Histological outcome for chronic hepatitis B patients treated with entecavir vs lamivudine-based therapy

AIM: To compare the histological outcome of chronic hepatitis B(CHB) patients treated with entecavir(ETV) or lamivudine(LAM)-based therapy.METHODS: We conducted a retrospective analysis of data from 42 CHB patients with advanced fibrosis(baseline Ishak score ≥ 2) or cirrhosis who were treated with ETV or LAM-based therapy in Beilun People's Hospital, Ningbo between January 2005 and May 2012. The patients enrolled were more than 16 years of age and underwent a minimum of 12 mo of antiviral therapy. We collected data on the baselinecharacteristics of each patient and obtained paired liver biopsies pre- and post-treatment. The Knodell scoring system and Ishak fibrosis scores were used to evaluate each example. An improvement or worsening of necroinflammation was defined as ≥ 2-point change in the Knodell inflammatory score. The progression or regression of fibrosis was defined as ≥ 1-point change in the Ishak fibrosis score. The continuous variables were compared using t-test or Mann-Whitney test, and the binary variables were compared using χ2 test or Fisher's exact test. The results of paired liver biopsies were compared with a Wilcoxon signed rank test.RESULTS: Nineteen patients were treated with ETV and 23 patients were treated with LAM therapy for a mean duration of 39 and 42 mo, respectively. After long-term antiviral treatment, 94.74%(18/19) of the patients in the ETV arm and 95.65%(22/23) in the LAM arm achieved an HBV DNA level less than 1000 IU/m L. The majority of the patients(94.74% in the ETV arm and 73.91% in the LAM arm) had normalized ALT levels. The median Knodell necroinflammatory score decreased from 11 to 0 in the patients receiving ETV, and the median Knodell score decreased from 9 to 3 in the patients receiving LAM(P = 0.0002 and < 0.0001, respectively). The median Ishak fibrosis score showed a 1-point reduction in ETV-treated patients and a 2-point reduction in LAM-treated patients(P = 0.0019 and 0.0205, respectively). The patients receiving ETV showed a more significant improvement in necroinflammation than the LAM-treated patients(P = 0.0003). However, there was no significant difference in fibrotic improvement between the two arms. Furthermore, two patients in each arm achieved a fibrosis score of 0 post-treatment, which indicates a full reversion of fibrosis after antiviral therapy.CONCLUSION: CHB patients with advanced fibrosis or cirrhosis benefit from antiviral treatment. ETV is superior to LAM therapy in improving necroinflammatory but not fibrotic outcome.

Response-guided treatment of cirrhotic chronic hepatitis B patients: Multicenter prospective study

AIM: To observe the effect of response-guided add-on therapy with adefovir(ADV) and lamivudine(LAM) in cirrhotic hepatitis B(CHB) patients.METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus(HBV) DNA level after 24 wk LAM monotherapy: Arm A(complete response, HBV DNA ≤ 60 IU/m L, n = 49), Arm B(partial response, HBV DNA: 60-2000 IU/m L, n = 31) and Arm C(inadequate response, HBV DNA > 2000 IU/m L, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24was associated with maintained viral suppression(undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations(mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/m L. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.

The combination of creatine kinase-myocardial band isoenzyme and point-of-care cardiac troponin/contemporary cardiac troponin for the early diagnosis of acute myocardial infarction

BACKGROUND:The early diagnosis of acute myocardial infarction(AMI)remains challenging,especially for institutions without the high-sensitive cardiac troponin(hs-c Tn)assay.Herein,we aim to assess the value of creatine kinase-myocardial band isoenzyme(CK-MB)combined with different cardiac troponin(c Tn)assays in AMI diagnosis.METHODS:This multicenter,observational study included 3,706 patients with acute chest pain from September 1,2015,to September 30,2017.We classified the participants into three groups according to the c Tn assays:the point-of-care c Tn(POC-c Tn)group,the contemporary c Tn(c-c Tn)group,and hs-c Tn group.The diagnostic value was quantified using sensitivity and the area under the curve(AUC).RESULTS:Compared to the single POC-c Tn/c-c Tn assays,combining CK-MB and POC-c Tn/c-c Tn increased the diagnostic sensitivity of AMI(56.1%vs.63.9%,P<0.001;82.7%vs.84.3%,P=0.025).In contrast,combining CK-MB and hs-c Tn did not change the sensitivity compared with hs-c Tn alone(95.0%vs.95.0%,P>0.999).In the subgroup analysis,the sensitivity of combining CKMB and c-c Tn increased with time from symptom onset<6 h compared with c-c Tn alone(72.8%vs.75.0%,P=0.046),while the sensitivity did not increase with time from symptom onset>6 h(97.5%vs.98.3%,P=0.317).The AUC of the combination of CK-MB and POC-c Tn significantly increased compared to the single POC-c Tn assay(0.776 vs.0.750,P=0.002).The AUC of the combined CKMB and c-c Tn/hs-c Tn assays did not significantly decrease compared with that of the single c-c Tn/hs-c Tn assays within 6 h.CONCLUSIONS:The combination of CK-MB and POC-c Tn or c-c Tn may be valuable for the early diagnosis of AMI,especially when hs-c Tn is not available.

Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenationinduced cardiomyocyte injury

BACKGROUND:Disturbance of mitochondrial fi ssion and fusion(termed mitochondrial dynamics)is one of the leading causes of ischemia/reperfusion(I/R)-induced myocardial injury.Previous studies showed that mitochondrial aldehyde dehydrogenase 2(ALDH2)conferred cardioprotective effect against myocardial I/R injury and suppressed I/R-induced excessive mitophagy in cardiomyocytes.However,whether ALDH2 participates in the regulation of mitochondrial dynamics during myocardial I/R injury remains unknown.METHODS:In the present study,we investigated the effect of ALDH2 on mitochondrial dynamics and the underlying mechanisms using the H9c2 cells exposed to hypoxia/reoxygenation(H/R)as an in vitro model of myocardial I/R injury.RESULTS:Cardiomyocyte apoptosis was significantly increased after oxygen-glucose deprivation and reoxygenation(OGD/R),and ALDH2 activation largely decreased the cardiomyocyte apoptosis.Additionally,we found that both ALDH2 activation and overexpression significantly inhibited the increased mitochondrial fission after OGD/R.Furthermore,we found that ALDH2 dominantly suppressed dynamin-related protein 1(Drp1)phosphorylation(Ser616)and adenosine monophosphate-activated protein kinase(AMPK)phosphorylation(Thr172)but not interfered with the expression levels of mitochondrial shaping proteins.CONCLUSIONS:We demonstrate the protective effect of ALDH2 against cardiomyocyte H/R injury with a novel mechanism on mitochondrial fission/fusion.

Lower respiratory tract samples are reliable for severe acute respiratory syndrome coronavirus 2 nucleic acid diagnosis and animal model study

Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) and coronavirus disease 2019(COVID-19) continue to impact countries worldwide.At present, inadequate diagnosis and unreliable evaluation systems hinder the implementation and development of effective prevention and treatment strategies. Here, we conducted a horizontal and longitudinal study comparing the detection rates of SARS-Co V-2 nucleic acid in different types of samples collected from COVID-19 patients and SARS-Co V-2-infected monkeys. We also detected anti-SARS-Co V-2 antibodies in the above clinical and animal model samples to identify a reliable approach for the accurate diagnosis of SARS-Co V-2 infection. Results showed that, regardless of clinical symptoms, the highest detection levels of viral nucleic acid were found in sputum and tracheal brush samples, resulting in a high and stable diagnosis rate. Anti-SARS-Co V-2 immunoglobulin M(Ig M) and G(Ig G) antibodies were not detected in6.90% of COVID-19 patients. Furthermore,integration of nucleic acid detection results from the various sample types did not improve the diagnosis rate. Moreover, dynamic changes in SARS-Co V-2 viral load were more obvious in sputum and tracheal brushes than in nasal and throat swabs. Thus,SARS-Co V-2 nucleic acid detection in sputum and tracheal brushes was the least affected by infection route, disease progression, and individual differences. Therefore, SARS-Co V-2 nucleic acid detection using lower respiratory tract samples alone is reliable for COVID-19 diagnosis and study.

Differential analysis of intestinal microbiota and metabolites in mice with dextran sulfate sodium-induced colitis

BACKGROUND Intestinal micro-ecological imbalances impair the intestinal barrier and induce intestinal inflammation,for example,ulcerative colitis(UC).According to the latest research,abnormalities in intestinal microbiota structure and their metabolites play a dominant role in UC progression;in addition,they could affect the mucus barrier based on different factors.Although numerous studies have confirmed the important role of intestinal microbiota in UC pathogenesis,the intricate connection between microbiota and metabolites and mucus barrier in UC occurrence remains unclear,and correlation analyses of differential microbiota and their metabolites under UC are relatively scarce.AIM To reveal the differential intestinal microbiota and metabolites in UC pathogenesis and explore more sensitive biomarker compositions.METHODS We used the antibiotic combination method to establish intestinal pseudo-aseptic mice;afterward,dextran sulfate sodium(DSS)was applied to establish an acute experimental colitis mice model.Colitis severity,assessed based on disease activity index,colorectal length,colorectal wet weight,and histological lesions,and mucus-related staining(mucopolysaccharide alcian blue and immunofluorescence of mucin),was compared between the pseudo-aseptic and bacterial colitis mice.Finally,differential intestinal microbiota,metabolites,and their association and correlations,were analyzed by 16s rDNA sequencing in combination with non-targeted metabolomics,through gas chromatography-mass spectrometry.RESULTS Compared with the pseudo-aseptic mice,intestinal bacteria positive mice were more severely ill and their intestinal mucus loss was more pronounced in DSS-induced colitis(P<0.05),suggesting that different microbiota and metabolites could cause the different degrees of colitis.Subsequently,we observed that in addition to Klebsiella,and Bacteroides,which were widely associated with colitis,Candidatus Stoquefichus,Anaerobiospirillum,Muribaculum,and Negativibacillus may be involved in protection against colitis.Furthermore,differential metabolites of the microbiota were mainly enriched in the synthesis-related pathways of key structural sequences of mucin.In combination with the mucin-related staining and immunofluorescence results,the findings indicate that the differential microbiota and their metabolites potentially regulate the composition and function of mucus under colitis.CONCLUSION Microbiota and their metabolites are major factors regulating the composition and function of mucus,in turn influencing the function and structure of intestinal mucus barrier under colitis.The different microbiota and metabolites identified in the present study could be novel biomarkers for colitis.

Testing and data reduction of the Chinese Small Telescope Array(CSTAR) for Dome A,Antarctica

The Chinese Small Telescope Array （CSTAR） is the first Chinese astronomical instrument on the Antarctic ice cap. The low temperature and low pressure testing of the data acquisition system was carried out in a laboratory refrigerator and on the 4500 m Pamirs high plateau, respectively. The results from the final four nights of test observations demonstrated that CSTAR was ready for operation at Dome A, Antarctica. In this paper, we present a description of CSTAR and the performance derived from the test observations.

South Galactic Cap u-band Sky Survey(SCUSS):Project Overview

The South Galactic Cap u-band Sky Survey （SCUSS） was established in 2009 in order to provide a photometric input catalog for target selection of the Large Sky Area Multi-Object Fiber Spectroscopic Telescope （LAMOST） project. SCUSS is an international cooperative project between National Astronomical Observatories, Chinese Academy of Sciences, and Steward Observatory at the University of Arizona, using the 90 inch （2.3 m） Bok telescope on Kitt Peak. The telescope is equipped with a prime focus camera that is composed of a mosaic of four 4096 × 4096 CCDs and has a field of view of about 1 deg2. From 2009 to 2013, SCUSS performed a sky survey of an approximately 5000 deg2 field of the South Galactic Cap in u band, including the Galactic anticenter area and the SDSS-IV extended imaging area. The limiting magnitude of SCUSS is deeper than 23 mag （at a signal-to-noise ratio of 5）. In this paper, we briefly describe the goals of this project, method of observations and data reduction, and we also introduce current and potential scientific activities related to the SCUSS project.

Effects of triaxial deformation on the fission barrier in the Z=118−120 nuclei

By using potential energy surface(PES)calculations in the three-dimensional space(β_(2),γ,β_(4))within the framework of the macroscopic-microscopic model,the fission trajectory and fission barrier for Z=118(Og),119,120 nuclei has been systematically investigated.The calculated PES includes macroscopic liquid-drop energy,microscopic shell correction and pairing correction.Taking the ^(294)Og176 nucleus as an example,we discuss the next closed shell after Z=82 and N=126 with the calculated Woods-Saxon single-particle levels.Then,the results of PES in ^(294)Og is illustrated from the(X,Y)scale to the(β_(2),γ)scale.Theγdegree of freedom reveals the shape evolution clearly during the fission process.The structure near the minimum and saddle point of the PES in the Z=118,119,120 nuclei is demonstrated simultaneously.Based on the potential energy curves,general trends of the evolution of the fission barrier heights and widths are also studied.The triaxial deformation in these superheavy mass regions plays a vital role in the first fission barrier,showing a significant reduction in both triaxial paths.In addition,the model-dependent fission barriers of proton-rich nuclei ^(295)Og,296119,and 297120 are analyzed briefly.Our studies could be valuable for synthesizing the superheavy new elements in the forthcoming HIAF and other facilities.

Analysis of potential factors contributing to refusal of invasive strategy after ST-segment elevation myocardial infarction in China

Background:Reduced application of percutaneous coronary intervention(PCI)is associated with higher mortality rates after STsegment elevation myocardial infarction(STEMI).We aimed to evaluate potential factors contributing to the refusal of PCI in STEMI patients in China.Methods:We studied 957 patients diagnosed with STEMI in the emergency departments(EDs)of six public hospitals in China.The differences in baseline characteristics and 30-day outcome were investigated between patients who refused PCI and those who underwent PCI.Multivariable logistic regression was used to evaluate the potential factors associated with refusing PCI.Results:The potential factors contributing to refusing PCI were older than 65 years(odds ratio[OR]2.66,95%confidence interval[Cl]1.56-4.52,P<0.001),low body mass index(BMI)(OR 0.91,95%Cl 0.84-0.98,P=0.013),not being married(OR 0.29,95%Cl 0.17-0.49,P<0.001),history of myocardial infarction(MI)(OR 2.59,95%Cl 1.33-5.04,P=0.005),higher heart rate(HR)(OR 1.02,95%Cl 1.01-1.03,P=0.002),cardiac shock in the ED(OR 5.03,95%Cl 1.48-17.08,P=0.010),pre-hospital delay(>12 h)(OR 3.31,95%Cl 1.83-6.02,P<0.001)and not being hospitalized in a tertiary hospital(OR 0.45,95%Cl 0.27-0.75,P=0.002).Compared to men,women were older,were less often married,had a lower BMI and were less often hospitalized in tertiary hospitals.Conclusions:Patients who were older,had lower economic or social status,and had poorer health status were more likely to refuse PCI after STEMI.There was a sex difference in the potential predictors of refusing PCI.Targeted efforts should be made to improve the acceptance of PCI among patients with STEMI in China.

A near-infrared plasma membrane-specific AIE probe for fluorescence lifetime imaging of phagocytosis

Phagocytosis is a biological process that plays a key role in host defense and tissue homeostasis.Efficient approaches for real-time imaging of phagocytosis are highly desired but limited.Herein,an AIE-active near-infrared fluorescent probe,named TBTCP,was developed for fluorescence lifetime imaging of phagocytosis.TBTCP could selectively label the cell plasma membrane with fast staining,wash-free process,high signal-to-background ratio,and excellent photostability.Cellular membrane statuses under different osmolarities as well as macrophage phagocytosis of bacteria or large silica particles in early stages could be reported by the fluorescence lifetime changes of TBTCP.Compared with current fluorescence imaging methods,which target the bioenvironmental changes in the late phagocytosis stage,this approach detects the changes in the cell membrane,thus giving a faster response to phagocytosis.This article provides a functional tool to report the phagocytic dynamics of macrophages which may greatly contribute to the studies of phagocytic function-related diseases.

Reference intervals for steroid hormones in healthy 6-to 15-year-old girls based on liquid chromatography-tandem mass spectrometry in China

To the Editor:Adrenal and gonadal function can be evaluated by analyzing steroid hormone levels in different age groups,especially adolescent girls.Liquid chromatography-tandem mass spectrometry(LC-MS/MS or highperformance LC[HPLC]-MS/MS)offers a combination of the physical separation capabilities of HPLC and the mass analysis capabilities of tandem MS,which improves sensitivity and specificity in measuring steroid hormone levelsJ1,21 This method is more sensitive,effective,specific,and homogenous than other methods for analyzing children’s steroid hormone levels in the clinic.Studies on the reference intervals of steroid sex hormones have more commonly performed with Caucasian subjects than with Chinese subjects.^31 LC-MS/MS-based reference intervals for steroid hormones in China,especially for healthy girls,have not yet been reported.With LC-MS/MS becoming increasingly common,the establishment of reference intervals is growing more urgent.Here,we define appropriate reference ranges for pregnenolone,17ahydroxyprogesterone,corticosterone,dehydroepiandrosterone,androstenedione,and free testosterone.