Ceftazidime/avibactam combined with colistin: a novel attempt to treat carbapenem-resistant Gram-negative bacilli infection.

BACKGROUND: The rapid global emergence and spread of carbapenem-resistant Gram-negative bacilli (CR-GNB) is recognized as a major public health concern, and there are currently few effective treatments for CR-GNB infection. The aim of this study was to investigate the clinical characteristics and outcomes of patients with CR-GNB infections treated with ceftazidime/avibactam (CAZ/AVI) combined with colistin from October 2019 to February 2023 in China. METHODS: A total of 31 patients with CR-GNB infections were retrospectively identified using the electronic medical record system of Zhejiang Provincial People's Hospital. RESULTS: Thirty-one patients were treated with CAZ/AVI combined with colistin. Respiratory tract infections (87%) were most common. The common drug-resistant bacteria encompass Klebsiella pneumonia (54.8%), Acinetobacter baumannii (29.0%), and Pseudomonas aeruginosa (16.1%). The 30-day mortality rate was 29.0%, and the 7-day microbial clearance rate was 64.5%. The inflammatory marker CRP changes, but not PCT and WBC, were statistically significant on days 7 and 14 after combination therapy. There were seven patients developing acute renal injury (AKI) after combination therapy and treating with continuous renal replacement therapy (CRRT). Two patients developed diarrhea. CONCLUSION: The combination of CAZ/AVI and colistin has potential efficacy in patients with CR-GNB infection, but more studies are needed to determine whether it can reduce 30-day mortality rates and increase 7-day microbial clearance. At the same time, the adverse reactions of combination therapy should not be ignored.

Galectin-3 promotes brain injury by modulating the phenotype of microglia via binding TLR-4 after intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a stroke subtype with high mortality and disability rate, and neuroinflammation is involved in secondary brain injury. Galectin-3 (Gal-3) is one of the scaffold proteins of Galectins. Studies have indicated that Gal-3 plays an important role in the physiological and pathological state of the nervous system. Here we focus on the role of Gal-3 in ICH, especially in neuroinflammation. METHODS: Injection of autologous blood into the right basal ganglia was used to simulate ICH injury, and the level of Gal-3 in brain was regulated by related means. The changes of Gal-3 were detected by western blot and immunofluorescence, the level of neuroinflammation by immunofluorescence staining and ELISA. Apoptosis and neuron loss were detected by TUNEL staining FJB staining and Nissl staining, and neurological deficits were judged by neurobehavioral tests. RESULTS: The protein level of Gal-3 increased at 24 h after ICH. Downregulation of Gal-3 level can reduce the infiltration of M1-type microglia and peripheral inflammatory cells, thus alleviating post-ICH neuroinflammation, and reducing cell apoptosis and neuron loss in brain tissue. ICH-induced neurological damage was rescued. Meanwhile, the promotion in the expression level of Gal-3 increased neuroinflammatory activation and nerve cell death, aggravating ICH-induced brain injury. CONCLUSIONS: This study proves that Gal-3 is involved in neuroinflammation and nerve damage after ICH. Gal-3 expression should not be encouraged early on to prevent neuroinflammation. which provides a new possibility for clinical treatment for ICH patients.

Homologous recombination repair gene-based risk model predicts prognosis and immune microenvironment for primary lung cancer after previous malignancies.

BACKGROUND: Homologous recombination repair (HRR) plays an important role in cancer development, drug resistance, and immune escape, but the role of HRR genes in primary lung cancer (PLC) after previous malignancies is unclear. METHODS: We used HRR-related score constrcted by HRR genes to classify patients into two groups and compared clinical progression, differential genes, and their functions between them. Then, we constructed a prognostic risk model based on HRR-related score and screened key differentially expressed genes. We evaluated the potential roles, mutational information, and immune correlations of key genes. Finally, we compared the long-term prognosis and immune correlations of different prognostic risk subgroups. RESULTS: We found that HRR-related score was associated with T-stage, immunotherapy sensitivity, and prognosis of PLC after previous malignancies. Differential genes between HRR-related low-score and high-score groups are mainly involved in DNA replication and repair processes, such as the cell cycle. We identified three key genes, ABO, SERPINE2, and MYC, by machine learning, and MYC had the highest amplification mutation frequency. We verified that the key gene-based prognostic model can better assess the prognosis of patients. The risk score of the prognostic model was associated with immune microenvironment and efficacy of immunotherapy. CONCLUSIONS: Overall, we identified three key genes ABO, SERPINE2, and MYC associated with HRR status in PLC after previous malignancies. The risk model based on key genes is associated with immune microenvironment and can well predict the prognosis for PLC after previous malignancies.

Effectiveness and complication of achalasia treatment: A systematic review and network meta-analysis of randomized controlled trials.

Achalasia(AC) is an esophageal motility disorder characterized by decreased esophageal motility and impaired relaxation of lower esophageal sphincter(LES). The treatment of achalasia is continuously improved for the development of technology, but each treatment has its own advantages and disadvantages. This article was to compare the efficacy and complication of different treatment on AC. PUBMED/MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched for eligible studies. A random-effects model within a Bayesian framework was applied to compare treatment effects as odds ratio (OR) with their corresponding 95% credible interval (CI), also OR was applied to compare complication with 95% CI. The surface under the cumulative ranking area (SUCRA) was calculated to make the ranking of the treatments for outcomes. Twenty-seven randomized controlled trials (RCTs) were eligible. According to SUCRA ranking, anterior peroral endoscopic myotomy (APOEM) (SUCRA = 84.6%) might have the highest probability to be the best treatment for dysphagia remission in AC patients, followed by POEM (SUCRA = 78.4%). For gastroesophageal reflux disease (GERD) assessment, the corresponding SUCRA values indicated that botulinum toxin(BT) (SUCRA = 18.3%) might have lowest GERD incidence rate and POEM ranked the worst (SUCRA = 69.8%).. APOEM might have the highest probability to be the best therapeutic strategy for dysphagia remission in a short-term of follow-up, but the GERD incidence rate was high. BT injection might have the lowest probability to treat dysphagia, but the risk of GERD was the lowest. In the future, more RCTs with higher qualities are needed to make head-to-head comparison between 2 or more treatments.

Alpha-Lipoic Acid Protects Against Doxorubicin-Induced Cardiotoxicity by Regulating Pyruvate Dehydrogenase Kinase 4.

As a widely used anti-tumor anthracycline, the accumulation of Doxorubicin (DOX) in body causes irreparable cardiomyocyte damage and therefore is limited in clinical application. Strategies to prevent from DOX-associated cardiotoxicity are urgent for patients who undergo DOX-based chemotherapy. Since oxidative stress injury being the major reason for myocardial toxicity of DOX, here we demonstrated that, Alpha-lipoic acid (ALA), which is a reductive agent, plays a cardioprotective role in attenuating DOX-induced cardiotoxicity by inhibiting pyruvate dehydrogenase kinase 4 (PDK4) expression. In vivo, the beneficial effect of ALA was evidenced by increased survival rate, mechanical contraction, and oxidative phosphorylation, while decreased reactive oxidative species (ROS) and apoptosis. In vitro, PDK4 overexpression remarkably increased DOX-induced apoptosis and ROS production in H9C2 cells. Notably, the protective effect of ALA was abrogated by PDK4 overexpression. We further used PDK4 knockout mice to identify the role of PDK4 in DOX-induced cardiotoxicity. Results elicited that PDK4 deficiency showed a consistent effect in protecting DOX cardiotoxicity as ALA treatment, which was evidenced by restored redox homeostasis and mitochondrial metabolism, finally inhibited myocardial injury. In conclusion, the cardioprotective role of ALA against DOX cardiotoxicity was dependent on PDK4-mediated regulation of oxidative stress and mitochondria metabolism.

Prognostic value of pulmonary ultrasound score combined with plasma miR-21-3p expression in patients with acute lung injury.

PURPOSE: The aim of this study was to explore the value of the combination between lung ultrasound score (LUS) and the expression of plasma miR-21-3p in predicting the prognosis of patients with acute lung injury (ALI). PATIENTS AND METHODS: A total of 136 ALI patients were divided into survival (n = 86) and death groups (n = 50), or into low/middle-risk (n = 77) and high-risk groups (n = 59) according to APACHE II scores. Bioinformatics was used to explore the mechanism of action of miR-21-3p in humans. Real-time fluorescent quantitative PCR was used to detect the expression of miR-21-3p in plasma, and LUS was recorded. Receiver operator characteristic (ROC) curve and Pearson correlation were also used. RESULTS: The LUS and expression level of plasma miR-21-3p in the death and high-risk groups were significantly higher than those in the survival and low/middle-risk groups (p < 0.01 and p < 0.05). miR-21-3p expression leads to pulmonary fibrosis and promotes the deterioration of ALI patients by regulating fibroblast growth factor and other target genes. ROC curve analysis showed that the best cutoff values for LUS and plasma miR-21-3p expression were 18.60 points and 1.75, respectively. LUS score and miR-21-3p combined predicted the death of ALI patients with the largest area under the curve (0.907, 95% CI: 0.850-0.964), with sensitivity and specificity of 91.6% and 85.2%, respectively. The expression level of plasma miR-21-3p was positively correlated with LUS in the death group (r = 0.827, p < 0.01). CONCLUSION: LUS and expression level of miR-21-3p in plasma are correlated with the severity and prognosis of ALI patients, and their combination has a high value for the prognostic assessment of ALI patients.

lncRNA-SNHG14 Plays a Role in Acute Lung Injury Induced by Lipopolysaccharide through Regulating Autophagy via miR-223-3p/Foxo3a.

lncRNAs play important roles in lipopolysaccharide- (LPS-) induced acute lung injury. But the mechanism still needs further research. In the present study, we investigate the functional role of the lncRNA-SNHG14/miR-223-3p/Foxo3a pathway in LPS-induced ALI and tried to confirm its regulatory effect on autophagy. Transcriptomic profile changes were identified by RNA-seq in LPS-treated alveolar type II epithelial cells. The expression changes of lncRNA-SNHG14/miR-223-3p/Foxo3a were confirmed using qRT-PCR and west blot. The binding relationship of lncRNA-SNHG14/miR-223-3p/and miR-223-3p/Foxo3a was verified using dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Using gain-of-function or loss-of-function approaches, the effect of lncRNA-SNHG14/miR-223-3p/Foxo3a was investigated in LPS-induced acute lung injury mice model and in vitro. Increasing of lncRNA-SNHG14 and Foxo3a with reducing miR-223-3p was found in LPS-treated A549 cells and lung tissue collected from the LPS-induced ALI model. lncRNA-SNHG14 inhibited miR-223-3p but promoted Foxo3a expression as a ceRNA. Artificially changes of lncRNA-SNHG14/miR-223-3p/Foxo3a pathway promoted or protected cell injury from LPS in vivo and in vitro. Autophagy activity could be influenced by lncRNA-SNHG14/miR-223-3p/Foxo3a pathway in cells with or without LPS treatment. In conclusion, aberrant expression changes of lncRNA-SNHG14 participated alveolar type II epithelial cell injury and acute lung injury induced by LPS through regulating autophagy. One underlying mechanism is that lncRNA-SNHG14 regulated autophagy by controlling miR-223-3p/Foxo3a as a ceRNA. It suggested that lncRNA-SNHG14 may serve as a potential therapeutic target for patients with sepsis-induced ALI.

Homocysteine level and gestational diabetes mellitus: a systematic review and meta-analysis.

AIMS: It is reported that elevated homocysteine (Hcy) level represents an independent risk factor for gestational diabetes mellitus (GDM). However, the relationship between Hcy level and GDM remains controversial. Our study aimed to systematically review available literature linking Hcy to GDM for a comprehensive understanding of the relationship between circulating Hcy level and GDM in humans. METHODS: PubMed, The Cochrane Library, and Web of Science were searched for studies published up to January 2021. Manual searches of references of the relevant studies were also conducted. Standard mean difference (SMD) with 95% confidence interval (95%CI) were calculated to evaluate the relationship between Hcy level and GDM using the Review Manager 5.3 and Stata 12.0. RESULTS: Of 106 references reviewed, 12 studies with a total of 712 GDM patients contributed to the present meta-analysis. Hcy level was significantly elevated in women with GDM compared with those without GDM (SMD = 0.55; 95% CI: 0.25-0.85, p = .0003). In the subgroup meta-analyses, this evidence was more consistent among women with Hcy sampling during the second trimester (SMD = 0.76, 95% CI: 0.34-1.18, p = .0004) and with average age ≥30 years (SMD = 0.69, 95% CI: 0.25-1.12, p = .002). CONCLUSION: The evidence indicated that the level of circulating Hcy was significantly elevated among women with GDM compared with those with normal glucose tolerance, especially with mean age ≥30 years and in the second trimester.

Visfatin level and gestational diabetes mellitus: a systematic review and meta-analysis.

It is reported that elevated visfatin level is associated with gestational diabetes mellitus (GDM). However, the relationship between visfatin level and GDM remains controversial. The aim of our study was to systematically review available literature linking visfatin to GDM for a comprehensive understanding of the relationship between circulating visfatin level and GDM in human. PubMed, The Cochrane Library and Web of Science were searched for studies published up to July 2020. Standard mean difference with 95% confidence interval was calculated to evaluate the relationship between visfatin level and GDM using the Review Manager 5.3 and Stata 12.0. The evidence indicated that no significant difference was observed in the level of circulating visfatin between the women with GDM and normal glucose tolerance, suggesting circulating visfatin level is not independently related to GDM. Nevertheless, visfatin is involved in the development of GDM in obese women.

Dexmedetomidine protects against acute kidney injury in patients with septic shock.

BACKGROUND: This study aimed to assess the relationship between the use of dexmedetomidine and the incidence of acute kidney injury (AKI) in septic shock patients undergoing mechanical ventilation and reveal the potential mechanism. METHODS: Septic shock patients undergoing mechanical ventilation were included. Patients were randomized into two groups including propofol group and dexmedetomidine group. Plasma samples were obtained from veins at 0, 12, 24, 72 and 120 h after receiving mechanical ventilation in ICU. RESULTS: Cohorts with septic shock after mechanical ventilation in ICU had similar baseline and demographic characteristics. Serum creatinine (SCr) and blood urea nitrogen (BUN) was lower in dexmedetomidine group (P<0.05) and also lower renal injury markers were detected in the dexmedetomidine group, compared with propofol group (P<0.05). Dexmedetomidine infusion reduced the TNF-α, IL-1 level in blood samples and maintained the balance of proportion of CD4+ and CD8+ T-lymphocytes. Patients receiving dexmedetomidine were less likely to develop AKI. The median ICU stay was decreased in dexmedetomidine group (P<0.05). Moreover, the case and duration of CRRT was also decreased by using dexmedetomidine (P<0.05). There was no significant difference between the cohorts with respect to the duration of mechanical ventilation. CONCLUSIONS: The use of dexmedetomidine infusion in ICU patients was associated with a decreased incidence of AKI and reduced ICU stay and CRRT performance. The mechanism may be related to antiinflammatory reaction and immunoregulation.

IGF-1 may predict the severity and outcome of patients with sepsis and be associated with microRNA-1 level changes.

IGF-1 functions as an anti-oxidative stress molecule and some critical patients with sepsis have a lower level of serum IGF-1. However, the association between IGF-1 and the severity or prognosis of sepsis remains unclear. This study aimed to elucidate the relationship between serum IGF-1 levels and the severity and prognosis of sepsis, and the possible mechanism was analyzed. Clinical characteristics of patients with sepsis were recorded and analyzed. Serum IGF-1 levels and micro (mi)RNA-1 levels were tested using radioimmunoassay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, respectively. The A549 cell line and HKC cell line were cultured in vitro and exposed to H2O2 with or without IGF-1 treatment. Cell death was detected by analyzing cell death markers via ELISA kits, and miRNA-1 levels were detected after H2O2 exposure using RT-qPCR analysis. miRNA-1 in cells was upregulated by transfection and IGF-1 mRNA was detected to determine its relationship with miRNA-1. Once again, cell ELISA kits were used to analyze cell death markers after transfection. Serum IGF-1 levels were reduced in patients with sepsis, whereas miRNA-1 levels were higher (P<0.05 vs. healthy control). Patients in the septic shock subgroup or dead patients had the lowest IGF-1 levels and the highest miRNA-1 levels (P<0.05 vs. sepsis and severe sepsis). IGF-1 levels were inversely proportional to the miRNA-1 level. In vitro, IGF-1 reduced the cell death caused by H2O2. miRNA-1 transfection effectively increased the sensitivity of cells to H2O2 damage by reducing the expression of IGF-1, which was able to prevent cells from injury caused by H2O2. The transfection of negative control miRNA did not influence the level of IGF-1 miRNA and the sensitivity to H2O2 damage. In conclusion, low IGF-1 levels in patients with sepsis may predict increased severity of the condition and poor prognosis. The possible mechanism is that the excessive miRNA-1 levels reduce IGF-1 levels, resulting in insufficient anti-oxidative action by IGF-1 which increases the injury caused by oxidative stress in patients with sepsis.

NF-κB-dependent transcriptional upregulation of cyclin D1 exerts cytoprotection against hypoxic injury upon EGFR activation.

Apoptosis of neural cells is one of the main pathological features in hypoxic/ischemic brain injury. Nuclear factor-κB (NF-κB) might be a potential therapeutic target for hypoxic/ischemic brain injury since NF-κB has been found to be inactivated after hypoxia exposure, yet the underlying molecular mechanisms of NF-κB inactivation are largely unknown. Here we report that epidermal growth factor receptor (EGFR) activation prevents neuron-like PC12 cells apoptosis in response to hypoxia via restoring NF-κB-dependent transcriptional upregulation of cyclin D1. Functionally, EGFR activation by EGF stimulation mitigates hypoxia-induced PC12 cells apoptosis in both dose- and time-dependent manner. Of note, EGFR activation elevates IKKß phosphorylation, increases IκBα ubiquitination, promotes P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as upregulates cyclin D1 expression. EGFR activation also abrogates the decrease of IKKß phosphorylation, reduction of IκBα ubiquitination, blockade of P65 nuclear translocation and recruitment at cyclin D1 gene promoter as well as downregulation of cyclin D1 expression induced by hypoxia. Furthermore, NF-κB-dependent upregulation of cyclin D1 is instrumental for the EGFR-mediated cytoprotection against hypoxic apoptosis. In addition, the dephosphorylation of EGFR induced by either EGF siRNA transfection or anti-HB-EGF neutralization antibody treatment enhances hypoxic cytotoxicity, which are attenuated by EGF administration. Our results highlight the essential role of NF-κB-dependent transcriptional upregulation of cyclin D1 in EGFR-mediated cytoprotective effects under hypoxic preconditioning and support further investigation of EGF in clinical trials of patients with hypoxic/ischemic brain injury.

Resolution acute respiratory distress syndrome through reversing the imbalance of Treg/Th17 by targeting the cAMP signaling pathway.

Acute respiratory distress syndrome (ARDS) is a severe cause of respiratory failure with a mortality rate as high as 40­46% and without any effective pharmacological treatment available. The present study provided a novel strategy for the treatment of ARDS by specifically interfering with cyclic adenosine monophosphate (cAMP) signaling. Pre-treatment with the phosphodiesterase antagonist pentoxifyllinum (PTX) obviously attenuated lung injury and reduced the mortality of mice with cecal ligature and puncture (CLP)­induced ARDS, while raising cAMP levels. In addition, pre­treatment with PTX attenuated CLP­induced increases in the number of T­regulatory cells (Tregs) and interleukin (IL)­17­producing T­helper lymphocytes (Th17) among spleen lymphocytes, while partially restoring the Treg/Th17 ratio. Correspondingly, CLP­induced increases in the secretion of IL­2, IL­6, IL­10 and IL­17 were attenuated. Furthermore, CLP­induced increases in forkhead box p3 and RAR­related orphan receptor Î³t (RORγt) expression as well as signal transducer and activator of transcription (STAT3) activation were attenuated by PTX. The results indicated that PTX­induced increases in cAMP may have partly restored the Treg/Th17 balance by modulating the transcription of Foxp3 and RORγt through the STAT3 pathway. In conclusion, the present study provided a novel treatment strategy for ARDS by modulating the balance of Treg/Th17 and the subsequent immune response via cAMP signaling, which requires pre-clinical and clinical validation.

Ventricular hypertrophy blocked delayed anesthetic cardioprotection in rats by alteration of iNOS/COX-2 signaling.

The aim of the current study was to determine whether ventricular hypertrophy affects the delayed isoflurane preconditioning against myocardial ischemia-reperfusion (IR) injury. Transverse aortic constriction (TAC) was performed on male Sprague-Dawley rats to induce left ventricular (LV) hypertrophy, then sham-operated or hypertrophied rat hearts were subjected to isoflurane preconditioning (2.1% v/v, 1 h). 24 h after exposure, the hearts were isolated and perfused retrogradely by the Langendorff for 30 min (equilibration) followed by 40 min of ischemia and then 120 min of reperfusion. The hemodynamics, infarct size, apoptosis, nitric oxide synthase (NOS), cyclooxygenase-2 (COX-2), Cleaved Caspase-3 and production of NO were determined. We found that the hemodynamic parameters were all markedly improved during the reperfusion period and the myocardial infarct size and apoptosis was significantly reduced by delayed isoflurane preconditioning in sham-operated rats. However, such cardiac improvement induced by delayed isoflurane preconditioning was not observed in hypertrophied hearts. The expression of iNOS, COX-2 and NO was markedly enhanced, whereas Cleaved Caspase-3 activity was inhibited by delayed isoflurane preconditioning in sham-operated rats, a phenomenon was not found in TAC-control groups pretreated with isoflurane. Our results demonstrated that ventricular hypertrophy abrogated isoflurane-induced delayed cardioprotection by alteration of iNOS/COX-2 pathway.

[Expression and role of CXC chemokine 5 in liver cancer cells].

OBJECTIVE: To explore the expression of CXC chemokine 5 (CXCL5) in liver cancer cells and its effect on cell proliferation, migration and invasion. METHODS: Real-time (RT)-PCR and enzyme-linked immunosorbent assay (ELISA) were used to detect the mRNA and protein levels of CXCL5 in 4 liver cancer cell lines with different metastatic potentials (in ascending order: HepG2, SMMC7721, MHCC97L and MHCC97H). HepG2 with a low expression of CXCL5 was treated with CXCL5. There were four groups: 0 nmol/L CXCL5, 0.1 nmol/L CXCL5, 1.0 nmol/L CXCL5 and 10.0 nmol/L CXCL5. Cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay. Transwell chambers and basement membrane matrix (Matrigel) were used to observe the cellular migration and invasion. Statistical analysis was performed with SPSS 16.0. Statistical comparison of the results was made by analysis of variance (ANOVA). RESULTS: The relative mRNA expression levels of CXCL5 in HepG2, SMMC7721, MHCC97L and MHCC97H were 0.002% ± 0.000%, 0.005% ± 0.000%, 1.030% ± 0.070% and 0.980% ± 0.190% (F = 33.88, P < 0.01) while their protein levels 14.3 ± 0.4, 25.7 ± 1.4, 82.8 ± 3.2 and 98.9 ± 1.7 respectively (F = 447.08, P < 0.01). The CCK-8 results showed that cell proliferation increased with the treatment of CXCL5, but no significant difference existed (F < 1.00, P > 0.05), cell numbers of migration of 0, 0.1, 1.0, 10.0 nmol/L CXCL5 groups were 29 ± 3, 56 ± 16, 113 ± 7 and 130 ± 15 (F = 51.94, P < 0.01), while cell numbers of invasion 17.3 ± 1.8, 33.0 ± 3.2, 65.7 ± 4.4 and 94.3 ± 3.5 respectively (F = 104.13, P < 0.01). CONCLUSIONS: Liver cancer cells with high metastatic potential have a higher expression of CXCL5. And exogenous CXCL5 can increase the proliferation, migration and invasion of liver cancer cells with low metastatic potential. Thus CXCL5 may be associated with the metastasis of liver cancer.

[Effect of let-7c on the proliferation of human hepatocellular carcinoma cell HCCLM3].

OBJECTIVE: To investigate let-7c's effect on the proliferation of human hepatocellular carcinoma cell HCCLM3 by transient transfection and the mechanism inside. METHODS: Lipofectamine 2000 was used to transfect miRNAs into HCCLM3 cells. The cells were divided into three groups, let-7c group: let-7c was transfected, negative control group: negative control miRNA was transfected, blank control group: nothing was transfected. The proliferation of HCCLM3 cells was evaluated using Cell Counting Kit-8 (CCK-8). The cell cycles of each group were assayed by flow cytometry. Western blot and Real time PCR were used to analyze the protein and mRNA expressions of cyclin D1. Statistical analysis was performed with SPSS 17.0. RESULTS: The absorbances of let-7c group were 0.70 ± 0.05, 0.77 ± 0.09 at 48 h and 72 h after transfection, lower than that of blank control group (0.97 ± 0.10, 1.21 ± 0.12) and negative control group (0.91 ± 0.07, 1.12 ± 0.09), 48 h: F = 14.431, P < 0.05, 72 h: F = 21.146, P < 0.05. The flow cytometry at 72 h after transfection revealed that let-7c increased the percentage of cells in G1 phase. The percentage of blank control group was 43.53% ± 0.86%, the negative control group was 44.82% ± 0.77%, and the let-7c group was 54.52% ± 0.13%, F = 240.739, P < 0.05. let-7c suppressed expressions of cyclin D1 at both protein and mRNA levels. The protein levels of cyclin D1 were 0.48 ± 0.09, 0.47 ± 0.06 and 0.23 ± 0.06 (F = 11.316, P < 0.05) in blank control group, negative control group and let-7c group, respectively. The mRNA levels were 1.03% ± 0.29%, 1.01% ± 0.11% and 0.63% ± 0.14% (F=6.315, P < 0.05) in the above three groups, respectively. CONCLUSION: Let-7c can inhibit proliferation of HCCLM3 cells and increase the proportion of cells in G1 phase. The mechanism may be that let-7c represses the expressions of cyclin D1 at both protein and mRNA levels.