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1.
To investigate the effects of lentiviral vector‐mediated shRNA suppressing CXCR7 on tumour invasion and metastasis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). HCCLM3 cell lines were cultured and assigned into the CXCR7‐shRNA, negative control (NC) and blank groups. The qRT‐PCR and Western blotting were applied to detect the mRNA and protein expressions of CXCR7, CXCR4 and MMP‐2 in HCCLM3 cells. Cell proliferation and invasion were evaluated by MTT and Transwell assays. A Buffalo rat model of HCC was established. Fifty model rats were divided into the CXCR7‐shRNA + TACE, CXCR7‐shRNA, TACE, NC and control groups. Immunohistochemistry was performed to detect the expressions of CXCR7, MMP‐2, vascular endothelial growth factor (VEGF) and intratumoral CD31‐positive vessel count in tumour tissues of mice. Compared with the blank and NC groups, the mRNA and protein expressions of CXCR7 and MMP‐2 were decreased in the CXCR7‐shRNA group. The cell proliferation and invasion rates of the CXCR7‐shRNA group were lower than the blank and NC groups. At the 4th week after TACE, tumour weight of the CXCR7‐shRNA + TACE group increased continuously. The CXCR7‐shRNA + TACE group showed longer survival time and smaller tumour sizes than other groups. Compared with other groups, the CXCR7‐shRNA + TACE and CXCR7‐shRNA groups had less number of lung metastatic nodules and lower expressions of CXCR7, MMP‐2, VEGF and CD31‐positive vessel count. CXCR7‐shRNA inhibits tumour invasion and metastasis to improve the efficacy of TACE in HCC by reducing the expressions of CXCR7, MMP‐2 and VEGF.  相似文献   

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Sorafenib in combination with Transarterial chemoembolization (TACE) is increasingly used in patients with unresectable hepatocellular carcinoma (HCC), but the current evidence is still controversial. The aim of this systematic review was to evaluate the effectiveness and safety of TACE plus sorafenib versus TACE alone for unresectable HCC. We searched PubMed, EMBASE and the Cochrane Library for clinical trials comparing TACE plus sorafenib with TACE alone for unresectable HCC. The study outcomes included overall survival (OS), time to progression (TTP), objective response and adverse events (AEs). Six studies including 1,181 patients were included. Meta-analysis of all studies suggested that the combination therapy group had significant longer OS than TACE group [hazard ratio (HR) = 0.64, 95 % confidence interval (CI) = 0.43–0.97], but the pooled HR of randomized controlled trials (RCTs) failed to achieve statistical significance. For TTP, meta-analysis in both RCTs subgroup and retrospective studies subgroup suggested that combination therapy was superior to TACE group. The combination therapy was also associated with better response to treatment (risk ratio = 1.45, 95 % CI = 1.04–2.02) when both RCTs and retrospective studies were pooled. However, the sorafenib associated AEs were more frequent in the combination therapy group. In conclusion, the combination of TACE and sorafenib is likely to improve OS, TTP and response to treatment when compared with TACE monotherapy. The combination group is also associated with more sorafenib-related AEs.  相似文献   

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《Translational oncology》2021,14(12):101238
BackgroundThe combination therapy of trans-arterial chemoembolization (TACE) and sorafenib were proved to be one of the effective methods for intermediate and advanced hepatocellular carcinoma (HCC). Although it has been confirmed that the combination therapy can prolong survival for advanced HCC effectively, the therapeutic efficacy and safety are still controversial and the clinical value has not been determined. This meta-analysis aims to evaluate the efficacy and safety of combination therapy and discuss the optimal timing of combination for better clinical benefits.Data sourcesPubMed, EMBASE, the Cochrane Library, MEDLINE, and Web of Science were systematically reviewed to search for relevant studies published before May 15, 2021. Studies comparing the efficacy and safety of TACE + sorafenib with TACE + placebo / alone were adopted. Two reviewers independently extracted study outcomes. The data were analyzed through fixed/random-effect meta-analysis models with Review Manager (Version 5. 3) software.Results7 randomized controlled trials (RCTs) were included with 1464 patients with unresectable HCC (734 in TACE + sorafenib group and 730 in TACE + placebo or alone group). Meta-analysis showed that objective response rate (ORR) and disease control rate (DCR) were slightly improved in TACE + sorafenib group (ORR: risk ratio = 1.24; 95% confidence interval: 1.08–1.42; P = 0.002; DCR: risk ratio = 1.09; 95% confidence interval: 1.01–1.18; P = 0.02). The combination therapy obviously improved time to progression (TTP) (hazard ratio: 0.73; 95% confidence interval: 0.55–0.96; P = 0.03) and progression-free survival (PFS) (hazard ratio 0.62; 95% confidence interval: 0.52–0.73, P < 0.00001) but not overall survival (OS) (hazard ratio: 0.93; 95% confidence interval: 0.59–1.46; P = 0.75) or time to untreatable progression (TTUP) (hazard ratio: 0.76; 95% confidence interval: 0.31–1.89; P = 0.56). In addition, the incidence of adverse reactions (AEs) in combination group were higher than TACE + placebo / alone group. Furthermore, the subgroup analysis showed that the heterogeneity of TTP was notably decreased (pre-TACE: P = 0.12, I2 = 48%; post-TACE: P = 0.58, I2 = 0%), and the hazard ratio was 0.59 (95% confidence interval: 0.51–0.68; P < 0.00001) in pre-TACE subgroup which indicated that combination before TACE significantly prolonged TTP but not in combination after TACE (hazard ratio: 0.88; 95% confidence interval: 0.62–1.24; P = 0.46). In term of AEs, sensitivity analysis indicated that the risk ratio for hand-foot skin reaction, diarrhea, rash/desquamation, and hypertension was 7.41, 2.58, 2.14, 1.55 in pre-TACE subgroup respectively and was 11.34, 3.26, 3.61, 4.11 in post-TACE subgroup respectively (All P < 0.05).ConclusionThe combination of TACE and sorafenib significantly can improve TTP and PFS, and reduce the level of risk of adverse reactions of unresectable HCC, especially in the combination before TACE.  相似文献   

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《Translational oncology》2022,15(12):101238
BackgroundThe combination therapy of trans-arterial chemoembolization (TACE) and sorafenib were proved to be one of the effective methods for intermediate and advanced hepatocellular carcinoma (HCC). Although it has been confirmed that the combination therapy can prolong survival for advanced HCC effectively, the therapeutic efficacy and safety are still controversial and the clinical value has not been determined. This meta-analysis aims to evaluate the efficacy and safety of combination therapy and discuss the optimal timing of combination for better clinical benefits.Data sourcesPubMed, EMBASE, the Cochrane Library, MEDLINE, and Web of Science were systematically reviewed to search for relevant studies published before May 15, 2021. Studies comparing the efficacy and safety of TACE + sorafenib with TACE + placebo / alone were adopted. Two reviewers independently extracted study outcomes. The data were analyzed through fixed/random-effect meta-analysis models with Review Manager (Version 5. 3) software.Results7 randomized controlled trials (RCTs) were included with 1464 patients with unresectable HCC (734 in TACE + sorafenib group and 730 in TACE + placebo or alone group). Meta-analysis showed that objective response rate (ORR) and disease control rate (DCR) were slightly improved in TACE + sorafenib group (ORR: risk ratio = 1.24; 95% confidence interval: 1.08–1.42; P = 0.002; DCR: risk ratio = 1.09; 95% confidence interval: 1.01–1.18; P = 0.02). The combination therapy obviously improved time to progression (TTP) (hazard ratio: 0.73; 95% confidence interval: 0.55–0.96; P = 0.03) and progression-free survival (PFS) (hazard ratio 0.62; 95% confidence interval: 0.52–0.73, P < 0.00001) but not overall survival (OS) (hazard ratio: 0.93; 95% confidence interval: 0.59–1.46; P = 0.75) or time to untreatable progression (TTUP) (hazard ratio: 0.76; 95% confidence interval: 0.31–1.89; P = 0.56). In addition, the incidence of adverse reactions (AEs) in combination group were higher than TACE + placebo / alone group. Furthermore, the subgroup analysis showed that the heterogeneity of TTP was notably decreased (pre-TACE: P = 0.12, I2 = 48%; post-TACE: P = 0.58, I2 = 0%), and the hazard ratio was 0.59 (95% confidence interval: 0.51–0.68; P < 0.00001) in pre-TACE subgroup which indicated that combination before TACE significantly prolonged TTP but not in combination after TACE (hazard ratio: 0.88; 95% confidence interval: 0.62–1.24; P = 0.46). In term of AEs, sensitivity analysis indicated that the risk ratio for hand-foot skin reaction, diarrhea, rash/desquamation, and hypertension was 7.41, 2.58, 2.14, 1.55 in pre-TACE subgroup respectively and was 11.34, 3.26, 3.61, 4.11 in post-TACE subgroup respectively (All P < 0.05).ConclusionThe combination of TACE and sorafenib significantly can improve TTP and PFS, and reduce the level of risk of adverse reactions of unresectable HCC, especially in the combination before TACE.  相似文献   

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目的 对益生菌联合口腔洁治治疗慢性萎缩性胃炎的有效性、安全性进行评价。 方法 选择2015年12月到2018年2月我院收治的102例慢性萎缩性胃炎患者为研究对象,随机分为对照组(n=51)与观察组(n=51)。对照组患者采用益生菌治疗,观察组在对照组基础上予以口腔洁治进行治疗。对两组患者治疗的有效性、安全性进行比较。 结果 观察组患者总有效率(92.16%)高于对照组(68.63%),差异有统计学意义(χ2=8.956,P=0.003)。治疗前,两组患者病理和症状评分差异无统计学意义(t=0.226、0.142,P=0.087、0.074)。治疗后,两组患者病理和症状评分均显著降低,且观察组患者病理评分(5.22±1.03)和症状评分(6.46±1.24)均低于对照组的病理评分(7.59±1.22)和症状评分(9.16±1.25),差异有统计学意义(t=10.600、10.951,P2=13.222,P2=9.871,P=0.001)。 结论 在慢性萎缩性胃炎治疗中应用益生菌联合口腔洁治具有显著效果,安全性较高,值得推广。  相似文献   

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目的探讨肿瘤坏死因子相关的凋亡诱导配体(tumor necrosis factor-related apoptosis inducing ligand,TRAIL)联合顺铂(cisplatin,DDP)对小鼠移植型肝癌的抑制作用及机制。方法将H22小鼠移植型肝癌模型随机分为生理盐水组、TRAIL组、TRAIL+DDP组和DDP组,称取瘤重并分析抑瘤率,Hoechst 33342荧光染色法检测细胞凋亡,免疫组织化学染色检测Caspase-3表达。结果与生理盐水组比较,TRAIL、DDP对小鼠移植型肝癌生长具有明显的抑制作用(P<0.05);TRAIL与DDP联合用药具有增效作用(P<0.05),可明显提高肝癌细胞的凋亡率(P<0.05)、上调Caspase-3表达(P<0.01)。结论 TRAIL与DDP联合用药对小鼠移植型肝癌生长具有协同抑制作用,其机制可能与其协同促进Caspase-3的表达有关。  相似文献   

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Li Y  Guo Z  Liu CF  Xing WG  Si TG  Liu F  Guo XY  Xing JZ 《Cryobiology》2012,65(1):56-59
ObjectiveTo analyze the effect of Argon-Helium cryosurgery (AHCS) combined with transcatheter renal arterial embolization (TRAE) on the differentiation of regulatory CD4+ CD25+ T cell (Treg) and its implication in patients with renal carcinoma.MethodsSeventy seven patients are included in the study, and divided into two groups: TRAE group (n = 45, receiving TRAE only) and TRAE + cryoablation group (n = 32, receiving cryoablation 2–3 weeks after TRAE). The percentage of Treg cells and T lymphocyte subsets (CD4+T, CD8+T, and CD4+T/CD8+T) in the peripheral blood is measured by flow cytometry previous to the therapy and 3 months after therapy. Meanwhile, the extent of tumor necrosis is measured by MRI or CT 1 month after therapy.ResultsThe percentages of Treg cells of patients in TRAE + cryoablation group decrease from (6.65 ± 1.22)% to (3.93 ± 1.16)%, (t = 42.768, P < 0.01), and the percentages of CD4+T and CD4+T/CD8+T increase significantly (P < 0.01). However, the results of patients in TRAE group show that the percentages of Treg, CD4+T, CD8+T and CD4+T/CD8+T increase slightly although the differences had no statistical significance (P > 0.05). The tumor necrosis rate of TRAE + cryoablation group is 57.5%, significantly higher than those of TRAE group, which shows 31.6% (t = 6.784, P < 0.01). The median survival duration of the TRAE + cryoablation group is 20 months, significantly longer than that of the TRAE group (χ2 = 7.368, P < 0.01). The decreasing extent of Treg cells is correlated with tumor necrosis rates (r = 0.90, P < 0.01) and life time (r = 0.67, P < 0.01).ConclusionThe therapy of TRAE combined with cryoablation contributes to reduce the percentage of Treg cells and improve the immune situation of patients with renal cell carcinoma, which consequently increase tumor necrosis rate and prolong the patients‘ survival duration.  相似文献   

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目的 探讨益生菌联合抗幽门螺杆菌(H. pylori)治疗对消化性溃疡患者的疗效及其对患者肠道菌群的影响。方法 将120例经14C呼气试验(14C-UBT)检测确定为H. pylori感染阳性的消化性溃疡患者随机分为观察组和对照组,每组60例。其中,对照组采用四联疗法(奥美拉唑+阿莫西林+克拉霉素+铋剂)治疗,观察组采用四联疗法联合益生菌治疗;比较两组患者H. pylori根除情况、溃疡愈合质量及不良反应情况。治疗前后留取全部患者的新鲜粪便标本进行细菌培养,比较两组患者肠道菌群数量和肠道微生物定植抗力(B/E值)。结果 观察组患者H. pylori根除率和溃疡愈合率分别为88.3%、95.0%,显著高于对照组的70.0%和76.7%(P<0.05),不良反应率为3.3%,显著低于对照组的20.0%(P<0.05)。与治疗前比,对照组患者治疗后肠道内产气荚膜梭菌、双歧杆菌及乳杆菌数量显著减少(P<0.05),肠杆菌、肠球菌及酵母菌数量显著增加(P<0.05),B/E值显著降低(P<0.05);观察组患者治疗后双歧杆菌和乳杆菌均显著增加(P<0.05),产气荚膜梭菌显著减少(P<0.05),肠杆菌、肠球菌及酵母菌无明显变化(P>0.05),B/E值显著升高(P<0.05)。结论 常规抗H. pylori治疗易引起消化性溃疡患者肠道菌群紊乱,降低肠道定植抗力。益生菌联合治疗可有效改善患者肠道微生态,提高H. pylori根除率和溃疡愈合质量,减少不良反应。  相似文献   

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目的探讨布拉酵母菌联合舍曲林对产后抑郁症(PPD)的临床疗效及安全性。方法选择2016年1月至2018年12月我院104例PPD患者为研究对象。入选患者随机分为观察组和对照组各52例,两组患者均给予舍曲林50 mg/次,1次/d,口服。观察组患者同时联用布拉酵母0.5 g/次,2次/d,口服,8周为一疗程。治疗前后检测患者孕酮及雌二醇水平,并于治疗前及治疗第4周、第8周时采用汉密顿抑郁量表(HAMD)评价患者治疗结果、临床疗效及安全性。结果治疗后,两组患者HAMD评分与治疗前比较均降低(t=8.162,P0.001;t=17.916,P0.001;t=16.995,P0.001;t=28.683,P0.001),且观察组患者降低幅度大于对照组(t=7.741,P0.001;t=13.073,P0.001)。观察组患者临床总有效率(90.38%)明显高于对照组(69.23%)。治疗后观察组患者孕酮水平低于对照组,雌二醇水平高于对照组,差异均有统计学意义(t=10.774,P0.001;t=7.239,P0.001)。两组母婴无明显不良反应。结论布拉酵母联合舍曲林对产后抑郁症的临床疗效明显,安全性高,值得临床推广。  相似文献   

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【摘 要】 目的 通过建立葡聚糖硫酸钠(DSS)诱导的急性期溃疡性结肠炎(UC)小鼠模型,观察嗜酸乳杆菌以及联合柳氮磺胺吡啶对小鼠溃疡性结肠炎(UC)的治疗作用,并检测Hsp70、Hsp27在肠黏膜的表达,探讨其可能的作用机制。方法 5% DSS 7 d建立急性UC动物模型。将60只BALB/c小鼠随机分为6组:正常对照组、模型组、阴性对照(生理盐水,NS)组、嗜酸乳杆菌组、柳氮磺胺吡啶组和嗜酸乳杆菌联合柳氮磺胺吡啶组,观察指标包括:疾病活动指数(DAI)、结肠黏膜肉眼改变及病理组织学积分;采用免疫组化SABC 法检测热休克蛋白(HSP70)和(HSP27)的表达量。结果 嗜酸乳杆菌可降低实验小鼠DAI积分和改善结肠组织损伤;与模型组、阴性对照组相比,嗜酸乳杆菌联合柳氮磺胺吡啶组的HSP70表达增加(P<0.05),其中以嗜酸乳杆菌联合柳氮磺胺吡啶组效果最佳。结论 嗜酸乳杆菌和柳氮磺胺吡啶对小鼠溃疡性结肠炎都有治疗作用,且二者疗效相当;两药联合应用效果最佳。其机制可能与增加结肠黏膜HSP70的表达有关。  相似文献   

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目的探讨益生菌联合美沙拉秦对轻、中度活动期溃疡性结肠炎患者的临床疗效和安全性以及比较患者治疗前后实验室多种指标的改变。方法 42例确诊的轻、中度溃疡性结肠炎患者,采用随机对照的研究方法分为两组。其中治疗组(养乐多1瓶/次+艾迪莎1g/次、1日3次)20例,对照组(艾迪莎1g/次、1日3次)22例,共观察6个月。治疗前、后两组患者临床表现、安全性和实验室多种指标也进行比较。结果治疗组临床治疗总有效率为90.00%,对照组为81.82%,治疗组临床完全缓解率为45.00%,对照组为31.82%,治疗组的完全缓解率和总有效率均显著高于对照组(χ2值分别为57.48、59.42,P0.05),前者总复发率显著低于后者(χ2=58.65,P0.05)。且治疗中未见不良反应和副作用。治疗组治疗6个月后血红蛋白、红细胞压积和白蛋白水平均显著升高(t值分别为2.82、2.21、2.18,P0.05),而对照组在治疗后血红蛋白、白蛋白和红细胞压积均没有发生明显改变(t值分别为0.10、0.11、0.20,P0.05);治疗组的血沉和c-反应蛋白均非常显著下降(t值分别为5.17、4.87,P0.01),而对照组血沉和c-反应蛋白均显著下降(t值分别为3.01、2.43,P0.05);治疗组的血清TNF-α、IL-17和IL-23细胞因子出现非常显著下降(t值分别为3.39、5.98、12.19,P0.01),而对照组的血清TNF-α、IL-17和IL-23细胞因子出现显著下降(t值分别为2.33、2.59、11.37,P0.05);治疗6个月后两组间上述指标差异均有统计学意义(t值分别为2.92、2.23、2.09、2.09、2.34、2.26、2.78、2.71,P0.05),治疗组血红蛋白、红细胞压积和白蛋白水平均显著高于对照组,血沉和c-反应蛋白均显著低于对照组,治疗组的血清TNF-α、IL-17和IL-23细胞因子均显著低于对照组。结论益生菌联合美沙拉秦对轻、中度活动期溃疡性结肠炎患者比单用美沙拉秦更能显著地降低促炎症性细胞因子水平,诱导活动期溃疡性结肠炎的缓解作用和维持缓解作用更强,显示出良好的安全性和有效的治疗效果,表明该益生菌对溃疡性结肠炎具有良好的辅助治疗作用。  相似文献   

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In our in-depth analysis carried out by the Illumina Solexa massive parallel signature sequencing, microRNA-99a (miR-99a) was found to be the sixth abundant microRNA in the miRNome of normal human liver but was markedly down-regulated in hepatocellular carcinoma (HCC). Compelling evidence has suggested the important roles of microRNAs in HCC development. However, the biological function of miR-99a deregulation in HCC remains unknown. In this study, we found that miR-99a was remarkably decreased in HCC tissues and cell lines. Importantly, lower miR-99a expression in HCC tissues significantly correlated with shorter survival of HCC patients, and miR-99a was identified to be an independent predictor for the prognosis of HCC patients. Furthermore, restoration of miR-99a dramatically suppressed HCC cell growth in vitro by inducing the G(1) phase cell cycle arrest. Intratumoral injection of cholesterol-conjugated miR-99a mimics significantly inhibited tumor growth and reduced the α-fetoprotein level in HCC-bearing nude mice. Insulin-like growth factor 1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) were further characterized as the direct targets of miR-99a. Furthermore, protein levels of IGF-1R and mTOR were found to be inversely correlated with miR-99a expression in HCC tissues. miR-99a mimics inhibited IGF-1R and mTOR pathways and subsequently suppressed expression of cell cycle-related proteins, including cyclin D1 in HCC cells. Conclusively, miR-99a expression was frequently down-regulated in HCC tissues and correlates with the prognosis of HCC patients, thus proposing miR-99a as a prospective prognosis predictor of HCC. miR-99a suppresses HCC growth by inducing cell cycle arrest, suggesting miR-99a as potential tumor suppressor for HCC therapeutics.  相似文献   

19.
胡玉海 《蛇志》2016,(4):428-429
目的分析普罗帕酮联合美托洛尔治疗小儿心律失常的临床疗效。方法将2014年5月~2015年4月我院收治的160例小儿心律失常患儿为研究对象,按照住院顺序分为对照组和观察组各80例,对照组患儿给予普罗帕酮治疗,观察组患儿在对照组治疗的基础上加美托洛尔治疗,比较两组患儿的临床治疗效果和不良反应情况。结果对照组患儿的临床总有效率为85%明显低于观察组的97.5%,两组比较差异有统计学意义(P0.05);观察组患儿的不良反应发生率为12.5%明显低于对照组的27.5%,差异有统计学意义(P0.05)。结论普罗帕酮联合美托洛尔治疗小儿心律失常的效果满意,安全性较高,值得临床推广。  相似文献   

20.
目的

评价微生态制剂治疗轻度肝性脑病(MHE)的有效性及安全性。

方法

检索自建库至2020年9月在中国知网、万方数据知识服务平台、维普、中国生物医学文献服务系统、PubMed、Web of Science、Embase、Cochrane Library等数据库收录的关于微生态制剂治疗MHE的临床随机对照试验。

结果

共纳入21篇文献, 包括1 543例患者。结果显示, 2组研究对象比较, 微生态制剂能提高双歧杆菌、乳杆菌水平, 差异有统计学意义[MD=1.82, 95%CI(1.19, 2.44), Z=5.70, P < 0.000 1;MD=1.74, 95%CI(0.95, 2.54), Z=4.30, P < 0.000 1], 降低肠杆菌水平[MD=-1.27, 95%CI(-1.97, -0.57), Z=3.55, P=0.000 4], 而肠球菌水平差异无统计学意义(P > 0.050 0);2组研究对象比较, 微生态制剂可显著降低血氨水平、ET水平[SMD=-0.83, 95%CI(-1.08, -0.58), Z=6.43, P < 0.000 1;MD=-0.08, 95%CI(-0.14, -0.01), Z=2.35, P=0.020 0];2组研究对象比较, 微生态制剂可显著降低数字连接试验A(NCT-A)用时[MD=-16.46, 95%CI(-21.33, -11.59), Z=6.63, P < 0.000 1], 而数字符号试验(DST)差异无统计学意义(P > 0.050 0);2组研究对象比较, 微生态制剂可降低终末期肝病模型评分(MELD)、Child-Pugh评分、OHE发生率[MD=-2.41, 95%CI(-3.87, -0.95), Z=3.24, P=0.001 0;MD=-1.54, 95%CI(-1.92, -1.16), Z=7.95, P < 0.000 1; OR=0.32, 95%CI(0.20, 0.52), Z=4.66, P < 0.000 1], 并显著提高临床有效率[OR=4.95, 95%CI(2.48, 9.86), Z=4.55, P < 0.000 1], 但不会增加不良反应[OR=0.48, 95%CI(0.12, 1.91), Z=1.04, P=0.300 0]。

结论

微生态制剂可基于调节肠道菌群平衡有效改善MHE, 可防止OHE的发生, 且安全性好, 有望成为治疗MHE的最新选择。

  相似文献   

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