Mediterranean diet in the targeted prevention and personalized treatment of chronic diseases: evidence, potential mechanisms, and prospects.

The prevalence of chronic diseases is currently a major public health issue worldwide and is exploding with the population growth and aging. Dietary patterns are well known to play a important role in our overall health and well-being, and therefore, poor diet and malnutrition are among the most critical risk factors for chronic disease. Thus, dietary recommendation and nutritional supplementation have significant clinical implications for the targeted treatment of some of these diseases. Multiple dietary patterns have been proposed to prevent chronic disease incidence, like Dietary Approaches to Stop Hypertension (DASH) and Diabetes Risk Reduction Diet (DRRD). Among them, the MedDiet, which is one of the most well-known and studied dietary patterns in the world, has been related to a wide extent of health benefits. Substantial evidence has supported an important reverse association between higher compliance to MedDiet and the risk of chronic disease. Innovative strategies within the healthcare framework of predictive, preventive, and personalized medicine (PPPM/3PM) view personalized dietary customization as a predictive medical approach, cost-effective preventive measures, and the optimal dietary treatment tailored to the characteristics of patients with chronic diseases in primary and secondary care. Through a comprehensive collection and review of available evidence, this review summarizes health benefits of MedDiet in the context of PPPM/3PM for chronic diseases, including cardiovascular disease, hypertension, type 2 diabetes, obesity, metabolic syndrome, osteoporosis, and cancer, thereby a working hypothesis that MedDiet can personalize the prevention and treatment of chronic diseases was derived.

Population pharmacokinetics of intravenous colistin sulfate and dosage optimization in critically ill patients.

Aims: To explore the population pharmacokinetics of colistin sulfate and to optimize the dosing strategy for critically ill patients. Methods: The study enrolled critically ill adult patients who received colistin sulfate intravenously for more than 72 h with at least one measurement of plasma concentration. Colistin concentrations in plasma or urine samples were measured by ultraperformance liquid chromatography tandem mass spectrometry (LC-MS/MS). The population pharmacokinetics (PPK) model for colistin sulfate was developed using the Phoenix NLME program. Monte Carlo simulation was conducted to evaluate the probability of target attainment (PTA) for optimizing dosing regimens. Results: A total of 98 plasma concentrations from 20 patients were recorded for PPK modeling. The data were adequately described by a two-compartment model with linear elimination. During modeling, creatinine clearance (CrCL) and alanine aminotransferase (ALT) were identified as covariates of the clearance (CL) and volume of peripheral compartment distribution (V2), respectively. In addition, colistin sulfate was predominantly cleared by the nonrenal pathway with a median urinary recovery of 10.05% with large inter-individual variability. Monte Carlo simulations revealed a greater creatinine clearance associated with a higher risk of sub-therapeutic exposure to colistin sulfate. The target PTA (≥90%) of dosage regimens recommended by the label sheet was achievable only in patients infected by pathogens with MIC ≤0.5 mg/L or with renal impairments. Conclusion: Our study showed that the dose of intravenous colistin sulfate was best adjusted by CrCL and ALT. Importantly, the recommended dosing regimen of 1.0-1.5 million units daily was insufficient for patients with normal renal functions (CrCL ≥80 ml/min) or those infected by pathogens with MIC ≥1.0 mg/L. The dosage of colistin sulfate should be adjusted according to renal function and drug exposure.

Naringin improves sepsis-induced intestinal injury by modulating macrophage polarization via PPARγ/miR-21 axis.

Naringin exhibited various pharmacological activities. However, its biological function and underlying mechanism in regulating macrophage polarization remain elusive. This study aimed to investigate the regulatory network between naringin and macrophage polarization in sepsis-induced intestinal injury. Cecal ligation and puncture (CLP) was used to establish the animal model of sepsis. Chromatin immunoprecipitation and a luciferase reporter assay were used to determine the interplay between peroxisome proliferator-activated receptor γ (PPARγ) and miR-21 promoter, as well as miR-21 and its target genes. Naringin enhanced the overall survival of septic mice and alleviated the CLP-induced inflammatory response and intestinal damage. This was accompanied by the increased expression of PPARγ in the intestines and the stimulation of ileal macrophages toward the M2 phenotype. Furthermore, in lipopolysaccharide-stimulated bone marrow-derived macrophages, naringin stimulated M2 polarization. Mechanistically, PPARγ inhibition attenuated the promotion of M2 polarization caused by naringin, and the naringin/PPARγ regulatory work was compromised by miR-21 inhibition. The present study suggested that naringin promoted M2 polarization via the PPARγ/miR-21 axis, thus relieving sepsis-induced intestinal injury. This study provides novel insights into the mechanism by which naringin alleviated sepsis-induced intestinal injury through regulation of macrophage polarization.

Long Non-coding RNA FENDRR Modulates Autophagy Through Epigenetic Suppression of ATG7 via Binding PRC2 in Acute Pancreatitis.

Acute pancreatitis (AP) is an inflammatory, complicated pancreatic disease, carrying significant morbidity and mortality. However, the molecular and cellular mechanisms involved in AP pathogenesis remain to be elucidated. Here, we explore the role of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) in AP progression. Caerulein with or without LPS- induced or taurolithocholic acid 3-sulfate (TLC-S)-induced AP mouse models and cell models were performed for the validation of FENDRR expression in vivo and in vitro, respectively. Histopathological examinations of pancreatic tissues were performed to evaluate the severity of AP. Transmission electron microscopy was utilized to visualize the autophagic vacuoles. siRNA specifically targeting FENDRR was further applied. Flow cytometry was employed to assess cell apoptosis. ELISA, immunoflureoscence, and western blotting analysis were also performed to determine the levels of inflammatory cytokines and autophagy activity. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were carried out to reveal the epigenetic regulation of FENDRR on ATG7. Additionally, silencing FENDRR was also verified in AP mouse models. Higher FENDRR and impaired autophagy were displayed in both AP mouse models and cell models. FENDRR knockdown dramatically attenuated caerulein- or TLC-S-induced AR42J cells apoptosis and autophagy suppression. Further mechanistic experiments implied that the action of FENDRR is moderately attributable to its repression of ATG7 via direct interaction with the epigenetic repressor PRC2. Moreover, the silencing of FENDRR significantly induced the promotion of ATG7, thus alleviating the development of AP in vivo. Our study highlights FENDRR as a novel target that may contribute to AP progression, suggesting a therapeutic target for AP treatment.

Sesamin attenuates intestinal injury in sepsis via the HMGB1/TLR4/IL-33 signalling pathway.

CONTEXT: Sepsis is currently one of the leading causes of death in intensive care units (ICUs). Sesamin was previously reported to inhibit inflammation. However, no studies have revealed the impact of sesamin on sepsis. OBJECTIVE: We studied the mechanism underlying the effect of sesamin on the pathophysiology of sepsis through the HMGB1/TLR4/IL-33 signalling pathway. MATERIALS AND METHODS: Fifty male BALB/c mice (n = 10 per group) were used to establish a caecal ligation and puncture (CLP) mouse model, and given daily injections of sesamin at a low, middle, or high concentration (25, 50, or 100 µM) during the seven-day study period; survival curves were generated by the Kaplan-Meier method. H&E staining and TUNEL staining were performed to assess changes in intestinal morphology intestinal damage in the mouse intestinal epithelium. Molecules related to the HMGB1/TLR4/IL-33 pathway were assessed by RT-qPCR and Western blotting. RESULTS: We found mice in the sepsis group survived for only 4 days, while those treated with sesamin survived for 6-7 days. In addition, sesamin significantly relieved the increase in the levels of MPO (21%, 33.3%), MDA (40.5% and 31.6%), DAO (1.24-fold and 2.31-fold), and pro-inflammatory cytokines such as TNF-α (75% and 79%) and IL-6 (1-fold and 1.67-fold) 24 and 48 h after sepsis induction and downregulated the expression of HMGB1, TLR4, and IL-33 while upregulating the expression of ZO-1 and occludin. DISCUSSION AND CONCLUSIONS: Sesamin improved the 7-day survival rate of septic mice, suppressed the inflammatory response in sepsis through the HMGB-1/TLR4/IL-33 signalling pathway, and further alleviated intestinal injury.

Hyperglycemia is a strong predictor of poor prognosis in COVID-19.

AIMS: The objective of this study is to explore the association between documented diabetes, fasting plasma glucose (FPG), and the clinical outcomes of Coronavirus disease 2019 (COVID-19). METHODS: This retrospective study included 255 patients with COVID-19. Of these, 214 were admitted to isolation wards and 41were admitted to intensive care units (ICUs). Demographic, clinical, treatment, and laboratory data were collected and compared between ICU and non-ICU patients. Multivariable logistic regression models were used to explore the risk factors associated with poor clinical outcomes (ICU admission or death). RESULTS: There were significant changes in several clinical parameters in ICU patients (leukopenia, lymphopenia, elevated D-dimer, as well as higher levels of FPG, cardiac troponin, serum ferritin, IL-6, and high-sensitivity C-reactive protein)compared with non-ICU patients. The prevalence of known diabetes was substantially higher in ICU than non-ICU patients (31.7% vs. 17.8%, P = 0.0408). Multivariable regression analysis showed that a history of diabetes [odds ratio (OR), 0.099; 95% confidence interval (CI), 0.016-0.627; P = 0.014], high FPG at admission (OR, 1.587; 95% CI, 1.299-1.939, P < 0.001), high IL-6 (OR, 1.01; 95% CI, 1.002-1.018, P = 0.013), and D-dimer higher than 1 mg/L at admission (OR, 4.341; 95% CI, 1.139-16.547, P = 0.032) were independent predictors of poor outcomes. Cox proportional hazards analysis showed that compared with FPG < 7 mmol/L, FPG levels of 7.0-11.1 mmol/L and ≥ 11.1 mmol/L were associated with an increased hazard ratio (HR) for poor outcome (HR, 5.538 [95% CI, 2.269-13.51] and HR, 11.55 [95% CI, 4.45-29.99], respectively). CONCLUSION: Hyperglycemia and a history of diabetes on admission predicted poor clinical outcomes in COVID-19.

Rare purulent pericarditis caused by carbapenem-resistant Acinetobacter baumannii: A case report.

BACKGROUND: Pericardial infection caused by Acinetobacter baumannii is rare, particularly that of carbapenem-resistant A baumannii (CRAB). CASE PRESENTATION: We describe a rare case of purulent pericarditis due to CRAB in a 76-year-old man with acute myocardial infarction and acute kidney injury. The man was admitted to the intensive care unit for a catheter-related bloodstream infection. Pericardial effusion was detected via the bedside X-ray and ultrasound, and pericardiocentesis was performed. Cultures of the pericardial fluid, catheter tip, and blood independently revealed the presence of CRAB. These findings confirmed a diagnosis of purulent pericarditis. CONCLUSIONS: Clinicians should be reminded that CRAB infection can lead to purulent pericarditis, particularly in patients with congestive heart failure or renal insufficiency.

Treatment of invasive fungal disease: A case report.

BACKGROUND: In recent years, the incidence of fungal infection has been increasing, often invading one or more systems of the body. However, it is rare for lymph nodes to be invaded without the involvement of other organs. CASE SUMMARY: A 21-year-old man was admitted to hospital for repeated cough for 2 mo and abdominal pain for 1 mo. Physical examination revealed multiple lymph nodes enlargement, especially those in the left neck and groin. CT scan showed multiple lymph nodes enlargement in the chest, especially left lung, abdominal cavity, and retroperitoneum. The first lymph node biopsy revealed granulomatous lesions of lymph nodes, so intravenous infusion of Cefoperazone tazobactam combined with anti-tuberculosis drugs were given. Because fever and respiratory failure occurred 4 d after admission, mechanical ventilation was given, and Caspofungin and Voriconazole were used successively. However, the disease still could not be controlled. On the 11th day of admission, the body temperature reached 40° C. After mycosis of lymph nodes was confirmed by the second lymph node biopsy, Amphotericin B was given, and the patient recovered and was discharged from the hospital. CONCLUSION: No fixed target organ was identified in this case, and only lymph node involvement was found. Caspofungin, a new antifungal drug, and the conventional first choice drug, Voriconazole, were ineffective, while Amphotericin B was effective.

miR­1 reverses multidrug resistance in gastric cancer cells via downregulation of sorcin through promoting the accumulation of intracellular drugs and apoptosis of cells.

Gastric cancer (GC) is one of the most common cancers worldwide and results in the second greatest rate of cancer­associated mortality globally. Multidrug resistance (MDR) often develops during the chemotherapy, resulting in the failure of treatment. To investigate the molecular mechanism of MDR, the roles of microRNA (miR)­1 were studied in GC. Reverse transcription­quantitative polymerase chain reaction and western blotting were used to investigate the expression levels of miR­1 and sorcin in SGC7901/ADM and SGC7901/VCR cell lines. The effect of miR­1 on the half maximal inhibitory concentration (IC50), cell apoptosis rates and drug accumulation was uncovered by MTT assay and flow cytometric analysis. Furthermore, dual­luciferase assay and western blotting were used to determine the target of miR­1 in GC. It was demonstrated that miR­1 was highly downregulated in MDR GC cell lines, including SGC7901/ADM and SGC7901/VCR. Overexpression of miR­1 in MDR GC cells decreased IC50, but increased the cell apoptosis rates and promoted the drug accumulation in cancer cells. Dual­luciferase activity assay indicated that sorcin was the target of miR­1 in GC. In addition, overexpression of sorcin could partially reverse the effect of miR­1 in MDR GC cells. The role of miR­1 in MDR GC cells makes it a potential therapeutic target for a successful clinical outcome.

Dp71 depleted HBE cells displayed increased DNA damage and apoptosis induced by H2O2.

Human bronchial epithelium (HBE)-Dp71 anti-sense(AS)cells with stably transfected Dp71 siRNA plasmids were prepared for further exploration of Dp71 biological traits in cells other than PC12. HBE-Dp71AS cells displayed increased DNA damage induced by H2O2. Apoptosis of HBE-Dp71AS cells induced by H2O2 was increased via enhancing caspase 3, caspase 8 and caspase 9. HBE-Dp71AS cells also displayed decreased proliferation and clonogenic formation. RAD51 was proved to be a new binding partner of Dp71 by co-immunoprecipitation (Ip) and immunofluorescence. Reduced RAD51 mRNA and protein levels were observed in HBE-Dp71AS cells. Decreased lamin B1, focal adhesion kinase (FAK), phosphorylated focal adhesion kinase (p-FAK) and phosphorylated protein kinase B (p-AKT) were detected in the HBE-Dp71AS cells, which functioned together with RAD51 as the molecular explanations for the character alterations of HBE-Dp71AS cells.

MicroRNA-30d/JAG1 axis modulates pulmonary fibrosis through Notch signaling pathway.

Pulmonary fibrosis (PF) is a fibroproliferative disease which can finally end up fatal lung failure. PF is characterized by abnormal proliferation of fibroblast, dysregulated fibroblast differentiation to myofibroblast and disorganized collagen and extracellular matrix (ECM) production, deposition and degradation. JAG1/Notch signaling has been reported to play a key role in tissue fibrosis including PF. Herein, we confirmed the abnormal upregulation of JAG1 mRNA expression and protein levels in PF tissue specimens; JAG1 knockdown reduced TGF-ß1-induced α-SMA and Collagen I protein levels. From the aspect of miRNA regulation, we searched for candidate miRNAs which might target JAG1 to inhibit its expression. Among the selected miRNAs, miR-30d expression was downregulated in PF tissues; miR-30d overexpression attenuated TGF-ß1-induced primary normal human lung fibroblast (NHLF) proliferation, as well as α-SMA and Collagen I protein levels. Through directly binding to the 3'-UTR of JAG1, miR-30d significantly inhibited JAG1 mRNA expression and protein level. Furthermore, JAG1 overexpression partially reversed the effect of miR-30d on NHLF proliferation and α-SMA and Collagen I proteins upon TGF-ß1 stimulation; miR-30d could suppress TGF-ß1 function on NHLFs through blocking JAG1/Notch signaling. Rescuing miR-30d expression to suppress TGF-ß1-induced activation of JAG1/Notch signaling may present a promising strategy for PF treatment.

The CD40 rs1883832 Polymorphism Affects Sepsis Susceptibility and sCD40L Levels.

Sepsis is a severe and progressive disease characterized by systemic inflammatory response syndrome (SIRS). CD40 serves as a vital link between immune response and inflammation. This study was designed to investigate the potential association between a functional single-nucleotide polymorphism (SNP) of CD40 (rs1883832) and susceptibility to sepsis. We first performed a case-control study to explore the relationship between the CD40 rs1883832 polymorphism and sepsis. CD40 mRNA expression and protein expression were determined by real-time PCR and western blotting, respectively, in peripheral blood mononuclear cells (PBMCs) from sepsis patients and healthy controls. The plasma sCD40L levels in the two groups were measured by ELISA. The results showed that the frequencies of the TT genotype and the CD40 rs1883832 T allele were significantly higher in sepsis patients than in healthy controls. Plasma sCD40L levels were also significantly increased in sepsis patients. In addition, TT genotype carriers among sepsis patients displayed the highest CD40 expression at both the mRNA and protein levels, accompanied by the highest plasma sCD40L concentrations. In conclusion, the CD40 rs1883832 T allele acts as a risk factor for increased susceptibility to sepsis and may be involved in the process of sepsis through regulation of CD40 expression and plasma sCD40L levels.

Comparison of bone marrow tissue- and adipose tissue-derived mesenchymal stem cells in the treatment of sepsis in a murine model of lipopolysaccharide-induced sepsis.

Mesenchymal stem cells (MSCs) have been reported to regulate the systemic inflammatory response and sepsis-induced immunologic injury pre-clinically. However, whether MSCs from different sources elicit identical effects remains to be elucidated. The present study compared the effect of bone marrow­derived MSCs (BMSCs) and adipose tissue-derived MSCs (ADMSCs) in a murine model of lipopolysaccharide (LPS)­induced sepsis. SPF BALB/c mice were induced with an injection of LPS (10 mg/kg; 1 mg/ml) via the tail vein. To compare the effect of MSCs on the septic mice, either saline, BMSCs or ADMSCs were injected via the tail vein 5 min following the administration of LPS. The survival rates and body temperatures of the mice were observed regularly up to 48 h. The serum levels of pro­inflammatory cytokines, including tumour necrosis factor­α, interleukin (IL)­6 and IL­8, anti­inflammatory cytokines, including IL­2, IL­4 and IL­10, and biochemical markers, including lactate, creatinine, alanine aminotransferase and aspertate aminotransferase, were analyzed at 6 h. The BMSCs and ADMSCs significantly reduced mortality rates, body­temperature fluctuations, serum levels of biochemical markers and the majority of cytokines. However, the levels of IL­8 in the BMSC and ADMSC groups were increased and decreased, respectively. These findings suggested that BMSCs and ADMSCs ameliorated sepsis-associated organ injury and mortality, and had a similar regulatory effect on pro­ and anti­inflammatory cytokines despite the different MSC sources. Therefore, BMSCs and ADMSCs may serve as novel treatment modalities for sepsis.

[Role of local citrate anticoagulation in continuous blood purification to patients at high risk of bleeding in ICU].

OBJECTIVE: To evaluate the safety and efficiency of citrate anticoagulant-based continuous blood purification in patients at high risk of bleeding. 
 Methods: One hundred and fifty-two patients at high risk of bleeding were divided into local citrate group (group A, n=68) and heparin group (group B, n=84). Clotting function, change of pH, ionized sodium, bicarbonate ion, ionized calcium, activated clotting time (ACT) and complications were monitored before and during treatment. 
 Results: Compared to the group A, the incidence of clotting in filter and chamber, the degree of bleeding or fresh bleeding were significantly reduced in the group B (P<0.05). ACT of post-filter at 4, 8 and 12 h during the treatment in the group A was significantly extended compared with that without treatment (P<0.05), while there was no significant change in group B (P>0.05). The pH value, the levels of ionized sodium, bicarbonate ion and ionized calcium during the treatment were maintained in normal range in both group A and group B.
 Conclusion: Local citrate-based continuous blood purification can achieve effective anticoagulation and decrease the incidence of bleeding. It is an ideal choice for patients at high risk of bleeding.

Genome-wide analysis of long noncoding RNA expression profiles in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder poising burgeoning health problem to humans. Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases. Since the roles of lncRNA in NAFLD remain unknown, they were investigated in the study. Microarray expression profiling of mRNAs and lncRNAs was conducted using RNA extracted from patients with and without NAFLD. One thousand seven hundred thirty-five lncRNAs and 1485 mRNA were found differentially expressed in NAFLD samples compared with those in control samples. Among them 535 and 1,200 lncRNAs were upregulated and downregulated in NAFLD, respectively; 760 and 725 mRNAs were upregulated and downregulated in NAFLD, respectively. Moreover, seven lncRNAs and seven mRNAs that were highly up- or downregulated in NAFLD samples were validated by quantitative real-time polymer chain reactions. Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology analysis for the differentially expressed mRNAs showed that these RNAs are involved in various metabolic processes, cellular components, and molecular functions. Our findings indicate that the expression profiles of lncRNAs have changed in NAFLD as compared with normal liver, and the identified regulated RNAs may provide novel insight into the molecular mechanisms underlying the disease and potential novel diagnostic or therapeutic targets for NAFLD.

Systemic inflammation and multiple organ injury in traumatic hemorrhagic shock.

Traumatic hemorrhagic shock (HS) is a severe outcome of traumatic injury that accounts for numerous traumatic deaths. In the process of traumatic HS, both hemorrhage and trauma can trigger a complex cascade of posttraumatic events that are related to inflammatory and immune responses, which may lead to multiple organ injury or even death. From a mechanistic perspective, systemic inflammation and organ injury are involved coagulation, the complement system, impaired microcirculation and inflammatory signaling pathways. In this review, we discuss the systemic inflammation and multiple organ injury in post-traumatic HS.

Protective effect of pioglitazone on sepsis-induced intestinal injury in a rodent model.

BACKGROUND: Pathogenesis and treatment of inflammatory gut barrier failure is an important problem in critical care. In this study, we examined the role of pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, in gut barrier failure during experimental peritonitis in rats. MATERIALS AND METHODS: Male rats were randomly divided into three groups as follows: sham, sepsis, and sepsis + pioglitazone. Sepsis was achieved by means of the cecal ligation and puncture (CLP). Pioglitazone was administered intraperitoneally (10 mg/kg/d) for 7 d before the experiment. Animals were killed at 24 h or followed 72 h for survival. The tissue level of tumor necrosis factor-α, interleukin-6, superoxide dismutase, malondialdehyde, and myeloperoxidase was measured. Intestinal mucosa injury was assessed histologically. The plasma fluorescein isothiocyanate-dextran, D-lactic acid, and intestinal diamine oxidase were determined to evaluate the permeability and integrity of intestinal mucosal epithelium. Vena cava blood and tissue samples were used to monitor bacterial translocation. RESULTS: Intestinal inflammation, oxidize stress, neutrophil infiltration, morphology injury, and impaired permeability of the small intestine in the CLP group were found more severe than those in the sham group. Application of pioglitazone not only minimized all the indicators of intestinal injury and barrier failure but also improved the survival of septic rats induced by CLP. CONCLUSIONS: Our novel findings suggest that pioglitazone could protect against intestinal injury and maintain intestinal barrier integrity and might be a useful strategy to ameliorate intestinal failure in polymicrobial sepsis.

miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty liver disease by targeting HMGCR.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health issue with a prevalence of 15-30% in Western populations and 6-25% in Asian populations. Certain studies have revealed the alteration of microRNA (miRNA or miR) profiles in NAFLD and it has been suggested that miR-21 is associated with NAFLD. In the present study, we measured the serum levels of miR-21 in patients with NAFLD and also performed in vitro experiments using a cellular model of NAFLD to further investigate the effects of miR-21 on triglyceride and cholesterol metabolism. Furthermore, a novel target through which miR-21 exerts its effects on NAFLD was identified. The results revealed that the serum levels of miR-21 were lower in patients with NAFLD compared with the healthy controls. In addition, 3-hydroxy-3-methylglutaryl-co-enzyme A reductase (HMGCR) expression was increased in the serum of patients with NAFLD both at the mRNA and protein level. To mimic the NAFLD condition in vitro, HepG2 cells were treated with palmitic acid (PA) and oleic acid (OA). Consistent with the results obtained in the in vivo experiments, the expression levels of miR-21 were decreased and those of HMGCR were increased in the in vitro model of NAFLD. Luciferase reporter assay revealed that HMGCR was a direct target of miR-21 and that miR-21 exerted an effect on both HMGCR transcript degradation and protein translation. Furthermore, the results from the in vitro experiments revealed that miR-21 decreased the levels of triglycerides (TG), free cholesterol (FC) and total cholesterol (TC) in the PA/OA-treated HepG2 cells and that this effect was attenuated by HMGCR overexpression. Taken together, to the best of our knowledge, the present study is the first to report that miR-21 regulates triglyceride and cholesterol metabolism in an in vitro model of NAFLD, and that this effect is achieved by the inhibition of HMGCR expression. We speculate that miR-21 may be a useful biomarker for the diagnosis and treatment of NAFLD.

[Risk factors for septic shock in patients with solid organ transplantation and complication of bacteremias].

OBJECTIVE: To explore the risk factors for septic shock in patients with solid organ transplantation and complication of bacteremias. METHODS: Clinical data of 98 solid organ transplant cases with complication of bacteremias were retrospectively studied. All episodes of bacteremias met the CDC criteria. Six possible risk factors contributing to septic shock were evaluated by univariate analysis and multivariate logistic regression analysis. RESULTS: Among the 98 patients, 133 times of bacteremias have been reported and 39 patients developed septic shock. Among the 39 patients with septic shock, 43.5%, 38.5%, 15.4% and 2.6% of bacteremias were induced by multiple bacteria, gram-negative bacteria, gram-positive bacteria and fungi, respectively. The lung was the main source of bacteremias (41.8%), followed by intraabdominal/ biliary focus (24.5%). Risk factors for developing septic shock included the bacteremias happened in the 2nd to 8th week post transplant (P=0.014), polymicrobial etiology (P=0.001), intra-abdominal/ biliary focus (P=0.011), and liver transplant (P=0.002). Only bacteremias occurred in the 2nd to 8th week post transplant and polymicrobial etiology were significant risk factors by multivariate analysis. CONCLUSION: Risk factors for developing septic shock in bacteremias after SOT are early-onset (the 2nd-8th week post transplant) and polymicrobial etiology.

[Risk factors for bloodstream infections in liver or kidney transplantation recipients].

OBJECTIVE: To investigate the possible risk factors for death among liver or kidney recipients with bloodstream infections (BSIs). METHODS: A retrospective study of 138 episodes of bloodstream infections documented in 103 patients was conducted to assess potential risk factors for mortality. The risk factors were identified by logistic regression analysis. RESULTS: The mean age of the patients was 12-66 (42.3±12.7) years. The majority of infections were nosocomial (78.6%). The BSIs-related mortality rate was 39.8% (41/103). The following variables were identified as risk factors for BSIs-related mortality by univariate analysis: intraabdominal/ biliary focus (P=0.003), polymicrobial infection (P<0.001), liver transplant (P<0.001), platelet count <50000/mm3 (P<0.001), and septic shock (P<0.001). Platelet count < 50000/mm3 (P=0.002) and septic shock (P<0.001) showed significantly difference between the mortality group and the survival groups in the multivariate logistic regression analysis. CONCLUSION: Decreased platelet count and septic shock are risk factors for increased