Case Report: Semi-Ex Vivo Hepatectomy Combined with Autologous Liver Transplantation for Alveolar Echinococcosis in Children.

Hepatic alveolar echinococcosis (AE) is a zoonotic disease caused by the metacestode of Echinococcus multilocularis. Although surgical resection is the optimal treatment for hepatic AE, some patients with hepatic AE located in special introhepatic sites cannot be radically cured by conventional surgery. Here, we report that a 10-year-old female patient was admitted to the hospital with occupying liver lesions for 6 months. Computed tomography examination showed irregular mixed-density masses in the right lobe and caudate lobe of the liver, with partial invasion of the right hepatic artery, right hepatic vein, and right branch of the portal vein. The patient was preoperatively diagnosed with hepatic AE, which cannot be cured by conventional liver lobectomy. The patient underwent semi-ex vivo liver resection with autologous liver transplantation (second hepatic portal reconstruction, posterior hepatic inferior vena cava repair, and hepatic artery repair) and biliary-intestinal anastomosis. After hospital discharge, she has kept living a healthy life without disease recurrence for 13 months until the end of the last follow-up. This case shows that semi-ex vivo hepatectomy with autologous liver transplantation might be a feasible and safe choice for certain patients with AE located in special introhepatic sites, which has provided novel experiences for the surgical treatment of hepatic AE.

Laparoscopic versus conventional open treatment of hepatic cystic hydatidosis: a systematic review and meta-analysis of cohort studies.

Introduction: There still exist controversies about the advantages and disadvantages of laparoscopic and traditional open surgery. Aim: This meta-analysis aimed to compare the efficacy and safety of laparoscopic versus traditional laparotomy in hepatic cystic hydatidosis. Material and methods: A systematic literature search was conducted for studies about liver hydatid surgery. After the quality assessment and relevant data extraction, the article was screened and included according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.3 software. Results: Thirteen studies included 1211 cases, 362 in the laparoscopic group, and 849 in the open surgery group. According to meta-analysis, laparoscopic surgery is superior to traditional open surgery in terms of length of hospital stay, the recovery time of gastrointestinal function, total complications, and the risk of incision infection. There were no significant differences between laparoscopic surgery and traditional open surgery in operation time, postoperative time of abdominal drainage tube removal, recurrence rate, bile leakage rate, biliary fistula rate, and residual cavity infection rate. Conclusions: Laparoscopy is superior to traditional open surgery in terms of length of hospital stay, the recovery time of gastrointestinal function, total complications, and the risk of incision infection. There was no significant difference in postoperative recurrence between laparoscopy and open surgery. In addition, we think laparoscopy can achieve the same clinical effect as laparotomy. However, the reliability and validity of our conclusion need to be verified by more randomized controlled trials (RCTs).

Misdiagnosis of hepatic cystic echinococcosis complicated with hepatocellular carcinoma: A case report.

RATIONALE: Hepatic cystic echinococcosis (CE) is a common zoonotic parasitic disease caused by the entry of Echinococcus granulosus eggs into human body. Surgical resection is the optimal treatment choice for hepatic CE. However, Coexistence of CE and hepatocellular carcinoma (HCC) have been reported with a rare incidence rate, which led to unsatisfactory prognosis after the operation. PATIENT CONCERNS: A 69-year-old male patient was admitted to hospital because of "Upper abdominal pain and discomfort for more than 1 month and an aggravation for 10 days." DIAGNOSIS: An elderly male herder who was initially diagnosed as hepatic CE, and none of the preoperative imaging test revealed the existence of HCC. Co-existence of hepatic CE and HCC was confirmed by the postoperative pathological examination. INTERVENTIONS: The patient underwent "combined hepatic segmental resection, portal vein thrombectomy, portal vein repairment, hepatic hydatid internal capsule removal and external subtotal resection, cholecystectomy". OUTCOMES: During follow-up after discharge, the patient did not regularly review and get further treatment and died 8 months after operation. LESSONS: May improve the clinicians' understanding of CE complicated with HCC, and reduce the misdiagnosis of similar case, as well as provide guidance for clinical treatment.

SLCO4A1 is a Prognosis-Associated Biomarker Involved in Neutrophil-Mediated Immunity in Thyroid Cancer.

OBJECTIVE: The study aimed to investigate the value of solute carrier organic anion transporter family member 4A1 (SLCO4A1) in thyroid cancer mainly from three aspects: expression, prognosis, and biological function analyses. METHODS: Based on various bioinformatic approaches, genes co-expressed with vascular endothelial growth factor C (VEGFC) in thyroid cancer were used for further survival and expression analyses to identify the target gene. After evaluation of the SLCO4A1 expression levels in thyroid cancer, Cox regression analysis was utilized to predict the risk factors for survival of thyroid cancer patients. And receiving operating characteristic curve analysis was performed to validate the prognostic value of SLCO4A1. Additionally, WebGestalt was employed for enrichment analysis of SLCO4A1 and its co-expressed genes. Further, the relation between SLCO4A1 and neutrophil was analyzed, followed by exploring the association of SLCO4A1 with immunomodulators. RESULTS: A total of 38 consistent VEGFC co-expressed genes were generated, and SLCO4A1 was selected as the target gene due to its oncogenic characteristics. SLCO4A1 was highly expressed in thyroid cancer at both gene and protein levels, and SLCO4A1 mRNA expression was significantly associated with the cancer stage (all P <0.05). Besides, high SLCO4A1 expression led to unfavorable progression-free survival (PFS) of thyroid cancer patients (P =0.0066). Further, Cox regression analysis indicated that high SLCO4A1 expression was an independent predictor of poor PFS in patients with papillary thyroid cancer, particularly in patients at stage 1 and female patients (all P <0.001). The enrichment analysis results showed that SLCO41A was involved in the neutrophil-mediated immunity pathway. Moreover, SLCO4A1 had a positive relation with neutrophils (all P <0.05). Finally, a significant correlation between SLCO4A1 and immunomodulators was observed (all P <0.001). CONCLUSION: SLCO4A1 was a potential prognostic biomarker for papillary thyroid cancer patients. And SLCO4A1 might affect PFS in thyroid cancer patients by positive regulation of neutrophil-mediated immunity pathway.

Abnormal Indexes of Liver and Kidney Injury Markers Predict Severity in COVID-19 Patients.

BACKGROUND: SARS-CoV-2 can damage not only the lungs but also the liver and kidney. Most critically ill patients with coronavirus disease 2019 (COVID-19) have liver and kidney dysfunction. We aim to investigate the levels of liver and kidney function indexes in mild and severe COVID-19 patients and their capability to predict the severity of the disease. METHODS: The characteristics and laboratory indexes were compared between patients with different conditions. We applied binary logistic regression to find the independent risk factors of severe patients. Receiver operating characteristic (ROC) analysis was used to predict the severity of COVID-19 using the liver and kidney function indexes. RESULTS: This study enrolled 266 COVID-19 patients, including 235 mild patients and 31 severe patients. Compared with mild patients, severe patients had lower albumin (ALB) and higher alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urea nitrogen (BUN) (all p<0.001). Binary logistic regression analysis also identified ALB [OR=0.273 (0.079-0.947), p=0.041] and ALT [OR=2.680 (1.036-6.934), p=0.042] as independent factors of severe COVID-19 patients. Combining ALB, ALT, BUN, and LDH exhibited the area under ROC at 0.914, with a sensitivity of 86.7% and specificity of 83.0%. CONCLUSION: COVID-19 patients, especially severe patients, have damage to liver and kidney function. ALT, AST, LDH, and BUN could be independent factors for predicting the severity of COVID-19. Combining the ALB, ALT, BUN, and LDH could predict the transition from mild to severe in COVID-19 patients.

Clinical Efficacy of Polymyxin B in Patients Infected with Carbapenem-Resistant Organisms.

PURPOSE: Carbapenem-resistant organisms (CROs) pose great challenges for clinical treatment. Polymyxin B (PMB) is one of the "last resort" choices of CRO infections. We explored the possible factors affecting PMB efficacy. PATIENTS AND METHODS: This retrospective study involved CRO-infected patients treated with PMB for ≥72 h. The endpoint indicator was clinical efficacy. We compared the characteristics (demographics, pathogenic bacteria, PMB treatment) between patients who had "clinical success" (CS) and "clinical failure" (CF). RESULTS: A total of 191 patients were enrolled: 110 in the CS group and 81 in the CF group. The total cumulative dose for the CS group was higher than the CF group [1100 (700-1443.75) vs 800 (500-1112.5) mg; P = 0.001]. Treatment duration in the CS group was longer than the CF group [11 (8-14) vs 8 (6-11) days; P < 0.000]. Multivariate logistic regression analysis showed mechanical ventilation, vasoactive agents, multiple-site infection, and total cumulative dose to be independently associated with clinical efficacy. Cox survival analysis for 30-day mortality also showed that the use of vasoactive agents and the total cumulative dose of PMB could influence survival time and mortality rate independently. CONCLUSION: PMB had good efficacy and a low prevalence of adverse reactions. The total cumulative dose, duration of PMB treatment, mechanical ventilation, vasoactive agents, and multiple-site infection were factors associated with the clinical efficacy of PMB.

Super-enhancers: a new frontier for epigenetic modifiers in cancer chemoresistance.

Although new developments of surgery, chemotherapy, radiotherapy, and immunotherapy treatments for cancer have improved patient survival, the emergence of chemoresistance in cancer has significant impacts on treatment effects. The development of chemoresistance involves several polygenic, progressive mechanisms at the molecular and cellular levels, as well as both genetic and epigenetic heterogeneities. Chemotherapeutics induce epigenetic reprogramming in cancer cells, converting a transient transcriptional state into a stably resistant one. Super-enhancers (SEs) are central to the maintenance of identity of cancer cells and promote SE-driven-oncogenic transcriptions to which cancer cells become highly addicted. This dependence on SE-driven transcription to maintain chemoresistance offers an Achilles' heel for chemoresistance. Indeed, the inhibition of SE components dampens oncogenic transcription and inhibits tumor growth to ultimately achieve combined sensitization and reverse the effects of drug resistance. No reviews have been published on SE-related mechanisms in the cancer chemoresistance. In this review, we investigated the structure, function, and regulation of chemoresistance-related SEs and their contributions to the chemotherapy via regulation of the formation of cancer stem cells, cellular plasticity, the microenvironment, genes associated with chemoresistance, noncoding RNAs, and tumor immunity. The discovery of these mechanisms may aid in the development of new drugs to improve the sensitivity and specificity of cancer cells to chemotherapy drugs.

A Comparative Study of the Microbiological Efficacy of Polymyxin B on Different Carbapenem-Resistant Gram-Negative Bacteria Infections.

Objective: The emergence of carbapenem-resistant gram-negative bacteria (CR-GNB) has brought great challenges to clinical anti-infection treatment around the world. Polymyxins are often considered as the last line of defense in the treatment of CR-GNB infections. In this study, we explored the microbiological efficacy of Polymyxin B (PMB) on different CR-GNB infections as well as the factors influencing microbiological efficacy. Methods: CR-GNB infected patients with PMB-based regimens were enrolled. Clinical and microbiological data were collected from the medical electronic record system of the Second Xiangya hospital. The efficacy of PMB on different CR-GNB was evaluated by the clearance rate at 7-days and within the course of treatment, as well as the 30-day mortality rate. Results: A total of 294 CR-GNB infected patients were enrolled: 154 CR-Acinetobacter baumannii (CRAB), 55 CR-Klebsiella pneumoniae (CRKP), and 85 CR-Pseudomonas aeruginosa (CRPA). The CRAB group had the highest 7-day bacterial clearance rate [(CRAB: 39.0%) vs. (CRKP: 29.4%) vs. (CRPA: 14.5%), P = 0.003] and total bacterial clearance rate [(CRAB: 49.0%) vs. (CRKP: 39.8%) vs. (CRPA: 18.2%), P < 0.001] among the three groups, while the bacterial clearance rate of the CRPA group was the lowest. Multivariate logistic regression showed that the differences among the three groups were multiple CR-GNB infections (P = 0.004), respiratory infections (P = 0.001), PMB resistance (P < 0.001), and the combination of tigecycline (P < 0.001). Binary logistic regression showed that multiple CR-GNB infection [(7-day bacterial clearance: P = 0.004) & (total bacterial clearance: P = 0.011)] and bacterial species [(7-day bacterial clearance: P < 0.001) & (total bacterial clearance: P < 0.001)] were independent risk factors for microbiological efficacy. Conclusion: PMB exhibited differential microbiological efficacy on different types of CR-GNB infections; it had the best effect on CRAB, followed by CRKP and CRPA. Multiple CR-GNB infections and bacterial species were independent risk factors for microbiological efficacy.

An overview of COVID-19.

Pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China in December 2019. By Feb. 11, 2020, the World Health Organization (WHO) officially named the disease resulting from infection with SARS-CoV-2 as coronavirus disease 2019 (COVID-19). COVID-19 represents a spectrum of clinical manifestations that typically include fever, dry cough, and fatigue, often with pulmonary involvement. SARS-CoV-2 is highly contagious and most individuals within the population at large are susceptible to infection. Wild animal hosts and infected patients are currently the main sources of disease which is transmitted via respiratory droplets and direct contact. Since the outbreak, the Chinese government and scientific community have acted rapidly to identify the causative agent and promptly shared the viral gene sequence, and have carried out measures to contain the epidemic. Meanwhile, recent research has revealed critical aspects of SARS-CoV-2 biology and disease pathogenesis; other studies have focused on epidemiology, clinical features, diagnosis, management, as well as drug and vaccine development. This review aims to summarize the latest research findings and to provide expert consensus. We will also share ongoing efforts and experience in China, which may provide insight on how to contain the epidemic and improve our understanding of this emerging infectious disease, together with updated guidance for prevention, control, and critical management of this pandemic.

[Emergency plan for inter-hospital transfer of newborns with SARS-CoV-2 infection].

Since December 2019, the outbreak of coronavirus disease (COVID-19) has become the most serious public health issue. As the special population with immature immune function, newborns with COVID-19 have been reported. Newborns with suspected or confirmed COVID-19 should be transferred to designated hospitals for isolation treatment. An emergency transfer response plan for newborns with COVID-19 has been worked out. This plan puts forward the indications for neonatal COVID-19 transfer, organization management, protection strategies for medical staff, work procedures, and disinfection methods for transfer equipment, in order to provide guidance and suggestions for the inter-hospital transfer of suspected or confirmed neonatal COVID-19.

Evaluation of neutrophil-lymphocyte ratio in predicting bloodstream infection.

Aim: The prognostic role of neutrophil-to-lymphocyte ratio (NLR) in bloodstream infection (BSI) deserves further investigation. Patients & methods: The NLR values were measured and compared in BSI patients and healthy controls. The receiver operating characteristic of NLR and cut-off values were measured in BSI patients and subgroups. Results: We have measured the NLR of study group with 2160 BSI patients and normal group with 2523 healthy controls, which was significantly high in study group (11.36 ± 21.38 vs 2.53 ± 0.86; p < 0.001) and the area under the curve was 0.834 (95% CI: 0.825-0.842; p < 0.001). The critical value of NLR for diagnosis of BSI was 3.09, with a sensitivity of 75.3%, and a specificity of 93.6%. Conclusion: NLR is an effective diagnostic indicator of including BSIs of Gram-negative bacteria, Gram-positive bacteria and fungus.

The immunological roles in acute-on-chronic liver failure: An update.

BACKGROUND: Acute-on-chronic liver failure (ACLF) refers to the acute deterioration of liver function that occurs in patients with chronic liver disease. ACLF is characterized by acute decompensation, organ failure and high short-term mortality. Numerous studies have been conducted and remarkable progress has been made regarding the pathophysiology and pathogenesis of this disease in the last decade. The present review was to summarize the advances in this field. DATA SOURCES: A comprehensive search in PubMed and EMBASE was conducted using the medical subject words "acute-on-chronic liver failure", "ACLF", "pathogenesis", "predictors", and "immunotherapy" combined with free text terms such as "systemic inflammation" and "immune paralysis". Relevant papers published before October 31, 2018, were included. RESULTS: ACLF has two marked pathophysiological features, namely, excessive systemic inflammation and susceptibility to infection. The systemic inflammation is mainly manifested by a significant increase in the levels of plasma pro-inflammatory factors, leukocyte count and C-reactive protein. The underlying mechanisms are unclear and may be associated with decreased immune inhibitory cells, abnormal expression of cell surface molecules and intracellular regulatory pathways in immune cells and increased damage-associated molecular patterns in circulation. However, the main cause of susceptibility to infection is immune paralysis. Immunological paralysis is characterized by an attenuated activity of immune cells. The mechanisms are related to elevations of immune inhibitory cells and the concentration of plasma anti-inflammatory molecules. Some immune biological indicators, such as soluble CD163, are used to explore the pathogenesis and prognosis of the disease, and some immunotherapies, such as glucocorticoids and granulocyte colony-stimulating factor, are effective on ACLF. CONCLUSIONS: Overwhelming systemic inflammation and susceptibility to infection are two key features of ACLF. A better understanding of the state of a patient's immune system will help to guide immunotherapy for ACLF.

Expression of serum sCD163 in patients with liver diseases and inflammatory disorders.

OBJECTIVE: To investigate the diagnostic values of soluble cluster of differentiation 163 (sCD163) in patients with liver failure or various inflammations. METHODS: Serum samples were collected from patients admitted to the First Affiliated Hospital, Zhejiang University from October 2013 to January 2015 for treatment of with liver diseases, including liver failure (n=38), hepatitis B virus (HBV)-induced liver cancer (HBsAg positive) (n=40), HBV-induced hepatic cirrhosis (HBsAg positive) (n=40), chronic hepatitis B (n=38), HBV carrier (n=40), fatty liver patients without HBV infection (n=40), chronic glomerulonephritis (n=38), community acquired pneumonia (n=38) and acute pancreatitis (n=38). The CD163/sCD163 was determined using commercial ELISA kits according to the manufacturer's instructions. RESULTS: Significant decrease was noticed in the sCD163 in patients with fatty liver and HBV carrier compared with that of patients with chronic hepatitis B (P < 0.05). Compared with the healthy controls, the level of sCD163 was remarkably increased in the other groups (P < 0.05). The serum sCD163 in patients with HBV-induced liver cancer showed statistical difference compared with those of the patients with fatty liver, HBV carrier, as well as those with liver failure (P < 0.05). The expression of sCD163 was remarkably elevated in patients with liver failure compared with the patients with liver cancer, HBV-induced hepatic cirrhosis, chronic hepatitis B, fatty liver, or HBV carrier (P < 0.05). No significant difference was noticed in the sCD163 in patients with chronic hepatitis B, community acquired pneumonia, chronic glomerulonephritis, and acute pancreatitis (P > 0.05). CONCLUSIONS: sCD163 is a sensitive marker protein for liver failure. The elevation of sCD163 was closely related to the progression of the liver failure. No statistical difference was noticed in the sCD163 in patients with inflammatory disorders, indicating sCD163 showed no organ specificity.

Effects of storage conditions on the stability of serum CD163, NGAL, HMGB1 and MIP2.

BACKGROUND: Several cytokines have been involved in the diagnosis and prognosis for the pathogenesis and severity of chronic hepatitis B (CHB) such as cluster of differentiation 163 (CD163), neutrophil gelatinase-associated lipocalin (NGAL), high-mobility group box 1 (HMGB1) and macrophage inflammatory protein-2 (MIP-2). Nevertheless, the stability and reliability of these cytokines can be greatly influenced by handling and storage processes. METHODS: In this study, potential utility of serum samples of a CHB cohort was evaluated to investigate several processes that might impact cytokine profiles such as temperature, storage time and number of freeze-thaw cycles. Blood samples collected from 100 patients with CHB were separated immediately and divided into two groups. In one group, samples (n=50) stored at -80 °C were subject to 1-3 freeze-thaw cycles. In the other group, samples (n=50) were stored at 4 °C and 25 °C for 3 h, 9 h, 24 h, 48 h, 72 h, and 7 d time points, respectively. To assess the influence of different storage conditions on cytokines, the levels of CD163, NGAL, HMGB1 and MIP-2 were measured using enzyme-linked immunosorbent assays (ELISA) kits. RESULTS: No significant differences of these four cytokines after 1-3 repeated freeze-thaw cycles. Significant differences of NAGL levels were seen between 9 h and 7 d (P<0.05), and also in HMGB1 at 25 °C, while the other cytokines were relatively stable at the two storage temperatures over the various time points. CONCLUSION: This study indicated that these four cytokines remained stable within three freeze-thaw cycles and 7 d at 4 °C. No perceptible effects on CD163 and MIP-2 levels were presented under the storage condition of 7 d at room temperature, whereas the degradation of NGAL and HMGB1 were notable.

MicroRNA expression profiles related to early stage murine concanavalin A-induced hepatitis.

BACKGROUND: Fulminant hepatitis is a severe liver disease characterized by massive hepatocyte necrosis and clinical signs of liver failure. This study explores the expression profile of microRNAs, which are regulators of a number of pathophysiological processes, during the early stage of concanavalin A (Con A)-induced hepatitis. METHODS: Balb/c mice were given ConA injections to induce fulminant hepatitis. miRNA expression profiling in liver tissues was carried out by microarray analysis. The differentially expressed miRNAs were subjected to time sequence profile analysis, gene-miRNA regulatory network analysis, and gene ontology-miRNA regulatory network analysis. RESULTS: Eleven miRNAs among multiClass were found to be significantly differentially expressed between liver tissue in early stage fulminant hepatitis and normal control liver tissue. Mmu-miR-133a was the most differentially expressed with the strongest regulatory ability, regulating 47 mRNAs. Mmu-miR-10a was the most highly expressed in the microRNA-GO-Network and also exerted a strong regulatory ability. The expression profiles of miR-133a and miR-10a were verified by RT-PCR. CONCLUSIONS: These results show that, in the early stage, ConA-induced fulminant hepatitis induces a distinct miRNA expression profile. This differential miRNA expression profile may provide pathogenic clues and potential diagnostic and prognostic markers in acute and severe liver disease.

Interferon-associated retinopathy risk in patients with diabetes and hypertensive hepatitis C.

AIM: To investigate the association of hypertension and diabetes mellitus (DM) with interferon-associated retinopathy (IAR) risk in chronic hepatitis C (CHC). METHODS: Two investigators independently searched PubMed and Embase for eligible articles published prior to December 2013; additional studies were identified by reviewing the bibliographies. Only case-control or cohort studies that evaluated the association between hypertension and/or DM and IAR incidence in CHC patients were included. IAR was characterized by the presence of cotton-wool spots and/or retinal hemorrhage, and was defined as the primary efficacy measure. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were estimated using data extracted from papers based on random-effects models. RESULTS: Eight eligible studies were included in the present meta-analysis. The outcomes showed that patients with CHC and hypertension were at higher risk of IAR (48/189 vs 96/455, RR = 1.90; 95%CI: 1.15-3.15, P < 0.05). Patients with DM receiving interferon (IFN)-based therapy for CHC infection may be at higher risk for IAR (18/72 vs 60/256, RR = 1.56, 95%CI: 1.11-2.20, P < 0.05); however, the outcome was not stable. There was no significant difference in IAR risk between genotype-1-infected patients and non-genotype-1-infected patients (RR = 1.09, 95%CI: 0.64-1.87, P > 0.05). Comparable incidences of IAR were also found between patients treated with pegylated interferon (PIFN) α-2a and those treated with PIFN α-2b (RR = 0.84, 95%CI: 0.56-1.24, P > 0.05) and between patients treated with IFN α and those treated with PIFN α (RR = 1.04, 95%CI: 0.72-1.50, P > 0.05). CONCLUSION: Patients with hypertension have a higher risk of retinopathy when receiving IFN-based therapy for CHC.

[Influence of miR-122 on IFN-α treatment for HCV infection].

OBJECTIVE: To investigate the influence of miR-122 on IFN-α treatment for HCV infection. METHODS: Huh7.5.1 cells infected with HCV were treated with miR-122 mimics (20 nmol/L, 100 nmol/L, 400 nmol/L) and/or IFN-α (1000 IU/ml). The relative expression of HCV RNA was detected by real-time polymerase chain reaction (PCR). Huh7.5.1 cells were treated with different amounts of HCV (107 copies, 106 copies and 105 copies) and/or IFN-α (1000 IU/ml). RESULTS: IFN-α suppressed the replication of HCV in a time-dependent manner, resulting in a ≊ 83% reduction of HCV at 48 h. MiR-122 mimics facilitated replication of HCV RNA in a dose-dependent manner (P<0.05). The antiviral effect of IFN-α was inverted to levels of miR-122 mimics (20 nmol/L, 100 nmol/L, 400 nmol/L), (73.3% ± 3.5% compared with 84% ± 4.5%, P>0.05; 64.67% ± 5.5% compared with 84% ± 4.5%, P>0.05; 56.33% ± 5.1% compared with 84% ± 4.5%, P<0.05). The antiviral effect of IFN-α was inverted to HCV load (105 copies group compared with 107 copies group, P<0.05). CONCLUSION: MiR-122 facilitates replication of HCV RNA in the cell culture system; and the expression of miR-122 may partly counteract the anti-HCV effect of IFN-α.

[Effects of miR-122 on expression of hepatitis B virus proteins].

OBJECTIVE: To investigate the effect of miR-122 on the expression of hepatitis B virus (HBV) proteins. METHODS: Anti-sense oligodeoxynucleotide (ASODN) of two different sequences against miR-122, anti-miR-122 and LNA-antimiR-122 (Locked nucleic acid), human miR -122 (hsa-miR-122), or the negative control anti-GFP were designed and synthesized, then transfected into HepG2.2.15 cells. After 24 h and 48 h, the levels of HBsAg and HBeAg in the supernatant were determined with a time-resolved immunofluorometric assay (TRFIA). HBV DNA in supernatant and miR-122 in cells were measured by quantitative real-time PCR. RESULTS: After 48 h expressions of miR-122 in the LNA-antimiR-122 and anti-miR-122 groups were significantly suppressed and lower than those in the negative control (P<0.001), while the level of miR-122 in the hsa-miR-122 group was higher than that in the negative control (P<0.001). The expression of HBeAg and HBsAg in hsa-miR-122 group was lower than that in the negative control (P<0.01) 24 h and 48 h after transfection. The expression of HBeAg and HBsAg in the anti-miR-122 group and LNA-antimiR-122 group was significantly lower than that in negative control (P>0.001). The levels of viral DNA at both time-points in the various test groups were not significantly different from those of negative control group (P>0.05). CONCLUSION: miR-122 may regulate HBV antigens and potentially affect the progress of pathogenesis, which might be the new targets for treatment of HBV infection.

[The relationship between systemic inflammatory response syndrome and severity of acute pancreatitis combined with plateau erythrocythemia].

OBJECTIVE: To explore the relationship between systemic inflammatory response syndrome(SIRS) and severity of acute pancreatitis combined with plateau erythrocythemia in the high altitude. METHODS: A retrospective analysis on the clinical data which involved acute pancreatitis combined with plateau erythrocythemia (n = 40) and without plateau erythrocythemia (n = 40) admitted from September 2006 to September 2009 was conducted. According to the unified standards, these cases were divided into plateau erythrocythemia group and no plateau erythrocythemia group. The patients in plateau erythrocythemia group were further divided into severe group and mild group according to scores of APACHEII. The data was analyzed according to the patient with (or without) SIRS, SIRS's standard indicators, diagnostic parameter and relation of severity and duration of SIRS in acute pancreatitis combined with plateau erythrocythemia. RESULTS: There was significantly discrepancy between plateau erythrocythemia group and no plateau erythrocythemia group not only in the incidence of patients who developed SIRS, but also in two items of patients fulfilling or not fulfilling diagnostic criteria of SIRS (P < 0.05). There was significant statistical difference in three items of diagnostic parameter of SIRS between plateau erythrocythemia group and no plateau erythrocythemia group (P < 0.05). Significant difference in two and three diagnostic parameter was found on severity of SIRS in acute pancreatitis combined with plateau erythrocythemia (P < 0.05). The more severity acute pancreatitis combined with plateau erythrocythemia was, the longer duration of SIRS was. CONCLUSION: SIRS is highly correlated with the severity of SIRS in acute pancreatitis combined with plateau erythrocythemia in the high altitude.

IQGAP1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation by Akt activation.

The scaffold protein IQGAP1 shows elevated levels in several cancer types, but its expression in hepatocellular carcinoma is unknown. We found that 58% of human hepatocellular carcinoma tissue samples had increased IQGAP1 expression compared to adjacent normal tissue. Overexpressing IQGAP1 raised the in vivo tumorigenicity of hepatocellular carcinoma cells, and forced overexpression of IQGAP1 in vitro stimulated cell proliferation. Cell growth was reduced by knockdown or mutation of IQGAP1, or by treatment of cells with a phosphotidylinositol 3-kinase inhibitor. To determine the mechanism by which IQGAP1 overexpression affected hepatocellular carcinoma cells, we confirmed its interaction in these cells with mammalian target of rapamycin (mTOR), a serine/threonine kinase that integrates signals about nutrient and energy status with downstream effectors that influence cell division. In addition, we discovered a new interaction involving IQGAP1, mTOR and Akt, which is a downstream target of mTOR. Akt phosphorylation on Ser-473, which is catalyzed by mTOR and required for Akt activation, increased with increasing amounts of IQGAP1, and decreased with IQGAP1 mutation. We hypothesize that IQGAP1 is a scaffold that facilitates mTOR and Akt interaction.