Risk of HBV reactivation in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors in the antiviral era.

BACKGROUND: Although routine antiviral therapy has been implemented in HCC patients, the risk of HBV reactivation (HBVr) remains with the use of programmed cell death-1(PD-1) blockade-based combination immunotherapy and the relevant risk factors are also unclear. Therefore, we aimed to identify the incidence and risk factors of HBVr in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors and concurrent first-line antivirals. METHODS: We included a total of 218 HBV-related HCC patients with first-line antivirals who received PD-1 inhibitors alone or together with angiogenesis inhibitors. According to the anti-tumor therapy modalities, patients were divided into PD-1 inhibitors monotherapy group (anti-PD-1 group) and combination therapy group (anti-PD-1 plus angiogenesis inhibitors group). The primary study endpoint was the incidence of HBVr. RESULTS: HBVr occurred in 16 (7.3%) of the 218 patients, 2 cases were found in the anti-PD-1 group and the remaining 14 cases were in the combination group. The Cox proportional hazard model identified 2 independent risk factors for HBVr: combination therapy (hazard ratio [HR], 4.608, 95%CI 1.010-21.016, P = 0.048) and hepatitis B e antigen (HBeAg) positive (HR, 3.695, 95%CI 1.246-10.957, P = 0.018). Based on the above results, we developed a simple risk-scoring system and found that the high-risk group (score = 2) developed HBVr more frequently than the low-risk group (score = 0) (Odds ratio [OR], 17.000, 95%CI 1.946-148.526, P = 0.01). The area under the ROC curve (AUC-ROC) was 7.06 (95%CI 0.581-0.831, P = 0.006). CONCLUSION: HBeAg-positive patients receiving combination therapy have a 17-fold higher risk of HBVr than HBeAg-negative patients with PD-1 inhibitors monotherapy.

Development and Validation of a Novel Prognosis Model Based on a Panel of Three Immunogenic Cell Death-Related Genes for Non-Cirrhotic Hepatocellular Carcinoma.

Purpose: The accurate prediction of non-cirrhotic hepatocellular carcinoma (NCHCC) risk facilitates improved surveillance strategy and decreases cancer-related mortality. This study aimed to explore the correlation between immunogenic cell death (ICD) and NCHCC prognosis using The Cancer Genome Atlas (TCGA) datasets, and the potential prognostic value of ICD-related genes in NCHCC. Methods: Clinical and transcriptomic data of patients with NCHCC patients were retrieved from TCGA database. Weighted gene co-expression network analysis was performed to obtain the NCHCC phenotype-related module genes. Consensus clustering analysis was performed to classify the patients into two clusters based on intersection genes among differentially expressed genes (DEGs) between cancer and adjacent tissues, NCHCC phenotype-related genes, and ICD-related genes. NCHCC-derived tissue microarray was used to evaluate the correlation of the expression levels of key genes with NCHCC prognosis using immunohistochemical staining. Results: Cox regression analyses were performed to construct a prognostic risk score model comprising three genes (TMC7, GRAMD1C, and GNPDA1) based on DEGs between two clusters. The model stratified patients with NCHCC into two risk groups. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. Univariable and multivariable Cox regression analyses revealed that these signature genes are independent predictors of OS. Functional analysis revealed differential immune status between the two risk groups. Next, a nomogram was constructed, which demonstrated the potent distinguishing ability of the developed model based on receiver operating characteristic curves. In vitro functional validation revealed that the migration and invasion abilities of HepG2 and Huh7 cells were upregulated upon GRAMD1C knockdown but downregulated upon TMC7 knockdown. Conclusion: This study developed a prognostic model comprising three genes, which can aid in predicting the survival of patients with NCHCC and guide the selection of drugs and molecular markers for NCHCC.

Expression characteristics of non-virion protein of Hirame novirhabdovirus and its transfection induced response in hirame natural embryo cells.

The non-virion (NV) protein is the signature of genus Novirhabdovirus, which has been of considerable concern due to its potential role in viral pathogenicity. However, its expression characteristics and induced immune response remain limited. In the present work, it was demonstrated that Hirame novirhabdovirus (HIRRV) NV protein was only detected in the viral infected hirame natural embryo (HINAE) cells, but absent in the purified virions. Results showed that the transcription of NV gene could be stably detected in HIRRV-infected HINAE cells at 12 h post infection (hpi) and then reached the peak at 72 hpi. A similar expression trend of NV gene was also found in HIRRV-infected flounders. Subcellular localization analysis further exhibited that HIRRV-NV protein was predominantly localized in the cytoplasm. To elucidate the biological function of HIRRV-NV protein, NV eukaryotic plasmid was transfected into HINAE cells for RNA-seq. Compared to empty plasmid group, some key genes in RLR signaling pathway were significantly downregulated in NV-overexpressed HINAE cells, indicating that RLR signaling pathway was inhibited by HIRRV-NV protein. The interferon-associated genes were also significantly suppressed upon transfection of NV gene. This research would improve our understanding of expression characteristics and biological function of NV protein during HIRRV infection process.

An enhanced method for nucleic acid detection with CRISPR-Cas12a using phosphorothioate modified primers and optimized gold-nanopaticle strip.

CRISPR-Cas12a system has been shown promising for nucleic acid diagnostics due to its rapid, portable and accurate features. However, cleavage of the amplicons and primers by the cis- and trans-activity of Cas12a hinders the attempts to integrate the amplification and detection into a single reaction. Through phosphorothioate modification of primers, we realized onepot detection with high sensitivity using plasmids of SARS-CoV-2, HPV16 and HPV18. We also identified the activated Cas12a has a much higher affinity to C nucleotide-rich reporter than others. By applying such reporters, the reaction time required for a lateral-flow readout was significantly reduced. Furthermore, to improve the specificity of the strip-based assay, we created a novel reporter and, when combined with a customized gold-nanopaticle strip, the readout was greatly enhanced owing to the elimination of the nonspecific signal. This established system, termed Targeting DNA by Cas12a-based Eye Sight Testing in an Onepot Reaction (TESTOR), was validated using clinical cervical scrape samples for human papillomaviruses (HPVs) detection. Our system represents a general approach to integrating the nucleic acid amplification and detection into a single reaction in CRISPR-Cas systems, highlighting its potential as a rapid, portable and accurate detection platform of nucleic acids.

A simple and rapid diagnostic method for 13 types of high-risk human papillomavirus (HR-HPV) detection using CRISPR-Cas12a technology.

Cervical carcinoma is the second most common cancer in women worldwide with greater than 99% of the cases caused by human papillomaviruses (HPVs). Early detection of HPVs especially the high risk types (HR-HPVs) are essential to prevent the disease progression. The existing methods for HPV detection, such as qPCR are of high sensitivity and specificity, but the need for expensive machinery and well-trained personnel slow down the disease detection. The emerging Cas12a-based method presents a new technique for nucleic acid detection. However, it is time-consuming and labor-intensive when used for HPV detection, as several reactions are required in order to identify multiple HPV infections. We herein present a non-genotyping method for 13 types of HR-HPV detection in a single reaction by combining the isothermal recombinase polymerase amplification (RPA) method with CRISPR-Cas12a technology. The result could be achieved in 35 min with high sensitivity (500 copies per reaction). This assay represents great advances for the application of RPA-Cas12a system and holds a great potential to address the key challenges facing the HPV diagnostics.

Rapid detection of SARS-CoV-2 with CRISPR-Cas12a.

The recent outbreak of betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is responsible for the Coronavirus Disease 2019 (COVID-19) global pandemic, has created great challenges in viral diagnosis. The existing methods for nucleic acid detection are of high sensitivity and specificity, but the need for complex sample manipulation and expensive machinery slow down the disease detection. Thus, there is an urgent demand to develop a rapid, inexpensive, and sensitive diagnostic test to aid point-of-care viral detection for disease monitoring. In this study, we developed a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated proteins (Cas) 12a-based diagnostic method that allows the results to be visualized by the naked eye. We also introduced a rapid sample processing method, and when combined with recombinase polymerase amplification (RPA), the sample to result can be achieved in 50 minutes with high sensitivity (1-10 copies per reaction). This accurate and portable detection method holds a great potential for COVID-19 control, especially in areas where specialized equipment is not available.

Fungal Polyketides with Three Distinctive Ring Skeletons from the Fungus Penicillium canescens Uncovered by OSMAC and Molecular Networking Strategies.

Four unusual polyketides possessing three unambiguous chemical architectures were discovered from the fermentation of Penicillium canescens assisted by the one strain-many compounds (OSMAC) strategy and MS2-based molecular networking. Penicanone (1) is the first naturally occurring polyketide characterized by a 6/6/8 tricyclic carbon skeleton incorporating an unusual bicyclo[5.3.1]hendecane core. Penicanesones A-C (2-4) are aromatic polyketide dimers simultaneously featuring inconsistent 6/5/5/6 and 6/6/5/6 heterotetracyclic ring cores. Their plausible biosynthetic pathways and screening of biological activity were described here.

Highly oxygenated meroterpenoids from the Antarctic fungus Aspergillus terreus.

Eleven highly oxygenated meroterpenoids, named terreustoxins A-K, along with five known analogues, were isolated from the Antarctic fungus Aspergillus terreus. The structures and absolute configurations of these undescribed compounds were characterized by NMR spectroscopy, single-crystal X-ray crystallography, and ECD experiments. Terreustoxins A-D are the first examples of meroterpenoids with two ortho-hydroxy groups at C-6 and C-7 in the terretonins family. Terreustoxin C and terretonin inhibited the proliferation of Con A-induced murine T cells at the concentration of 10 µM.

Fusaresters A-E, new γ-pyrone-containing polyketides from fungus Fusarium sp. Hungcl and structure revision of fusariumin D.

Marine-derived fungi have been regarded as an under-explored and promising reservoir of structurally novel and bioactive natural products. In this study, five new γ-pyrone-containing polyketides, fusaresters A-E (1-5), were isolated and identified from the culture extracts of a marine-derived fungus Fusarium sp. Hungcl. The structures of compounds 1-5 were elucidated on the basis of their HRESIMS and NMR spectroscopic data as well as 13C NMR calculation and electronic circular dichroism (ECD) analyses. Remarkably, the structure of fusariumin D was revised to (9S*,11S*)-3. All these isolates were tested for the cytotoxicity against seven human cancer cell lines, including SW480, HL-60, A549, MCF-7, HepG2, HeLa and SMMC-7721, and the inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). The results revealed that only compound 2 showed a weak inhibition rate of 56% at 40 µM.

Dynamic distribution of formalin-inactivated Edwardsiella tarda in flounder (Paralichthys olivaceus) post intraperitoneal vaccination.

In order to investigate the dynamic distribution of antigen in different tissues post vaccination, an absolute real-time quantitative PCR was employed to detect the amount of antigen in flounder (Paralichthys olivaceus) post intraperitoneal (i.p.) injection with three concentrations (107, 108, 109 CFU ml-1) of formalin-inactivated Edwardsiella tarda bacterin. The results showed that the amount of uptaken antigen quickly increased and then decreased in different tissues. The peak occurred first in the spleen and head kidney at 6-9 h after injection, and in the liver and blood at 9-15 h, then in the gill, intestine and skin at 15-24 h, finally in the muscle at 24-36 h. The amount of antigen was highest in the spleen and head kidney, followed by the blood, liver and gill, and lowest in the intestine, skin and muscle. Among the three concentration groups, the amount of antigen increased with the increasing concentration of the vaccine in the blood, liver, gill, intestine, skin and muscle, except for the spleen and head kidney, in which more antigens were found in the 108 CFU ml-1 group than that in 109 CFU ml-1 group. Moreover, IIFA and western blotting was performed to examine the tissue distribution of antigen at 9 h after vaccination with 108 CFU ml-1 formalin-inactivated E. tarda. The bacteria were mainly observed in the spleen and head kidney, then the liver, gill and blood, and least in the intestine, skin and muscle, which was roughly in accordance with the results of absolute qPCR. Furthermore, the expressions of CD4-1, MHC IIα, CD8α and MHC Iα in different tissues were detected by RT-qPCR, and the expression levels of these genes were highest in the spleen and head kidney, then in the blood, gill, liver, and lowest in the intestine, skin and muscle. All these results provided useful information for dynamic transportation of antigen uptake post vaccination, and also deepened the understanding of immune response to the injection vaccination.

Dibrefeldins A and B, A pair of epimers representing the first brefeldin A dimers with cytotoxic activities from Penicillium janthinellum.

Dibrefeldins A and B (1 and 2), two unexpected brefeldin A (BFA) dimers, as well as brefeldin F (3), brefeldin G (4), and 14-hydroxy-BFA (5), three new BFA derivatives, together with three new naturally occurring BFA derivatives (6-8) and four known analogues (9-12), were isolated from the fungus Penicillium janthinellum. Dibrefeldins A and B (1 and 2) represent the first examples of BFA dimers formed by an esterification between two BFA monomer units. Brefeldin F (3) has an α,ß-unsaturated γ-lactone ring, and this moiety was first discovered in naturally occurring BFA derivatives. The structures and relative/absolute configurations of these derivatives were elucidated by extensive spectroscopic methods, 13C NMR calculations, and single-crystal X-ray diffraction. Compounds 1, 2, 8, and 9 showed excellent cytotoxic activities against six cancer cell lines with IC50 values ranging from 0.01 to 4.45 µM.

Emeridones A-F, a Series of 3,5-Demethylorsellinic Acid-Based Meroterpenoids with Rearranged Skeletons from an Endophytic Fungus Emericella sp. TJ29.

Six new 3,5-demethylorsellinic acid-based meroterpenoids, emeridones A-F (1-6), and eight known analogues (7-14) were isolated from Emericella sp. TJ29. Their structures and absolute configurations were elucidated by comprehensive spectroscopic analyses, single-crystal X-ray diffraction experiments, and electronic circular dichroism calculations. Emeridone A (1) represents the first meroterpenoid featuring a unique rigid 6/6/5/6 tetracyclic carbon ring system with two additional lactone rings. Emeridones B and C (2 and 3) possess a 2,6-dioxabicyclo[2.2.1]heptane and a spiro[bicyclo[3.2.2]nonane-2,1'-cyclohexane] moiety, respectively, and both functionalities were found for the second time in meroterpenoids. These new compounds were evaluated for their cytotoxic activities against five human cancer cells, and compounds 2, 4, and 6 exhibited moderate cytotoxic activities, with IC50 values ranging from 8.19 to 18.80 µM.

Meta-analysis of randomized controlled trials of 4 weeks or longer suggest that curcumin may afford some protection against oxidative stress.

Oxidative stress (OS) is associated with aging and multiple diseases, yet the effects of curcumin in humans are not definite. We undertook a meta-analysis of the effects of curcumin on OS biomarkers. In January 2018, we searched PubMed, Books@Ovid, Journals@Ovid, EMBASE, MEDLINE(R), and Web of Science to identify randomized controlled trials conducted ≥4 weeks and investigating the effects of curcumin on OS biomarkers, including glutathione peroxidase (GPX) activity in red blood cells (RBC), serum malondialdehyde (MDA) concentrations, and superoxide dismutase (SOD) activity. The standardized mean difference (SMD) with a 95% confidence interval (CI) was used to present the results. The meta-analysis included eight clinical studies (626 patients). There was a significant reduction in circulating MDA concentrations (SMD = -0.769, 95% CI: -1.059 to -0.478) and a significant increase in SOD activity (SMD = 1.084, 95% CI: 0.487 to 1.680) following curcumin supplementation. There was no change in the GPX activity in RBC. There was no significant association between the MDA-lowering effect of curcumin with underlying diseases or treatment duration. However, curcumin showed the MDA-lowering effect at curcuminoids doses ≥600 mg/d (P < .0001). This effect was greater when combined with piperine than curcuminoids alone (SMD = -1.085, 95% CI: -1.357 to -0.813; SMD = -0.850, 95% CI: -1.158 to -0.542). Curcumin may play an anti-oxidative role by reducing circulating MDA concentrations and increasing SOD activity. Further research of curcumin in different populations with multiple biomarkers of redox status is required.

Cytochalasans Produced by the Coculture of Aspergillus flavipes and Chaetomium globosum.

The cocultivation of Aspergillus flavipes and Chaetomium globosum, rich sources of cytochalasans, on solid rice medium, resulted in the production of 13 new, highly oxygenated cytochalasans, aspochalasinols A-D (1-4) and oxichaetoglobosins A-I (5-13), as well as seven known compounds (14-20). Of these compounds, 13 is a novel cytochalasan with an unexpected 2-norindole group. The isolated compounds were characterized by NMR spectroscopy, single-crystal X-ray crystallography, and ECD experiments. Compounds 1-4 represent the first examples of Asp-type cytochalasans with C-12 hydroxy groups, which may be a result of the coculture, as hydroxylated Me-12 groups are frequently found in Chae-type cytochalasans from C. globosum. In addition, 5-10 are unusual cytochalasans with an oxygenated C-10. Interestingly, 13 is the first example of a naturally occurring cytochalasan possessing a uniquely degraded indole ring that is derived from chaetoglobosin W, with 11 and 12 both serving as its biosynthetic intermediates. In the coculture of A. flavipes and C. globosum, most of these cytochalasans are more functionalized than normal cytochalasans, and the underlying causes may attract substantial attention from synthetic biologists. The cytotoxicities against five human cancer cell lines (SW480, HL-60, A549, MCF-7, and SMMC-7721) and the immunomodulatory activities of these new compounds were evaluated in vitro.

Castanea mollissima shell prevents an over expression of inflammatory response and accelerates the dermal wound healing.

ETHNOPHARMACOLOGICAL RELEVANCE: Castanea mollissima shell (CMS) has been used for wound healing in China as traditional medicine. The shell is directly applied on the wounded skin as fine powder or as water maceration. AIM OF THE STUDY: To investigate the wound healing activity of CMS and the potential mechanism of anti-inflammatory activity. MATERIALS AND METHODS: The effects of ethanol extract of CMS (ECMS) on nitricoxide (NO), tumor necrosis factor (TNF)-α and interleukin (IL)- 6 productions in lipopolysaccharide (LPS)-treated RAW 264.7 cells were explored by enzyme linked immunosorbent assay (ELISA) in vitro. To study wound healing properties of ECMS in vivo, excision and incision wound models were performed on rats. Inflammatory cytokines from wound biopsies such as NO, TNF-α and IL-6 production were tested by ELISA. mRNA levels of iNOS, cyclooxygenase (COX) -2 and TNF-α were detected by real-time Polymerase Chain Reaction (PCR), and protein levels of IL-1ß and Heme Oxygenase (HO) -1 were analyzed by Western blotting. RESULTS: ECMS potently inhibited LPS-induced production of IL-6, NO and TNF-α in RAW 264.7 cells. The presence of quercetin, kaempferol, ursolic acid and gallic acid in ECMS might be responsible for its anti-inflammatory activity. 3% and 5% w/w ECMS significantly accelerated the wound healing process in both wound models, evidenced by the faster rate of wound contraction, epithelialization, increased hydroxyproline content, high tensile strength, decreased level of inflammatory markers compared to the control group. Histopathological studies also revealed the amelioration of wound healing by re-epithelialization, collagenation and vascularization of wounded skin sample in ECMS treated groups. CONCLUSION: The experimental data revealed that CMS had ability to prevent exaggerated inflammation and accelerates wound epithelialization and might be beneficial for healing dermal wounds.

Efficacy and safety of turmeric and curcumin in lowering blood lipid levels in patients with cardiovascular risk factors: a meta-analysis of randomized controlled trials.

BACKGROUND: Dyslipidemia is an important and common cardiovascular risk factor in the general population. The lipid-lowering effects of turmeric and curcumin are unconfirmed. We performed a meta-analysis to assess the efficacy and safety of turmeric and curcumin in lowering blood lipids in patients at risk of cardiovascular disease (CVD). METHODS: A comprehensive literature search was conducted on PubMed, Embase, Ovid, Medline and Cochrane Library databases to identify randomized controlled trials (published as of November 2016) that assessed the effect of turmeric and curcumin on blood lipid levels including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was used to assess the effect. RESULTS: The analysis included 7 eligible studies (649 patients). Turmeric and curcumin significantly reduced serum LDL-C (SMD = -0.340, 95% confidence interval [CI]: -0.530 to -0.150, P < 0.0001) and TG (SMD = -0.214, 95% CI: -0.369 to -0.059, P = 0.007) levels as compared to those in the control group. These may be effective in lowering serum TC levels in patients with metabolic syndrome (MetS, SMD = -0.934, 95% CI: -1.289 to -0.579, P < 0.0001), and turmeric extract could possibly have a greater effect on reducing serum TC levels (SMD = -0.584, 95% CI: -0.980 to -0.188, P = 0.004); however, the efficacy is yet to be confirmed. Serum HDL-C levels were not obviously improved. Turmeric and curcumin appeared safe, and no serious adverse events were reported in any of the included studies. CONCLUSIONS: Turmeric and curcumin may protect patients at risk of CVD through improving serum lipid levels. Curcumin may be used as a well-tolerated dietary adjunct to conventional drugs. Further research is required to resolve uncertainties related to dosage form, dose and medication frequency of curcumin.

Molecular mechanism of C-reaction protein in promoting migration and invasion of hepatocellular carcinoma cells in vitro.

Hepatocellular carcinoma (HCC) is one of most common malignant cancers and is the second leading cause of cancer related deaths. The prognosis and survival of patients are closely related to the degree of tumor metastasis. The mechanism of HCC metastasis is still unclear. In the present study, we investigated the molecular mechanism of C-reaction protein in promoting migration and invasion of hepatocellular carcinoma cells in vitro. We estimated that CRP is overexpressed in liver cancer tissues and that it promotes invasion and metastasis of HCC in vitro. In the present study, we employed iTRAQ-based mass spectrometry to analyze the HepG2 secretory proteins of CRP siRNA-treated cells and negative control siRNA-treated cells. We identified 109 differentially expressed proteins after silencing CRP, of which 45 were upregulated and 64 were downregulated. Some of the differentially expressed proteins were confirmed by western blot analysis and real-time quantitative PCR. Furthermore, we found that knockdown of CRP substantially abrogates HIF-1α expression levels, the luciferase activity of HIF-1α and ERK and Akt phosphorylation in HepG2 cells. The present study provides a novel mechanism by which CRP promotes the proliferation, migration, invasion and metastasis of hepatocellular carcinoma cells. Inhibition of CRP suppressed migration, invasion and healing of hepatoma carcinoma cells by decreasing HIF-1α activity and CTSD.

Inhibition of FASN suppresses migration, invasion and growth in hepatoma carcinoma cells by deregulating the HIF-1α/IGFBP1 pathway.

Hepatocellular carcinoma is the second most common cause of cancer-related deaths worldwide. Due to a high propensity to metastasize, active angiogenesis and rapid proliferation, recurrence and poor prognosis are major obstacles for treatment and cure of this disease. However, the detailed mechanisms of how fatty acid synthase (FASN) promotes migration, invasion and healing in tumor cells remain unclear. In the present study, the previous results that FASN was expressed higher in cancer samples than in non-cancerous samples, and influenced migration, invasion of hepatoma carcinoma cells, were verified by immunohistochemistry, tissue microarrays, Transwell assay and wound healing assay. The secretory proteins of hepatocellular carcinoma cells with or without FASN knockdown were analyzed using the isobaric tags for relative and absolute quantitation (iTRAQ) method to identify differentially expressed proteins (DEPs). The DEPs were verified by RT-PCR and western blot analysis, and were consistent with the iTRAQ results. Inhibition of FASN can decrease the levels of IGFBP1, and the expression, activity, and ubiquitination of HIF-1α. Inhibition of FASN can suppress migration, invasion and healing of hepatoma carcinoma cells by decreasing HIF-1α, and IGFBP1.

Efficacy of Tenofovir-Based Combination Therapy versus Tenofovir Monotherapy in Chronic Hepatitis B Patients Presenting with Suboptimal Responses to Pretreatment: A Meta-Analysis.

Background/Aims. It remains unclear whether tenofovir disoproxil fumarate- (TDF-) based combination therapy produces better outcomes than TDF monotherapy in chronic hepatitis B (CHB) patients. The aim of this study was to compare the efficacy of the two regimens by performing a meta-analysis. Methods. A comprehensive literature search was performed on the comparison of TDF-based combination therapy and monotherapy for CHB patients in the PubMed, Embase, Web of Science, and the Cochrane Libraries. Both dichotomous and continuous variables were extracted and pooled outcomes were expressed as risk ratio (RR) or standard mean difference (SMD). Results. Nine eligible studies (1089 subjects in total) were included in our analysis. The proportion of patients with undetectable HBV DNA at 24, 48, and 96 weeks were similar between the two comparable groups (62.5% versus 70.9%, P = 0.086; 78.1% versus 83.7%, P = 0.118; 86.4% versus 87.9%, P = 0.626, resp.). HBV DNA reduction, rates of ALT normalization, hepatitis B e antigen (HBeAg) loss, and HBeAg seroconversion were also similar between the two groups. Conclusions. On the current data, TDF-based combination therapy seemed to be no better than those achieved by monotherapy. Further studies are needed to verify this comparison.

Efficacy and safety of oral branched-chain amino acid supplementation in patients undergoing interventions for hepatocellular carcinoma: a meta-analysis.

Most hepatocellular carcinoma (HCC) patients have complications, including cirrhosis and malnutrition. The efficacy of dietary supplementation with oral branched-chain amino acids (BCAAs) in HCC patients undergoing interventions has not been confirmed. Relevant publications on the efficacy and safety of oral BCAA supplementation for HCC patients undergoing anti-HCC interventions through September, 2014 were searched for identification in the PubMed, Embase, Web of Science, and the Cochrane Library databases. The pooled risk ratio (RR) and standardized mean difference (SMD) were used to assess the supplementation effects. A total of 11 eligible studies (974 patients in total) were evaluated and included in our analysis. Oral BCAA supplementation helped to maintain liver reserve with higher serum albumin (SMD = 0.234, 95% CI: 0.033-0.435, P = 0.022), and lower rates of ascites (RR = 0.545, 95% CI: 0.316-0.938, P = 0.029) and edema (RR = 0.494, 95% CI: 0.257-0.952, P = 0.035) than in the control group. BCAA supplementation seemed to be effective in improving mortality, especially in Child-Pugh class B patients, but the efficacy was not confirmed. Apparent effects were not found in improving HCC recurrence, total bilirubin, ALT, or AST. BCAA supplementation was relatively safe without serious adverse events. BCAA supplementation may be clinically applied in improving liver functional reserve for HCC patients and further improving the quality of life.