Acta Poloniae Pharmaceutica - Drug Research最新文献

Role of L-, N- and T-type Calcium Channels in Achieving Maximum Analgesic and Minimum Toxic Effect of Tramadol L、N 和 T 型钙通道在实现曲马多最大镇痛作用和最小毒性作用中的作用

Acta Poloniae Pharmaceutica - Drug Research Pub Date : 2024-04-09 DOI: 10.32383/appdr/179230

M. Yilmaz, B. Suleyman, R. Mammadov, D. Altuner, T. Coban, S. Bulut, H. Suleyman, Resid Coskun

{"title":"Role of L-, N- and T-type Calcium Channels in Achieving Maximum Analgesic and Minimum Toxic Effect of Tramadol","authors":"M. Yilmaz, B. Suleyman, R. Mammadov, D. Altuner, T. Coban, S. Bulut, H. Suleyman, Resid Coskun","doi":"10.32383/appdr/179230","DOIUrl":"https://doi.org/10.32383/appdr/179230","url":null,"abstract":"The aim of the study was to investigate the effects of lacidipine, amlodipine and benidipine on the analgesic activity and toxicity of tramadol. Rats (n=6/each group) were divided into five groups as control(CG), tramadol(TRD), lacidipine+tramadol(LTRD), amlodipine+tramadol(ATRD) and benidipine+tramadol(BTRD). Tramadol was administered once at a dose of 50 mg/kg and lacidipine, amlodipin, benidipin were administered at a dose of 4 mg/kg orally, once a day for 10 days. After the animals were sacrificed malondialdehyde(MDA) and total glutathione(tGSH) levels were measured in brain, heart, liver and kidney tissues. Troponin I(Tp I), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), and creatinine levels were determined in serum. Paw pain thresholds were measured 1 hour before and after drug administration. Analgesic effect of tramadol was increased the most by benidipine, while amlodipine and lacidipine increased it equally. Lacidipine failed to suppress MDA increase and tGSH decrease in brain tissue. Benidipine suppressed MDA increase and tGSH decrease in brain tissue better than amlodipine. All three drugs suppressed cardiac tissue oxidative stress and the release of TP I into the circulation. Lacidipine and amlodipine could not prevent tramadol-induced oxidative stress in liver and kidney tissues, whereas benidipine prevented excessive MDA increase and tGSH decrease. Benidipine significantly suppressed the increase of ALT, AST, BUN, and creatinine. Analgesic activity was 35.1% in TRD, 43.7% in LTRD 50.4% in ATRD and 67,5% in BTRD. Study results show that benidipine and tramadol co-treatment is better than co-treatment with lacidipine or amlodipine in achieving minimal toxic effects and maximum analgesia.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140720748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Current State of Community Pharmacist-Physician Collaboration — A Cross-sectional Survey Among Pharmacistsin Poland 社区药剂师与医生合作的现状 - 波兰药剂师横断面调查

Acta Poloniae Pharmaceutica - Drug Research Pub Date : 2024-04-09 DOI: 10.32383/appdr/183708

Iwona Wrześniewska - Wal, J. Pinkas, Mateusz Jankowski

{"title":"Current State of Community Pharmacist-Physician Collaboration — A Cross-sectional Survey Among Pharmacists\u0000in Poland","authors":"Iwona Wrześniewska - Wal, J. Pinkas, Mateusz Jankowski","doi":"10.32383/appdr/183708","DOIUrl":"https://doi.org/10.32383/appdr/183708","url":null,"abstract":"A patient-centered partnership between different healthcare professionals is critical to improving the quality of health services. While the cooperation of physicians, nurses, midwives, and paramedics is well documented, more and more attention is paid to the role of pharmacists in interdisciplinary care. This study aimed to evaluate the pharmacist’s perception of the current state of community pharmacist-physician collaborative working as well as to identify barriers to the implementation of the community pharmacist-physician collaborative working model in Poland. This cross-sectional survey was carried out between October and December 2022 among community pharmacists in Poland. A total number of 1327 pharmacists from one of the largest franchise chain pharmacy networks in Poland were invited to take part in this study. The study questionnaire included 23 questions on the current state of pharmacist-physician collaborative working, the scope of cooperation, barriers to cooperation, and educational and organizational needs. Completed questionnaires were received from 635 pharmacists (response rate of 47.9%). Formal correction of the prescription (91.3%) was the most common cause of pharmacist-physician collaborative working. Moreover, 62.7% of pharmacists indicated that modification of ordered drugs was the reason for pharmacist-physician collaborative working. Only 3.3% of community pharmacists indicated that they collaborate with physicians during the drug review. Lack of IT systems enabling pharmacist-physician collaborative working (67.6%) and lack of recommendations on pharmacist-physician collaborative working (57.3%) were the most common barriers to collaboration with the physician. Pharmacists declare their readiness to cooperate with physicians, but there is a need to strengthen trust between both groups.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140723899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of Method for Determining Topiramate in Various Biological Matrices (Plasma, Saliva, Hair) and Its Application in Clinical Practice 开发测定各种生物基质（血浆、唾液、毛发）中托吡酯的方法及其在临床实践中的应用

Acta Poloniae Pharmaceutica - Drug Research Pub Date : 2024-04-09 DOI: 10.32383/appdr/186004

J. Kuczyńska, Alicja Zakrzewska-Sito, Anna Bochyńska, Halina Sienkiewicz-Jarosz, M. Dermanowski, Paweł Mierzejewski

{"title":"Development of Method for Determining Topiramate in Various Biological Matrices (Plasma, Saliva, Hair) and Its Application in Clinical Practice","authors":"J. Kuczyńska, Alicja Zakrzewska-Sito, Anna Bochyńska, Halina Sienkiewicz-Jarosz, M. Dermanowski, Paweł Mierzejewski","doi":"10.32383/appdr/186004","DOIUrl":"https://doi.org/10.32383/appdr/186004","url":null,"abstract":"The aim of this work was to develop and validate of method for the determination of topiramate (TPM) by a high-performance liquid chromatographic method coupled to triple-quadrupole mass spectrometry (LC-MS/MS) in MRM mode in the human plasma, saliva, and hair, and implementation of this method for the determination of TPM in patients with epilepsy. Saliva may as an alternative matrix for monitoring drug level, and hair drug content may be a reliable biomarker of the history of drug exposure, allowing to assess patient long-term compliance. Chromatographic separation was achieved in 3 min on a Kinetex analytical column (5 μm C18 100 Å, 100×2.1 mm) using an isocratic elution of acetonitrile and 10 mM ammonium acetate at a ratio of 80:20 (v/v) and a flow rate of 0.2 mL/min. Detection of TPM and internal standard (IS) (TPM-d12) was performed in negative ion mode (ESI−). The following transitions were used m/z 338 → 77.90; 338 → 95.90 for TPM and 350.3 → 78.20 for IS. The method showed to be selective, accurate, precise, and linear for TPM over the concentration ranges of 0.20-30 μg/mL (plasma, saliva), and 5.0-500.0 ng/mL (hair). The simple and robust LC-MS/MS method was successfully applied for the determination of TPM in patients with epilepsy.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140721546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exosomes and Their Application as Drug Delivery System in Cancer Therapy 外泌体及其作为药物输送系统在癌症治疗中的应用

Acta Poloniae Pharmaceutica - Drug Research Pub Date : 2024-04-09 DOI: 10.32383/appdr/183063

Kun Yang, Bingsuo Ma, Ting Yu, Kexin Li, Liangming Zhang, Xiaoyan Yuan, Haizhu Zhang, Zijun Yan, Tong Chen

引用次数: 0

Indole-3-Carboxylic Acid Enhanced Anti-cancer Potency of Doxorubicin via Induction of Cellular Senescence in Colorectal Cells 吲哚-3-羧酸通过诱导结直肠癌细胞衰老增强多柔比星的抗癌效力

Acta Poloniae Pharmaceutica - Drug Research Pub Date : 2024-04-09 DOI: 10.32383/appdr/178491

Yao Zhou, Yi Tang, Qingping Luo, Yuhang Hu, Wei Peng

{"title":"Indole-3-Carboxylic Acid Enhanced Anti-cancer Potency of Doxorubicin via Induction of Cellular Senescence in Colorectal Cells","authors":"Yao Zhou, Yi Tang, Qingping Luo, Yuhang Hu, Wei Peng","doi":"10.32383/appdr/178491","DOIUrl":"https://doi.org/10.32383/appdr/178491","url":null,"abstract":"Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy. Doxorubicin (DOX) is a widely utilized chemotherapy drug, but its efficacy is limited due to dose-dependent toxicity. Here, we aim to explore the effect of indole-3-carboxylic acid on DOX-induced senescence of CRC.\u0000Methods: Healthy adult rats and aged rats were compared in terms of their metabolites and functions through non-targeted metabolomics. LS180 cells were treated with DOX to induce senescence, followed by indole-3-carboxylic acid. The effects of this combination were evaluated in xenograft tumor mice. Cell viability, proliferation, and cell cycle were assessed with the Cell Counting Kit-8, colony formation assays, and flow cytometry. The levels of senescence-associated heterochromatin foci (SAHF) were detected by immunofluorescence. Senescence-associated-beta-galactosidase (SA-β-gal) expression was assessed by SA-β-gal staining and immunohistochemistry. Western blot was used to detect the expression of p21 and p53.\u0000Results: Compared to healthy adult rats, the serum metabolome in aging rats was altered, and the abundance of indole metabolites, including indoxyl sulfate, indole-3-carboxylic acid, and indole-5-carboxylic acid, was decreased significantly. In LS180 cells, indole-3-carboxylic acid amplified DOX-induced cell senescence, inhibiting cell proliferation and promoting cell cycle arrest. It also boosted DOX-triggered upregulation of SA-β-gal, SAHF, and p21. In nude mice, indole-3-carboxylic acid increased the inhibitory effect of DOX on xenograft tumors.\u0000Conclusion: Indole-3-carboxylic acid enhances the cellular senescence and growth arrest induced by DOX, suppressing mouse tumor growth. These findings suggest that a combined treatment of indole-3-carboxylic acid and DOX could be an effective strategy for CRC treatment.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140726135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of 4-Hydroxybenzaldehydeon on Interactions With Neurovascular Unit-Related Cells 4-Hydroxybenzaldehydeon 对与神经血管单元相关细胞相互作用的影响

Acta Poloniae Pharmaceutica - Drug Research Pub Date : 2024-04-09 DOI: 10.32383/appdr/185428

Yang Yuan, Dai Rong

{"title":"Effects of 4-Hydroxybenzaldehydeon on Interactions With Neurovascular Unit-Related Cells","authors":"Yang Yuan, Dai Rong","doi":"10.32383/appdr/185428","DOIUrl":"https://doi.org/10.32383/appdr/185428","url":null,"abstract":"4-hydroxybenzaldehyde (4-HBd) is one of the active compounds with neuroprotective effects, which has been confirmed to have anti cerebral ischemical reperfusion injury (CIRI) effect in previous study. In this study, we explored the protective effect of 4-HBd on the neurovascular unit (NVU) after CIRI and its mechanism through in vivo and in vitro experiments. Establish rat of middle cerebral artery occlusion/reproduction (MCAO/R) model, transwell chamber was used to establish an in vitro primary cell co-culture model to simulate NVU, causing oxygen glucose deprivation/reperfusion (OGD/R) injury, simulating the pathological of CIRI in vivo. Longa 5-point method was used to evaluate the neurological function of the rats, and transmission electron microscope was used to observe the ultrastructural changes of NVU. Western Blot was used to detect the expression of neuronal protein in rat brain. The mRNA expressions of ang-1/tie-2 signaling pathway and bdnf/trkb signaling pathway were detected by qPCR. In vivo results showed that 4-HBd reduced neurological function scores and improved the ultrastructure of NVU after MCAO/R rats. 4-HBd could up-regulate the expression of microtubule associated protein-2 (Map-2), glial fibrillary acidic protein (GFAP) and occludin. In vitro results showed that 4-HBd could activate ang-1/tie-2 signaling pathway, increased occludin mRNA expression and protect the blood brain barrier (BBB). 4-HBd can activate bdnf/trkb signaling pathway, up-regulate map-2 mRNA expression, and promote neuronal repair. In vitro and in vivo results indicated 4-HBd can affect the ang-1/tie-2 and bdnf/trkb signaling pathways, and BBB damage is alleviated and NVU homeostasis is maintained to improve CIRI.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140724620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Research Progress in the Relationship Between P2X7 and Flavonoids in Cardiovascular Disease 心血管疾病中 P2X7 与类黄酮关系的研究进展

Acta Poloniae Pharmaceutica - Drug Research Pub Date : 2024-04-09 DOI: 10.32383/appdr/181979

Peng Zhou

引用次数: 0

Drug-Related Problems Prior to Hospitalization on Internal Medicine Wards 内科病房住院前的药物相关问题

Acta Poloniae Pharmaceutica - Drug Research Pub Date : 2024-04-09 DOI: 10.32383/appdr/182840

Ivana Draganov, Aneta Drndarević, Milena Kovačević, B. Miljković, M. Vuksanović, Aleksandar Janković, Ana Kalaba, S. Vezmar Kovačević

{"title":"Drug-Related Problems Prior to Hospitalization on Internal Medicine Wards","authors":"Ivana Draganov, Aneta Drndarević, Milena Kovačević, B. Miljković, M. Vuksanović, Aleksandar Janković, Ana Kalaba, S. Vezmar Kovačević","doi":"10.32383/appdr/182840","DOIUrl":"https://doi.org/10.32383/appdr/182840","url":null,"abstract":"Drug-related hospitalisations pose a significant burden to the health-care system. The aim was to investigate the prevalence of drug-related problems (DRPs) and their association with hospital admissions in five internal medicine wards. The study included patients admitted to the nephrology, cardiology, gastroenterology, endocrinology and geriatric ward. Pharmaceutical Care Network Europe classification V9.1 was used for identifying DRPs. In total 535 patients participated in the study. We identified 954 DRPs (range 1-7) in 80.7% of patients. Most DRPs were identified on the endocrinology, cardiology and geriatric ward, and they were associated with the efficacy of treatment (71.4%), adverse drug events (10.2%) and unnecessary drug treatment (18.4%). DRPs were associated with the cause of hospitalisation in 74.4% of patients on the nephrology ward, 60.1% and 60.6% of patients in the cardiology and endocrinology ward, respectively, whereas this number was lower in the geriatric and gastroenterology wards (26.9% and 8.9%, respectively). Suboptimal drug treatment due to medication omissions, was often associated with the potential cause of hospital admission. Focusing on patients with specific diseases and DRPs, rather than reducing the number of medications in primary care, may be potentially rational in the attempt to reduce drug-related hospitalisations.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140725607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Are Polish Hospital Pharmacies Ready for Changes in Drug Distribution? 波兰医院药房准备好应对药品配送的变化了吗？

Acta Poloniae Pharmaceutica - Drug Research Pub Date : 2024-04-09 DOI: 10.32383/appdr/185879

K. Wylegała, Marcin Czech, Urszula Religioni, Dariusz Stencel

{"title":"Are Polish Hospital Pharmacies Ready for Changes in Drug Distribution?","authors":"K. Wylegała, Marcin Czech, Urszula Religioni, Dariusz Stencel","doi":"10.32383/appdr/185879","DOIUrl":"https://doi.org/10.32383/appdr/185879","url":null,"abstract":"All tasks performed by hospital pharmacies concern the management of medicinal products. The aim of this work is to analyze the functioning and implemen-tation costs of unit-dose and multi-dose automatic drug distribution systems in comparison with the classical mode of so-called ward medicine cabinets. The study was conducted from January 2020 to October 2021. It included quantitative study, conducted to verify the functioning of hospital phar-macies based on an original questionnaire, which was completed by 26 masters of pharmacy em-ployed in pharmacies hospitals, of which 92.4% were pharmacy head, and in-depth face-to-face interviews conducted in 4 facilities with unit-dose systems and one center that uses the multi-dose system. The work presents the functioning of hospital pharmacies, and the advantages and disadvantages of classical distri-bution model. Opinions on the operation of unit-dose and multi-dose systems as well as experiences related to their implementation in the hospital, including the necessary changes in the structure and organization of the hospital, were also presented. In conclusion, despite high purchase costs, auto-mated drug distribution systems bring many benefits in the field of hospital functioning, mainly in relation to patient care, improving the effectiveness, safety and individualization of pharmacothera-py. The main barriers to implementation of these systems are high costs, lack of IT infrastructure adaptation, the need to change the organization of staff work and the lack of factory-prepared col-lective packaging. In the opinion of pharmacists, changes in the distribution of drugs are necessary and beneficial from proper pharmacotherapy perspective.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140722899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of ACEA 1021 on Neurotoxicity Induced by Dexamethasone — Initial Behavioral Study ACEA 1021 对地塞米松引起的神经毒性的影响--初步行为研究

Acta Poloniae Pharmaceutica - Drug Research Pub Date : 2024-04-09 DOI: 10.32383/appdr/185546

Beata Krasuska-Grzegorczyk, Łukasz Komsta, Z. Danilczuk

{"title":"Effect of ACEA 1021 on Neurotoxicity Induced by Dexamethasone — Initial Behavioral Study","authors":"Beata Krasuska-Grzegorczyk, Łukasz Komsta, Z. Danilczuk","doi":"10.32383/appdr/185546","DOIUrl":"https://doi.org/10.32383/appdr/185546","url":null,"abstract":"Considerable evidence suggests that glucocorticoids (GCs) play an important role in neurodegeneration. Chronic elevated levels of GCs can result in neuronal degeneration of the hippocampal piramidal neurons, which are paralleled by cognitive deficits. Moreover, GCs potentiate stress or ischemia-induced accumulation of excitatory amino acids (EAA) in the extracellular space of hippocampus. ACEA 1021 (licostinel), a selective antagonist of the N-methyl-D-aspartate (NMDA) receptor, has been reported to prevent the excitotoxic action of high extracellular glutamate levels. The aim of this study was to investigate the effect of ACEA 1021 on neurotoxic effect of dexamethasone (DEX - a synthetic GCs receptor agonist). The experiments were carried out on Albino Swiss mice (25-30 g). ACEA 1021, at the doses: 1.25 and 2.5 mg/kg/day, ip, was administered 15 min before DEX (16 mg/kg/day, ip). The long-term memory acquisition (passive avoidance test) and the motor performance (“chimney” test) were evaluated 14 days after the drugs administration. The prolongation of climbing time in the “chimney” test and decrease of the retention time in the memory task of mice treated with DEX for 14 days. In mice treated with DEX for 14 days, ACEA 1021 at the both doses reduced the climbing time in the “chimney” test, at the dose of 1.25 mg/kg improved memory acquisition. The above findings suggest that ACEA 1021 could prevent the neurotoxic effects induced by DEX, but further study needs to be carried out to explain this effect.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140724615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0