A novel necroptosis signature for predicting survival in lung adenocarcinoma.

BACKGROUND: To explore the necroptosis-related genes (NRGs) signature and its predictive values in lung adenocarcinoma (LUAD). METHODS: The training cohort consisted of tumor samples from The Cancer Genome Atlas, and the validation set comprised data from the Gene Expression Omnibus. Univariate and multivariate Cox regression analyses were applied to identify the prognostic NRG signature as an independent molecular indicator. Correlation analysis was used for the association assessment between the NRG signature and immune checkpoint molecules. RESULTS: NRGs involved in necroptosis and immune NOD-like receptor signaling. The NRG signature based on eight NRGs can divide tumors into high-risk and low-risk groups, which was significantly associated with worse survival. Multivariate Cox regression analysis showed that this NRG signature remained an independent prognostic indicator. Stratification analyses demonstrated that this NRG signature was still effective for predicting survival in each stratum of age, gender, and tumor stage. The ROC curve showed a good predictive ability using the NRG signature in the validation cohort (AUC = 0.81). The NRG signature was related to immune checkpoint molecules PD - 1, PD-L1, and PD-L2. CONCLUSIONS: The NRG signature could be a novel predictor of the prognosis and may become a potential therapeutic target in LUAD.

MicroRNA miR-19b-3p mediated G protein γ subunit 7 (GNG7) loss contributes lung adenocarcinoma progression through activating Hedgehog signaling.

G protein γ subunit 7 (GNG7) is a subunit of heterotrimeric G protein. It has been demonstrated low expressed GNG7 in various cancers. Nevertheless, the role of GNG7 in lung adenocarcinoma (LUAD) remains unclear. In the present study, GNG7 expression in LUAD tissues and cell lines was analyzed by RT-qPCR, western blot and immunohistochemical. Kaplan-Meier analysis was performed for determining the prognostic value of GNG7 expression. Then, the function of GNG7 in LUAD progression was examined by cell proliferation, invasion and mouse xenograft assays. In addition, the underlying biological mechanisms of GNG7 in LUAD progression were explored via the bioinformatics analysis and experimental validation. We found GNG7 was markedly down-regulated in LUAD tissues and cell lines. Clinically, low expression of GNG7 was associated with the dismal prognosis of LUAD patients. Gain-of-function analysis showed that GNG7 overexpression inhibited proliferation and invasion of LUAD cell in vitro, and compromised tumor formation ability in vivo. Besides, mechanistic study revealed that overexpression of GNG7 affected the progression of LUAD via inhibiting activation of Hedgehog signaling. Moreover, bioinformatics prediction and experimental verification confirmed that GNG7 was targeted by miR-19b-3p, which was elevated expression in LUAD and promoting the progression of LUAD. Furthermore, rescue experiments demonstrated that GNG7 reintroduction weakened miR-19b-3p-mediated aggressive tumor phenotypes of LUAD cells. These findings suggested miR-19b-3p/GNG7 axis contributed to the progression of LUAD through Hedgehog signaling, which might be a potential therapeutic target for LUAD treatment.

miRNA-770-5p expression is upregulated in patients with type 2 diabetes and miRNA-770-5p knockdown protects pancreatic ß-cell function via targeting BAG5 expression.

MicroRNA (miR)-770-5p expression is increased in patients with type 2 diabetes mellitus (T2DM) compared with healthy controls; however, the roles and molecular mechanism underlying miR-770-5p in T2DM are not completely understood. In the present study, the reverse transcription-quantitative PCR (RT-qPCR) results indicated that miR-770-5p expression was significantly increased and Bcl-2 associated athanogene 5 (BAG5) expression was significantly decreased in the serum of patients with T2DM compared with healthy volunteers. TargetScan and a dual luciferase reporter gene system were used to predict and verify BAG5 as a target gene of miR-770-5p. Additionally, the RT-qPCR results demonstrated that miR-770-5p expression was significantly increased and BAG5 expression was significantly decreased in uric acid (UA)-treated Min6 cells compared with control cells. Min6 cells were transfected with miR-770-5p inhibitor and BAG5-small interfering (si)RNA to alter expression levels. The results indicated that miR-770-5p negatively regulated BAG5. The effect of miR-770-5p knockdown on UA-induced pancreatic ß-cell damage and dysfunction was subsequently assessed. Min6 cells were transfected with miR-770-5p inhibitor or miR-770-5p inhibitor + BAG5-siRNA for 48 h, followed by treatment with or without 5 mg/dl UA for 24 h. Cell viability, apoptosis, apoptosis-related factor expression levels and insulin secretion were assessed. The results demonstrated that UA treatment significantly reduced cell viability, increased cell apoptosis and reduced insulin secretion in Min6 cells compared with the control group. miR-770-5p inhibitor significantly attenuated UA-induced injury and dysfunction of Min6 cells, whereas BAG5 knockdown abolished the protective effects of miR-770-5p inhibitor on UA-damaged Min6 cells. In conclusion, miR-770-5p was highly expressed in the serum of patients with T2DM compared with healthy volunteers. In UA-treated pancreatic ß-cells, compared with the inhibitor control group, miR-770-5p knockdown regulated the expression of apoptosis-related genes, increased cell viability, inhibited cell apoptosis and increased insulin secretion by targeting BAG5. Therefore, the present study suggested that miR-770-5p inhibitor may serve a protective role in T2DM.

TIM-3 as a Prognostic Marker and a Potential Immunotherapy Target in Human Malignant Tumors: A Meta-Analysis and Bioinformatics Validation.

BACKGROUND: As a novel immune checkpoint molecular, T-cell immunoglobulin mucin 3 (TIM-3) is emerging as a therapeutic target for cancer immunotherapy. However, the predictive role of TIM-3 in cancer remains largely undetermined. This study was designed to investigate the role of TIM-3 in cancer. METHODS: Publications were searched using multiple databases. The hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. To further confirm the prognostic effect of TIM-3, The Cancer Genome Atlas (TCGA) data were applied. Functional analysis of TIM-3 was also investigated. RESULTS: 28 studies with 7284 patients with malignant tumors were identified. Based on multivariate Cox regression analysis, TIM-3 was an independent prognostic indicator for poor overall survival (OS) (HR= 1.54, 95% CI = 1.19-1.98, P = 0.001). However, TIM-3 was not correlated with cancer-specific survival and disease-free survival (DFS). Particularly, TIM-3 showed a worse prognosis in non-small cell lung carcinoma and gastric cancer; but it showed a favorable prognosis in breast cancer. Functional analysis showed that TIM-3 was closely correlated with immune responses such as T-cell activation and natural killer cell-mediated cytotoxicity. Moreover, TIM-3 expression was found to be related to worse OS in 9491 TCGA patients (HR = 1.2, P < 0.001), but was not associated with DFS. CONCLUSIONS: TIM-3 was an independent prognostic factor. Meanwhile, TIM-3 played a crucial role in tumor immune responses. This supports TIM-3 as a promising target for cancer immunotherapy.

Down-regulation of lncRNA SNHG5 relieves sepsis-induced acute kidney injury by regulating the miR-374a-3p/TLR4/NF-κB pathway.

Sepsis is an acute systemic infectious disease engendered by infectious factors, which can cause the dysfunction of multiple organs, including acute kidney injury (AKI). Recently, more and more researchers are focussing on long noncoding RNA (lncRNA) that is closely associated with the development and progression of various diseases; however, the role and mechanism of lncRNA in sepsis-induced AKI are not fully understood. Here, we found a significant increase in the expression of lncRNA small nuclear RNA host gene 5 (SNHG5) in the serum of patients with sepsis than healthy controls. Similar results were obtained from mouse model of sepsis. Further investigations revealed that knockdown of SNHG5 improves the viability and reduces the rate of apoptosis and the generation of inflammatory cytokines in HK-2 and TCMK-1 cells treated with lipopolysaccharide. Mechanistically, we showed that SNHG5 can combine with microRNA-374a-3p (miR-374a-3p), which inhibits nuclear factor-κB (NF-κB) activity by targeting TLR4. In conclusion, our results demonstrate that SNHG5 may regulate sepsis-induced AKI via the miR-374a-3p/TLR4/NF-κB pathway, therefore providing a new insight into the treatment of this disease.

HMGB1 mediates acute liver injury in sepsis through pyroptosis of liver macrophages.

Sepsis is a systemic inflammatory response syndrome caused by infection. Septic patients often show an acute liver dysfunction during the onset of sepsis in ICU. We found the levels of ALT, AST, TBIL increased significantly in septic patients and returned after recovery from sepsis in our ICU (P<0.05), and had a similar trend for HMGB1. To explore the role of hepatic macrophage in acute liver injury, we simulated the process of acute liver injury by cecal ligation and puncture (CLP) in mice. We assessed the inflammatory infiltration of the liver by HE, and examined the levels of ALT and AST in serum and the expression of HMGB1, IL-1ß in the serum and the relative expression of mRNA in the liver at the different time of CLP model. Also we found the rate of pyroptosis cells in liver was about 18.19%, while 16.29% in macrophages by Flow cytometry. So our study has demonstrated that HMGB1 may promote the pyroptosis of liver macrophages to mediate acute liver injury in sepsis.

HDAC inhibitors promote pancreatic stellate cell apoptosis and relieve pancreatic fibrosis by upregulating miR-15/16 in chronic pancreatitis.

In chronic pancreatitis, PSCs are activated by proinflammatory cytokines to induce pancreatic fibrogenesis. HDAC inhibition protected against the pancreatic fibrosis and the apoptosis of PSCs through induced apoptosis and depressed inflammation. In our study, we found that miR-15 and miR-16 decreased significantly in chronic pancreatitis and HDAC inhibition could recover the levels of these two miRNAs. HDAC regulated the transcription of miR-15 and miR-16, which then modulate the apoptosis and fibrosis of PSCs. And we proved that Bcl-2 and Smad5 were the target genes of miR-15 and miR-16, which illustrated how HDAC inhibition alleviated the apoptosis and fibrogenesis of PSCs in chronic pancreatitis. These results suggested that HDAC inhibition protects against CP by promoting apoptosis and TGF-ß/Smads signaling pathways, and indicated that HDAC inhibition is a potential therapy to alleviate CP patients in clinic, and these need to be explored further.

Long non­coding RNA CASC2 ameliorates sepsis­induced acute kidney injury by regulating the miR­155 and NF­κB pathway.

Sepsis is a systemic inflammatory response syndrome that can cause multiple­organ damage, including acute kidney injury (AKI). Studies have shown that the long non­coding RNA cancer susceptibility candidate 2 (CASC2) is involved in the occurrence and development of multiple human diseases, although its expression and role in AKI has not yet been reported. The present study demonstrated that the expression of CASC2 was significantly decreased in the serum of patients with sepsis compared with healthy subjects. In addition, the CASC2 level was negatively associated with the severity of AKI. Further experiments revealed that CASC2 promoted cell viability and inhibited inflammatory factor secretion, apoptosis and oxidative stress in lipopolysaccharide­stimulated human renal tubular epithelial HK­2 cells. Importantly, the current study observed that CASC2 was negatively associated with a pro­inflammatory microRNA (miR)­155. In addition, the upregulation of CASC2 significantly suppressed the nuclear factor κB (NF­κB) signaling pathway. In conclusion, the results of the present study suggested that CASC2 may serve as a potential target for treating sepsis­induced AKI by inhibiting the miR­155 and NF­κB pathway­mediated inflammation.

The effect of early mobilization in critically ill patients: A meta-analysis.

BACKGROUND: The aim of this meta-analysis was to assess if early mobilization and rehabilitation in the intensive care unit (ICU) could reduce ICU-acquired weakness (ICU-AW), improve functional recovery, improve muscle strength, shorten the length of ICU and hospital stays, and reduce the mortality rate. METHODS: A comprehensive literature search in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China), and National Knowledge Infrastructure, China (CNKI) was performed. Results were expressed as a risk ratio (RR) with 95% confidence intervals (95% CIs) or weight mean difference (WMD) with 95% CIs. Pooled estimates were calculated using a fixed-effects or random-effects model according to the heterogeneity among studies. RESULTS: Fifteen randomized controlled trials involving a total of 1941 patients were included in this meta-analysis. Pooled estimates suggested that early mobilization significantly reduced the incidence of ICU-AW (RR = 0.49, 95% CI: 0.26, 0.91; P = .025), shortened the length of ICU (WMD = -1.82 days, 95% CI: -2.88, -0.76; P = .001) and hospital (WMD = -3.90 days, 95% CI: -5.94, -1.85; P < .001) stays, and improved the Medical Research Council score (WMD = 4.47, 95% CI: 1.43, 7.52; P = .004) and Barthel Index score at hospital discharge (WMD = 21.44, 95% CI: 10.97, 31.91; P < .001). Moreover, early mobilization also decreased complications such as deep vein thrombosis (RR = 0.16, 95% CI: 0.04, 0.59; P = .006), ventilator-associated pneumonia (RR = 0.26, 95% CI: 0.11, 0.63; P = .003), and pressure sores (RR = 0.14, 95% CI: 0.04, 0.44; P = .001). However, early mobilization did not reduce the ICU mortality rate (RR = 1.31, 95% CI: 0.97, 1.76; P = .074), improve the handgrip strength (WMD = 4.03 kg, 95% CI: -0.68, 8.74; P = .094), and shorten the duration of mechanical ventilation (WMD = 0.20 days, 95% CI: -0.10, 0.50; P = .194). CONCLUSION: This study indicated that early mobilization was effective in preventing the occurrence of ICU-AW, shortening the length of ICU and hospital stay, and improving the functional mobility. However, it had no effect on the ICU mortality rate and ventilator-free days. RELEVANCE TO CLINICAL PRACTICE: ICU-AW is a common neuromuscular complication of critical illness, and it is predictive of adverse outcomes. Early mobilization of critically ill patients is a candidate intervention to reduce the incidence and severity of ICU-AW. Some clinical studies have demonstrated this, whereas others found opposite results. The aim of our study is to assess if early mobilization and rehabilitation in the ICU could reduce the ICU-AW, improve functional recovery, improve muscle strength, shorten length of ICU and hospital stay, and reduce the mortality rate.

[Effect of intensive insulin therapy on high mobility group box-1/nuclear factor-ΚB pathway in severe traumatic brain injury patient with stress hyperglycemia].

OBJECTIVE: To explore the effect of intensive insulin therapy (IIT) on high mobility group box-1/nuclear factor-ΚB (HMGB1/NF-ΚB) signaling pathway in severe traumatic brain injury (sTBI) patient with stress hyperglycemia. METHODS: Sixty-one sTBI patients with stress hyperglycemia [Glasgow coma scale (GCS) ≤ 8, three times of random blood glucose levels > 11.1 mmoL/L, glycosylated hemoglobin (HbA1c) < 0.065] admitted to the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from July 2015 to October 2017 were enrolled. Patients were divided into IIT group (29 cases, keeping blood glucose at 4.4-7.8 mmol/L) and conventional glycemic therapy (CGT) group (32 cases, keeping blood glucose at 7.8-12.2 mmo/L) according to the random number table method. Before treatment and 1, 7 and 14 days after treatment, the levels of plasma HMGB1 and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA); C-reactive protein (CRP) was determined by automatic biochemical analyzer, and NF-ΚB p65 gene expression in peripheral blood mononuclear cells was detected by real-time quantitative polymerase chain reaction (PCR). RESULTS: Nine patients were withdrawn from the observation because the 4 consecutive blood glucose monitoring did not reach the target value, combined with severe infection, or abandoned the treatment with serious brain damage. Finally, 52 patients were enrolled in the analysis, including 28 in CGT group and 24 in IIT group. The levels of plasma HMGB1, TNF-α, CRP and the expression of NF-ΚB gene in monocytes of the two groups at 1 day after treatment were significantly higher than those before treatment, and reached the peak value, then gradually decreased. After 7 days of treatment, they were significantly lower than 1 day. The levels of plasma CRP and TNF-α in the IIT group were significantly lower than those in the CGT group [CRP (mg/L): 36.7±4.4 vs. 45.1±6.1, TNF-α (ng/L): 42.4±9.7 vs. 53.2±9.1, both P < 0.05], the level of HMGB1 in plasma and the expression of NF-ΚB p65 in monocytes were significantly lower than those in the CGT group after 14 days of treatment [HMGB1 (µg/L): 60.1±8.7 vs. 80.5±9.1, NF-ΚB p65 (ΔCt): 35.8±8.5 vs. 53.5±7.3, both P < 0.05]. CONCLUSIONS: IIT inhibits the inflammatory response in sTBI patients with stress hyperglycemia through HMGB1/NF-ΚB pathway.

Platelet-derived growth factor B attenuates lethal sepsis through inhibition of inflammatory responses.

Sepsis is a systemic inflammatory response during infection and remains a major clinical problem with high morbidity and mortality. Platelet-derived growth factor B (PDGF-B) is a member belongs to PDGF family and has been recently reported higher expressed in survivors of severe sepsis patients. However, the exact role and underlying mechanisms of PDGF-BB in sepsis remains unclear. In this study, we found that PDGF-BB levels were significantly elevated in patients with sepsis, and higher PDGF-BB levels were negatively correlated with the levels of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-8), and chemokines (CXCL-1 and CCL2). PDGF-BB was also found increased in experimental sepsis in mice. Blockade of PDGF-BB using Tyrphostin AG 1296 aggravated, whereas recombinant PDGF-BB treatment improved survival and tissues injury in both two murine models of CLP-induced sepsis and LPS- induced endotoxemia. PDGF-BB blockade increased, whereas PDGF-BB administration decreased the inflammatory responses, as reflected by proinflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-8), and chemokines (CXCL-1 and CCL2). PDGF-BB also showed inhibitory effect on immune cell activation and cytokines production in vivo and in vitro. Therefore, our findings suggest that PDGF-BB plays a protective role in sepsis by decreasing the production of pro-inflammatory cytokines and chemokines. PDGF-BB thus may be a potential therapeutic strategy for treating sepsis.

Comparison of the Preference of Nutritional Support for Patients With Severe Acute Pancreatitis.

This study aimed to compare the preference of different methods of nutritional support for patients with severe acute pancreatitis (SAP). Patients with SAP were divided into the enteral nutrition group (EN group, 16 cases), total the parenteral nutrition group (TPN group, 14 cases), and the enteral plus total parenteral nutrition group (EN+TPN group, 15 cases). At 7 days after admisson, TPN and EN+TPN groups showed significantly increased Ranson scores compared with the EN group (p < .05). At 14 and 21 days after admisson, TPN and EN+TPN groups exhibited significantly increased Acute Physology and Chronic Health Evaluation (APACHE) II scores, Ranson scores, and intra-abdominal pressure compared with the EN group (p < .05 or p < .01). The incidences of multiple organ dysfunction syndrome and its complication in the EN group were significantly lower than the TPN and EN+TPN groups (p < .05). Hospital stay was significantly lower, but the incidences of abdominal distenson and regurgitation complications were significantly higher in the EN group than in the TPN and EN+TPN groups (p < .05). In concluson, early enteral nutrition could significantly improve nutritional status of patients with SAP, shorten the course of the disease, and reduce the incidences of infection, death, and complication, but also increase the risk of abdominal distenson and regurgitation.

Coculture with Clostridium difficile promotes apoptosis of human intestinal microvascular endothelial cells.

OBJECTIVE: The clostridial triose-phosphate isomerase ( tpi) gene is a housekeeping gene that specifically distinguishes Clostridium difficile from other bacteria. This retrospective cohort study was performed to analyze and compare the TPI protein-positive rates in outpatients and hospitalized patients with and without diarrhea (control group). METHODS: Western blotting, methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and flow cytometry were used to investigate the pathogenic mechanism of C. difficile in the development and progression of diarrhea in patients with inflammatory bowel disease (IBD). RESULTS: The TPI protein-positive rates were significantly higher in patients with diarrhea but without IBD than in the healthy control group as well as in patients with diarrhea and IBD than in patients with diarrhea but without IBD. Coculture with C. difficile inhibited aquaporin-1 protein expression in human intestinal microvascular endothelial cells, which significantly reduced the proliferation of these cells and promoted their apoptosis. CONCLUSIONS: Clostridium difficile infection is associated with diarrhea and may be an important risk factor for diarrhea in patients with IBD. Coculture with C. difficile may inhibit the proliferation of intestinal mucosal cells and promote their apoptosis, reduce intestinal aquaporin-1 expression, and inhibit intestinal water uptake. Clostridium difficile is one cause of C. difficile-associated diarrhea.

The alleviative effects of metformin for lipopolysaccharide-induced acute lung injury rat model and its underlying mechanism.

For patients who have sepsis, acute lung injury (ALI) causes most of death. Metformin (Met) is an anti-hyperglycemic agent and it has extensive pharmacological properties. This study aimed to analyze the influence of Met on lipopolysaccharide (LPS) -induced ALI. Met (1, 2, and 4 mg/kg) were injected and LPS was injected 30 min later. The data suggested Met can reduce release of inflammatory cytokines and bronchoalveolar lavage fluid (BALF) protein expression, reduce lung wet/dry ratio, and significantly improve LPS-induced lung destruction during ALI. In addition, Met inhibits LPS-induced neutrophil and macrophage infiltration, reduces MPO activity, and promotes AMPK-α1 expression in lung tissues. Our data suggested that metformin alleviates capillary injury during ALI via AMPK-α1.

Higher serum procalcitonin and IL-6 levels predict worse diagnosis for acute respiratory distress syndrome patients with multiple organ dysfunction.

AIMS: To study the clinical significance and prognostic value of monitoring procalcitonin (PCT) and interleukin 6 (IL-6) levels in acute respiratory distress syndrome (ARDS) patients with multiple organ dysfunction (MODS). METHODS: We enrolled 24 ARDS patients with MODS (ARDS+MODS group), 18 patients with ARDS but without MODS (ARDS group), and 55 patients with MODS but without ARDS as controls (control group). We detected the oxygenation index, serum PCT, IL-6, C-reactive protein (CRP) and white blood cell count (WBC) values of the patients after 1, 7, 14, 21 and 28 days of hospitalization in all three groups; we also analyzed the receiver operating characteristic (ROC) curves of PCT, CRP, WBC and (or) IL-6 in the patients in the ARDS+MODS group. RESULTS: The serum PCT and IL-6 levels in the ARDS+MODS group were significantly higher than those in the ARDS and MODS groups (P<0.01). The PCT and IL-6 levels increased with elevated ARDS illness severity (P<0.01); the sensitivity of PCT and IL-6 was high in all groups, but the specificity was low. Moreover, the PCT and IL-6 values were closely associated with patient survival. The lower PCT and IL-6 values indicated the higher survival rate. The PCT and IL-6 combined prophetic sensitivity of MODS complicated with ARDS area under the ROC curve was 0.911; thus, the index of PCT combined with IL-6 was the highest sensitive biological marker for the predicted occurrence of MODS with ARDS. CONCLUSIONS: The serum PCT and IL-6 levels were significant for the diagnosis of ARDS patients with MODS, and the serum levels of PCT and IL-6 were associated with the severity of MODS with ARDS. Combined monitoring of PCT and IL-6 values and their dynamic changes is helpful for detecting the incidence of early ARDS in patients with MODS, and the index can predict whether ARDS will occur. The combined assessment of PCT and IL-6 can predict the prognosis of ARDS patients with MODS.

Differential analysis of clinical efficacy on patients with serious infection in ICU by different meropenem regimens.

To investigate the difference in clinical efficacy and safety of different meropenem regimens on patients with serious infection in ICU. Then, 228 patients with serious infection in ICU were divided by random into control group (intermittent administration in 1000mg/30min single dose) and research group (continuous administration in 200mg/10min +800mg/180min), respectively. The blood concentration of meropenem were recorded in two groups at different time points, and difference in treatment effectiveness, iconographic effectiveness, bacterial eradication rate, 28-day survival rate and many other clinical scoring indices (SOFA, APACHEII, CPIS, and SIRS) were compared between two groups. There were 212 patients completing the whole research, including 104 patients in research group and 108 patients in control group. The difference in treatment effectiveness (77.8% vs 53.7%), iconographic effectiveness (51.0% vs 18.5%), and 28-day survival rate (86.5% vs 64.8%) between two groups performed statistical significance (P<0.05). However, the difference in bacterial eradication rate (48.0% vs 46.3%) performed no statistical significance. Eight hours later, the difference in average blood concentration between two groups (9.61±3.63µg/ml vs 1.5±0.51µg/ml) showed statistical significance. Moreover, the difference in clinical scoring indices except APACHE II score between two groups performed statistical significance. It was helpful to maintain the blood concentration of meropenem by extending the transfusion time. Therefore, it could increase the clinical cure rate and 28-day survival of patients with serious infection in ICU, improve clinical indices, and reduce the usage amount of antibiotics.