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Background and aims. To investigate the clinical implications of serum HBV RNA, serum hepatitis B core-related antigen (HBcrAg), and quantitative anti-HBc in treatment-naïve patients with chronic HBV infection. Methods. A total of 111 patients in total from different disease phases were recruited, including 21 in immune-tolerant (IT) phase, 49 in immune-clearance (IC) phases, 29 in immune-control or low replicative (LR) phase, and 12 in reactivation phases. Serum HBV RNA, anti-HBc, HBcrAg, and intrahepatic covalently closed circular DNA (cccDNA) were quantified and each of these indicator’s correlation with liver inflammation was analyzed. Results. HBeAg-positive individuals had significant higher serum levels of HBV RNA and HBcrAg than those who were HBeAg negative, similar to that of serum HBV DNA. Comparatively, HBV RNA ( r =0.79, P < 0.01 ) and HBcrAg ( r =0.78, P < 0.01 ) had almost same higher overall correlation with the cccDNA, as that of HBV DNA ( r =0.81, P < 0.01 ). Serum anti-HBc level ( r = -0.52, P < 0.05 ) is negatively correlated with cccDNA level at IT phase rather than the other three phases. When set the cutoff value at 4.00 log10 IU/mL, serum anti-HBc showed potential to indicate liver inflammation, with AUC as 0.79 and the specificities as 78.85% for HBeAg positive, and with AUC as 0.72 and the specificities as 62.16% for HBeAg-negative patients, respectively. Conclusions. In treatment-naïve patients, levels of serological markers HBV RNA and HBcrAg could mirror intrahepatic cccDNA level, but were not superior to HBV DNA level. Serum anti-HBc level had certain potential to be used as a predicting marker for liver inflammation.

Increasing evidence supports long non-coding RNA-ZFAS1 as master protein regulators involved in a variety of human cancers. However, the molecular mechanism is not fully understood in colorectal cancer (CRC) and remains to be elucidated. Here, we uncovered a previously unreported mechanism linking RNA helicase DDX21 regulated by lncRNA ZFAS1 in control of POLR1B expression in CRC initiation and progression. Specifically, ZFAS1 exerted its oncogenic functions and was significantly up-regulated accompanied by elevated DDX21, POLR1B expression in CRC cells and tissues, which further closely associated with poor clinical outcomes. Notably, ZFAS1 knockdown dramatically suppressed CRC cell proliferation, invasion, migration, and increased cell apoptosis, which were contrary to the effect caused by ZFAS1 up-regulation. We further revealed that the inhibitory effect caused by ZFAS1 knockdown could be reversed by DDX21 overexpression in vitro and in vivo. Mechanistically, our research found that ZFAS1 could directly recruit DDX21 protein by harboring the specific motif (AAGA or CAGA). Finally, POLR1B was identified as the downstream target of DDX21 regulated by ZFAS1, which was also up-regulated in CRC cells and tissues and closely related to poor prognosis. The unrecognized ZFAS1/DDX21/POLR1B signaling regulation axis may provide new biomarkers and targets for CRC treatment and prognostic evaluation.

BACKGROUND It is unclear whether immune escape-associated mutations in the major hydrophilic region of hepatitis B virus surface antigen (HBsAg) are associated with nucleoside/nucleotide analog resistance. AIM To evaluate the association between immune escape-associated mutations and nucleoside/nucleotide analog resistance mutations. METHODS In total, 19440 patients with chronic hepatitis B virus infection, who underwent resistance testing at the Fifth Medical Center of Chinese PLA General Hospital between July 2007 and December 2017, were enrolled. As determined by sequence analysis, 6982 patients harbored a virus with resistance mutations and 12458 harbored a virus lacking resistance mutations. Phenotypic analyses were performed to evaluate HBsAg production, replication capacity, and drug-induced viral inhibition of patient-derived drug-resistant mutants with or without the coexistence of sA159V. RESULTS The rate of immune escape-associated mutation was significantly higher in 9 of the 39 analyzed mutation sites in patients with resistance mutations than in patients without resistance mutations. In particular, these mutations were sQ101H/K/R, sS114A/L/T, sT118A/K/M/R/S/V, sP120A/L/Q/S/T, sT/I126A/N/P/S, sM133I/L/T, sC137W/Y, sG145A/R, and sA159G/V. Among these, sA159V was detected in 1.95% (136/6982) of patients with resistance mutations and 1.08% (134/12,458) of patients lacking resistance mutations (P < 0.05). The coexistence of sA159V with lamivudine (LAM) and entecavir (ETV)-resistance mutations in the same viral genome was identified during follow-up in some patients with drug resistance. HBsAg production was significantly lower and the replication capacity was significantly higher, without a significant difference in LAM/ETV susceptibility, in sA159V-containing LAM/ETV-resistant mutants than in their sA159V-lacking counterparts. CONCLUSION In summary, we observed a close link between the increase in certain immune escape-associated mutations and the development of resistance mutations. sA159V might increase the fitness of LAM/ETV-resistant mutants under environmental pressure in some cases.

Most multiphase flow separation detection methods used commonly in oilfields are low in efficiency and accuracy, and have data delay. An online multiphase flow detection method is proposed based on magnetic resonance technology, and its supporting device has been made and tested in lab and field. The detection technology works in two parts: measure phase holdup in static state and measure flow rate in flowing state. Oil-water ratio is first measured and then gas holdup. The device is composed of a segmented magnet structure and a dual antenna structure for measuring flowing fluid. A highly compact magnetic resonance spectrometer system and intelligent software are developed. Lab experiments and field application show that the online detection system has the following merits: it can measure flow rate and phase holdup only based on magnetic resonance technology; it can detect in-place transient fluid production at high frequency and thus monitor transient fluid production in real time; it can detect oil, gas and water in a full range at high precision, the detection isn't affected by salinity and emulsification. It is a green, safe and energy-saving system.

Increasing evidence supports that long noncoding RNAs (lncRNAs) act as master regulators involved in tumorigenesis and development at the N6-methyladenine (m6A) epigenetic modification level. However, the underlying regulatory mechanism in breast cancer (BRCA) remains elusive. Here, we unveil that LINC00942 (LNC942) exerts its functions as an oncogene in promoting METTL14-mediated m6A methylation and regulating the expression and stability of its target genes CXCR4 and CYP1B1 in BRCA initiation and progression. Specifically, LNC942 and METTL14 were significantly upregulated accompanied with the upregulation of m6A levels in BRCA cells and our included BRCA cohorts (n = 150). Functionally, LNC942 elicits potent oncogenic effects on promoting cell proliferation and colony formation and inhibiting cell apoptosis, subsequently elevating METTL14-mediated m6A methylation levels and its associated mRNA stability and protein expression of CXCR4 and CYP1B1 in BRCA cells. Mechanistically, LNC942 directly recruits METTL14 protein by harboring the specific recognize sequence (+176–+265), thereby stabilized the expression of downstream targets of LNC942 including CXCR4 and CYP1B1 through posttranscriptional m6A methylation modification in vitro and in vivo. Therefore, our results uncover a novel LNC942-METTL14-CXCR4/CYP1B1 signaling axis, which provides new targets and crosstalk m6A epigenetic modification mechanism for BRCA prevention and treatment.

Circular RNA (circRNA) has been reported to have great scientific significance and clinical value in multiple cancers including colorectal cancer (CRC). However, the biological function of most circRNAs in CRC is still in its infancy. Herein, we discovered the differential expressed circRNAs (DECs) between CRC tissues and matched adjacent using deep RNA sequencing and further confirmed the DECs expression by combining with another Gene Expression Omnibus dataset. Furthermore, we validated the expression of the top four upregulated circRNAs (hsa_circ_0030632, hsa_circ_0004887, hsa_circ_0001550, and hsa_circ_0001681) in both of paired CRC tissues and CRC cell lines. Then, a circRNA/microRNA/messenger RNA regulatory network was established and the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed these four circRNAs participated in various biological processed including apoptotic process and multiple metabolic processes. Moreover, based on the regulatory network, three bioactive compounds (pergolide, pivampicillin, and methylergometrine) for the treatment of CRC were also found. In conclusion, this study improved our understanding of circRNAs and may also facilitate the finding of promising targets and biomarkers in CRC.

Background Accumulating evidence shows that N6-methyladenine (m6A) modulators contribute to the etiology and progression of colorectal cancer (CRC). However, the exact mechanisms of m6A reader involved in glycolytic metabolism remain vague. This article aimed to crosstalk the m6A reader with glycolytic metabolism and reveal a new mechanism for the progression of CRC. Methods The relationship between candidate lncRNA and m6A reader was analyzed by bioinformatics, ISH and IHC assays. In vivo and in vitro studies (including MTT, CFA, trans-well, apoptosis, western blot, qRT-PCR and xenograft mouse models) were utilized to explore the biological functions of these indicators. Lactate detection, ATP activity detection and ECAR assays were used to verify the biological function of the downstream target. The bioinformatics, RNA stability, RIP experiments and RNA pull-down assays were used to explore the potential molecular mechanisms. Results We identified that the crosstalk of the m6A reader IMP2 with long-noncoding RNA (lncRNA) ZFAS1 in an m6A modulation-dependent manner, subsequently augmented the recruitment of Obg-like ATPase 1 (OLA1) and adenosine triphosphate (ATP) hydrolysis and glycolysis during CRC proliferation and progression. Specifically, IMP2 and ZFAS1 are significantly overexpressed with elevated m6A levels in CRC cells and paired CRC cohorts (n = 144). These indicators could be independent biomarkers for CRC prognostic prediction. Notably, IMP2 regulated ZFAS1 expression and enhanced CRC cell proliferation, colony formation, and apoptosis inhibition; thus, it was oncogenic. Mechanistically, ZFAS1 is modified at adenosine +843 within the RGGAC/RRACH element in an m6A-dependent manner. Thus, direct interaction between the KH3–4 domain of IMP2 and ZFAS1 where IMP2 serves as a reader for m6A-modified ZFAS1 and promotes the RNA stability of ZFAS1 is critical for CRC development. More importantly, stabilized ZFAS1 recognizes the OBG-type functional domain of OLA1, which facilitated the exposure of ATP-binding sites (NVGKST, 32–37), enhanced its protein activity, and ultimately accelerated ATP hydrolysis and the Warburg effect. Conclusions Our findings reveal a new cancer-promoting mechanism, that is, the critical modulation network underlying m6A readers stabilizes lncRNAs, and they jointly promote mitochondrial energy metabolism in the pathogenesis of CRC.

Liuweiwuling Tablet (LWWL) is a licensed Chinese patent medicine (approval number: Z20060238) included in the national health insurance for anti-inflammation of chronic HBV infection, whereas its anti-HBV effect remains clarification. The study aimed to clarify its antiviral effect and related mechanisms. HepG2.2.15 cells (wild-type HBV-replicating cells) and HepG2. A64 cells (entecavir-resistant HBV-replicating cells) were used for in vitro test. Hydrodynamic injection-mediated HBV-replicating mouse model was used for in vivo test. Active compounds and related mechanisms for antiviral effect of LWWL were analyzed using network pharmacology and transcriptomics. The inhibition rates of LWWL (0.8 mg/ml) on HBV DNA, HBsAg, and pgRNA were 57.06, 38.55, and 62.49% in HepG2.2.15 cells, and 51.57, 17.57, and 53.88% in HepG2. A64 cells, respectively. LWWL (2 g kg−1 d−1 for 4 weeks)-treated mice had 1.16 log10 IU/mL decrease of serum HBV DNA, and more than 50% decrease of serum HBsAg/HBeAg and hepatic HBsAg/HBcAg. Compared to tenofovir control, LWWL was less effective in suppressing HBV DNA but more effective in suppressing HBV antigens. Thirteen differentially-expressed genes were found in relation to HBV-host interaction and some of them were enriched in interferon (IFN)-β pathway in LWWL-treated HepG2.2.15 cells. CD3+CD4+ T-cell frequency and serum IFN-γ were significantly increased in LWWL-treated mice compared to LWWL-untreated mice. Among 26 compounds with potential anti-HBV effects that were predicted by network pharmacology, four compounds (quercetin, luteolin, wogonin, and kaempferol) were experimentally confirmed to have antiviral potency. In conclusion, LWWL had potent inhibitory effect on both wild-type and entecavir-resistant HBV, which might be associated with increasing IFN-β and IFN-γ production.

As the open reading frames of hepatitis B virus (HBV) genomes are overlapping, resistance mutations (MTs) in HBV polymerase may result in stop codon MTs in hepatitis B surface proteins, which are usually detected as a mixed population with wild-type (WT) HBV. The question was raised how the coexistence of nucleos(t)ide analogs (NAs) resistance MTs and WT sequences affects HBV replication. In the present study, HBV genomes with frequently detected reverse transcriptase (RT)/surface truncation MTs, rtA181T/sW172*, rtV191I/sW182* and rtM204I/sW196*, were phenotypically characterized alone or together with their WT counterparts in different ratios by transient transfection in the absence or presence of NAs. In the absence of NAs, RT/surface truncation MTs impaired the expression and secretion of HBV surface proteins, and had a dose-dependent negative effect on WT HBV virion secretion. However, in the presence of NAs, coexistence of MTs with WT maintained viral replication, and the presence of WT was able to rescue the production of MT HBV virions. Our findings reveal that complementation of WT and MT HBV genomes is highly effective under drug treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00143-y) contains supplementary material, which is available to authorized users.

This paper is concerned with the construction of efficient preconditioners for systems arising from implicit Runge-Kutta time discretization methods for one-dimensional and two-dimensional space fractional diffusion equations. We consider the third-order, two-stage Radau-IIA method, which leads to a coupled 2 × 2 block system. Our approach is based on a Schur complement formulation for the unknown at the second stage. We present an approximate factorization of the Schur complement and derive the eigenvalue bounds of the preconditioned system. The components of the approximate factorization have the same structure as the system derived from implicit Euler discretization of the problem. Therefore, we reuse the available high performance of implicit Euler discretization preconditioners as the building block for our preconditioners. Several numerical experiments are presented to show the effectiveness of our approaches.

Multidrug-resistance hepatitis B virus (MDR HBV), defined as those with mutations resistant to both nucleoside analogs lamivudine/telbivudine/entecavir (LAM/LdT/ETV) and nucleotide analog adefovir (ADV), has potential to cause treatment difficulty. To clarify clinical prevalence and virological features of MDR HBV, we investigated serum samples from 28,236 chronic HBV-infected patients with treatment of nucleoside/nucleotide analogs. All patients underwent resistance testing in the Fifth Medical Center of Chinese PLA General Hospital between 2007 and 2019. MDR mutations were screened by direct sequencing; MDR strains (with mutations co-located on the same viral genome) were verified by clonal sequencing (≥20 clones/sample) and subjected to phenotypic analysis if necessary. MDR mutations were detected in 0.81% (229/28,236) patients. MDR strains were verified in 83.0% (190/229) of MDR mutation-positive patients. As ETV-resistance mutation (ETVr) had additional mutation(s) on LAMr conferring more resistance, MDR mutations fell into LAMr + ADVr and ETVr + ADVr subsets. Sixteen mutation patterns of MDR strains were verified, including eight with LAMr + ADVr and eight with ETVr + ADVr. Refractory to sequential therapies of LAM/LdT/ETV and ADV were closely linked with MDR HBV development. Ten representative MDR strains (five LAMr + ADVr and five ETVr + ADVr) tested all had decrease in replication capacity compared to wild-type strains and decrease extent was positively related with the number of primary resistance on viral genome. Compared to ADV + ETV, TDF/TDF + ETV showed higher inhibitory rates on MDR HBV, especially for the five ETVr + ADVr strains (74.5%-97.6% vs. 60.2%-79.5%, all P 0.05). This study significantly extends the knowledge on MDR HBV and has clinical implications for resistance management.

With the depletion of reservoirs, it is inevitable that once very prolific conventional and unconventional wells become stripper wells characterized as producing no more than 35 barrels of liquid equivalent per day over a 12-month period. The conventional metering strategy is not economical for its huge investment in facilities, equipment, sensors, and ongoing maintenance compared to current low production. This paper presents an innovative method utilizing state-of-art artificial intelligent algorithms to predict the production rate from real-time IIot testing and producing data with very low cost and reliable accuracy. Abundant real-time field and well data acquired from IIot and digital field facilities establish a fundamental foundation for developing a machine learning application. This paper presents a method to predict the real-time production rate from real-time IIot data. In our method, we start with constructing our datasets from different data sources by combining the dynamometer cards, pumping stroke and rate, pump, rod, wellbore and reservoir parameters as inputs and the corresponded production rate as targets. The machine-learning model contains two neural networks: first, a deep autoencoder to extract the feature representations from all the dynamometer cards, then another neural network combining all related features to predict the real-time production. The deep autoencoder derived features from dynamometer cards are used as parts of inputs to further real-time production prediction models, which eliminate the disadvantage of conventional hand-crafted features. Hand-crafted features can lose important information whereas autoencoder is designed to minimize information loss by learning high level features that can be used to reconstruct the cards. The production prediction model with pump and producing data combining more informative abstract features generate good accordance with the history data. After tested testing and validating data in several fields in one operator’s fields in China, the model demonstrates very high accuracy and with R2 more than 0.92, MAE less than 0.5 of wells producing less 5m3/day, RMSE less than 1.6 of wells producing 5-10m3/day and RMSE less than 2.2 of wells producing more than 10m3/day. The model has also been tested on hundreds of newly producing wells and with error in 10%, compared with high resolution real-time metering equipment. The method described in this paper can be fully utilized to metering the real-time production with ultra-low cost in wells as long as acquiring a real-time dynamometer card. With the fast development of artificial intelligence technology and expanding training datasets, artificial intelligence is a good choice to lower the investment and maintenance cost for conventional and unconventional fields in the low oil price trend.

Hepatitis B virus (HBV) infection is a global epidemic. The main transmission route of chronic HBV infection is from mother to child, yet the mechanisms underlying HBV intrauterine infection remain unclear. In the present study, the effect and the mechanism underlying hepatitis B virus X antigen (HBxAg) on HBV replication and EGFR activation in trophoblasts was investigated. Serum samples from pregnant women with HBV infection were used to infect trophoblasts and HBxAg expression was detected using ELISA. HBV plasmids carrying either full length hepatitis B virus X (HBx) or HBx with a deletion mutation (ΔHBx) were transfected into trophoblasts and expression levels of HBV DNA, hepatitis B e-antigen and pregenomic (pg)RNA, and structural maintenance of chromosomes (Smc) 5/6 were assessed. The association between HBx and EGFR promoters was characterized using a luciferase reporter assay and EGFR/PI3K/phosphorylated (p)-AKT expression and apoptosis rate were also monitored. The results of the present study indicated that HBxAg expression increased with the increasing titre of HBV DNA (P

In the milling process, the coupling deflection and the dynamic characteristics of the cutter–workpiece system are time variant as the material removal and the change of cutter position. The milling stability of the system is dynamic because of the time-varying stiffness. In this study, the model of time-varying system has been developed. Variable pitch cutter (VPC) and variable spindle speed (VSS) are, respectively, typical method of passive control and active control to suppress the chatter, and two methods are compatible. The arithmetic of VPC and VSS combined method has been developed and verified effectively. Dynamic milling stability prediction of stiffness time-varying system for thin-walled components based on VPC and VSS combined method has been developed. And then, the dynamic milling stability of stiffness time-varying system for thin-walled components has been predicted.

Increasing evidence supports that long noncoding RNAs (lncRNAs) act as master regulators involved in tumorigenesis and development at the N6-methyladenine (m

This study aimed to investigate anti-HBV effect and major active compounds of Su-duxing, a medicine extracted from Chinese herbs. HBV-replicating cell lines HepG2.2.15 (wild-type) and HepG2.A64 (entecavir-resistant) were used for in vitro test. C57BL/6 mice infected by adeno-associated virus carrying 1.3 mer wild-type HBV genome were used for in vivo test. Inhibitory rates of Su-duxing (10 μg/mL) on HBV replicative intermediate and HBsAg levels were 75.1%, 51.0% in HepG2.2.15 cells and 65.2%, 42.9% in HepG2.A64 cells. The 50% inhibitory concentration of Su-duxing and entecavir on HBV replicative intermediates had 0.2-fold and 712.5-fold increase respectively for entecavir-resistant HBV compared to wild-type HBV. Su-duxing and entecavir combination showed a better anti-HBV effect than each single of agents. Mice treated with Su-duxing (45.0 mg kg−1 d−1 for 2 weeks) had 1.39 log10 IU/mL decrease of serum HBV DNA, and 48.9% and 51.7% decrease of serum HBsAg and HBeAg levels. GeneChip and KEGG analysis proposed that anti-HBV mechanisms included relief of HBx stability and viral replication, deregulation of early cell cycle checkpoints, and induction of type I interferon. Quantitative RT-PCR verified that CCNA2, ATF4, FAS and CDKN1A expression levels had significant difference between Su-duxing-treated and control groups. Six active compounds (Matrine, Oxymatrine, Chlorogenic acid, Sophocarpine, Baicalein, and Wogonin) against HBV were identified in Su-duxing. Greater anti-HBV effects were observed in some compound pairs compared to each single compound. In conclusion, Su-duxing had potent inhibitory effects on both wild-type and entecavir-resistant HBV. Its effects were associated with coordinated roles of active compounds in its composition.

Background A unique chronic hepatitis B patient was followed over 189 months of nucleoside/nucleotide analogue (NA) therapies with the analysis of multiple drug-resistance HBV mutants. Methods Clonal sequencing (≥20 clones/sample) was performed on sera sampled at 41 time points, and the phenotypic features of eight representative mutants were analysed. Results Lamivudine (LAM)-, adefovir dipivoxil (ADV)-, entecavir (ETV)- and repeat ADV-resistance mutants emerged upon individual sequential NA monotherapy. The efficacy of NA combination rescue therapies ranked as LAM+ADV < ETV+ADV < ETV+ tenofovir disoproxil fumarate (TDF). Specifically, LAM+ADV and ETV+ADV suppressed viral loads to Conclusions Taken together, viral drug susceptibility, replication capacity, and perhaps immunological adaptation may play coordinated roles in the fitness of drug-resistance mutants. ETV+TDF therapy is the preferred option for treating chronic hepatitis B patients with multiple drug failure.

Limited data are available regarding the association of hepatitis B virus (HBV) mutations with liver fibrosis in HBV infection. The study aimed to clarify whether HBV preS deletion mutation is associated with liver fibrosis progression. A total of 469 patients were enrolled, including 324 with chronic hepatitis B (CHB), 28 with HBV-related compensated liver cirrhosis (LC), and 117 with HBV-related decompensated LC. All CHB and compensated LC patients received liver biopsy. Fibrosis grade was assessed using METAVIR score. HBV preS deletion was determined by direct sequencing and verified by clonal sequencing. Overall preS deletion was detected in 12.6% (59/469) patients, specifically, in 7.51% (13/173), 10.60% (16/151), and 20.69% (30/145) of patients with no-to-mild liver fibrosis (F0–1), moderate-to-severe liver fibrosis (F2–3), and cirrhosis (F4), respectively (p

Background This study was aimed at evaluating the clinical significance of serum HBV RNA, hepatitis B core-related antigen (HBcrAg) and hepatitis B core antibody (anti-HBc) levels in chronic hepatitis B patients with undetectable HBV DNA during nucleoside/nucleotide analogue (NA) treatment. Methods Fifty-seven patients who received long-term NA treatment of median 5.83 (25%, 75% percentiles 4.67, 7.75) years were enrolled, and 285 serum samples at five time points for each patient were quantitatively analysed for the three serum markers together with serum HBV DNA and hepatitis B surface antigen (HBsAg) levels. Results The HBV RNA level significantly correlated with HBcrAg ( r=0.629; P10 copies/ml, 1.14 [0.62, 2.21] log10 U/ml, respectively) compared with those in seven patients without HBeAg loss (0.74 [0.10, 1.08] log10 copies/ml and 0.41 [0.21, 0.69] log10 U/ml, respectively). Overall, serum HBV RNA, HBcrAg, HBsAg and anti-HBc levels gradually decreased with time during NA treatment. At the end of observation, HBV RNA and HBcrAg reached an undetectable level in 26 and 6 (46% and 11%) patients, respectively. Conclusions: Monitoring of HBV RNA and HBcrAg levels is useful for NA-treated patients with undetectable HBV DNA. The attainment of HBV RNA undetectability usually occurs prior to HBcrAg undetectability.

// Yangxin Xie 1, 2, * , Bo Tu 2, * , Xin Zhang 2 , Jingfeng Bi 3 , Lei Shi 2 , Peng Zhao 2 , Weiwei Chen 2 , Suxia Liu 4 , Dongping Xu 3 and Enqiang Qin 1 1 Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China 2 Chinese PLA General Hospital, Medical School, Beijing, China 3 Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing, China 4 Treatment and Research Center for Liver Failure, Beijing 302 Hospital, Beijing, China * These authors have contributed equally to this work Correspondence to: Dongping Xu, email: xudongping302@sina.com Enqiang Qin, email: qeq2004@sina.com Keywords: liver cirrhosis; gram-negative bacterial bloodstream infection; nosocomial infection Received: March 15, 2017 Accepted: June 04, 2017 Published: December 22, 2017 ABSTRACT Objective: The study aimed at analyzing the epidemiology and outcomes of liver cirrhosis patients undergoing gram-negative bacterial bloodstream infection. Results: Totally 508 eligible patients were collected, with 25.79% 30-day mortality, and 58.86% patients were confirmed as nosocomial infection. The most common isolates were Escherichia coli (48.29%) and Klebsiella pneumoniae (19.29%), and multidrug-resistant isolates accounted for 36.61%. The bacterial distributions were similar between survivors and non-survivors ( P >0.05), but showed close association with acquisition sites of infection ( P

We read with great interest the article entitled "HBV RNA profiles in chronic hepatitis B patients under different disease phases and anti-viral therapy" authored by Mak et al(1). The authors proposed that the reverse transcription efficiency in HBeAg-positive patients was significantly higher than that in HBeAg-negative patients, based on the RNA: DNA ratio in the two groups of patients (0.79 vs. 0.53; p< 0.001). We had found that a higher ratio of serum HBV RNA to HBV DNA was inversely related with reverse transcription efficiency of HBV pgRNA(2), and HBeAg-positive patients had a lower reverse transcription efficiency of HBV pgRNA than HBeAg-negative patients did. We here suggest that the ratio of serum HBV DNA: (HBV DNA + HBV RNA) is more reliable to assess the reverse transcriptional efficiency of pgRNA. The medians of ratio in our cohort were 0.56 (n = 54), 0.56 (n = 23), 0.69 (n = 64) and 0.66 (n = 4), for patients with HBeAg-positive chronic infection, HBeAg-positive chronic hepatitis, HBeAg-negative chronic infection, and HBeAg-negative chronic hepatitis, respectively. Inconsistent with the report by Mak et al., our data showed that the reverse transcriptional efficiency was lower in HBeAg-positive patients than in HBeAg-negative patients (0.56 vs. 0.68; p< 0.001). A schematic diagram for illustrating the efficiencies of covalently closed circular DNA (cccDNA) transcription and reverse transcription of pgRNA are shown in Figure 1.