-state level of mitochondrial tRNA and further leads to cell dysfunction, indicating that <i>YARS2</i> p.G191V and m.4435A>G mutations have a synergistic effect in this family and jointly participate in the occurrence and development of essential hypertension.</p>","PeriodicalId":24007,"journal":{"name":"Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences","volume":" ","pages":"184-193"},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11057996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}