The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological ...The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).展开更多
Hepatocellular carcinoma(HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection(HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introductio...Hepatocellular carcinoma(HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection(HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introduction of the new direct acting antivirals(DAAs) has revolutionized the management of HCV worldwide, with high rates of sustained virologic response in patients who could not have tolerated the previous interferon based treatments. However, recently there have been reports raising caution about the long term effects of DAAs, particularly a possible increased risk of HCC. Therefore this review explores the current molecular studies as well as clinical data that investigate the impact of DAAs on occurrence and recurrence of HCC.展开更多
The object of the study was to develop a quick and reproducible accelerated in vitro release method to predict and deduce the function of the real time(37 °C) release for long acting PLGA microspheres. The method...The object of the study was to develop a quick and reproducible accelerated in vitro release method to predict and deduce the function of the real time(37 °C) release for long acting PLGA microspheres. The method could be described in several steps. First, the release of the microspheres were studied using the sample and separate method at 37 °C with normal orbital shaking and elevated temperatures with magnetic stirring to further accelerate the release. Second, the most similar profile at elevated temperatures with the real time release was chosen with the help of the n value in the fitted Korsmeyer-Peppas Function. Third,the Weibull function and conversion ratio were used to deduce the function of real time release according to the chosen profile at elevated temperatures. The key point in this study was to provide a quick and precise method to predict the real time release for long acting progesterone PLGA microspheres. So the elevated temperatures coupled with magnetic stirring were used to accelerate the release further, and when there have many similar release profiles with the real time release at elevated temperatures, releasing time at elevated temperatures and the R2 of the final deduced function will be used to help choosing the most similar release profile with the real time release. Four different types of progesterone PLGA microspheres were used to verify the method, and all the deduced function correlated well with the real time releases, for R2 = 0.9912, 0.9781, 0.9918 and 0.9972, respectively.展开更多
Hepatitis C virus(HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and welltolerated therapies. In the last 3 years, the approval of n...Hepatitis C virus(HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and welltolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylatedinterferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.展开更多
AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due t...AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49 ± 6 wk) as compared to the control group (28 ± 1 wk) and to the SSTR negative group (28 ± 2 wk), LR = 20.39, df = 2, P < 0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the f irst year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group respectively.CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.展开更多
Autoimmune phenomena are common in patients with chronic hepatitis C. Management of chronic hepatitis C/autoimmune hepatitis syndrome has until recently been problematic due to the adverse effects of interferon on aut...Autoimmune phenomena are common in patients with chronic hepatitis C. Management of chronic hepatitis C/autoimmune hepatitis syndrome has until recently been problematic due to the adverse effects of interferon on autoimmune processes and immunosuppression on viral replication. In this report we describe 3 patients with chronic hepatitis C/autoimmune hepatitis overlap syndrome who responded rapidly to direct acting antiviral therapy. The resolution of the autoimmune process supports a direct viral role in its pathophysiology.展开更多
The effects of methylene methanedisulfonate(MMDS) on the high-temperature(0℃) cycle performance of LiMnO/graphite cells are investigated.By addition of 2 wt%MMDS into a routine electrolyte,the high-temperature cy...The effects of methylene methanedisulfonate(MMDS) on the high-temperature(0℃) cycle performance of LiMnO/graphite cells are investigated.By addition of 2 wt%MMDS into a routine electrolyte,the high-temperature cycling performance of LiMn204/graphite cells can be significantly improved.The analysis of differential capacity curves and energy-dispersive X-ray spectrometry(EDX) indicates that MMDS decomposed on both cathode and anode.The three-electrode system of pouch cell is used to reveal the capacity loss mechanism in the cells.It is shown that the capacity fading of cells without MMDS in the electrolytes is due to irreversible lithium consumption during cycling and irreversible damage of LiMnOmaterial,while the capacity fading of cell with 2 wt%MMDS in electrolytes mainly originated from irreversible lithium consumption during cycling.展开更多
BACKGROUND Alterations in health-related quality of life(HRQoL)and neuropsychological disorders were described in the hepatitis C virus(HCV)patients.Although several studies investigated the modifications of HRQoL aft...BACKGROUND Alterations in health-related quality of life(HRQoL)and neuropsychological disorders were described in the hepatitis C virus(HCV)patients.Although several studies investigated the modifications of HRQoL after HCV eradication,no data exists on the modifications of neuropsychological symptoms.AIM To investigate the effect of directly acting antivirals(DAAs)treatment on HRQoL and neuropsychological symptoms.METHODS Thirty nine patients with HCV infection underwent a neuropsychological assessment,including Zung-Self Depression-Rating-Scale,Spielberg State-Trait Anxiety Inventory Y1-Y2 and the Toronto-Alexithymia Scale-20 items before and after DAAs treatment.HRQoL was detected by Short-Form-36(SF-36).RESULTS All HRQoL domains,but role limitation physical and bodily pain,significantly improved after treatment.Interestingly,after DAAs treatment,all domains of HRQoL returned similar to those of controls.Each neuropsychological test significantly improved after HCV eradication.A significant correlation was observed among each psychological test and the summary components of SF-36.At multiple linear regression analysis including each psychological test as possible covariates,Zung-Self Depression Rating Scale(Zung-SDS)score was independently and significantly related to summary components of the SF-36 in the basal state and the difference between Zung-SDS score before and after treatment was the only variable significantly and independently related to the modification of HRQoL induced by the treatment.CONCLUSION Neuropsychological symptoms strongly influenced HRQoL in HCV patients and there was a significant improvement of neuropsychological tests and HRQoL after DAAs treatment.展开更多
AIM To assess the efficacy and safety of combined directly acting antivirals(DAAs) for the treatment of Chinese chronic hepatitis C(CHC) patients in a real-world setting.METHODS Hospitalized CHC patients who were trea...AIM To assess the efficacy and safety of combined directly acting antivirals(DAAs) for the treatment of Chinese chronic hepatitis C(CHC) patients in a real-world setting.METHODS Hospitalized CHC patients who were treated with DAAs at Peking University First Hospital between January 2015 and December 2016 were enrolled. Samples and clinical data were collected at 0 wk, 2 wk, 4 wk, 8 wk, 12 wk, or 24 wk during DAAs treatment and at 4 wk, 12 wk, and 24 wk after the end of treatment. RESULTS Fifty-four patients who underwent DAAs treatment were included in our study, of whom 83.3%(45/54) achieved rapid virological response at 2 wk after treatment initiation(RVR 2) and 94.4%(51/54)achieved sustained virological response at 24 wk after the end of treatment(SVR 24). Serum creatinine and uric acid levels at the end of treatment were significantly increased compared with baseline levels(83.6 ± 17.9 vs 88.8 ± 19.4, P 01 < 0.001; 320.8 ± 76.3 vs 354.5 ± 87.6, P 01 < 0.001), and no significant improvements were observed at 24 w after the end of treatment(83.6 ± 17.9 vs 86.8 ± 19.1, P 02 = 0.039; 320.8 ± 76.3 vs 345.9 ± 89.4, P 02 = 0.001). The total frequency of adverse events(AEs) during treatment was 33.3%(18/54), with major AEs being fatigue(16.7%), headache(7.4%), anorexia(7.4%), and insomnia(5.6%). CONCLUSION Though based in a small cohort of patients, the abnormal changes in renal function indices and relative high frequency of AEs during combined DAAs treatment should be taken as a note of caution.展开更多
Intramuscular injections can cause damage to arteries, veins and nerves. Achieving maximum effects of medications through precise intramuscular (IM) injections must be assured and with certainty, particularly with lon...Intramuscular injections can cause damage to arteries, veins and nerves. Achieving maximum effects of medications through precise intramuscular (IM) injections must be assured and with certainty, particularly with long-acting injection drugs (LAI). The purpose of this study is to determine precision in IM LAIs of patients with schizophrenia. These evidences estimate “Distance from the Epidermis to the Under-Fascia” (DEUF) and “Distance from Epidermis to the Upper-Arm Bone” (DEB) of the deltoid muscle. Explanatory variables include body height, weight, body-mass index (BMI), deltoid-muscle circumference, fat percentage and muscle mass measured by body composition monitor. Sixty nine subjects are included based on the Diagnostic Statistical Manual of Mental Disorders (DSM-IV, 1994), and receive treatments of typical and atypical antipsychotic LAI. There are 46 males and 23 females with average age of 51.41 (Standard Deviation = 13.58) and ranging from 21 to 81 years who are all right-handed. Ultrasonographic data and those from explanatory variables are calculated using Spearman’s rank correlation coefficients. Multiple regression analysis (step-wise method/forced input method) is performed assuming DEUF or DEB as dependent variables. Significant correlations are found with highest adjusted R-square. Paired t-tests show differences in average values of actual ultrasonographic measurements assigned to DEUF or DEB, and the regression equations for accuracy. Ultrasonographic values are assigned multiple-regression equations as true values, and the calculated values are compared with those obtained by regression equations. There are no significant differences observed for either the right or left arm. The multiple regression equations for BMI and fat percentages (upper extremity estimation) of DEUF, and for BMI and injection site circumference of estimated DEB, successfully value the DEUF and DEB. By using these multiple regression equations for IM injection to the deltoid-muscle, DEUF can better ensure accurate LAI into the muscle through body monitor, DEB, and measured values of the deltoid-muscle injection site circumference.展开更多
Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have step...Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents(DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.展开更多
Twitter has become very popular among celebrities. It is the main platform used by them to publish press releases and, especially, to reach out to their fans. Given the pervasiveness of celebrities on the site, people...Twitter has become very popular among celebrities. It is the main platform used by them to publish press releases and, especially, to reach out to their fans. Given the pervasiveness of celebrities on the site, people with related interests may be especially likely to start using the service due to the perception of direct access to a famous person. As for the celebrities, it is a way of being close to the public and giving them an insight in to the life of a celebrity. Although most celebrity Twitter accounts are only used for promotion purposes, many celebrities use their personal accounts for the purpose of communicating with their fans, friends and other celebrities. These celebrities tweet personal photos and share their inner thoughts for various reasons and to different audiences. Thus in this study I ask: What are celebrity speech patterns on Twitter? Are they talking mostly to fans, and if not, who are they talking to? How are they talking to these different audiences? I address these questions by analyzing the tweets publicly available on four active celebrities’ Twitter timelines. The findings support that these celebrities indeed address different audiences on Twitter, including fans, friends, family and other celebrities. The findings further reveal that celebrities tend to communicate using different speech acts when talking to these different audiences. In light of this evidence, I attempt to highlight patterns that may be relevant with regards to the celebrities’ gender.展开更多
The publishing conference of the Chinese version of National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (hereinafter referred to as NCCN Guidelines) and the inaugural peer reviewe...The publishing conference of the Chinese version of National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (hereinafter referred to as NCCN Guidelines) and the inaugural peer reviewer meeting of NCCN Clinical Practice Guidelines in Oncology: Digestive System Cancers (hereinafter referred to as NCCN Guidelines on Digestive System Cancers) were held in People's Medical Publishing House in January 28^th, 2016 (Figure 1).展开更多
[Objective] The aim was to explore the achievement motivation of the university student village officials in the suburbs of Beijing.[Method] The research made an investigation on 429 university student village officia...[Objective] The aim was to explore the achievement motivation of the university student village officials in the suburbs of Beijing.[Method] The research made an investigation on 429 university student village officials in the suburbs of Beijing by the Achievements Motive Scale(AMS).[Result] The achievement motivation of these student village officials was not on a high level,but they tended to pursue the success motivation rather than the motivation to avoid failures obviously.There was a significant difference in the achievement motivation between different genders,majors and jobs.The males' motivation for success was higher than the females'.The motivation of avoiding failures among officials in Humanities was higher than in Science and in Fine Art.And the university student village officials in professional and technical posts or in business posts rated the motivation to avoid failures more important than in basic management posts.But achievement motivations in different urban-rural areas,educational levels,political backgrounds,whether student leaders or not,and durations were no definite differences.Besides,it had a significant effect on these student village officials' achievement motivation whether advices and suggestions were accepted;if yes,the motivation was higher.[Conclusion] This study had provided stability and development for building rural talent groups.展开更多
Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Cons...Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.展开更多
The use of direct-acting antivirals(DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response(around 90%-95%) as compared with the standard treatment of peginterfer...The use of direct-acting antivirals(DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response(around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants(RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These preexisting RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.展开更多
MicroRNAs (miRNAs) are derived from distinct loci in the genome and play crucial roles in RNA-mediated gene silencing mechanisms that regulate cellular processes during development and stress responses of plants. Th...MicroRNAs (miRNAs) are derived from distinct loci in the genome and play crucial roles in RNA-mediated gene silencing mechanisms that regulate cellular processes during development and stress responses of plants. The miRNAs are approximately 21 nucleotides long and code for the complementary strand to a larger genic mRNA. They are often found within the complementary primary transcript (pri-miRNAs). In the past few years, a growing number of soybean miRNAs have been discovered, however, little is known about the transcriptional regulation of these miRNAs. In this study, promoters and cis-acting elements of soybean miRNAs were analyzed using the genomic data for the first time. A total of 82 miRNAs were located among 122 loci in genome, some were present as double or multiple copies. Five clusters that included ten miRNAs were found in genome, and only one cluster share the same promoter. A total of 191 promoters from 122 loci of the soybean miRNA sequences were found and further analyzed. The results indicated that the conserved soybean miRNA genes had a greater proportion of promoters than that of non-conserved ones, and the distribution of the transcript start sites (TSSs) and TATA-boxes found had different motif styles between conserved and non-conserved miRNA genes. Furthermore, the cis-acting elements 5' of the TSSs were analyzed to obtain potential function and spatiotemporal expression pattern of miRNAs. The data obtained here may lead to the identification of specific sequences upstream of pre-miRNAs and the functional annotation of miRNAs in soybean.展开更多
BACKGROUND Direct acting antiviral(DAA)therapy has enabled hepatitis C virus infection to become curable,while histological changes remain uncontained.Few valid noninvasive methods can be confirmed for use in surveill...BACKGROUND Direct acting antiviral(DAA)therapy has enabled hepatitis C virus infection to become curable,while histological changes remain uncontained.Few valid noninvasive methods can be confirmed for use in surveillance.Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid(Gd-EOB-DTPA)is a liver-specific magnetic resonance imaging(MRI)contrast,related to liver function in the hepatobiliary phase(HBP).Whether Gd-EOB-DTPA-enhanced MRI can be used in the diagnosis and follow up of hepatic fibrosis in patients with chronic hepatitis C(CHC)has not been investigated.AIM To investigate the diagnostic and follow-up values of Gd-EOB-DTPA-enhanced MRI for hepatic histology in patients with CHC.METHODS Patients with CHC were invited to undergo Gd-EOB-DTPA-enhanced MRI and liver biopsy before treatment,and those with paired qualified MRI and liver biopsy specimens were included.Transient elastography(TE)and blood tests were also arranged.Patients treated with DAAs who achieved 24-wk sustained virological response(SVR)underwent Gd-EOB-DTPA-enhanced MRI and liver biopsy again.The signal intensity(SI)of the liver and muscle were measured in the unenhanced phase(UEP)(SI_(UEP-liver),SI_(UEP-muscle))and HBP(SI_(HBP-liver),SI_(HBP-muscle))via MRI.The contrast enhancement index(CEI)was calculated as[(SI_(HBP-liver)/SI_(HBP-muscle))]/[(SI_(UEP-liver)/SI_(UEP-muscle))].Liver stiffness measurement(LSM)was confirmed with TE.Serologic markers,aspartate aminotransferase-to-platelet ratio index(APRI)and Fibrosis-4(FIB-4),were also calculated according to blood tests.The grade of inflammation and stage of fibrosis were evaluated with the modified histology activity index(mHAI)and Ishak fibrosis score,respectively.Fibrosis regression was defined as a≥1-point decrease in the Ishak fibrosis score.The correlation between the CEI and liver pathology was evaluated.The diagnostic and follow-up values of the CEI,LSM,and serologic markers were compared.RESULTS Thirty-nine patients with CHC were enrolled[average age,42.3±14.4 years;20/39(51.3%)male].Twenty-one enrolled patients had eligible paired Gd-EOB-DTPA-enhanced MRI and liver tissues after achieving SVR.The mHAI median significantly decreased after SVR[baseline 6.0(4.5-13.5)vs SVR 2.0(1.5-5.5),Z=3.322,P=0.017],but the median stage of fibrosis did not notably change(P>0.05).Sixty pairs of qualified MRI and liver tissue samples were available for use to analyze the relationship between the CEI and hepatic pathology.The CEI was negatively correlated with the mHAI(r=-0.56,P<0.001)and Ishak score(r=-0.69,P<0.001).Further stratified analysis showed that the value of the CEI decreased with the progression of the stage of fibrosis rather than with the grade of necroinflammation.For patients with Ishak score≥5,the areas under receiver operating characteristics curve of the CEI,LSM,APRI,and FIB-4 were approximately at baseline,0.87–0.93,and after achieving SVR,0.83–0.91.The CEI cut-off value was stable(baseline 1.58 and SVR 1.59),but those of the APRI(from 1.05 to 0.24),FIB-4(from 1.78 to 1.28),and LSM(from 10.8 kpa to 7.1 kpa)decreased dramatically.The APRI and FIB-4 cannot be used as diagnostic means for SVR in patients with Ishak score≥3(P>0.05).Seven patients achieved fibrosis regression after achieving SVR.In these patients,the CEI median increased(from 1.71 to 1.83,Z=-1.981,P=0.048)and those of the APRI(from 1.71 to 1.83,Z=-2.878,P=0.004)and LSM(from 6.6 to 4.8,Z=-2.366,P=0.018)decreased.However,in patients without fibrosis regression,the medians of the APRI,FIB-4,and LSM also changed significantly(P<0.05).CONCLUSION Gd-EOB-DTPA-enhanced MRI has good diagnostic value for staging fibrosis in patients with CHC.It can be used for fibrotic-change monitoring post SVR in patients with CHC treated with DAAs.展开更多
文摘The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).
文摘Hepatocellular carcinoma(HCC) is a major cause of morbidity and mortality worldwide. Chronic hepatitis C virus infection(HCV) is the most common cause of HCC in many European countries, Japan and Pakistan. Introduction of the new direct acting antivirals(DAAs) has revolutionized the management of HCV worldwide, with high rates of sustained virologic response in patients who could not have tolerated the previous interferon based treatments. However, recently there have been reports raising caution about the long term effects of DAAs, particularly a possible increased risk of HCC. Therefore this review explores the current molecular studies as well as clinical data that investigate the impact of DAAs on occurrence and recurrence of HCC.
文摘The object of the study was to develop a quick and reproducible accelerated in vitro release method to predict and deduce the function of the real time(37 °C) release for long acting PLGA microspheres. The method could be described in several steps. First, the release of the microspheres were studied using the sample and separate method at 37 °C with normal orbital shaking and elevated temperatures with magnetic stirring to further accelerate the release. Second, the most similar profile at elevated temperatures with the real time release was chosen with the help of the n value in the fitted Korsmeyer-Peppas Function. Third,the Weibull function and conversion ratio were used to deduce the function of real time release according to the chosen profile at elevated temperatures. The key point in this study was to provide a quick and precise method to predict the real time release for long acting progesterone PLGA microspheres. So the elevated temperatures coupled with magnetic stirring were used to accelerate the release further, and when there have many similar release profiles with the real time release at elevated temperatures, releasing time at elevated temperatures and the R2 of the final deduced function will be used to help choosing the most similar release profile with the real time release. Four different types of progesterone PLGA microspheres were used to verify the method, and all the deduced function correlated well with the real time releases, for R2 = 0.9912, 0.9781, 0.9918 and 0.9972, respectively.
文摘Hepatitis C virus(HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and welltolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylatedinterferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.
文摘AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC). METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5mg s.c. every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg i.m. and at the end of wk 12 and every 4 wk octreotide LAR 30mg i.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner. RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49 ± 6 wk) as compared to the control group (28 ± 1 wk) and to the SSTR negative group (28 ± 2 wk), LR = 20.39, df = 2, P < 0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the f irst year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group respectively.CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.
文摘Autoimmune phenomena are common in patients with chronic hepatitis C. Management of chronic hepatitis C/autoimmune hepatitis syndrome has until recently been problematic due to the adverse effects of interferon on autoimmune processes and immunosuppression on viral replication. In this report we describe 3 patients with chronic hepatitis C/autoimmune hepatitis overlap syndrome who responded rapidly to direct acting antiviral therapy. The resolution of the autoimmune process supports a direct viral role in its pathophysiology.
基金supported by the Key Project of the National Natural Science Foundation of China(Grant No.21233004)
文摘The effects of methylene methanedisulfonate(MMDS) on the high-temperature(0℃) cycle performance of LiMnO/graphite cells are investigated.By addition of 2 wt%MMDS into a routine electrolyte,the high-temperature cycling performance of LiMn204/graphite cells can be significantly improved.The analysis of differential capacity curves and energy-dispersive X-ray spectrometry(EDX) indicates that MMDS decomposed on both cathode and anode.The three-electrode system of pouch cell is used to reveal the capacity loss mechanism in the cells.It is shown that the capacity fading of cells without MMDS in the electrolytes is due to irreversible lithium consumption during cycling and irreversible damage of LiMnOmaterial,while the capacity fading of cell with 2 wt%MMDS in electrolytes mainly originated from irreversible lithium consumption during cycling.
文摘BACKGROUND Alterations in health-related quality of life(HRQoL)and neuropsychological disorders were described in the hepatitis C virus(HCV)patients.Although several studies investigated the modifications of HRQoL after HCV eradication,no data exists on the modifications of neuropsychological symptoms.AIM To investigate the effect of directly acting antivirals(DAAs)treatment on HRQoL and neuropsychological symptoms.METHODS Thirty nine patients with HCV infection underwent a neuropsychological assessment,including Zung-Self Depression-Rating-Scale,Spielberg State-Trait Anxiety Inventory Y1-Y2 and the Toronto-Alexithymia Scale-20 items before and after DAAs treatment.HRQoL was detected by Short-Form-36(SF-36).RESULTS All HRQoL domains,but role limitation physical and bodily pain,significantly improved after treatment.Interestingly,after DAAs treatment,all domains of HRQoL returned similar to those of controls.Each neuropsychological test significantly improved after HCV eradication.A significant correlation was observed among each psychological test and the summary components of SF-36.At multiple linear regression analysis including each psychological test as possible covariates,Zung-Self Depression Rating Scale(Zung-SDS)score was independently and significantly related to summary components of the SF-36 in the basal state and the difference between Zung-SDS score before and after treatment was the only variable significantly and independently related to the modification of HRQoL induced by the treatment.CONCLUSION Neuropsychological symptoms strongly influenced HRQoL in HCV patients and there was a significant improvement of neuropsychological tests and HRQoL after DAAs treatment.
基金Supported by National Natural Science Foundation of China,No.81373056Beijing Municipal Committee of Science and Technology,No.D161100002716003National Major Project for Infectious Diseases Control,No.2012ZX10002003-004-003
文摘AIM To assess the efficacy and safety of combined directly acting antivirals(DAAs) for the treatment of Chinese chronic hepatitis C(CHC) patients in a real-world setting.METHODS Hospitalized CHC patients who were treated with DAAs at Peking University First Hospital between January 2015 and December 2016 were enrolled. Samples and clinical data were collected at 0 wk, 2 wk, 4 wk, 8 wk, 12 wk, or 24 wk during DAAs treatment and at 4 wk, 12 wk, and 24 wk after the end of treatment. RESULTS Fifty-four patients who underwent DAAs treatment were included in our study, of whom 83.3%(45/54) achieved rapid virological response at 2 wk after treatment initiation(RVR 2) and 94.4%(51/54)achieved sustained virological response at 24 wk after the end of treatment(SVR 24). Serum creatinine and uric acid levels at the end of treatment were significantly increased compared with baseline levels(83.6 ± 17.9 vs 88.8 ± 19.4, P 01 < 0.001; 320.8 ± 76.3 vs 354.5 ± 87.6, P 01 < 0.001), and no significant improvements were observed at 24 w after the end of treatment(83.6 ± 17.9 vs 86.8 ± 19.1, P 02 = 0.039; 320.8 ± 76.3 vs 345.9 ± 89.4, P 02 = 0.001). The total frequency of adverse events(AEs) during treatment was 33.3%(18/54), with major AEs being fatigue(16.7%), headache(7.4%), anorexia(7.4%), and insomnia(5.6%). CONCLUSION Though based in a small cohort of patients, the abnormal changes in renal function indices and relative high frequency of AEs during combined DAAs treatment should be taken as a note of caution.
文摘Intramuscular injections can cause damage to arteries, veins and nerves. Achieving maximum effects of medications through precise intramuscular (IM) injections must be assured and with certainty, particularly with long-acting injection drugs (LAI). The purpose of this study is to determine precision in IM LAIs of patients with schizophrenia. These evidences estimate “Distance from the Epidermis to the Under-Fascia” (DEUF) and “Distance from Epidermis to the Upper-Arm Bone” (DEB) of the deltoid muscle. Explanatory variables include body height, weight, body-mass index (BMI), deltoid-muscle circumference, fat percentage and muscle mass measured by body composition monitor. Sixty nine subjects are included based on the Diagnostic Statistical Manual of Mental Disorders (DSM-IV, 1994), and receive treatments of typical and atypical antipsychotic LAI. There are 46 males and 23 females with average age of 51.41 (Standard Deviation = 13.58) and ranging from 21 to 81 years who are all right-handed. Ultrasonographic data and those from explanatory variables are calculated using Spearman’s rank correlation coefficients. Multiple regression analysis (step-wise method/forced input method) is performed assuming DEUF or DEB as dependent variables. Significant correlations are found with highest adjusted R-square. Paired t-tests show differences in average values of actual ultrasonographic measurements assigned to DEUF or DEB, and the regression equations for accuracy. Ultrasonographic values are assigned multiple-regression equations as true values, and the calculated values are compared with those obtained by regression equations. There are no significant differences observed for either the right or left arm. The multiple regression equations for BMI and fat percentages (upper extremity estimation) of DEUF, and for BMI and injection site circumference of estimated DEB, successfully value the DEUF and DEB. By using these multiple regression equations for IM injection to the deltoid-muscle, DEUF can better ensure accurate LAI into the muscle through body monitor, DEB, and measured values of the deltoid-muscle injection site circumference.
文摘Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents(DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.
文摘Twitter has become very popular among celebrities. It is the main platform used by them to publish press releases and, especially, to reach out to their fans. Given the pervasiveness of celebrities on the site, people with related interests may be especially likely to start using the service due to the perception of direct access to a famous person. As for the celebrities, it is a way of being close to the public and giving them an insight in to the life of a celebrity. Although most celebrity Twitter accounts are only used for promotion purposes, many celebrities use their personal accounts for the purpose of communicating with their fans, friends and other celebrities. These celebrities tweet personal photos and share their inner thoughts for various reasons and to different audiences. Thus in this study I ask: What are celebrity speech patterns on Twitter? Are they talking mostly to fans, and if not, who are they talking to? How are they talking to these different audiences? I address these questions by analyzing the tweets publicly available on four active celebrities’ Twitter timelines. The findings support that these celebrities indeed address different audiences on Twitter, including fans, friends, family and other celebrities. The findings further reveal that celebrities tend to communicate using different speech acts when talking to these different audiences. In light of this evidence, I attempt to highlight patterns that may be relevant with regards to the celebrities’ gender.
文摘The publishing conference of the Chinese version of National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (hereinafter referred to as NCCN Guidelines) and the inaugural peer reviewer meeting of NCCN Clinical Practice Guidelines in Oncology: Digestive System Cancers (hereinafter referred to as NCCN Guidelines on Digestive System Cancers) were held in People's Medical Publishing House in January 28^th, 2016 (Figure 1).
文摘[Objective] The aim was to explore the achievement motivation of the university student village officials in the suburbs of Beijing.[Method] The research made an investigation on 429 university student village officials in the suburbs of Beijing by the Achievements Motive Scale(AMS).[Result] The achievement motivation of these student village officials was not on a high level,but they tended to pursue the success motivation rather than the motivation to avoid failures obviously.There was a significant difference in the achievement motivation between different genders,majors and jobs.The males' motivation for success was higher than the females'.The motivation of avoiding failures among officials in Humanities was higher than in Science and in Fine Art.And the university student village officials in professional and technical posts or in business posts rated the motivation to avoid failures more important than in basic management posts.But achievement motivations in different urban-rural areas,educational levels,political backgrounds,whether student leaders or not,and durations were no definite differences.Besides,it had a significant effect on these student village officials' achievement motivation whether advices and suggestions were accepted;if yes,the motivation was higher.[Conclusion] This study had provided stability and development for building rural talent groups.
文摘Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.
文摘The use of direct-acting antivirals(DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response(around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants(RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These preexisting RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.
基金supported by the National High-Tech R&D Program of China (863 Program,2006AA100104-4)the Project of 948 from Ministryof Agriculture of China (2006-G5)+5 种基金the National Nature Science Foundation of China (30971810,60932008)the National Basic Research Program ofChina (973 Program, 2009CB118400)the Postdoctoral Fund in Heilongjiang Province, China (LBH-Z07228)the Foundation Projects of Northeast Agricultural University, Chinathe Technology Project of Education Ministry of Heilongjiang Province, China(11541025)the Technology Project of Harbin,China (2009RFQXN085)
文摘MicroRNAs (miRNAs) are derived from distinct loci in the genome and play crucial roles in RNA-mediated gene silencing mechanisms that regulate cellular processes during development and stress responses of plants. The miRNAs are approximately 21 nucleotides long and code for the complementary strand to a larger genic mRNA. They are often found within the complementary primary transcript (pri-miRNAs). In the past few years, a growing number of soybean miRNAs have been discovered, however, little is known about the transcriptional regulation of these miRNAs. In this study, promoters and cis-acting elements of soybean miRNAs were analyzed using the genomic data for the first time. A total of 82 miRNAs were located among 122 loci in genome, some were present as double or multiple copies. Five clusters that included ten miRNAs were found in genome, and only one cluster share the same promoter. A total of 191 promoters from 122 loci of the soybean miRNA sequences were found and further analyzed. The results indicated that the conserved soybean miRNA genes had a greater proportion of promoters than that of non-conserved ones, and the distribution of the transcript start sites (TSSs) and TATA-boxes found had different motif styles between conserved and non-conserved miRNA genes. Furthermore, the cis-acting elements 5' of the TSSs were analyzed to obtain potential function and spatiotemporal expression pattern of miRNAs. The data obtained here may lead to the identification of specific sequences upstream of pre-miRNAs and the functional annotation of miRNAs in soybean.
基金Supported by National Natural Science Foundation of China,No. 81870406Nature Science Foundation of Beijing Municipality,No. 7182174
文摘BACKGROUND Direct acting antiviral(DAA)therapy has enabled hepatitis C virus infection to become curable,while histological changes remain uncontained.Few valid noninvasive methods can be confirmed for use in surveillance.Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid(Gd-EOB-DTPA)is a liver-specific magnetic resonance imaging(MRI)contrast,related to liver function in the hepatobiliary phase(HBP).Whether Gd-EOB-DTPA-enhanced MRI can be used in the diagnosis and follow up of hepatic fibrosis in patients with chronic hepatitis C(CHC)has not been investigated.AIM To investigate the diagnostic and follow-up values of Gd-EOB-DTPA-enhanced MRI for hepatic histology in patients with CHC.METHODS Patients with CHC were invited to undergo Gd-EOB-DTPA-enhanced MRI and liver biopsy before treatment,and those with paired qualified MRI and liver biopsy specimens were included.Transient elastography(TE)and blood tests were also arranged.Patients treated with DAAs who achieved 24-wk sustained virological response(SVR)underwent Gd-EOB-DTPA-enhanced MRI and liver biopsy again.The signal intensity(SI)of the liver and muscle were measured in the unenhanced phase(UEP)(SI_(UEP-liver),SI_(UEP-muscle))and HBP(SI_(HBP-liver),SI_(HBP-muscle))via MRI.The contrast enhancement index(CEI)was calculated as[(SI_(HBP-liver)/SI_(HBP-muscle))]/[(SI_(UEP-liver)/SI_(UEP-muscle))].Liver stiffness measurement(LSM)was confirmed with TE.Serologic markers,aspartate aminotransferase-to-platelet ratio index(APRI)and Fibrosis-4(FIB-4),were also calculated according to blood tests.The grade of inflammation and stage of fibrosis were evaluated with the modified histology activity index(mHAI)and Ishak fibrosis score,respectively.Fibrosis regression was defined as a≥1-point decrease in the Ishak fibrosis score.The correlation between the CEI and liver pathology was evaluated.The diagnostic and follow-up values of the CEI,LSM,and serologic markers were compared.RESULTS Thirty-nine patients with CHC were enrolled[average age,42.3±14.4 years;20/39(51.3%)male].Twenty-one enrolled patients had eligible paired Gd-EOB-DTPA-enhanced MRI and liver tissues after achieving SVR.The mHAI median significantly decreased after SVR[baseline 6.0(4.5-13.5)vs SVR 2.0(1.5-5.5),Z=3.322,P=0.017],but the median stage of fibrosis did not notably change(P>0.05).Sixty pairs of qualified MRI and liver tissue samples were available for use to analyze the relationship between the CEI and hepatic pathology.The CEI was negatively correlated with the mHAI(r=-0.56,P<0.001)and Ishak score(r=-0.69,P<0.001).Further stratified analysis showed that the value of the CEI decreased with the progression of the stage of fibrosis rather than with the grade of necroinflammation.For patients with Ishak score≥5,the areas under receiver operating characteristics curve of the CEI,LSM,APRI,and FIB-4 were approximately at baseline,0.87–0.93,and after achieving SVR,0.83–0.91.The CEI cut-off value was stable(baseline 1.58 and SVR 1.59),but those of the APRI(from 1.05 to 0.24),FIB-4(from 1.78 to 1.28),and LSM(from 10.8 kpa to 7.1 kpa)decreased dramatically.The APRI and FIB-4 cannot be used as diagnostic means for SVR in patients with Ishak score≥3(P>0.05).Seven patients achieved fibrosis regression after achieving SVR.In these patients,the CEI median increased(from 1.71 to 1.83,Z=-1.981,P=0.048)and those of the APRI(from 1.71 to 1.83,Z=-2.878,P=0.004)and LSM(from 6.6 to 4.8,Z=-2.366,P=0.018)decreased.However,in patients without fibrosis regression,the medians of the APRI,FIB-4,and LSM also changed significantly(P<0.05).CONCLUSION Gd-EOB-DTPA-enhanced MRI has good diagnostic value for staging fibrosis in patients with CHC.It can be used for fibrotic-change monitoring post SVR in patients with CHC treated with DAAs.