Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Hepatitis B vaccine by intradermal route in non responder patients:An update

Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus (HBV) infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90% of general population. Individuals who develop an anti-HBs titer less than 10 mIU/mL after primary vaccination cycle are defined “no responders”. Many factors could cause a non response to the HBV vaccination, such as administration of the vaccine in buttocks, impaired vaccine storage conditions, drug abuse, smoking, infections and obesity. Moreover there are some diseases, like chronic kidney disease, human immunodeficiency virus infection, chronic liver disease, celiac disease, thalassaemia, type I diabetes mellitus, down’s syndrome and other forms of mental retardation that are characterized by a poorer response to HBV vaccination than healthy subjects. To date it is still unclear how to treat this group of patients at high risk of hepatitis B infection. Recent studies seem to indicate that the administration of HBV recombinant vaccine by the intradermal route is very effective and could represent a more useful strategy than intramuscular route. This review focuses on the use of anti hepatitis B vaccine by intradermal route as alternative to conventional intramuscular vaccine in all non responder patients. A comprehensive review of the literature using PubMed database, with appropriate terms, was undertaken for articles in English published since 1983. The literature search was undertaken in September 2013.

Recent advances in vaccination of non-responders to standard dose hepatitis B virus vaccine

Hepatitis B virus(HBV) infection is a global health problem. It is estimated there are more than 2 billion individuals exposed to the virus and 250 million are chronically infected. Hepatitis B is the cause of more than 600000 annual deaths due to cirrhosis and hepatocellular carcinoma. An effective vaccine exists and preventative initiatives center around universal vaccination especially in those at highest risk. Effective vaccination algorithms have led to a significant decline in the development of new infections and its devastating consequences. The vaccine is administered intramuscularly in three doses, with 95% showing long lasting serologic immunity. An additional fourth dose or a repeated higher dose three course regimen is given to those that fail to show immunity. Despite these additional regimens, some remain vulnerable to hepatitis B and are deemed nonresponders. Individuals with chronic disease states such as kidney disease, liver disease, diabetes mellitus, as well as those with a genetic predisposition, and those on immunomodulation therapy, have the highest likelihood of non-response. Various strategies have been developed to elicit an immune response in these individuals. These include increased vaccination dose, intradermal administration, alternative adjuvants, alternative routes of administration, co-administration with other vaccines, and other novel therapies. These alternative strategies can show improved response and lasting immunity. In summary, HBV vaccination is a major advance of modern medicine and all individuals at risk should be sought and vaccinated with subsequent adequate titers demonstrated.

Clinical characteristics of null responders to Peg-IFNα2b/ ribavirin therapy for chronic hepatitis C

AIM: To predict which chronic hepatitis C patients are likely to be late-responders, we herein investigated the clinical characteristics of null-responders at 36 wk with hepatitis C virus (HCV) genotype Ib and a high viral load during the course of pegylated interferon (Peg-IFN)/ ribavirin ther apy. METHODS: One hundred forty-two patients with genotype Ib HCV and a high viral load were included in this study. Peg-IFNα2b (1.5 μg/kg once a week) and ribavirin (600-1000 mg per day according to body weight) were administered for 48 wk. We def ined nullresponders as the cases that never cleared serum HCV RNA as determined using RT-PCR until 36 wk. Other patients were def ined as responders. We compared the clinical characteristics (age, gender, body mass index, previous treatment) and HCV RNA titer during the therapy between null-responders and responders.RESULTS: The HCV RNA clearance rate was 17.9% (24/134), 46.3% (62/134), 60.6% (86/142), 86.6% (123/142), and 88.0% (125/142) at 4, 8, 12, 24, and 36 wk, respectively. There were 17 patients (12.0%) who were still null-responders at 36 wk. There were no differences in the clinical characteristics between the responders and null-responders except for the titer and decline rates of HCV RNA at 1 wk and 4 wk. The HCV RNA titers at 1 wk and after 4 wk of treatment were significantly higher in the null-responders in comp arison to the responders (P <0.01). The serum HCV RNA titers of the responders decreased by 1.3 log after 1 wk of treatment, and 1.6 log after 4 wk of treatm ent, respectively. On the other hand, the titers of the null responders decreased by only 0.5 log after 1 wk, and 0.7 log after 4 wk of treatment, respectively. The decrease rates of HCV RNA after 1 and 4 wk of treatm ent were signif icantly worse for null responders than for the responders (P <0.01). CONCLUSION: The HCV RNA titer at 1 wk and 4 wk after initiating treatment may be useful for predicting null-responders to Peg-IFNα2b/ribavirin therapy. However, further investigation is needed to determine the optimal time at which the decision to discontinue the Peg-IFNα2b/ribavirin therapy for null-responders can be made.

Based on the Characteristics of Respondents and the Voice of the Urban Neighborhood Public Space Business Facilities Noise Environment Evaluation Research

Comfort is one of the important indicators evaluation of voice. In order to understand the urban neighborhood public space environment of comfort,this paper is to explore characteristics of consumer society on the public space environment evaluation of the effect,and using the questionnaire survey method,to evaluate the Harbin city neighborhood area public space as the typical case analysis. Based on one of the main sound source in neighborhood public space,environment,business facilities environment as the breakthrough point,it is to consider neighborhood public space environment evaluation and social characteristics.

Cumulative Live Birth Rate after Three Ovarian Stimulation IVF Cycles for Poor Ovarian Responders According to the Bologna Criteria

Summary： This study explored the cumulative live birth rate after three ovarian stimulation in vitro fer- tilization （IVF） cycles for poor ovarian responders according to the Bologna criteria. In this retrospec- tive cohort study, 479 poor ovarian responders according to the Bologna criteria in the first ovarian stimulation IVF cycle between July 2006 and January 2012 in our IVF centre were included. The cu- mulative live birth rate was calculated by optimistic and pessimistic methods. The cumulative live birth rate after three ovarian stimulation IVF cycles for poor ovarian responders according to the Bologna criteria was 12.7%-20.5%. The three-cycle cumulative live birth rate was 18.5%--24.5%, 13.2%-27.4% and 8.6%-14.9% for poor responders aged ≤35 years, 36-39 years and 〉40 years, re- spectively. In conclusion, poor responders according to the Bologna criteria can receive an acceptable cumulative live birth, rate after three ovarian stimulation IVF cycles, especially poor responders aged 〈40 years.

Does ‘super-responder’ patients to cardiac resynchronization therapy still have indications for neuro-hormonal antagonists? Evidence from long-term follow-up in a single center

Background Whether cardiac resynchronization therapy super-responders (CRT-SRs) still have indications for neuro-hormonal antagonists or not remains uninvestigated.Methods We reviewed clinical data from 376 patients who underwent CRT implantation in Fuwai Hospital from 2009 to 2015 and followed up to 2017.CRT-SRs were defined by an improvement of the New York Heart Association functional class and left ventricular ejection fraction to ≥ 50% in absolute values at 6-month follow-up.All CRT-SRs were assigned into two groups on the basis of whether persistently receiving neuro-hormonal antagonists (NHA)(defined as angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers and β-blockers) after 6-month follow-up and then we compared long-term outcome.Results A total of 60 patients met criteria for super-response.One of thirteen (7.7%) CRT-SRs without NHA had all-cause death,which also occurred in 2 of 47 (4.3%) in CRT-SRs with NHA (P = 0.526).However,3 of 13 (23.1%) CRT-SRs without NHA had heart failure (HF) hospitalization,1 of 47 (2.1%) CRT-SRs with NHA had this endpoint (P = 0.040).Besides,subgroup analysis indicated that,for ischemic etiology group,CRT-SRs receiving NHA had considerably lower incidence of HF hospitalization than those without NHA (0 vs.75%,P = 0.014),which was not observed in non-ischemic etiology group (2.6% vs.0,P = 1.000) during long-term follow-up.Conclusions Our study found that for ischemic etiology,compared with CRT-SRs with NHA,CRT-SRs without NHA were associated with a higher risk of HF hospitalization.However,for non-ischemic etiology,we found that CRT-SRs with NHA or without NHA at follow-up were associated with similar outcomes,which needed further investigation by prospective trials.

Responding Depth of Photocatalytic Activity of TiO_2 Self-assembled Films

The electrostatically self-assembly method is getting strategically important to prepare multilayer thin films. With careful choice of component materials, this method should allow for the preparation of multilayer thin films with a variety of excellent technological properties. Ti02/PSS multilayer thin films with ordered structure were prepared by electrostatic self-assembly method. UV-Vis-NIR spectrophotometer, X-ray photoelectron spectroscopy (XPS), and atom force microscopy (AFM) were used to characterize the structure and performance of the multilayer films. Because electrostatically self-assembly method allows molecular-level control over the film composition and thickness, this paper studied the responding depth of photocatalytic activity of Ti02 self-assembled films in detail.

Critical velocity and dynamic respondency of pipe conveying fluid

Presents the calculation of critical velocity, natural frequency and dynamic respondency of fluid conveying pipe are calculated under different boundary conditions using finite element method, and the use of calculation results to design and research rocket pipes feeding fuel and watery turbine pipes conveying water etc.

Responding to fire in an intensive care unit: Management and lessons learned

Healthcare institutions are vulnerable to disruptionfrom events such as earthquakes, fires, and floods, andthe damage incurred can endanger the lives of patientsin the hospital.[1] In this type of scenario hospital staffhave primary responsibility for the hospitalized patients＇safety, since patients are neither fit to respond to sucha disaster, nor do they know how to respond.[2,3] Thesituation becomes more difficult and challenging if thedisaster occurs in critical care areas such as intensivecare units （ICUs） and operating rooms.

Aromatase Inhibitors for IVF Poor Responders

Objective To evaluate whether letrozole enhanced follicular recruitment, embryo numbers, and pregnancy rates in poor responders undergoing IVF. Methods We reviewed all IVF cycles between January 2002 and September 2003 using letrozole at Stanford University Medical Center. The entry criteria were the requirement of at least 450 IU/d of injectable gonadotropins in a prior failed cycle, which was used as a control. Results A total of 27 charts were reviewed revealing information on 54 cycles. The number of oocytes retrieved, fertilization, embryo quality and embryos transferred yielded no statistical significance, although there appeared to be a trend toward higher numbers of each in the letrozole group. The clinical pregnancy rate was 9/27 （33.3%, P〈0.001） with a viable pregnancy rate of 7/27 （25.9%, P=0. 002） in the Ietrozole cycle. Conclusion Our study is one of the first to evaluate letrozole with in vitro fertilization. Although this study showed no difference in number of oocytes or embryos, 25.9% of these ＂poor responding＂ patients achieved a pregnancy after a failed cycle at our center.

Ribavirin monotherapy increases sustained response rate in relapsers of end treatment virologic responders

AIM: To assess the efficacy of ribavirin monotherapy in patients with biochemical relapse after combination therapy.METHODS: Twenty-four weeks of ribavirin monotherapy was given to biochemical relapsers of end treatment biochemical responders within 6 mo after combination therapy, including non-responders with HCV-RNA level ≤0.2 Meq/mL and end treatment virologic responders (ETVRs) with or without reappearance of HCV-RNA.RESULTS: Sixty-two chronic HCV-infected patients completed 24 wk of interferon-α plus ribavirin combination therapy. Fifty patients (80%) achieved end treatment biochemical response including 16 non-responders and 34 of 36 ETVRs. Twenty-six patients (41.9%) were nonresponders. Ribavirin monotherapy was given to 20biochemical relapsers including 12 non-responders with HCV-RNA levels ≤0.2 Meq/mL, four of eight HCV-RNA reappearing ETVRs, and four HCV-RNA negative ETVRs.After 24 wk of ribavirin monotherapy, one of 12 nonresponders, two of four HCV-RNA reappearing ETVRs and all four RNA-negative biochemical relapsers of ETVRs showed sustained virologic response. Two of 12monotherapy treated non-responders showed persistent normalization of liver function test. In total, 50% (31/62)of patients achieved sustained virologic response.CONCLUSION: Resumption of ribavirin monotherapy in ETVRs at signs of viral rebound and recurrent biochemical abnormalities rather than continuation of monotherapy appears to be the key to success of ribavirin monotherapy after interferon-related combination therapy.

The Challenge of Improving IVF Results in Normogonadotrophic (Unexpected) Young Poor Ovarian Responders: The Predictive Value of a Flexible Treatment Protocol Based on the “Biophysical Profile of the Uterus”

Objective: To study whether the unexpected poor ovarian responders optimization of uterine receptivity with a flexible controlled ovarian hyper stimulation protocol based on the Biophysical Profile of the Uterus, has an impact on their reproductive performance. Design: Observational Prospective study. Setting(s): i) General hospital-IVF and Infertility Centre;ii) University hospital. Patient(s): 44 normogonadotrophic young women (26 - 38 yrs) with previous “unexpected” poor ovarian response underwent IVF/ICSI treatment on a protocol based on the Biophysical Profile of their uterus (Group A). The same patients were used as controls in a preceded IVF cycle on the conventional stimulation protocol. Intervention(s): None. Main outcome measure(s): Pregnancy, miscarriage and home take baby rates, amount and duration of gonadotropins required, number and quality of embryos resulted, Biophysical Profile of the Uterus score. Result(s). Treatment in Group A in comparison to Group B resulted in significantly larger number of eggs retrieved per patient, and improved fertilization rates and higher number of embryos/ET (p = 0.011, 0.010 and 0.034 respectively). Group A also demonstrated a trend for higher rates of clinical pregnancy (29.5% v.s. 15.9%), viable stage pregnancies ≥ 24 weeks (33.3% v.s. 20%) and home take babies (26.6% v.s. 16%). The amount of gonadotropins used per patient (IU) was similar in the two groups (p = 0.264). Cancellation, implantation and miscarriage rates as well as embryos quality, although superior in the treatment Group A, showed no significant difference. The number of pregnancies achieved in Group A, were directly related with the score in the Biophysical Profile of the Uterus 12 point scale. Conclusion(s): Unexpected Poor Ovarian Responders on the flexible IVF/ICSI protocol (Group A), adjusting the management according to the Biophysical Profile of their uterus (duration of stimulation, day of HCG and day of embryo transfer), had a significantly better performance in comparison to the Group B managed on the conventional protocol in this difficult to manage and so far, rather understudied population.

Revisiting the Outsiders: Innovative Recruitment of a Marijuana User Network via Web-Based Respondent Driven Sampling

This study uses an innovative, network-based recruitment strategy (non-monetary, web-based respondent driven sampling) to gather a sample of il/legal marijuana users. Network-driven effects amongst marijuana users are examined to test the explanatory validity of several theories of social deviance. The study finds that respondent driven sampling techniques lack effectiveness without primary monetary incentives, even when meaningful secondary incentives are utilized. Additionally, the study suggests that marijuana user networks exhibit strong homophilic attachment tendencies.

Biomarkers,a Useful Correction for Respondent Error in Survey Research

One long standing limitation of survey research is the issue of respondent error.Until present there have been no research methods able to correct for this problem.In this study we present two approaches to correct for respondent error.In the first approach,we demonstrate how a valid instrument can be used,and the second approach requires two additional indicators.One is used to measure the response error and the second is used to correct for endogeneity.The second half of this study presents possible sources for valid indicators to correct for respondent error and make consistent estimation possible.

GnRH Antagonist Protocol: Is It Effective for Expected Poor Ovarian Responders with Tubal Factor Undergoing IVF?

Background: This study aimed to determine if the gonadotropin releasing hormone (GnRH) antagonist protocol is optimal for expected poor ovarian responders with tubal factor undergoing in vitro fertilization-embryo transfer (IVF-ET). Methods: A total of 341 IVF-ET cycles were retrospectively identified. The following inclusion criteria were applied: age ≥ 40 years and patients with tubal factors. The cycles were divided into two groups: a GnRH antagonist group (157 cycles) and a GnRH agonist group (184 cycles). Results: The duration of stimulation and the total doses of gonadotropin in the GnRH agonist group were significantly more than those in the GnRH antagonist group (P < 0.05). There were significant differences in LH and P values on the hCG measurement days between the two groups (0.91 ± 1.17 vs. 4.82 ± 4.69 U/L and 0.69 ± 0.42 vs. 1.03 ± 0.50 ng/mL, P < 0.05). The implantation rate of the GnRH antagonist group was 12.24%, which was slightly higher than that of the GnRH agonist group (10.10%, P = 0.437). The clinical pregnancy rate of the two groups showed no statistical differences (23.36% vs. 23.03%, P = 1.000). Conclusion: For expected poor ovarian responders, the GnRH antagonist protocol was, to some extent, superior to the GnRH agonist protocol in terms of the implantation and clinical pregnancy rates.

Emplacement Depths and Exhumation of Mesozoic Granitoids Responding to Lithospheric Destruction in the Jiaodong Peninsula, North China Craton

1 Introduction The North China Craton(NCC)has experienced lithospheric destruction in Mesozoic accompanied with crustal exhumation.Fission track or(U-Th)/He dating of zircon and apatite for the Mesozoic granitoids in the

INTRAMUSCULAR VERSUS INTRADERMAL HEPATITIS B REVACCINATIONIN HEALTHY NON-RESPONDER CHILDREN: A 5-YEAR PROSPECTIVE RANDOMIZED STUDY

Objective With the same times of injection to compare low-dose intradermal regimen with routine-dose intramuscular inoculation in revaccination of non-responders to hepatitis B vaccine. Methods 40 healthy non-responder children collected by screening were administrated a three-dose revaccination randomly by intramuscular or intradermal route (10vs 2g per dose), and regularly tested for serologic markers up to five years. By the end of follow-up, a booster dose (5μg) was given to those who had lost anti-HBs of ≥10mIU/mL (seroprotection) and anamnestic response was estimated thereafter. Results All 17 intramuscular and 22 of 23 intradermal children effected seroprotection after revaccination. Intradermal children lost seroprotection over time significantly rapider compared with intramuscular children (Log Rank test, P= 0.029). In year 5, 50% of intramuscular but only 18.2% of intradermal children still maintained seroprotection (P=0.075). 12-14 days after the booster dose, all the eight intramuscular children developed an anamnestic response with anti-HBs titer increasing greater, but two of the 18 intradermal children failed to mount seroprotective level. Conclusion Three-routine-dose intramuscular revaccination was significantly effective than low-dose intradermal one with the same times of injection, especially in long-term immunity. We recommend routine-dose intramuscular protocol in revaccination of non-responders.

China Responds to Trade Tensions Responsibly

IN March 2018, the United States slapped tariffs of 25 percent on steel imports and 10 percent on aluminum in the name of national security under Section 232 of the Trade Expansion Act of 1962. Then, the Office of the United States Trade Representative released a report on the investigation of China under Section 301 of the Trade Act of 1974, claiming China＇s acts, policies, and practices regarding technology transfer, intellectual property, and innovation are “unreasonable and discriminatory, and burden U.S. commerce.”