Interim analysis of the PARADISE study: Benefits of add-on peginterferon-α in NA-treated patients with CHB.

This study aimed to investigate whether peginterferon-α (IFN) add-on nucleos(t)ide analogs(NAs) can further reduce hepatocellular carcinoma(HCC) risk compared with NAs monotherapy in NA-treated patients with chronic hepatitis B(CHB). In this multi-center randomized controlled trial "PARADISE study" (NCT05671315), CHB patients with intermediate to high risk of HCC after more than 24-week NAs pretreatment were recruited, randomized to two groups at a ratio of 1:2 and followed up for 240 weeks. NAs group maintained NAs monotherapy, while IFN + NAs group received IFN add-on NAs therapy for 48 weeks, then switched to NAs monotherapy. Totally, 196 patients were included in interim analysis (NAs group 68, IFN + NAs group 128). The 96-week cumulative HCC incidence was lower in IFN + NAs group than NAs group (0% vs. 4.5%, p < 0.05). Compared with NAs group, IFN + NAs group had significantly higher rates of HBsAg loss at week 48 and 96 (22.7% vs. 0%; 16.7% vs. 0%, both p < 0.05). A new scoring system was established to predict HBsAg decline >2log10 IU/ml, HBsAg <10 IU/ml or HBsAg loss at the end of 48-week IFN treatment. The area under ROC curve was 0.914, 0.922 or 0.905 in the original cohort (n = 128) and 0.896, 0.896 or 0.864 in the external validation cohort (n = 162) for the aforementioned three outcomes, respectively. IFN add-on NAs therapy may suggest the dual benefits of reducing HCC development and facilitating HBsAg loss among NA-treated CHB patients with intermediate to high risk of HCC. The new scoring system helps to make the most of IFN treatment for a higher cost-effectiveness in healthcare.

Predictors of HBsAg seroclearance in patients with chronic HBV infection treated with pegylated interferon-α: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The identification of reliable predictors for hepatitis B surface antigen (HBsAg) seroclearance remains controversial. We aimed to summarize potential predictors for HBsAg seroclearance by pegylated interferon-α (PegIFNα) in patients with chronic HBV infection. METHODS: A systematic search of the Cochrane Library, Embase, PubMed, and Web of Science databases was conducted from their inception to 28 September 2022. Meta-analyses were performed following the PRISMA statement. Predictors of HBsAg seroclearance were evaluated based on baseline characteristics and on-treatment indicators. RESULTS: This meta-analysis encompasses 27 studies, including a total of 7913 patients. The findings reveal several factors independently associated with HBsAg seroclearance induced by PegIFNα-based regimens. These factors include age (OR = 0.961), gender (male vs. female, OR = 0.537), genotype (A vs. B/D; OR = 7.472, OR = 10.738), treatment strategy (combination vs. monotherapy, OR = 2.126), baseline HBV DNA (OR = 0.414), baseline HBsAg (OR = 0.373), HBsAg levels at week 12 and 24 (OR = 0.384, OR = 0.294), HBsAg decline from baseline to week 12 and 24 (OR = 6.689, OR = 6.513), HBsAg decline from baseline ≥ 1 log10 IU/ml and ≥ 0.5 log10 IU/ml at week 12 (OR = 18.277; OR = 4.530), and ALT elevation at week 12 (OR = 3.622). Notably, subgroup analysis suggests no statistical association between HBsAg levels at week 12 and HBsAg seroclearance for treatment duration exceeding 48 weeks. The remaining results were consistent with the overall analysis. CONCLUSIONS: This is the first meta-analysis to identify predictors of HBsAg seroclearance with PegIFNα-based regimens, including baseline and on-treatment factors, which is valuable in developing a better integrated predictive model for HBsAg seroclearance to guide individualized treatment and achieve the highest cost-effectiveness of PegIFNα.

The potential effect of HBV vaccination on off-treatment HBsAg reversion after interferon-induced HBsAg clearance.

Off-treatment HBsAg reversion occurs in a considerable number of chronic hepatitis B(CHB) patients after IFN(interferon)-induced HBsAg clearance. HBV vaccination protects the general population against HBV infection. However, it remains unclear whether HBV vaccination could prevent off-treatment HBsAg reversion in CHB patients with HBsAg clearance. CHB patients (n = 199) with HBsAg clearance were included in the current study, comprising spontaneous HBsAg clearance group (n = 51), NA (nucleoside/nucleotide analogues)-induced group (n = 36) and IFN-induced group (n = 112). Log-rank test was performed to compare the cumulative incidences of HBsAg reversion between groups. Cox regression model was used to identify the factors associated with off-treatment HBsAg reversion. The 5-year cumulative incidence of HBsAg reversion in IFN-induced group was significantly higher than that in NA-induced group or spontaneous group (27.6% vs. 3.3% vs. 8.1%, both p < .05). In IFN-induced group, 66.7% of CHB patients received HBV vaccination. The cumulative incidence of HBsAg reversion in individuals with strong responses to HBV vaccination (HBsAb level >100mIU/ml) was significantly lower than that in those with weak responses to HBV vaccination (HBsAb level ≤100mIU/ml) or without HBV vaccination in IFN-induced group (7.7% vs. 58.5% vs. 31.9%, both p < .05). Multivariate Cox regression analysis confirmed strong responses to HBV vaccination were independently associated with a lower cumulative incidence of HBsAg reversion after IFN-induced HBsAg clearance (HR = 0.246, 95%CI: 0.066-0.907, p = .035). HBV vaccination has potential to prevent off-treatment HBsAg reversion in CHB patients after IFN-induced HBsAg clearance via a sufficiently high level of HBsAb, helping clinicians optimize the clinical management of such patients.

Evaluation of the Rapid Antigen Detection Test for Diagnosing SARS-CoV-2 during the COVID-19 Pandemic: Experience from a Centralized Isolation Site in Shanghai, China.

Rapid and reliable diagnosis is important for the management of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid antigen detection test (RADT) is a rapid, inexpensive, and easy method. Several studies have reported that RADTs performed well in many countries; however, very few studies have been reported in China. In this study, we assessed the performance of the RADT (Ediagnosis COVID-19 antigen test kit). This study was conducted in a centralized isolation site in Shanghai and enrolled 716 patients with COVID-19 and 203 noninfected participants. Nasopharyngeal swabs from all participants were collected on the same day and tested using the RADT and real-time reverse transcription-PCR (RT-PCR). The performance of the RADT was evaluated in different scenarios, such as threshold cycle (CT) values, symptomatic phase, and symptoms on the day of testing. The results demonstrated that the sensitivity for patients with CT values lower than 20 was 96.55% (95% confidence interval [CI], 87.05 to 99.4). The sensitivities were 78.4% (95% CI, 69.96 to 85.05) for participants within 5 days after the first RT-PCR-positive result and 90.77% (95% CI, 80.34 to 96.19) within 5 days after symptom onset. Moreover, the sensitivity of the RADT was more than 80% for patients with symptoms on the day of testing, including fever (89.29%), cough (86.84%), stuffy nose (92.59%), runny nose (92%), sore throat (81.25%), and muscle pain (80.77%), especially for those with upper respiratory tract symptoms. The specificity of the RADT was good in all scenarios. During the SARS-CoV-2 epidemic, Ediagnosis performed excellently in individuals with a higher viral load (evidenced by lower CT values), individuals in the early symptomatic phase, and especially those with upper respiratory tract symptoms. IMPORTANCE RADTs have demonstrated excellent performance in many counties for screening SARS-CoV-2 infection, but very few studies have been conducted in China. The performance of RADTs is largely related to different real-life scenarios. In our study, the performance of the RADT was evaluated in different scenarios, such as CT values, symptomatic phase, and symptoms on the day of testing. The results demonstrated that Ediagnosis (an RADT made in China) performed excellently for individuals with a higher viral load (evidenced by lower CT values), individuals in the early symptomatic phase, and especially those with upper respiratory tract symptoms.

COVID-19 vaccines in patients with decompensated cirrhosis: a retrospective cohort on safety data and risk factors associated with unvaccinated status.

BACKGROUND: Safety data reported from the large-scale clinical trials of the coronavirus disease 2019 (COVID-19) vaccine are extremely limited in patients with decompensated cirrhosis. The vaccination campaign in this specific population could be difficult due to uncertainty about the adverse events following vaccination. We aimed to assessed the COVID-19 vaccination rate, factors associated with unvaccinated status, and the adverse events following vaccination in patients with decompensated cirrhosis. METHODS: This is a retrospective study from Ruijin Hospial (Shanghai, China) on an ongoing prospective cohort designed for long-term survival analysis of decompensated cirrhotic patients who recovered from decompensating events or acute-on-chronic liver failure (ACLF) between 2016 and 2018. We assessed the COVID-19 vaccination rate, the number of doses, type of vaccine, safety data, patient-reported reasons for remaining unvaccinated, factors associated with unvaccinated status, and the adverse events of COVID-19 vaccine. Binary logistic regression was used for identifying factors associated with unvaccinated status. RESULTS: A total of 229 patients with decompensated cirrhosis without previous SARS-CoV-2 infection participated (mean age, 56 ± 12.2 years, 75% male, 65% viral-related cirrhosis). Mode of decompensation were grade II‒III ascites (82.5%), gastroesophageal varices bleeding (7.9%), hepatic encephalopathy (7.9%). Eighty-five participants (37.1%) received at least one dose of vaccination (1 dose: n = 1, 2 doses: n = 65, 3 doses: n = 19) while 62.9% remained unvaccinated. Patient-reported reasons for remaining unvaccinated were mainly fear of adverse events (37.5%) and lack of positive advice from healthcare providers (52.1%). The experience of hepatic encephalopathy (OR = 5.61, 95% CI: 1.24-25.4) or ACLF (OR = 3.13, 95% CI: 1.12-8.69) and post-liver transplantation status (OR = 2.47, 95% CI: 1.06-5.76) were risk factors of remaining unvaccinated independent of residential areas. The safety analysis demonstrated that 75.3% had no adverse events, 23.6% had non-severe reactions (20% injection-site pain, 1.2% fatigue, 2.4% rash) and 1.2% had a severe event (development of acute decompensation requiring hospitalization). CONCLUSIONS: Patients with decompensated cirrhosis in eastern China are largely remained at unvaccinated status, particularly those with previous episodes of ACLF or hepatic encephalopathy and liver transplantation recipients. Vaccination against COVID-19 in this population is safe.

Pantothenate Kinase 1 Inhibits the Progression of Hepatocellular Carcinoma by Negatively Regulating Wnt/ß-catenin Signaling.

Hyperactivation of Wnt/ß-catenin signaling has been reported in hepatocellular carcinoma (HCC). However, the mechanisms underlying the hyperactivation of Wnt/ß-catenin signaling are incompletely understood. In this study, Pantothenate kinase 1 (PANK1) is shown to be a negative regulator of Wnt/ß-catenin signaling. Downregulation of PANK1 in HCC correlates with clinical features. Knockdown of PANK1 promotes the proliferation, growth and invasion of HCC cells, while overexpression of PANK1 inhibits the proliferation, growth, invasion and tumorigenicity of HCC cells. Mechanistically, PANK1 binds to CK1α, exerts protein kinase activity and cooperates with CK1α to phosphorylate N-terminal serine and threonine residues in ß-catenin both in vitro and in vivo. Additionally, the expression levels of PANK1 and ß-catenin can be used to predict the prognosis of HCC. Collectively, the results of this study highlight the crucial roles of PANK1 protein kinase activity in inhibiting Wnt/ß-catenin signaling, suggesting that PANK1 is a potential therapeutic target for HCC.

The Protein Kinase Activity of NME7 Activates Wnt/ß-Catenin Signaling to Promote One-Carbon Metabolism in Hepatocellular Carcinoma.

Metabolic reprogramming by oncogenic signaling is a hallmark of cancer. Hyperactivation of Wnt/ß-catenin signaling has been reported in hepatocellular carcinoma (HCC). However, the mechanisms inducing hyperactivation of Wnt/ß-catenin signaling and strategies for targeting this pathway are incompletely understood. In this study, we find nucleoside diphosphate kinase 7 (NME7) to be a positive regulator of Wnt/ß-catenin signaling. Upregulation of NME7 positively correlated with the clinical features of HCC. Knockdown of NME7 inhibited HCC growth in vitro and in vivo, whereas overexpression of NME7 cooperated with c-Myc to drive tumorigenesis in a mouse model and to promote the growth of tumor-derived organoids. Mechanistically, NME7 bound and phosphorylated serine 9 of GSK3ß to promote ß-catenin activation. Furthermore, MTHFD2, the key enzyme in one-carbon metabolism, was a target gene of ß-catenin and mediated the effects of NME7. Tumor-derived organoids with NME7 overexpression exhibited increased sensitivity to MTHFD2 inhibition. In addition, expression levels of NME7, ß-catenin, and MTHFD2 correlated with each other and with poor prognosis in patients with HCC. Collectively, this study emphasizes the crucial roles of NME7 protein kinase activity in promoting Wnt/ß-catenin signaling and one-carbon metabolism, suggesting NME7 and MTHFD2 as potential therapeutic targets for HCC. SIGNIFICANCE: The identification of NME7 as an activator of Wnt/ß-catenin signaling and MTHFD2 expression in HCC reveals a mechanism regulating one-carbon metabolism and potential therapeutic strategies for treating this disease.

Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections.

The coronavirus disease 2019 (COVID-19) has caused global public health and economic crises. Thus, new therapeutic strategies and effective vaccines are urgently needed to cope with this severe pandemic. The development of a broadly neutralizing antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the attractive treatment strategies for COVID-19. Currently, the receptor-binding domain (RBD) of the spike (S) protein is the main target of neutralizing antibodies when SARS-CoV-2 enters human cells through an interaction between the S protein and the angiotensin-converting enzyme 2 expressed on various human cells. A single monoclonal antibody (mAb) treatment is prone to selective pressure due to increased possibility of targeted epitope mutation, leading to viral escape. In addition, the antibody-dependent enhancement effect is a potential risk of enhancing the viral infection. These risks can be reduced using multiple mAbs that target nonoverlapping epitopes. Thus, a cocktail therapy combining two or more antibodies that recognize different regions of the viral surface may be the most effective therapeutic strategy.

Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis.

BACKGROUND AND AIMS: Rifaximin has been recommended as a prophylactic drug for hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). This study aims to explore whether low-dose rifaximin can prevent overall complications and prolong survival in cirrhotic patients. METHODS: In this multi-centre randomized open-labelled prospective study, 200 patients with decompensated cirrhosis were randomly assigned at a ratio of 1:1. Patients in rifaximin group were administered 400 mg rifaximin twice daily for 6 months, and all other therapeutic strategies were kept unchanged in both groups as long as possible. The primary efficacy endpoints were the incidence of overall complications and liver transplantation-free survival. The secondary endspoints were the incidence of each major cirrhosis-related complication, as well as the Child-Pugh score and class. RESULTS: The major baseline characteristics were similar in the two groups except for HE. The cumulative incidence and frequency of overall complications were significantly lower in rifaximin group than in the control group (p < 0.001). Though liver transplantation-free survival was not significantly different between the two groups, subgroup analysis showed rifaximin markedly prolonged liver transplantation-free survival in patients with Child-Pugh score ≥ 9 (p = 0.007). Moreover, rifaximin markedly reduced the episodes of ascites exacerbation (p < 0.001), HE (p < 0.001) and gastric variceal bleeding (EGVB, p = 0.031). The incidence of adverse events was similar in the two groups. CONCLUSION: Low-dose rifaximin significantly decreases the occurrence of overall complications, leading to prolonged survival in patients with advanced stages of cirrhosis in this trail. Further study should be carried out to compare the effect of this low-dose rifaximin with normal dose (1200 mg/day) rifaximin in preventing cirrhosis-related complications. CLINICAL TRIAL NUMBER: NCT02190357.

DIAPH3 promotes pancreatic cancer progression by activating selenoprotein TrxR1-mediated antioxidant effects.

Pancreatic cancer is a highly malignant tumour of the digestive tract which is difficult to diagnose and treat. Approximately 90% of cases arise from ductal adenocarcinoma of the glandular epithelium. The morbidity and mortality of the disease have increased significantly in recent years. Its 5-year survival rate is <1% and has one of the worst prognoses amongst malignant tumours. Pancreatic cancer has a low rate of early-stage diagnosis, high surgical mortality and low cure rate. Selenium compounds produced by selenoamino acid metabolism may promote a large amount of oxidative stress and subsequent unfolded reactions and endoplasmic reticulum stress by consuming the NADPH in cells, and eventually lead to apoptosis, necrosis or necrotic cell death. In this study, we first identified DIAPH3 as a highly expressed protein in the tissues of patients with pancreatic cancer, and confirmed that DIAPH3 promoted the proliferation, anchorage-independent growth and invasion of pancreatic cancer cells using overexpression and interference experiments. Secondly, bioinformatics data mining showed that the potential proteins interacted with DIAPH3 were involved in selenoamino acid metabolism regulation. Selenium may be incorporated into selenoprotein synthesis such as TrxR1 and GPX4, which direct reduction of hydroperoxides or resist ferroptosis, respectively. Our following validation confirmed that DIAPH3 promoted selenium content and interacted with the selenoprotein RPL6, a ribosome protein subunit involved in selenoamino acid metabolism. In addition, we verified that DIAPH3 could down-regulate cellular ROS level via up-regulating TrxR1 expression. Finally, nude mice xenograft model experimental results demonstrate DIAPH3 knock down could decrease tumour growth and TrxR1 expression and ROS levels in vivo. Collectively, our observations indicate DIAPH3 could promote pancreatic cancer progression by activating selenoprotein TrxR1-mediated antioxidant effects.

Low expression of DCXR protein indicates a poor prognosis for hepatocellular carcinoma patients.

The aim of this study was to investigate the prognostic value of dicarbonyl/L-xylulose reductase (DCXR) in human hepatocellular carcinoma (HCC). Immunohistochemistry and tissue microarrays were used to evaluate DCXR protein expression levels. Image-Pro Plus was used to calculate the integral optic density (IOD) in each tissue sample, which represented the expression level of DCXR. DCXR proteins were found to be significantly lower in HCC tumor tissues (P < 0.0001) according to immunohistochemical analysis of DCXR protein levels in 74 paired HCC tissue and peritumoral non-cancer tissues. The prognostic value of DCXR in HCC was assessed in 290 cases of the training cohort and 74 cases of the validation cohort. Shorter overall survival (OS) time and shorter time to recurrence (TTR) in both the training and validation set were found to be associated with lower expression levels of DCXR. In the training set, the expression level of DCXR in HCC was an independent prognostic factor for OS according to univariate and multivariate analyses. In conclusion, DCXR expression is an independent prognostic factor for OS and TTR of post-operative HCC patients, and low expression levels of DCXR in HCC may indicate poor outcome of HCC patients after surgical resection.

NEDD4 Depletion Inhibits Hepatocellular Carcinoma Growth via Targeting PTEN.

BACKGROUND/AIMS: Neural precursor cell-expressed developmentally down-regulated gene 4 (NEDD4) plays an important role in tumor cell growth, yet its role in hepatocellular carcinoma (HCC) remains unclear. This study is to establish NEDD4 as a prognostic biomarker by which the survival of HCC patients can be predicted and to reveal the role of NEDD4 in hepatocellular carcinoma cell growth. METHODS: The expression of NEDD4 in 219 HCC specimens was assessed by immunohistochemistry. Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses. The roles of NEDD4 in hepatocellular carcinoma cell proliferation and invasion were determined. RESULTS: The patients with low NEDD4 expression tumors had an average cumulative survival of 64.9 ± 6.5 months during follow-up while the patients with high NEDD4 expression tumors had an average cumulative survival of 20.3 ± 15.8 months. NEDD4 silencing inhibited Huh7 cell proliferation and altered cell cytoskeletal assembly, and NEDD4 depletion furthermore seemed to suppress cell migration and invasion. A possible molecular mechanism for the observed effects might be that NEDD4 silence led to an increase in PTEN (phosphatase and tensin homologue) expression, which in turn resulted in the inactivation of STAT3, AKT, and ERK1/2. CONCLUSION: Our findings indicate that NEDD4 may participate in the HCC progression and may therefore be a potential target for HCC therapy.

Hepatitis B Virus Combo Mutations Improve the Prediction and Active Prophylaxis of Hepatocellular Carcinoma: A Clinic-Based Cohort Study.

We aimed to evaluate whether hepatitis B virus (HBV) mutations at the core promoter region could improve the prediction and specific prophylaxis of hepatocellular carcinoma (HCC) in chronic HBV-infected patients. A total of 2,114 HBV-infected patients enrolled between August 1998 and December 2007 were followed-up for 18,406 person-years. Of those, 612 received ≥48 week treatments with nucleos(t)ide analogue (NA) and/or IFNα. Baseline HBV mutations were identified by sequencing. Propensity score matching was applied to reduce baseline differences between antiviral and control cohorts. Multivariate Cox regression analyses, including baseline characteristics of 2,114 patients, showed that age, male, cirrhosis, and HBV mutations (C1653T, T1753V, and A1762T/G1764A) independently increased HCC risk. In control patients carrying A1762T/G1764A, addition of C1653T and/or T1753V significantly increased HCC risk (HR, 1.57; P = 0.038); combo mutations with C1653T, T1753V, and A1762T/G1764A improved the validity of HCC prediction by age, male, and cirrhosis (P = 0.002). In the matched cohorts, antiviral treatment reduced HCC incidence (13.90/1,000 vs. 7.70/1,000 person-years, P = 0.005); NA treatment for ≥60 months was required for the prophylaxis of HCC in cirrhotic patients (P = 0.03); antiviral treatment reduced HCC risk in patients carrying A1762T/G1764A (HR, 0.40; P = 0.002) or C1653T (HR, 0.45; P = 0.04) and in those without T1753V (HR, 0.42; P = 0.005), but could not reduce HCC risk in patients without A1762T/G1764A or C1653T and in those with T1753V. In summary, HBV mutation A1762T/G1764A, C1653T, and T1753V in combination improve HCC prediction in HBV-infected patients. To prevent HCC, patients infected with HBV carrying A1762T/G1764A or C1653T, but not T1753V, should be given priority of receiving antiviral treatments.

Treatment with baicalein attenuates methionine-choline deficient diet-induced non-alcoholic steatohepatitis in rats.

Baicalein, a naturally occurring flavone, has been proved as a promising chemopreventive compound for many chronic human diseases. The aim of this work was to investigate whether treatment with baicalein prevented nonalcoholic steatohepatitis (NASH) induced by methionine-choline-deficient (MCD) diet. Rats were divided into four experimental groups and fed for 8 weeks as follows: (1) control rats; (2) control rats treated with baicalein (intraperitoneal injection of 10mg/kg); (3) MCD-diet-fed rats; (4) MCD-diet-fed rats treated with baicalein. Treatment with baicalein prevented MCD-diet-induced NASH, as evidenced by reduced histological scores, apoptosis, activities of ALT and AST, and hepatic fat accumulation in rats. Treatment with baicalein abated MCD-diet-induced oxidative stress through enhancing Nrf2/HO-1 pathway and activities of SOD and catalase in livers. Treatment with baicalein preserved hepatic mitochondrial function in MCD-diet fed rats. Treatment with baicalein reduced hepatic NO formation through suppressing MCD-diet-induced iNOS activation, and suppressed MCD-diet-induced inflammation through suppressing NFκB activation and reducing IL-6 and TNFα expressions in livers. Treatment of MCD-diet fed rats with baicalein had a beneficial modulation on expression profiles of fatty acid metabolism genes in livers. The results support the investigation of baicalein as a therapeutic candidate for NASH induced by MCD diet in rats.

Consumption of hydrogen-rich water alleviates renal injury in spontaneous hypertensive rats.

In hypertensive animals and patients, oxidative stress represents the primary risk factor for progression of renal disease. Recently, it has been demonstrated that hydrogen, as a novel antioxidant, can selectively reduce hydroxyl radicals and peroxynitrite anion to exert therapeutic antioxidant activity. Herein, we investigated the protective effect of hydrogen-rich water (HW) against renal injury in spontaneously hypertensive rats (SHR). The 8-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into HW-treated (1.3 ± 0.2 mg/l for 3 months, drinking) and vehicle-treated group. Although treatment with HW had no significant effect on blood pressure, it significantly ameliorated renal injury in SHR. Treatment with HW lowered reactive oxygen species formation, upregulated the activities of superoxide dismutase, glutathione peroxidase, glutathione-S-epoxide transferase, and catalase, and suppressed NADPH oxidase activity. Treatment with HW in SHR depressed pro-inflammatory cytokines expression including TNF-α, IL-6, IL-1ß, and macrophage chemoattractant protein 1, which might be mediated by suppressing nuclear factor-κB activation. In addition, treatment with HW had protective effect on mitochondrial function including adenosine triphosphate formation and membrane integrity in SHR. In conclusion, consumption of HW is a promising strategy to alleviate renal injury as a supplement for anti-hypertensive therapy.

Nonleukemic myeloid sarcoma of the liver: a case report and review of literature.

Myeloid sarcoma (MS) is a neoplasm of immature granulocytes, monocytes, or both involving extramedullary sites. MS with no evidence of leukemia (nonleukemic MS) is very rare and the initial diagnosis can be difficult. This report describes an unusual case of nonleukemic MS of the liver in a 16-year-old patient presenting as debilitating hepatomegaly. A liver biopsy revealed diffuse infiltration by neoplastic cells of myeloid lineage (CD68, myeloperoxidase). A bone marrow biopsy showed no evidence of medullary involvement. The patient subsequently developed heart failure. Autopsy revealed infiltration of most organs by neoplastic cells but failed to identify abnormal myeloid cells in bone marrow.