Colorectal cancer (CRC) is a common malignancy with high morbidity and mortality globally. PD16, a novel steroidal saponin from Paris delavayi Franchet, shows cytotoxicity against HepG2 and U87MG cells, but its anti-CRC effects and related molecular mechanisms remain unknown. Our study revealed that PD16 significantly suppressed the growth of HCT116 and HT-29 CRC cells, without noticeable toxic effects on the non-cancerous NCM460 cells. Moreover, PD16 treatment reduced colony formation ability, impaired migration and invasion, and caused arrest of cells predominantly in the G0/G1 phase. PD16 promoted apoptosis, evidenced by elevated expression levels of cleaved caspase-9, cleaved caspase-3, cleaved PARP, and Bax, along with decreased expression of Bcl-2. Mechanistically, PD16 exposure weakened the phosphorylation of AKT and GSK3β. Additionally, combination treatment with the AKT inhibitor MK-2206 enhanced PD16-induced apoptotic effects and further suppressed AKT/GSK3β signaling. Molecular docking demonstrated PD16 had a good binding effect with AKT and GSK3β. In xenograft mouse models, PD16 markedly inhibited CRC tumor growth with concomitant downregulation of the AKT/GSK3β pathway, without major organ toxicity. Collectively, these findings provide the first evidence that PD16 exerts pro-apoptotic effects in CRC cells through the AKT/GSK3β pathway inhibition, thereby confirming it as a valuable novel therapeutic candidate for CRC.

Globally, colorectal cancer (CRC) ranked third in cancer prevalence and emerged as the primary contributor to cancer-related fatalities in 2022, with projections indicating substantial escalation by 2040. The malignant progression of healthy colonic cells involves complex interactions among multiple cellular pathways over extended periods (typically exceeding 10 years), influenced by dietary patterns, lifestyle factors, and genetic predispositions. In addition, marked disparities in CRC incidence and mortality appear to show large differences across geographic regions, demographic groups, and biological sexes, suggesting that there are traces of CRC. Therefore, timely intervention or regression of the development of CRC, particularly targeting high-risk populations, may be an excellent strategy to reduce CRC burden in forthcoming decades. Natural derived small molecule compounds (NDSMCs) exhibit significant advantages, including structural diversity, unique biological activities, low toxicity and multi-target effects. Increasing evidence suggests that NDSMCs demonstrate therapeutic potential against CRC through multi-target mechanisms, such as modulation of gut microbiota, induction of ferroptosis, and regulation of programmed cell death pathways (apoptosis/autophagy), thereby offering promising avenues for CRC treatment. However, comprehensive reviews in this field remain scarce. Consequently, this study systematically summarizes the research advancements over the past 5 years regarding the mechanisms of NDSMCs in combating CRC, aiming to provide valuable insights for therapeutic strategies, preventive measures, and novel drug development. Furthermore, the clinical progress and limitations of certain NDSMCs in CRC treatment are also discussed.

Foot-and-mouth disease virus (FMDV) are small, icosahedral viruses that cause serious clinical symptoms in livestock. The FMDV VP1 protein is a key structural component, facilitating virus entry. Here, we find that the E3 ligase RNF5 interacts with VP1 and targets it for degradation through ubiquitination at the lys200 of VP1, ultimately inhibiting virus replication. Mutations at this lysine site have been found to increase the replication of FMDV in mice. Importantly, the RNF5 pharmacological activator Analog-1 alleviates disease development in a mouse infection model. Furthermore, RNF5 recognizes the VP1 protein from several picornaviruses, suggesting that targeting RNF5 may be a broad-spectrum antiviral strategy. These findings shed light on the role of the ubiquitin-proteasome system in controlling virus replication, offering potential new strategies for treating viral infections.

Objectives PD15, a novel natural steroidal saponin extracted from the rhizomes of Paris delavayi Franchet, has demonstrated a strong cytotoxic effect against HepG2 and U87MG cells. However, its therapeutic effects on colorectal cancer (CRC) and the underlying molecular mechanisms remain unclear.Methods MTT assay, clonogenic assay, Hoechst 33258 staining, flow cytometry, molecular docking, and western blot were used to investigate the mechanism of PD15 in HCT116 cell lines. Additionally, the anti-CRC effects of PD15 were evaluated in vivo using HCT116 xenograft models.Key findings PD15 significantly inhibited cell proliferation and induced G0/G1 phase arrest in HCT116 cells. Furthermore, PD15 upregulated cleaved Caspase 3 and 9, cleaved PARP, and Bax expression levels while downregulating Bcl-2, leading to apoptosis. Further experiments revealed that PD15 downregulated the protein expression of p-Akt and p-GSK3 beta, with LY294002 (a PI3K/Akt inhibitor) enhancing PD15-induced apoptosis and its effects on Akt/GSK3 beta-associated proteins. In addition, molecular docking demonstrated that PD15 exhibited strong binding affinity with Akt and GSK3 beta. Critically, PD15 inhibited CRC growth in vivo without causing apparent toxicity in mice.Conclusions These findings indicate that PD15 could trigger apoptosis by suppressing the Akt/GSK3 beta signaling pathway in HCT116 cells.

Background: The aim of this study was to explore the association between lactate/albumin ratio and the prognosis of sepsis patients. Methods: A computerized search was performed in Pubmed, EMbase, Ovid, Medline, and Google Scholar to collate relevant studies. The results were compared using standardized mean differences (SMD)/odds ratio (OR) and 95% confidence intervals (CI). Prospective and retrospective cohort studies were both included in this study. Results: A total of nine studies involving 3039 participants were included. Pooled analysis revealed that survivors had substantially lower lactate/albumin ratio than non-survivors (SMD=-2.02, 95% CI: -2.76 to -1.28, I2=97.4%). Further, our results also indicated that elevated lactate/albumin ratio is an independent risk factor for mortality (OR=2.16, 95% CI: 1.58 to 2.95, I2=76.2%) and multiple organ dysfunction syndrome (MODS) (OR=3.41, 95% CI: 1.78 to 6.50, I2=0.0%) in septic patients. Moreover, according to the area under curve (AUC) results, the lactate/albumin ratio also presented good discriminatory power to predict mortality (AUC=0.75, 95% CI: 0.68 to 0.84, I2=92.9%) and MODS (AUC=0.78, 95% CI: 0.68 to 0.91, I2= 65.1%) in septic patients. Begg's and Egger's tests suggested no publication bias in the included studies. Conclusion: Our results highlighted that the lactate/albumin ratio is an important prognostic factor for MODS and mortality in sepsis patients, having good capabilities in identifying MODS and mortality. Elevated lactate/albumin ratio is an independent risk factor for mortality and multiple organ dysfunction syndrome (MODS) in septic patients. The lactate/albumin ratio also presented good discriminatory power to predict mortality and MODS in septic patients.

Colorectal cancer (CRC) is one of the most common types of malignant cancers worldwide. Although molecularly targeted therapies have significantly improved treatment outcomes, most of these target inhibitors are resistant. Novel inhibitors as potential anticancer drug candidates are still needed to be discovered. Therefore, in the present study, we synthesized a novel 4-(1,3,4-thiadiazole-2-ylthio)pyrimidine derivative (compound 4) using fragment- and structure-based techniques and then investigated the anticancer effect and underlying mechanism of anti-CRC. The results revealed that compound 4 significantly inhibited HCT116 cell proliferation with IC50 values of 8.04 ± 0.94 µmol L–1 after 48 h and 5.52 ± 0.42 µmol L–1 after 72 h, respectively. Compound 4 also inhibited colony formation, migration, and invasion of HCT116 cells in a dose-dependent manner, as well as inducing cell apoptosis and arresting the cell cycle in the G2/M phase. In addition, compound 4 was able to inhibit the activation of the MEK/ERK signaling in HCT116 cells. And compound 4 yielded the same effects as the MEK inhibitor U0126 on cell apoptosis and MEK/ERK-related proteins. These findings suggested that compound 4 inhi bited cell proliferation and growth, and induced cell apoptosis, indicating its use as a novel and potent anticancer agent against CRC via the MEK/ERK signaling pathway.

Denosumab is a newly approved treatment for osteoporosis in China. However, the clinical safety and advantages of denosumab have not been much established. The current study evaluates the real-world safety of denosumab versus zoledronic acid in treating cancer-free adults aged 50 years or older with osteoporosis to provide clinical settings guidelines. A head-to-head comparison of the safety profiles between denosumab (60 mg subcutaneously every 6 months) and zoledronic acid (5 mg, intravenously yearly) was performed in cancer-free adults aged 50 years or older with osteoporosis. MEDLINE, EMBASE, and Cochrane Library databases were searched for cohort studies comparing the safety of denosumab and zoledronic acid in cancer-free adults aged 50 years or older with osteoporosis till December 2021. The outcomes included the risk of fracture and other severe adverse events. Based on the Cochrane Handbook for Systematic Reviews of Interventions 5.0.2, we identified the eligible studies. Three cohort studies having 38,845 cancer-free adults aged 50 years or older were included in the study. The results showed that denosumab was not superior to zoledronic acid in reducing fracture risk [RR (95% CI): 1.05 (0.90, 1.23), P = 0.52]. However, denosumab had a low risk of composite cardiovascular disease [RR (95% CI): 0.82 (0.70, 0.96), P = 0.01]. There were no significant differences between the hazards of serious infection, and total adverse events (P > 0.05). The present meta-analysis demonstrated that for cancer-free adults aged 50 years or older with osteoporosis, denosumab was as safe as zoledronic acid for the risk of drug-induced fractures. However, denosumab had a lower incidence of composite cardiovascular disease, and may be a better option for the population with cardiovascular disease. Nonetheless, due to limitations like a short-term follow-up, gender, and incomplete types of adverse effects, more randomized controlled trials (RCTs) are required to further verify this conclusion.

目的:研究β-乳香酸对大鼠海马神经元细胞氧糖剥夺损伤的改善作用.方法:将大鼠海马神经元细胞分为正常对照组、模型组和β-乳香酸低、中、高浓度组(1、10、100μmol/L),除正常对照组外,其余各组细胞加入相应含药培养基,并进行氧糖剥夺培养以复制氧糖剥夺损伤模型.采用MTT法检测细胞的存活率,采用化学比色法检测细胞上清液中乳糖脱氢酶(LDH)活性,采用Hoechst-PI染色法观察细胞形态的变化,采用流式细胞仪检测细胞早期凋亡率,采用Western blot法检测细胞中凋亡相关蛋白[B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)、激活型胱天蛋白酶3(cleaved caspase-3)]的表达.结果:与模型组比较,β-乳香酸中、高浓度组细胞存活率、Bcl-2蛋白表达水平均显著升高(P<0.01),细胞上清液中LDH活性、细胞早期凋亡率和细胞中cleaved cas-pase-3、Bax蛋白表达水平均显著降低(P<0.05或P<0.01);细胞核致密浓染、碎片状现象明显减少.结论:β-乳香酸可改善大鼠海马神经元细胞氧糖剥夺损伤,其作用机制可能与下调cleaved caspase-3、Bax蛋白表达,上调Bcl-2蛋白表达有关.

目的 研究歪头菜全草中的黄酮类化学成分.方法 采用硅胶柱色谱,葡聚糖凝胶柱色谱以及半制备HPLC等方法分离纯化,根据MS和NMR数据鉴定化合物的结构.结果 从歪头菜中分离得到8个化合物,分别鉴定为山柰酚(1),槲皮素(2),异鼠李素-3-O-α-L-鼠李糖苷(3),槲皮素-3-O-α-L-鼠李糖苷(4),槲皮素-7-O-α-L-鼠李糖苷(5),萹蓄苷(6),杨梅苷(7),金丝桃苷(8).结论 化合物1～7为首次从该植物中分离得到.

目的:总结新型钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂鲁格列净治疗2型糖尿病(T2DM)的临床研究进展,为鲁格列净的合理应用提供参考.方法:以"SGLT2抑制剂""鲁格列净""糖尿病""SGLT2 inhibitor""Luseogliflozin""Diabetes"为主题词,在中国知网、维普、万方数据、PubMed、Elsevier和Web of Science等数据库中组合检索2010年1月1日-2018年12月31日发表的相关文献,对鲁格列净的作用机制、临床药动学、临床药效学、有效性和安全性等方面进行综述.结果 与结论:鲁格列净是一种SGLT2抑制剂类降糖药,其作用机制独立于β细胞外的非胰岛素依赖性口服降糖药物,是通过抑制肾脏近曲小管对葡萄糖的重吸收,增加尿中葡萄糖的排泄而达到控制血糖的目的.临床上,鲁格列净无论单药治疗还是联合胰岛素、二肽基肽酶4抑制剂、α-糖苷酶抑制剂等,均表现出显著的降血糖效果,同时还有减轻体质量、降低血压、改善脂质代谢和尿酸代谢的作用.该药的不良反应较轻、持续时间短暂,主要有鼻咽炎、上呼吸道感染、β2微球尿蛋白升高等;单用时不增加低血糖发生的风险,与胰岛素或磺脲类药物联用时,可一定程度降低患者体质量指数(BMI)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)等水平,但会增加低血糖发生风险.

The current study was designed to seek the role of the glycogen synthase kinase-3β (GSK-β)-regulated NF-E2-related factor 2 (Nrf2) pathway in the antioxidant effect induced by Apigenin-7-O-β-D-(-6”-p-coumaroyl)-glucopyranoside (APG). Rat primary cultured cortical neurons were challenged by oxygen and glucose deprivation/reoxygenation (OGD/R) and then treated with APG. Cell viability, phosphorylation of GSK-β at Ser9 and nuclear expression of Nrf2 were measured. Male Sprague Dawley rats challenged by 2-h middle cerebral artery occlusion were treated with 50 mg/kg APG, and the neurological score, infarct volume, phosphorylation of GSK-3β and nuclear expression of Nrf2 were analyzed. The neuroprotective effect of APG and the expression levels of antioxidant enzymes and oxidative products were also examined in the presence and absence of Nrf2-siRNA and PI3K inhibitors. APG reduced the apoptotic proportion, attenuated LDH release and increased cell viability, and in vivo, APG improved neurological scores and reduced infarct volume. APG increased GSK-3β phosphorylation and Nrf2 nuclear translocation, while these effects were prevented by PI3K inhibitors or Nrf2-siRNA treatment in both OGD/R cell cultures and ischemic/reperfusion rats. These findings reveal that GSK-3β phosphorylation-mediated Nrf2 activation is involved in the neuroprotective effect of APG.

Aim: The aim of this study was to develop a GX1-modified nanostructured lipid carrier (NLCs) and to evaluate its ability to improve the anti-gastric cancer tumor effects of paclitaxel (PTX). Main Methods: The GX1-modified NLCs were synthesized and loaded with PTX (GX1-PTX-NLCs) by emulsion solvent evaporation technique. The anti-tumor activity and phar-macodynamics were then evaluated by in vitro cell studies and animal experiments. Key Findings: The GX1-modified NLCs were successfully synthesized and confirmed by H-1 NMR and MALDI-TOF-MS. PTX-loaded NLCs produced particles with average size distribution less than or equal to 222 nm and good drug loading and entrapment efficiency. In vitro studies demonstrated that GX1-PTX-NLCs had a more obvious inhibitory effect on Co-HUVEC cells than PTX and unmodified PTX-NLCs. The cellular uptake results also showed that GX1-PTX-NLCs were largely concentrated in Co-HUVEC cells, and the uptake rates of GX1-PTX-NLCs in Co-HUVEC were higher than those of the free drug and the PTX-NLC. In vivo studies demonstrated that GX1-PTX-NLCs possess strong anti-tumor effect and showed higher tumor growth inhibition and lower toxicity in nude mice. Significance: These results suggest that GX1-modified NLCs enhanced the anti-tumor activity of PTX and reduced its toxicity effectively. GX1-PTX-NLCs may be considered as a potent drug delivery system for therapy of gastric cancer.

Colorectal cancer (CRC) represents one of the commonest malignancies around the world. PP9, a natural steroidal saponin, was firstly isolated from the rhizomes of Paris polyphylla var. latifolia. However, the therapeutic effects of PP9 on CRC and the underlying molecular mechanism remain undefined. Here, we demonstrated that treatment with PP9 time- and dose-dependently inhibited HT-29 and HCT116 cells without significantly inhibiting normal NCM460 cells. Furthermore, our results indicated that PP9 effectively induced G2/M phase arrest by upregulating p21 and suppressing cdc25C, Cyclin B1 and cdc2. Meanwhile, PP9 upregulated cleaved Caspase 3, cleaved Caspase 9 and cleaved PARP and Bax, while downregulating Bcl-2 to stimulate cell apoptosis. Mechanistically, PP9-suppressed PI3K/Akt/GSK3β signaling, while the PI3K inhibitor LY294002 augmented PP9-mediated apoptosis, G2/M arrest and effects on PI3K/Akt/GSK3β related proteins. Finally, we showed that PP9 (10 mg/kg) significantly reduced tumor growth in nude mouse CRC xenografts, more potently than 5-Fu (20 mg/kg). Jointly, these data firstly demonstrated that PP9 promotes G2/M arrest and apoptotic death in CRC cells through PI3K/Akt/GSK3β signaling suppression, suggesting that PP9 could be considered a new and promising candidate for CRC therapy.

目的:了解某院2016～2018年药品不良反应(ADR)的发生特点和规律,为ADR监测和临床安全用药提供参考.方法:收集该院2016～2018年上报的2 100份ADR报告,按患者性别、年龄、药物种类、给药途径、临床表现、反应分级及转归情况等进行回顾性分析.结果:ADR报告中,男1 119例(53.28％),女981例(46.72％);患者年龄分布以45～60岁最多,共820例(39.05％).一般的ADR为2 022例,新的ADR 13例,严重的ADR 64例,新的和严重的ADR仅有1例.医生上报ADR 551例,护士上报171例,临床药师上报1 378例.致ADR的怀疑药物主要为抗感染药物(396例,18.86％),给药方式以静脉滴注占比最高(1 104例,52.59％);累及系统/器官以消化系统受损为主(771例,36.71％).结论:ADR发生与多种因素有关,应加强ADR监测,减少ADR的发生,促进临床用药安全.

In this investigation, a series of 1-phenyl-3-(5-(pyrimidin-4-ylthio)-1,3,4- thiadiazol-2-yl)urea receptor tyrosine kinase inhibitors were synthesized by a simple and efficient structure-based design. Structure-activity relationship (SAR) analysis of these compounds based on cellular assays led to the discovery of a number of compounds that showed potent activity against human chronic myeloid leukemia (CML) cell line K562, but very weak or no cellular toxicity through monitoring the growth kinetics of K562 cell during a period of 72 h using the real-time live-cell imaging. Among these compounds, 1-(5-((6-((3-morpholinopropyl) amino)pyrimidin-4-yl)thio)-1,3,4-thiadiazol-2-yl)-3-(4-(trifluoromethyl)phenyl)urea (7) exhibited the least cellular toxicity and better biological activity in cellular assays (K562, IC50: 0.038 μM). Compound 7 also displayed very good induced-apoptosis effect for human CML cell line K562 and exerted its effect via a significantly reduced protein phosphorylation of PI3K/Akt signal pathway by Human phospho-kinase array analysis. In vitro results indicate that 1-phenyl-3-(5-(pyrimidin-4-ylthio)-1,3,4- thiadiazol-2-yl)urea derivatives are lead molecules for further development as treatment of chronic myeloid leukemia and cancer.

目的:研究甘青铁线莲皂苷(CTS)对大鼠心肌缺血/再灌注(MI/R)损伤的影响.方法:可逆性冠脉左前降支结扎缺血30 min再灌注3 h复制MI/R模型,将SD大鼠随机分为假手术组、模型组、CTS低、中、高剂量组(50,100,200 mg·kg-1),每组10只.采用伊文思蓝(EB)、2,3,5-氯化三苯基四氮唑蓝(TTC)双染法测定心肌梗死面积,苏木精-伊红(HE)染色法观察心肌病理学形态变化,并检测血清中乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、超氧化物歧化酶(SOD)及丙二醛(MDA)水平.结果:与模型组比较,中、高剂量的CTS可明显缩小心肌梗死面积,并显著降低血清中LDH、CK-MB、TNF-α、IL-6及MDA的水平,显著增加血清中SOD的活性(P<0.05或P<0.01),且CTS各剂量组心肌组织的病理损伤也低于模型组.结论:CTS对大鼠MI/R损伤具有保护作用,其机制可能与其抑制炎症因子的释放和调节氧化应激有关.

目的:通过对某院普外科肠外营养(PN)处方合理性进行调查分析,为药师处方审核及临床合理用药提供参考.方法:对某三甲医院普外科2018年1～12月住院患者的PN处方情况进行回顾性统计分析,依据相关指南对全营养混合液处方进行合理性评价.结果:本次调查的2 408例PN的处方中96.4％的患者具有PN指征;但仍存在微营养素缺失(14.7％)、氨基酸品种选用不当(3.4％)、热氮比不合理(20.3％)、糖脂比不合理(17.9％)、阳离子浓度不合理(2.3％)、胰岛素用量过大(2.8％)等问题.结论:该院普外科PN处方主要存在热氮比、糖脂比不合理和微营养素缺失等问题,临床药师应积极对PN处方进行审核与干预,确保临床安全合理用药.

Objective To establish quality standard and evaluate the pharmacodynamic effect of Laosawei tablets. Methods Thin layer chromatography (TLC) was used to identify Rhodiola rosea. The content of salidroside and rosavin in Rhodiola rosea was determined by HPLC. Anti-fatigue and anti-stress effects of Laosawei tablets were observed by weight-bearing swimming test, anti-hypoxia test, high-temperature resistance and low-temperature resistance test. The antitumor activity of Laosawei tablets was observed by the experiment of mice tumor inhibition rate. The immunomodulation effect of Laosawei tablets was evaluated by the expectorant carbonclearance, level of serum hemolysin antibody and the percentage of peripheral blood T lymphocytes in the mice. Results The TLC spots were clear, highly identified and well separated. The linear range of salidroside was 0.0601-0.601 μg (r = 0.9999). The average recovery was 99.9％ with RSD = 1.7％. The linear range of rosavin was 0.0501-0.501 μg (r = 0.9998). The average recovery was 100.9％ with RSD = 1.4％. Laosawei tablets significantly increased the loaded swimming time, the anti-hypoxia under atmospheric pressure time and high-temperature time, improved the survival rate of the mice under low temperature. Tumor growth inhibitionratio of Laosawei tablets was 31.1％-55.4％. Laosawei tablets significantly increased the englobement of the reticulo-endothelial system, HC50 and the percentage of peripheral blood T lymphocytes in the H22 bearing mice. Conclusion The method is simple, specific and can be used as the quality control method for Laosawei tablets. Laosawei tablets increase the anti-fatigue and anti-stress ability of mice, and increase the cellular immunity, humoral immunity and non-specific immune function of tumor-bearing mice.

目的:探索对中成药重点监控药品合理使用的有效药事管理措施.方法:基于药品销售金额、DDDs,和DUI为评价指标,通过四步筛选法确定中成药重点监控目录,结合用药合理性评价结果进行药事管控.通过对比监管前后某院医疗指标变化情况,对管理效果进行参考性评价.结果:在疗效相同的前提下,重点监控中成药的金额占比持续下降,中成药的药占比由24.4％下降至15.8％;中成药的人均药费由1 492.5元降至878.3元;而病种类数、收治人数、治愈率均无显著性差异.中成药的用药不合理使用率也大幅度下降.结论:通过建立重点监控中成药的管理措施,规范医疗机构药物使用并取得一定成效.为中成药的管理提供新的思路.

目的:促进质子泵抑制剂(PPIs)在围手术期中的合理用药.方法:采用PDCA(Plan、Do、Check、Action)循环管理方法,收集我院神经外科围手术期PPIs使用的300份病历的不合理情况,分析原因、制订相应的管理目标及措施并实施,再与管理后神经外科围手术期PPIs 300份病历中的不合理使用率及不合理类型占比进行比较来评价管理效果.结果:通过采取收集相关资料确定应激性溃疡风险因素、建立围手术期预防使用PPIs的合理性评判标准、对医务人员开展合理用药培训、拟定各种管理制度、加强监督管理等措施,我院PPIs不合理使用率明显降低,不合理用药病历数由管理前的240例减少为156例,其中无指征预防用药率由37.33％降至29.00％(P<0.05);给药剂量不合理率由11.33％降至6.33％(P<0.05);给药频次不合理率由12.67％降至5.00％(P<0.01).结论:我院采取的PDCA循环管理措施可规范神经外科围手术期PPIs的预防性使用,促进PPIs的合理使用.