Tenofovir disoproxil fumarate is superior to lamivudine plus adefovir in lamivudine-resistant chronic hepatitis B patients

AIM:To assess the efficacy of tenofovir disoproxil fumarate(TDF) in lamivudine(LAM)-resistant patients with a suboptimal response to LAM plus adefovir(ADV).METHODS:We retrospectively analyzed the efficacy of switching to tenofovir disoproxil fumarate in suboptimal responders to lamivudine plus adefovir.Charts were reviewed for LAM-resistant chronic hepatitis B(CHB) patients who visited the Zhejiang Province People's Hospital and The First Affiliated Hospital,College of Medicine,Zhejiang University,from June 2009 to May 2013.Patients whose serum hepatitis B virus(HBV) DNA remained detectable despite at least 6 mo of LAM plus ADV combination therapy were included.Patients with a suboptimal response to LAM plus ADV were randomized to switch to TDF monotherapy(300 mg/d orally; TDF group) or to continuation with LAM(100 mg/d orally) plus ADV(10 mg/d orally; LAM plus ADV group) and were followed for 48 wk.Serum HBV DNA was determined at baseline and weeks 4,12,24,36,and 48.HBV serological markers and biochemistry were assessed at baseline and weeks 12,24,and 48.Resistance surveillance and side effects were monitored during therapy.RESULTS:Fifty-nine patient were randomized to switch to TDF(n =28) or continuation with LAM plus ADV(n =31).No significant differences were found between the groups at baseline.Prior to TDF therapy,all patients had been exposed to LAM plus ADV for a median of 11 mo(range:6-24 mo).No difference was seen in baseline serum HBV DNA between the two groups [5.13 ± 1.08 log10 copies/m L(TDF) vs 5.04 ± 31.16 log10 copies/m L(LAM +ADV),P =0.639].There was no significant difference in the rates of achieving complete virological response(CVR) at week 4 between the TDF and LAM +ADV groups(17.86% vs 6.45%,P =0.24).The rate of achieving CVR in the TDF and LAM plus ADV groups was 75% vs 16.13% at week 12,82.14% vs 22.58% at week 24,89.29% vs 25.81% at week 36,and 96.43% vs 29.03% at week 48,respectively(P < 0.001).The rate of alanine aminotransferase normalization was significantly higher in the TDF than in the LAM plus ADV group at week 12(75% vs17.86%,P < 0.001),but not at week 24(78.57% vs 54.84%,P =0.097) or 48(89.26% vs 67.74%,P =0.062).Patients were hepatitis B e antigen(HBe Ag) positive at baseline.There was no significant difference in HBe Ag negativity between the TDF and LAM plus ADV groups at week 48(4% vs 0%,P =0.481).There were no drug-related adverse effects at week 48 in either group.CONCLUSION:Switching to TDF monotherapy was superior to continuous add-on therapy in patients with LAM-resistant CHB with a suboptimal response to LAM plus ADV.

Primary bone anaplastic lymphoma kinase positive anaplastic largecell lymphoma: A case report and review of the literature

BACKGROUND Primary bone lymphoma(PBL)is an uncommon extranodal disease that represents approximately 1%-3%of lymphomas.Anaplastic lymphoma kinase(ALK)positive anaplastic large-cell lymphoma(ALCL)is an extremely rare type of PBL.The aim of this report is describe the symptoms,diagnosis,and treatment of primary bone ALK-positive ALCL.CASE SUMMARY A 66-year-old man presented to our hospital with neck and shoulder pain and intermittent fever that lasted for 1 mo.After extensive evaluation,positron emission tomography-computed tomography(CT)examination showed multiple osteolytic bone lesions without other sites lesions.CT-guided biopsy of the T10 vertebral body was performed,and the pathology results showed that neoplastic cells were positive for ALK-1,CD30,and CD3.A diagnosis of primary bone ALK positive ALCL was ultimately made.The patient was in partial response after four cycle soft cyclophosphamide,doxorubicin,vincristine,and prednisone chemotherapy,and we planned to repeat the biopsy and radiological examination after completion of the fifth cycle of therapy.CONCLUSION Primary bone ALK positive ALCL is a rare disease and physicians should keep in mind that ALCL can present with isolated osseous involvement without nodal involvement,and lymphoma should be considered in the differential diagnosis of primary bone lesions.

Metabolic dysfunction is associated with steatosis but no other histologic features in nonalcoholic fatty liver disease

BACKGROUND Recently,nonalcoholic fatty liver disease(NAFLD)has been renamed metabolicassociated fatty liver disease(MAFLD).Based on the definition for MAFLD,a group of non-obese and metabolically healthy individuals with fatty liver are excluded from the newly proposed nomenclature.AIM To analyze the histologic features in the MAFLD and non-MAFLD subgroups of NAFLD.METHODS Eighty-three patients with biopsy-proven NAFLD were separated into MAFLD and non-MAFLD groups.The diagnosis of MAFLD was established as hepatic steatosis along with obesity/diabetes or evidence of metabolic dysfunction.The histologic features were compared according to different metabolic disorders and liver enzyme levels.RESULTS MAFLD individuals had a higher NAFLD activity score(P=0.002)and higher severity of hepatic steatosis(42.6%Grade 1,42.6%Grade 2,and 14.8%Grade 3 in MAFLD;81.8%Grade 1,13.6%Grade 2,and 4.5%Grade 3 in non-MAFLD;P=0.007)than the non-MAFLD group.Lobular and portal inflammation,hepatic ballooning,fibrosis grade,and the presence of nonalcoholic steatohepatitis(NASH)and significant fibrosis were comparable between the two groups.The higher the liver enzyme levels,the more severe the grades of hepatic steatosis(75.0%Grade 1 and 25.0%Grade 2 in normal liver function;56.6%Grade 1,39.6%Grade 2,and 3.8%Grade 3 in increased liver enzyme levels;27.8%Grade 1,27.8%Grade 2,and 44.4%Grade 3 in liver injury;P<0.001).Patients with liver injury(alanine aminotransferase>3×upper limit of normal)presented a higher severity of hepatocellular ballooning(P=0.021).Moreover,the grade of steatosis correlated significantly with hepatocellular ballooning degree(r=0.338,P=0.002)and the presence of NASH(r=0.466,P<0.001).CONCLUSION Metabolic dysfunction is associated with hepatic steatosis but no other histologic features in NAFLD.Further research is needed to assess the dynamic histologic characteristics in NAFLD based on the presence or absence of metabolic disorders.

575-fs passively mode-locked Yb:CaF2 ceramic laser

A Yb-doped CaF2 transparent ceramics was successfully fabricated by the hot-pressed method and its laser characteristics were studied.A broad tuning performance and mode-locked laser operation were demonstrated in this ceramics for the first time,to our best knowledge.A 60-nm continuous-wavelength tunable laser from 1019 nm to 1079 nm was obtained with a birefringent filter.By employing a semiconductor saturable absorber mirror without additional dispersion compensation elements,a continuous-wave mode-locked laser with pulse duration as short as 575 fs was delivered,at a central wavelength of 1048.5 nm.The oscillator is operated under a repetition rate of 55 MHz.These results indicate that the Yb:CaF2 transparent ceramics is an ideal candidate for the development of ultrafast lasers in the near-infrared regime.

Investigation of sex determination in starry flounder(Platichthys stellatus)reveals sex chromosome evolution in Pleuronectiformes and identifies a sex-specific marker

The identification of sex chromosomes is fundamental for exploring the mechanism and evolution of sex determination.Platichthys stellatus,a species exhibiting clear sexual dimorphism and homomorphic chromosome pairs,has received limited research concerning its sex determination mechanisms.Clarifying the sex chromosome of P.stellatus will enhance our understanding of sex chromosome evolution in Pleuronectiformes.This study employed whole-genome resequencing to investigate the sex chromosome and sex determination system in P.stellatus.Notably,Chr23 was identified as the sex chromosome in P.stellatus,with the sex-determining region(SDR)occupying 48.1%of the chromosome and featuring an XX/XY system.Sex chromosome turnover was observed within Pleuronectiformes,with P.stellatus,Verasper variegatus,and Hippoglossus hippoglossus sharing a common ancestral karyotype.No inversions were detected within the SDR of P.stellatus,although chromosomal rearrangements between sex chromosomes and autosomes were identified.Additionally,a sex-specific marker for P.stellatus was ascertained,enabling genetic sex identification,with significant implications for improving breeding programs and aquaculture practices.

Future urban transport management

The incorporation of disruptive innovations into the transportation industry will inevitably cause major upheavals in the transportation sector.However,existing research lacks systematic theories and methodologies to represent the underlying characteristics of future urban transport systems.Furthermore,emerging modes in urban mobility have not been sufficiently studied.The National Natural Science Foundation of China(NSFC)officially approved the Basic Science Center project titled“Future Urban Transport Management”in 2022.The project members include leading scientists and engineers from Beijing Jiaotong University,Beihang University,and Beijing Transport Institute.Based on a wide range of previous projects by the consortium on urban mobility and sustainable cities,this project will encompass transdisciplinary and interdisciplinary research to explore critical issues affecting future urban traffic management.It aims to develop fundamental theories and methods based on social and technological developments in the near future and explores innovative solutions to implement alongside these emerging developments in urban mobility.

Systemic air embolism in a fungal pneumonia patient with lung cavities formation and review of literature

Systemic air embolism is a rare but potentially fatal complication related to many factors.The purpose of this article is to alert clinicians once patients occurs an abnormal neurological and cardiovascular status,following minor traumatic treatment,air embolism should be considered.A 20-year-old man who presented with fungal pneumonia with lung cavities formation was adm让ted to an intensive care unit(ICU)and received positive airway pressure ventilation.Four days later,the fun gal pneumonia was improved,but the patient's blood pressure and arterial oxygen saturation deteriorated,so computed tomography(CT)scans were preformed to reevaluate him.The scans detected air embolism in the left atrium and ventricle,ascending aorta,aortic arch and its branches(right brachiocephalic,bilateral common carotid and right subclavian arteries),descending aorta and right coronary artery.A CT scan of the abdomen revealed air in the spleen,cauda pancreatic,superior mesenteric artery and right external iliac artery.The patient died two days later from multiple organ dysfunction.We suggest that vascular air embolism should be considered under mechanical ventilation when patients'neurologic and cardiovascular status deteriorates,and hyperbaric oxygen therapy should be conducted immediately.

MANAGING REDISTRIBUTION OF TOLL REVENUE WITH USER HETEROGENEITY

With the explicit consideration of user heterogeneity, i.e., each user has a different value of time （VOT）, this paper examines the system efficiency and social equity of toll revenue redistribution in a bi-mode transportation system. Three schemes of distributing the road toll revenue are proposed, which respectively consider efficiency, equity, as well as efficiency and equity together. With mild assumptions, we prove that the number of auto-motorists decreases and the total social cost increases with transit subsidy share when only marginal operating cost of the transit is covered by its fare. However, when average fixed cost of the transit is further covered, the total social cost is a ＂U＂ shape curve against the transit subsidy share. Numerical results show that the well designed toll revenue redistribution schemes can make the system more equitable while keeping high efficiency. With the increase of user heterogeneity, the Gini coefficient becomes larger while the total social cost goes down.

Stochastic Route Choice Equilibrium Assignment for Travelers with Heterogeneous Regret Aversions

Most route choice models assume that people are completely rational.Recently,regret theory has attracted researchers'attentions because of its power to depict real travel behavior.This paper proposes a multiclass stochastic user equilibrium assignment model by using regret theory.All users are differentiated by their own regret aversion.The route travel disutility for users of each class is defined as a linear combination of the travel time and anticipated regret.The proposed model is formulated as a variational inequality problem and solved by using the self-regulated averaging method.The numerical results show that users'regret aversion indeed influences their route choice behavior and that users with high regret aversion are more inclined to change route choice when the traffic congestion degree varies.