最新刊期

    35 4 2024
    • MEI Long,LI Sa,ZHANG Yuqing,ZHOU Shuo,ZHAO Zengwei,ZHANG Wei,SHEN Qunhong,ZHEN Jiancun
      Vol. 35, Issue 4, Pages: 385-389(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.01
      摘要:OBJECTIVETo investigate the basic situation of developing pharmacy outpatient departments in Chinese tertiary medical institutions and analyze the influencing factors.METHODSThe research targeted the pharmacy outpatient department managers of hospitals and conducted a survey through Sojump in March 2023. Various independent variables were selected from the hospital’s own characteristics, the management of the pharmacy outpatient departments, and the construction of the pharmacist team for Logistic and linear regression analysis, with the aim of separately analyzing the factors influencing the establishment of pharmacy outpatient departments and the factors affecting the total number of patients served by these departments throughout the year 2022. RESULTS &CONCLUSIONSA total of 1 304 medical institutions of different levels nationwide participated in this survey, with 714 tertiary hospitals. Among the tertiary hospitals, 377 (52.80%) had established pharmacy outpatient departments, including 321 grade-A tertiary hospitals, 48 grade-B tertiary hospitals and 8 other tertiary hospitals. The 377 tertiary hospitals collectively operated 1 739 pharmacy outpatient departments, covering 19 specialized fields, with the highest proportion found in the cardiovascular field (including anticoagulation) at 16.45%. Tertiary hospitals in North China, Central China, East China and South China regions had more pharmacy outpatient departments. The establishment of pharmacy outpatient departments was found to be influenced by tertiary grade-B status (P=0.010) and the annual outpatient volume of the hospital (P=0.008), although the impact was relatively small. The factors influencing the number of patients served by pharmacy outpatient departments were the annual outpatient volume of the hospital (P=0.042) and the number of pharmacists engaged in clinical pharmacy work (P=0.004). The proportion of tertiary hospitals in China that have established pharmacy outpatient departments is insufficient. It is necessary to further accelerate the construction of pharmacy outpatient departments and appropriately expand the talent pool of hospital pharmacy teams based on the needs of pharmacy outpatient departments and patients, in order to meet the requirements of medical practice and patient care.  
      关键词:influential factors;questionnaire;regression analysis   
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      发布时间:2024-02-23
    • ZHU Xiaodan,CHEN Xiao,CAO Weiling,ZENG Yuan,LU Zuojing,LI Xuejun,CHEN Wenying
      Vol. 35, Issue 4, Pages: 390-394(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.02
      摘要:OBJECTIVETo investigate the current situation of pharmaceutical management in compact medical consortium of Guangdong province, and to provide decision-making basis for promoting the high-quality construction and sustainable development of the provincial medical consortium.METHODSA self-designed questionnaire was used to select 50 compact medical consortiums in Guangdong province. The survey was answered by the heads of the pharmacy department of the general hospitals. The survey covered the basic scale of the consortium, the appointment of chief pharmacists, the implementation of pharmaceutical management and pharmaceutical care homogenization within the consortium, the difficulties in promoting the homogenization, and the expected provincial support. Descriptive statistical analysis was performed on the survey results.RESULTSA total of 50 questionnaires were collected, and the effective recovery rate was 100%. There were 16 chief pharmacists (32.00%) in charge of the pharmacy department of the general hospital in the medical consortium. Thirty-seven medical consortiums (74.00%) had established a drug supply support system within the consortium, 35 medical consortiums (70.00%) had carried out pharmaceutical management and coordination work within the medical consortium, 23 medical consortiums (46.00%) had established a clinical medication guidance system, 25 medical consortiums (50.00%) had established a bidirectional communication mechanism, and only 8 medical consortiums (16.00%) had developed new models of pharmaceutical care. At present, the difficulties in promoting the homogenization of pharmaceutical management and pharmaceutical care within the medical consortium were mainly found in three aspects: the wide gap in management level of each member unit, the lack and uneven level of pharmaceutical personnel, and insufficient policy support and implementation. Most medical consortiums hoped that relevant departments could promote the homogenization of pharmaceutical work by holding special training courses or special supervision.CONCLUSIONSAt present, the compact medical consortium in Guangdong province has achieved initial results in the implementation of the chief pharmacist system, the homogenization of pharmaceutical management and pharmaceutical care. However, it is still necessary to improve the coverage of chief pharmacist appointments in the medical consortium, implement the homogenization of pharmaceutical management, and accelerate the homogenization process of pharmaceutical care.  
      关键词:pharmacy administration;pharmaceutical care;homogenization;chief pharmacist system   
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      发布时间:2024-02-23
    • WANG Wei,GAN Xiaoyang,XU Huiqin,ZHU Yihui,SHU Anmei,FU Yingxue,YU Bin,LYU Gaohong
      Vol. 35, Issue 4, Pages: 395-400(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.03
      摘要:OBJECTIVETo investigate the protective effect and potential mechanism of cornuside on diabetic nephropathy (DN) model mice.METHODSMale KK-Ay mice were fed with high-fat and high-sugar diet for two weeks to reproduce the DN model. The successfully modeled mice were randomly grouped into model group, aminoguanidine group (positive control,100 mg/kg) and cornuside group (100 mg/kg), and male C57BL/6J mice were included as normal group, with 6 mice in each group. Administration groups were given relevant medicine intragastrically, and normal group and model group were given a constant volume of normal saline intragastrically, once a day, for 8 consecutive weeks. The levels of fasting blood glucose (FBG), 24 h urinary protein, serum interleukin-12 (IL-12), IL-10, blood urea nitrogen (BUN) and serum creatinine (Scr) were detected; the pathological injury, fibrotic change and glomerular microstructure of renal tissue were observed; the expressions of the receptor of advanced glycation end products (RAGE), collagen type Ⅳ (COL-Ⅳ) and inducible nitric oxide synthase (iNOS) in renal cortex were detected in each group.RESULTSCompared with normal group, the renal cortex of mice in model group showed obvious inflammatory cell infiltration and fibrotic changes; the mesangial hyperplasia of glomerulus was serious and the basement membrane had a large number of irregular dark dense deposits; the levels of FBG and 24 h urinary protein, the serum levels of IL-12, BUN and Scr, and the expression levels of RAGE, COL-Ⅳ and iNOS in the renal cortex were significantly increased, while the serum level of IL-10 was significantly decreased (P<0.01). Compared with the model group, the renal pathological injuries, fibrotic changes and glomerular microstructure of mice in administration groups were improved significantly, and the above quantitative indexes were generally improved (P<0.05 or P<0.01).CONCLUSIONSCornuside has a certain protective effect on DN model mice. It can inhibit the inflammatory response, reduce urinary protein excretion, and alleviate renal fibrosis, which may be related to the inhibition of the advanced glycation end products/RAGE signaling pathway.  
      关键词:diabetic nephropathy;advanced glycation end products/the receptor of advanced glycation end products signaling pathway;inflammation;renal fibrosis   
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      发布时间:2024-02-23
    • WANG Panpan,YANG Zan,LIU Donglan,ZHOU Yi
      Vol. 35, Issue 4, Pages: 401-406(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.04
      摘要:OBJECTIVETo investigate the effects of quercetin on mitochondrial energy metabolism function after myocardial ischemia.METHODSH9c2 cells were divided into blank group, model group, quercetin high-dose, medium-dose and low-dose groups (40, 20, 10 μmol/L), and positive control group (cyclosporine A, 1 μmol/L). Reactive oxygen species (ROS), mitochondrial membrane potential (MMP), openness of mitochondrial permeability transition pore (MPTP), adenosine triphosphate (ATP), malondialdehyde (MDA), lactate dehydrogenase (LDH) and creatine kinase (CK) were observed after cell hypoxia treatment. Rats were randomly assigned into sham operation group, model group, quercetin high-dose, medium-dose and low-dose groups (100, 50, 25 mg/kg), and positive control group (trimetazidine, 6.3 mg/kg), with 8 rats in each group. They were given relevant medicine intragastrically, once a day, for 7 consecutive days. After the last medication, myocardial ischemia model was induced by the ligation of the left anterior descending branch of the coronary artery. The contents of LDH, MDA, creatine kinase isoenzyme-MB (CK-MB), superoxide dismutase (SOD), complex Ⅰ, complex Ⅳ and ATP in serum were all determined.RESULTSCompared with the model group, ROS fluorescence intensity, openness of MPTP, the contents of CK, LDH and MDA were significantly decreased in quercetin low-dose, medium-dose and high-dose groups, and positive control group, while the contents of MMP and ATP were all increased significantly (P<0.01); the contents of CK-MB, LDH and MDA in serum were all decreased significantly in quercetin low-dose, medium-dose and high-dose groups, and positive control group, while the contents of SOD, complex Ⅰ, complex Ⅳ and ATP (except for positive control group) were increased significantly (P<0.05 or P<0.01).CONCLUSIONSQuercetin can effectively reduce myocardial hypoxic injury, promote endogenous energy production and improve mitochondrial function after myocardial ischemia.  
      关键词:myocardial ischemia;Myocardial ischemia;mitochondria;energy metabolism   
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      发布时间:2024-02-23
    • WEI Yibao,MA Zhenyuan,LIAO Taiyang,YANG Nan,WU Peng,WANG Peimin,HUANG Zhengquan
      Vol. 35, Issue 4, Pages: 407-412(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.05
      摘要:OBJECTIVETo investigate the improvement effect and potential mechanism of “Layers adjusting external application” paste on synovial fibrosis (SF) in rats with knee osteoarthritis (KOA).METHODSMale SD rats were randomly divided into sham operation group, KOA group and Layers adjusting external application group, with 8 rats in each group. KOA model was induced by the anterior cruciate ligament disruption method in KOA group and Layers adjusting external application group. Fourteen days after modeling, the Layers adjusting external application group was given “Layers adjusting external application” paste [Sanse powder (8 g for every 100 cm2), Compound sanhuang ointment (5 g for every 100 cm2)] on the knee joint, 8 h every day, for 28 d in total. After the last administration, the degree of synovitis and fibrosis in rats was observed, and Krenn scoring was performed in each group. The expressions of collagen Ⅰ, high mobility group protein B1 (HMGB1) and phosphorylated nuclear factor-κB p65 (p-NF-κB p65) were detected in the synovial membrane; the contents of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in serum as well as the expressions of fibrosis-related and HMGB1/Toll-like receptor 4 (TLR4)/NF-κB signaling pathway-related proteins and mRNA were detected in synovial tissue.RESULTSCompared with the sham operation group, the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement, the inflammatory cell infiltration and collagen fiber deposition were obvious; the positive expressing cells of collagen Ⅰ, HMGB1 and p-NF-κB p65 were increased significantly; the contents of IL-1β, IL-6 and TNF-α in serum, the expressions of fibrosis-related protein (transforming growth factor-β, collagen Ⅰ, tissue inhibitor of metalloproteinase 1, α-smooth muscle actin) and their mRNA as well as the expressions of HMGB1, TLR4 protein and their mRNA, the expressions of p-NF-κB p65 protein and NF-κB p65 mRNA were all increased significantly in synovial tissues of rats (P<0.01). Compared with the KOA group, the pathological changes in the synovial tissue of rats in Layers adjusting external application group were significantly improved, and the above quantitative indicators were significantly reversed (P<0.05 or P<0.01).CONCLUSIONS“Layers adjusting external application” paste could significantly improve SF in KOA rats, the mechanism of which may be associated with the inhibition of the activation of HMGB1/TLR4/NF-κB signaling pathway.  
      关键词:synovial inflammation;synovial fibrosis;high mobility group protein B1/Toll-like receptor 4/nuclear factor-κB signaling pathway   
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      发布时间:2024-02-23
    • JIANG Cheng,ZANG Zhenzhong,CHEN Lihua,ZHU Haiting,FU Shihua,ZHU Weifeng,WU Wenting,SHI Wei,GUAN Yongmei
      Vol. 35, Issue 4, Pages: 413-418(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.06
      摘要:OBJECTIVETo explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro.METHODSThe chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group, triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10, 1∶50, 1∶100 (hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups). After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h, the cumulative transdermal dose (Qn) of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography, and the transdermal absorption rate (Jss) was calculated. Human immortalized keratinocytes (HaCat) were used as a model, the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility.RESULTSA total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified, including Z-ligustilide, senkyunolide, and β-selinene. The Qn (P<0.01) and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups, while the Qn (P<0.05) and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group, the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36, 72 and 144 ng/mL (P<0.05 or P<0.01); while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group, but the difference was not statistically significant (P>0.05).CONCLUSIONSWhen the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50, it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.  
      关键词:triptolide;transdermal absorption;compatibility;synergism and attenuation;cytotoxicity   
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      发布时间:2024-02-23
    • HE Xudong,NI Haoyu,HE Jinbiao,LI Min,HU Yunkai,GONG Dihong,YAO Jinling,YU Jie,YANG Xingxin
      Vol. 35, Issue 4, Pages: 419-424(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.07
      摘要:OBJECTIVETo investigate the intervention effect of kushenol F (KSC-F) on ulcerative colitis (UC) mice.METHODSTotally 30 male C57BL/6J mice were randomly divided into the normal group, model group, positive drug group (sulfasalazine, 703 mg/kg), KSC-F 50 mg/kg group (KSC-F50 group), and KSC-F 100 mg/kg group (KSC-F100 group), with 6 mice in each group. Except for the normal group, the mice in the remaining groups were given 3% dextran sulfate sodium solution continuously for 7 days to induce UC model. Concurrently, administration groups received corresponding drug solution intragastrically, once a day, for 10 consecutive days. During the experiment, the changes in body weight and bowel movements of the mice were observed. Disease activity index scoring was performed after the last administration. The histopathological morphology of colonic tissue was examined. The levels of inflammatory factors in the serum and colon tissue were measured. Additionally, the mRNA expression of inflammatory factors, and the protein expressions of inflammation-related proteins [interleukin-1β (IL-1β), forkhead box O1(FOXO1), phosphoinositide 3-kinase(PI3K), phosphorylated PI3K(p-PI3K), p38 mitogen-activated protein kinase(p38 MAPK), phosphorylated p38 MAPK(p-p38 MPAK) and phosphorylated protein kinase B(p-Akt)] were determined in colonic tissue.RESULTSKSC-F could alleviate weight loss and colonic tissue damage in UC mice. KSC-F reduced the levels of IL-1β, IL-6, IL-8 and tumor necrosis factor-α (TNF-α) in serum, as well as IL-1β, IL-6, IL-17 and TNF-α in colonic tissue to varying degrees and increased the levels of IL-10 in both serum and colonic tissue (P<0.05 or P<0.01). Moreover, KSC-F decreased the expression levels of IL-1β, IL-17 and TNF-α mRNA, as well as p-PI3K, p-p38 MAPK, and p-Akt proteins in colonic tissue to varying degrees, and increased the expression levels of IL-10 mRNA and FOXO1 protein in colonic tissue (P<0.05 or P<0.01).CONCLUSIONSKSC-F effectively alleviates UC symptoms in mice by inhibiting PI3K, Akt and p38 MAPK activation, mitigating the release of pro-inflammatory factors such as IL-1β, IL-6, TNF-α, promoting the anti-inflammatory factor IL-10 secretion, and reducing inflammation-induced colonic tissue damage.  
      关键词:ulcerative colitis;inflammatory reaction;intervention effect   
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      发布时间:2024-02-23
    • WEN Niting,YANG Changgui,ZHOU Tao,KANG Chuanzhi,ZHAO Dan,WANG Sheng,JIANG Weike
      Vol. 35, Issue 4, Pages: 425-429(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.08
      摘要:OBJECTIVETo evaluate the comprehensive quality of Houttuynia cordata from different producing areas.METHODSUsing total flavonoids, water-soluble extract, moisture, total ash and acid-insoluble ash as indicators, the entropy weight method was used to objectively weigh each indicator, and the relative correlation degree (ri) calculated by grey correlation method was used as a measure to comprehensively evaluate the quality of H. cordata.RESULTSThe weights of total flavonoids, total ash, moisture, acid-insoluble ash, and water-soluble extract were 0.295 5, 0.227 3, 0.188 7, 0.145 1, and 0.143 4, respectively. The weights of total flavonoids and total ash were relatively large. The ri of 30 batches of H. cordata ranged from 0.233 2 to 0.673 9; the average ri of samples from Quanzhou County and Ziyuan County of Guangxi Zhuang Autonomous Region were the highest, which were 0.638 3 and 0.598 7, respectively, followed by samples from Lingchuan County of Guangxi Zhuang Autonomous Region (0.556 1) and Jianshui County of Yunnan Province (0.452 8). The quality of medicinal materials produced in the above producing areas was generally good and stable.CONCLUSIONSEntropy weight method combined with the grey correlation method can be used to comprehensively evaluate the quality of H. cordata. The overall quality of H. cordata produced in Quanzhou County of Guangxi Zhuang Autonomous Region is the best.  
      关键词:grey correlation method;entropy weight method;multi-index;comprehensive evaluation   
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      发布时间:2024-02-23
    • GUO Huanyu,WANG Weifang,XU Liwei,DONG Wenbo
      Vol. 35, Issue 4, Pages: 430-435(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.09
      摘要:OBJECTIVETo investigate the effect and mechanism of picroside Ⅱ on the malignant progression of non-small cell lung cancer (NSCLC).METHODSA549 cells were divided into the control group, picroside Ⅱ low-, medium- and high-concentration groups, K6PC-5 [sphingosine kinase 1 (SPHK1) activator] group, and picroside Ⅱ high-dose+K6PC-5 group. Cell proliferation, migration and invasion were detected. Besides, the expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), MMP-9, SPHK1, sphingosine-1-phosphate receptor 3 (S1PR3) and extracellular signal-regulated kinase 1/2 (ERK1/2) protein in the cells were also observed. BALB/c nude mice were subcutaneously inoculated with A549 cell suspension to establish NSCLC xenograft models. Then they were assigned to the nude mouse-control group, nude mouse-picroside Ⅱ low-, medium- and high-dose groups, nude mouse-K6PC-5 group, and nude mouse-picroside Ⅱ high-dose+K6PC-5 group (with 5 mice in each group) to investigate the effect of picroside Ⅱ on their tumor mass and volume.RESULTSCompared with the control group, the OD450 values, EdU-positive cell rates, scratch healing rates, cell invasion number, and the relative expression levels of PCNA, MMP-2, MMP-9, SPHK1, S1PR3 and ERK1/2 protein in the low-, medium- and high-concentration groups of picroside Ⅱ were significantly decreased. Compared with the nude mouse-control group, the tumor mass and volume in the nude mouse-low-, medium- and high-dose groups of picroside Ⅱ were significantly decreased or shrunk. The changes of above indicators were concentration/dose-dependent (P<0.05). The changing trend of the corresponding indicators in the K6PC-5 group and the nude mouse-K6PC-5 group was opposite (P<0.05). Compared with the picroside Ⅱ high-concentration group or the nude mice-picroside Ⅱ high-dose group, the above quantitative indicators in the picroside Ⅱ high-concentration+K6PC-5 group cells and the nude mouse-picroside Ⅱ high-dose+K6PC-5 group nude mice were significantly increased or enlarged (P<0.05).CONCLUSIONSPicroside Ⅱ may inhibit the malignant progression of NSCLC by inhibiting SPHK1/sphingosine-1-phosphate/S1PR3 signaling pathway.  
      关键词:non-small cell lung cancer;proliferation;migration;invasion;sphingosine kinase 1/sphingosine-1-phosphate/sphingosine-1-phosphate receptor 3 signaling pathway   
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      发布时间:2024-02-23
    • YIN Xiaoning,ZUO Xianhong,DUAN Liyun,ZHOU Jun
      Vol. 35, Issue 4, Pages: 436-441(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.10
      摘要:OBJECTIVETo investigate the potential mechanism of procyanidin on rats with gingivitis by regulating phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/vascular endothelial growth factor (VEGF) signaling pathway.METHODSThe rat model of gingivitis was constructed by sewing the neck of the first maxillary molar with silk thread+applying maltose on the gum+feeding with 20% sucrose solution and soft food. Forth-eight model rats were randomly divided into model group, procyanidin group (160 mg/kg), 740Y-P group (PI3K/Akt signaling pathway activator, 0.02 mg/kg), and procyanidin+740Y-P group (procyanidin 160 mg/kg+740Y-P 0.02 mg/kg), with 12 rats in each group; another 12 rats were selected as control group; each medication group was treated with corresponding drugs intragastrically or/and intraperitoneally, once a day, for 7 consecutive days. Twenty-four hours after the last administration, the gingival index of rats was measured; the levels of interleukin-18 (IL-18), inducible nitric oxide synthase (iNOS) and alkaline phosphatase (ALP) in gingival crevicular fluid, as well as the levels of superoxide dismutase (SOD), catalase (CAT) and reactive oxygen species (ROS) in gingival tissues of rats were detected; the pathological changes in gingival tissues were observed; the expression levels of PI3K/Akt/VEGF signaling pathway-related proteins in gingival tissues of rats were detected.RESULTSCompared with control group, the gingival tissues of rats in the model group had severe pathological damage, which was manifested as local tissue expansion and congestion, new capillaries, degeneration and loss of collagen fibers and disorder of arrangement, and a large number of inflammatory cell infiltration in the gingival sulcus wall. The gingival index, the levels of IL-18, iNOS, ALP in gingival crevicular fluid, the level of ROS in gingival tissues, the phosphorylations of PI3K and Akt, as well as the protein expression of VEGF in gingival tissues were significantly increased; the levels of SOD and CAT in gingival tissues of rats in model group were significantly decreased (P<0.05). Compared with model group, the pathological damage to the gingival tissues of rats in procyanidin group was reduced, and all quantitative indicators were significantly improved (P<0.05); 740Y-P could reverse the improvement effect of procyanidin on various indicators (P<0.05).CONCLUSIONSProcyanidin may alleviate gingival tissue damage, and improve gingival inflammation and oxidative stress in rats with gingivitis by inhibiting PI3K/Akt/VEGF signaling pathway.  
      关键词:gingivitis;gingival tissue;phosphoinositide 3-kinase/protein kinase B/vascular endothelial growth factor signaling pathway   
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      发布时间:2024-02-23
    • Wuriga,Weilisi,Wurilaga,Susi,Aruhan,TONG Lijun,Butuya,Hurilebagen
      Vol. 35, Issue 4, Pages: 442-448(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.11
      摘要:OBJECTIVETo explore the mechanism of Zadi-5 pill in improving myocardial ischemia-reperfusion injury (MIRI).METHODSThe targets and pathways of potential effects of Zadi-5 pill improving MIRI were screened based on the network pharmacology. Seventy-two rats were randomly divided into model group, sham operation group, Danshen group [Compound danshen dripping pills 80 mg/(kg·d)] and Zadi-5 pill high-dose, medium-dose and low-dose groups [1.6, 0.8, 0.4 g/(kg·d)], with 12 rats in each group. The rats in each group were given corresponding drugs intragastrically, once a day, for 14 consecutive days. After the last administration, MIRI model was established by ligating the anterior descending branch of left coronary artery in rats, while rats in the sham operation group were threaded without ligation. The contents of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), cardiac troponin T (CTn-T), apoptotic rate of cardiomyocyte, phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax) and caspase-3 in myocardial tissue were detected in each group after modeling; the morphological changes of myocardial tissue were observed.RESULTSA total of 177 active ingredients and 220 targets of Zadi-5 pill were obtained, including 51 targets involved in improving myocardial ischemia; the core target of Zadi-5 pill improving MIRI was AKT1, including PI3K-Akt, endoplasmic reticulum and hypoxia-inducible factor-1. Compared with model group, the contents of CK, LDH, AST and CTn-T, the apoptotic rate of cardiomyocyte as well as the protein expressions of caspase-3 and Bax were significantly decreased in Danshen group and Zadi-5 pill high-dose group (P<0.05 or P<0.01), while the protein expressions of PI3K, Akt and Bcl-2 in myocardial tissue were significantly increased (P<0.05 or P<0.01), respectively; the myocardial histopathological changes were significantly improved. The above indicators were improved to varying degrees in Zadi-5 pill low-dose and medium-dose groups, too.CONCLUSIONSZadi-5 pill may inhibit apoptosis by activating the PI3K-Akt signaling pathway, thus playing a role in improving MIRI.  
      关键词:myocardial ischemic-reperfusion injury;mechanism of action;phosphatidylinositol 3-kinase/Akt signaling pathway;apoptosis   
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      发布时间:2024-02-23
    • QIN Chunmeng,LI Wenjun,LI Liaoping,LIU Jie,LIU Songqing
      Vol. 35, Issue 4, Pages: 449-452(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.12
      摘要:OBJECTIVETo prepare the Eriodictyol chewable tablet and to evaluate its quality.METHODSThe chewable tablet was prepared by the wetting granulation method by using microcrystalline cellulose (MCC) and mannitol as fillers, polyvinylpyrrolidone (PVP) as adhesive, citric acid and sucralose as flavor correction agents, magnesium stearate as lubricant. The comprehensive evaluation was conducted on Eriodictyol chewable tablets with the dosage of each excipient as a factor using the appearance, taste, flavor and texture as indicators. The ratio of excipients was optimized by orthogonal test, and the quality of Eriodictyol chewable tablets prepared by optimized formulation was evaluated in terms of appearance, weight difference, hardness, fragility, eriodictyol content, dissolution and content uniformity.RESULTSThe optimal formulation was as follows: 26.4% eriodictyol (50 mg each piece), 45% mannitol, 25% MCC, 0.3% citric acid, 0.3% sucralose, 1% magnesium stearate, 2% PVP (preparing 5% solution using purified water). The scores of 3 batches of Eriodictyol chewable tablets in the validation test were 8.76, 8.75 and 8.80 (RSD=0.30%, n=3), respectively. The Eriodictyol chewable tablet had a complete appearance and a smooth surface; the average tablet weight was 192.57 mg, the average hardness was 57.36 N, the fragility was 0.09%, the average content of eriodictyol per tablet was 50.74 mg, the cumulative dissolution within 30 min was exceeding 80%, and the content uniformity was 5.51.CONCLUSIONSEriodictyol chewable tablet prepared by optimal formulation conforms to the requirements of the 2020 edition of Chinese Pharmacopoeia.  
      关键词:chewable tablet;formulation optimization;orthogonal test;quality evaluation   
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      发布时间:2024-02-23
    • LI Haishan,YANG Hejin,ZHENG Yongren
      Vol. 35, Issue 4, Pages: 453-458(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.13
      摘要:OBJECTIVETo investigate the anti-inflammatory activity and potential mechanism of Clematis ranunculoides extract.METHODSThe ear swelling was induced by xylene to establish an acute inflammation model of mice; using aspirin (0.25 g/kg) as a positive control, the effects of 1.25, 2.5, 5 g/kg C. ranunculoides extract on the degree of ear swelling were investigated. The chronic inflammation model of rats was also established by implanting cotton balls; using aspirin (0.17 g/kg) as a positive control, the effects of 0.88, 1.75, 3.5 g/kg C. ranunculoides extract on the net weight of granulomas were investigated. Furthermore, RAW264.7 cells were induced by lipopolysaccharide to establish an inflammatory injury model; the effects of 12.5, 25, 50 μg/mL C. ranunculoides extract on the contents of nitric oxide(NO), prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and monocyte chemotactic protein-1(MCP-1) in the cell supernatant, the protein expressions of inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2), p65 and phosphorylated p65(p-p65) in cells as well as nuclear translocation of p65 protein were assessed.RESULTSC. ranunculoides extract with 5 g/kg significantly relieved ear swelling in mice, and C. ranunculoides extract with 1.75, 3.5 g/kg significantly decreased the net weight of granulomas in rats (P<0.05). C. ranunculoides extract with 12.5, 25, 50 μg/mL significantly reduced the contents of NO (except for 12.5 μg/mL C. ranunculoides extract), PGE2, TNF-α, IL-6 and MCP-1 in the cell supernatant, as well as the relative expressions of iNOS and COX-2 protein, and relative expression ratio of p-p65 and p65 protein (P<0.05 or P<0.01); C. ranunculoides extract with 25, 50 μg/mL inhibited the translocation of p65 protein to the cell nucleus.CONCLUSIONSC. ranunculoides extract exhibits significant anti-inflammatory activity, the mechanism of which may be attributed to the inhibition of the activation of nuclear factor-κB signaling pathway, down-regulation of COX-2 and iNOS protein expression, and the reduction of inflammatory cytokines release.  
      关键词:anti-inflammatory activity;macrophages;nuclear factor-κB signaling pathway   
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      发布时间:2024-02-23
    • CONG Yue,LI Li,ZHAO Yimeng,XU Yuanyuan,GONG Jianting,GUAN Jiali
      Vol. 35, Issue 4, Pages: 459-463(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.14
      摘要:OBJECTIVETo explore the protective mechanism of amifostine on acute radiation injury mice.METHODSThirty C57BL/6J mice were randomly divided into normal control group, model group and amifostine group (150 mg/kg), with 10 mice in each group. Thirty minutes before irradiation, the mice in the amifostine group were intraperitoneally injected with amifostine; normal control group and model group were given constant volume of normal saline intraperitoneally; then acute radiation injury was induced by 4 Gy X-ray radiation in both model group and amifostine group. The white blood cell count (WBC), platelet count and red blood cell (RBC) count in mice were detected 2 hours before irradiation and on days 1, 4, 7, 10 and 14 after irradiation; the changes in the proportion of WBC (neutrophils, lymphocytes and monocytes) on the 7th day after irradiation were analyzed. The 16S rRNA high-throughput sequencing was used to analyze the structure of gut microbiota in mice feces on the 7th day after irradiation, then its correlation with WBC was analyzed.RESULTSThe counts of WBC on the 1st, 4th, 7th and 10th day after irradiation, platelet count on the 10th day after irradiation and RBC count on the 1st day after irradiation in the amifostine group were significantly higher than those in model group (P<0.05). Compared with normal control group,β diversity of gut microbiome showed significant change, relative abundance of Firmicutes increased and that of Bacteroidetes decreased in model group. Amifostine could reverse the change in β diversity of gut microbiome, and the relative abundance of Bacteroidetes and Firmicutes. The model group consisted of four distinct species, namely Allobaculum, Erysipelotrichia, Erysipelotrichales and Erysipelotrichaceae, which were significantly negatively correlated with the proportion of peripheral blood lymphocytes (P<0.01); amifostine group consisted of two distinct species, namely Lactobacillus murinus and L. crispatus, which were significantly negatively correlated with the proportion of neutrophils (P<0.05).CONCLUSIONSAmifostine significantly improves irradiation-induced injury by regulating dysbiosis of gut microbiota.  
      关键词:amifostine;gut microbiota;16S rRNA gene sequencing   
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    • GUO Xiaqing,LI Guofei,SUN Yuhua,ZHENG Donglin
      Vol. 35, Issue 4, Pages: 464-467(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.15
      摘要:OBJECTIVETo compare the efficacy and safety of lacosamide (LCM) and carbamazepine (CAR) as monotherapy in the treatment of adult patients with newly diagnosed epilepsy.METHODSBy methods of retrospective analysis, 84 adult patients with newly diagnosed epilepsy, were admitted to the Department of Neurology, Huaihe Hospital of Henan University during Sept. 2020-Jun. 2022, were divided into the control group (40 cases, receiving CAR treatment) and the observation group (44 cases, receiving LCM treatment) according to different medication regimens. Total response rate, epilepsy seizure frequency, blood lipid levels, and the occurrence of adverse events (AEs) of patients were compared between the 2 groups.RESULTSIn the first month after treatment, there was no statistically significant difference in the total response rate between the observation group (63.64%) and the control group (55.00%, P>0.05); the frequency of epilepsy seizure in both groups was significantly reduced compared to before treatment (P<0.05), but there was no statistically significant difference between 2 groups (P>0.05). In the third month after treatment, the total response rate of the observation group (90.91%) was significantly higher than control group (67.50%, P<0.05); the frequencies of epilepsy seizure in both groups were significantly reduced compared to before treatment, and the observation group was significantly lower than the control group (P<0.05). In the third month after treatment, the levels of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholestrol (LDL-C) in the control group and the level of LDL-C in the observation group were significantly higher than before treatment, and the levels of TC, TG and LDL-C in the observation group were significantly lower than those in the control group (P<0.05). There was no statistically significant difference in the incidence of AEs between the observation group (15.91%) and the control group (17.50%, P>0.05).CONCLUSIONSBoth LCM and CAR have certain effects in the treatment of newly diagnosed epilepsy in adults, which can reduce the frequency of epilepsy seizure in patients and have comparable safety. Meanwhile, LCM has better long-term efficacy than CAR in treating newly diagnosed epilepsy in adults, and its impact on the patient’s blood lipid is smaller than CAR.  
      关键词:carbamazepine;newly diagnosed epilepsy;adult patient;efficacy;safety   
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    • LONG Yi,LIU Qian,LI Rui,WU Guixin,HE Aiting,JIANG Zhengying
      Vol. 35, Issue 4, Pages: 468-471(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.16
      摘要:OBJECTIVETo investigate the effects of esketamine for multimodal analgesia on opioid consumption and gastric motility in mechanically ventilated non-surgical intensive care unit (ICU) patients.METHODSForty cases of mechanically ventilated non-surgical patients in the ICU of our hospital from February 1st, 2023 to July 31st, 2023 were selected and randomly divided into control group and esketamine (S-K) group using grouping method with opaque envelopes, with 20 cases in each group. Control group was given sufentanil, and S-K group was infused with Esketamine hydrochloride injection at a constant rate of 0.2 mg/(kg·h)+ sufentanil. The treatment period length, analgesic compliance rate, sedation level, analgesic and sedative consumption, and gastric motility indexes were compared between the two groups.RESULTSThere was no statistically significant difference in the treatment period length, analgesic compliance rate, sedation level, or the consumption of propofol and midazolam between the two groups (P>0.05). The consumption of sufentanil in the S-K group was significantly less than control group (P<0.05). Compared with 1 h after randomization, the antral contraction frequency, antral contraction amplitude and antral motility index of patients in the S-K group were significantly higher at 72 h after randomization and were significantly higher than control group (P<0.05).CONCLUSIONSEsketamine may reduce opioid consumption and improve gastric motility in mechanically ventilated non-surgical ICU patients while ensuring a level of analgesic sedation.  
      关键词:multimodal analgesia;mechanical ventilation;intensive care unit;gastric motility   
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    • DING Nianyang,LI Li,FANG Panqi,XU Silu,ZHAO Min,YAN Dan
      Vol. 35, Issue 4, Pages: 472-475(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.17
      摘要:OBJECTIVETo analyze the occurrence of adverse drug reactions (ADR) between bevacizumab biosimilars and original drugs, and to provide data support for rational use of drugs in clinical.METHODSADR reports of bevacizumab biosimilars and original drugs reported by Jiangsu Cancer Hospital from January to December 2022 were retrospectively analyzed.RESULTSA total of 6 818 patients were treated with bevacizumab, and 136 ADR patients were reported. The incidence of ADR caused by bevacizumab biosimilars was higher than original drugs (2.18% vs. 0.71%, P=0.004). In ADR reports, the main treatment plan was bevacizumab combined with other tumor drugs (129 patients); 118 patients were cured and improved; there were 108 general reports and 28 serious reports; the main system/organ involved in ADR was the cardiovascular system; there were no statistical significance in the incidence rates of hypertension/blood pressure increase, leukocyte/platelet decrease, diarrhea and fever caused by bevacizumab biosimilars and original drugs.CONCLUSIONSThe incidence of ADR related to bevacizumab biosimilars is significantly higher than that of the original drugs, but there is no significant difference in the clinical manifestation of ADR. Clinicians can use bevacizumab biosimilars or original drugs based on the willingness of patients and their families.  
      关键词:biosimilars;original drugs;adverse drug reactions;reasonable use   
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    • LI Jingfeng,SHI Zhengyuan,ZHANG Mengjie,GUAN Lei,JIANG Dechun
      Vol. 35, Issue 4, Pages: 476-480(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.18
      摘要:OBJECTIVETo establish a method for the determination of propofol concentration in human plasma and apply it in patients with lymphedema.METHODSThe concentration of propofol was determined by UPLC-MS/MS after protein precipitation of plasma samples using thymol as internal standard. The sample was eluted on a Kinetex C18 column with a mobile phase consisting of acetonitrile (A)-water (B) for gradient elution at the flow rate of 200 μL/min. The sample size was 5 μL, and the column temperature was set at 40 ℃. The sample chamber temperature was 15 ℃. Using multi-reaction monitoring mode, the ion pairs for quantitative analysis were m/z 177.0→161.2 (propofol) and m/z 149.0→133.1 (internal standard), respectively. The above method was used to determine the plasma concentration of propofol in 6 patients with lymphedema.RESULTSThe linear range of propofol was 50-5 000 ng/mL (r=0.995 0). RSDs of within- and between-batch precision were not more than 8.08%; no endogenous interference, carryover effect, or dilution effect was observed in blank plasma. The extraction recovery ranged from 89.80% to 93.73%, and matrix effects were within the range of 97.93%-101.73%. RSDs of the stability test were all lower than 3.27%. During intraoperative TCI 2-30 min, the plasma concentration of propofol in 6 patients was maintained in the range of 1 865.3-6 056.2 ng/mL, and the propofol was almost excreted within 4-8 h after operation.CONCLUSIONSThe established UPLC-MS/MS method in this study can achieve the determination of propofol and a simple and fast sample pretreatment process without derivatization; it is proved to be suitable for the concentration monitoring of propofol in plasma samples of patients with lymphedema.  
      关键词:propofol;lymphedema;plasma concentration   
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    • JIN Tanghui,ZHU Mengxin,XIE Cheng,XIA Fan,YU Di,LI Yue,LI Yun,XI Qinhua,ZHU Jianguo
      Vol. 35, Issue 4, Pages: 481-487(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.19
      摘要:OBJECTIVETo evaluate the quality of guidelines/consensus on therapeutic drug monitoring (TDM) of anti-tumor necrosis factor-α (TNF-α) in patients with inflammatory bowel disease (IBD) in China and globally.METHODSPubMed, Embase, CNKI, Wanfang data, VIP, and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data, the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized.RESULTSA total of 9 articles were included, 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions (scope and aims, participants, rigor of formulation, clarity of expression, application, and editorial independence) were 90.43%, 41.98%, 52.55%, 85.49%, 19.00%, and 76.85%, respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios, threshold ranges, strategy adjustments, detection methods, and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally, the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug.CONCLUSIONSThe overall quality of the included guidelines/consensus was fair, with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs, and interpret and apply results of TDM in combination with specific clinical treatment goals.  
      关键词:anti-TNF-α;therapeutic drug monitoring;guidelines;consensus   
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    • TUO Mingfu,TANG Cai’e,YANG Kun,SHEN Yabing,LEI Shixin,YANG Liang
      Vol. 35, Issue 4, Pages: 488-493(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.20
      摘要:OBJECTIVETo systematically evaluate the risk factors for cefoperazone/sulbactam-induced coagulation dysfunction in adult patients.METHODSRetrieved from CNKI, VIP, CBM, Wanfang data, PubMed, Embase and Cochrane Library, randomized controlled trial (RCT), case-control study or cohort study about cefoperazone/sulbactam-induced coagulation dysfunction in adult patients were collected from the inception to Apr. 30th, 2023. After literature screening, data extraction and quality evaluation, meta-analysis was carried out by using RevMan 5.3 software.RESULTSA total of 13 studies were included, among which 11 studies were case-control studies, and 2 studies were cohort studies, involving 18 387 patients in total. Meta-analysis showed that the proportion of advanced age [OR=2.04, 95%CI (1.14, 3.64), P=0.02], liver insufficiency [OR=5.95, 95%CI (4.21, 8.40), P<0.000 01], renal insufficiency [OR=3.51, 95%CI (3.04, 4.05), P<0.001], hypoproteinemia [OR=1.90, 95%CI(1.37, 2.62), P<0.001], poor diet [OR=7.25, 95%CI (5.13, 10.24), P<0.000 01], daily dose of cefoperazone/sulbactam ≥9 g [OR=3.95, 95%CI (2.45,6.37), P<0.001], medication duration of cefoperazone/sulbactam ≥10 d [OR=2.43, 95%CI (1.81, 3.28), P<0.001], combined use of anticoagulant drugs [OR=2.84, 95%CI (2.03, 3.97), P<0.001], combined with malignant tumor [OR=1.60, 95%CI (1.20, 2.15),P<0.001] in patients with abnormal coagulation function were significantly higher than those with normal coagulation function.CONCLUSIONSAdvanced age, liver insufficiency, renal insufficiency, complicated with malignant tumors and hypoalbuminemia, combined use of anticoagulant drugs, poor diet, daily dose ≥9 g, and medication duration≥10 days are risk factors for coagulation dysfunction caused by cefoperazone/sulbactam.  
      关键词:coagulation dysfunction;risk factors;systematic review   
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    • FU Suqin,HAO Chenye,PENG Jun
      Vol. 35, Issue 4, Pages: 494-499(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.21
      摘要:OBJECTIVETo analyze the current status and trend in the application of artificial intelligence in pharmaceutical service in China and globally.METHODSThe research literature on the application of artificial intelligence technology in the field of hospital pharmaceutical service from database establishment to June 16, 2023, was searched in Web of Science and CNKI. The authors, countries/regions, institutions and the co-occurrence, clustering, and emergence of keywords were visually processed and analyzed using tools including Endnote, CiteSpace, and Python. RESULTS &CONCLUSIONSOverall, 1 190 global literature and 178 Chinese literature were included. The number of publications issued in China and globally is increasing year by year, yet a gap remains in the quantity and quality of Chinese research compared with global research. Europe and the United States have built a close cooperation network in this field, while China’s regional development in this field remains imbalanced. Global research hotspots mainly focus on the development and application of high-end technologies such as machine learning, natural language processing, and deep learning; Chinese research concentrates more on actual medical services and medical policies, especially in promoting rational drug use, prescription review, and the development of traditional Chinese medicine.  
      关键词:pharmaceutical service;bibliometrics;visual analysis   
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    • JIANG Shuzheng,CHEN Xi,CHEN Feiyu,ZHANG Shaohui
      Vol. 35, Issue 4, Pages: 500-505(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.22
      摘要:OBJECTIVETo construct the integrated pharmaceutical care model of in-hospital pharmaceutical care+out-hospital pharmacy outpatient service for patients with lower extremity artery disease (LEAD), so as to improve patients’ disease self-management ability, and the efficacy and safety of therapy.METHODSThe in-hospital pharmaceutical care and out-hospital pharmacy outpatient service model was constructed for LEAD patients, including pharmaceutical evaluation, self-management ability education, and pharmacy follow-up, to perform long-term management of patients. Totally 65 LEAD patients admitted to the vascular surgery department of our hospital, receiving pharmacist management, from September, 2021 to December, 2022 were selected as the study objects, and pharmacists conducted in-hospital pharmaceutical care+continuous out-patient management. The efficacy indicators, safety indicators, and patients’s disease self-management ability indicators were compared before and after 3 months of pharmacist management.RESULTSAfter 3 months of pharmacists’ participation in the management of 65 patients, Fontaine stage decreased in 55 patients, there was the significant difference in Fontaine stage before and after management (P<0.001). The proportion of patients who completely followed the guidelines for medication increased from 63.1% to 96.9%; the incidence of small bleeding was reduced by 7.7% after pharmacists’ management. The scores of Morisky medication compliance and patients’ disease self-management ability were higher than 3 months ago (P<0.001). Patient proportion with “good” medical satisfaction increased by 18.4%.CONCLUSIONSThe in-hospital pharmaceutical care and out-hospital pharmacy outpatient service model of LEAD patients can effectively improve patients’ disease self-management ability, and improve the efficacy and safety of therapy.  
      关键词:disease self-management ability;pharmaceutical care;pharmaceutical clinic   
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    • SUN Xuelin,ZHENG Li,LI Hongsheng,HU Xin,ZHANG Yatong
      Vol. 35, Issue 4, Pages: 506-512(2024) DOI: 10.6039/j.issn.1001-0408.2024.04.23
      摘要:Diarrhea caused by chemotherapy is called chemotherapy-related diarrhea (CRD). CRD can lead to reduced treatment effectiveness and compliance, affect the long-term outcome of tumor patients, and can be life-threatening in severe cases. In addition to conventional chemotherapy drugs, many molecularly targeted drugs are also associated with CRD, including small molecule epidermal growth factor receptor (EGFR) inhibitors, anti-EGFR monoclonal antibodies, phosphoinositide 3-kinase inhibitors, small molecule inhibitors of vascular endothelial growth factor receptor, BCR-ABL1 and KIT inhibitors, human epidermal growth factor receptor 2 target inhibitors, cyclin-dependent protein kinase inhibitors, antibody-drug conjugates and other molecularly targeted drugs. The occurrence mechanism may be related to the intestinal mucosal injury or enteritis caused by molecularly targeted drugs. The clinical manifestations are increased stool frequency and/or loose imposition, and patients are often associated with excess hyperproduction and/or colic. The incidence of CRD varies with different drugs. Great importance should be attached to collecting medical history and differential diagnosis, actively intervening and conducting dynamic evaluation, strengthening patient education, and timely detecting and preventing the occurrence of intestinal toxicity.  
      关键词:tumor;targeted therapy;intestinal toxicity;adverse drug reactions   
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