Hepatitis B virus infection and replication in primarily cultured human fetal hepatocytes

AIM: To investigate the infection and replication of hepatitis B virus (HBV) in primarily cultured human fetal hepatocytes (HFHs). METHODS: The human fetal hepatocytes were cultured in serum-free medium, HBV-positive serum was added into the medium to study the susceptibility of hepatocytes to HBV infection. The supernatant was collected for ELISA assay of HBsAg and HBeAg, and quantitative fluorescence PCR for HBV-DNA assay daily. Albumin and HBcAg, CK8 and CK18 expressions were detected by immunohistochemistry in cultured hepatocytes. Content of lactate dehydrogenate (LDH) was measured to find out the integrity of the cell membrane. RESULTS: A stable hepatocyte culture system was established. HBV could infect the hepatocytes and replicate, and HBcAg expression could be detected by immunohistochemistry in hepatocyte-like cells. HBV- DNA in the supernatant could be detected from d 2 to d 18 and HBsAg and HBeAg were positive on d 3-d 18 after HBV infection. HBV in medium increased from d 0 to d 6 and subsequently decreased as the cells were progressively loosing their hepatocyte phenotypes. CONCLUSION: HBV could infect human fetal hepato- cytes and replicate. This in vitro model allowed a detailed study on early events associated with human HBV entry into cells and subsequent replication.

Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy

BACKGROUND High-dose methotrexate(HD-MTX)combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma(PCNSL);however,some patients have adverse reactions.AIM To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen.METHODS Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HDMTX until disease progression,intolerable toxicities,or physician/patientdirected withdrawal.Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria,respectively.The primary endpoint was the objective response rate(ORR),and the secondary endpoints were progression-free survival,overall survival(OS),and safety.RESULTS The median follow-up duration was 14.7 mo(range,3.9–30 mo).The ORR for all patients was 84.2%,and 2-year progression-free-and OS rates were 75.6%and 94.1%,respectively.All patients completed the induction phase,and nine patients underwent autologous stem cell transplantation as consolidation therapy,resulting in an ORR of 88.9%.Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%.All patients showed an acceptable safety profile.The sequencing results for cerebrospinal fluid(CSF)and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations.Circulating tumor DNA was correlated with disease relapse and response.CONCLUSION Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients.Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Hierarchical lichee-like Fe_(3)O_(4) assemblies and their high heating efficiency in magnetic hyperthermia

A nontoxic and biocompatible thermoseed is developed for the magnetic hyperthermia.Two kinds of thermoseed materials:hierarchical hollow and solid lichee-like Fe_(3)O_(4) assemblies,are synthesized by a facile hydrothermal method.The crystal structure of Fe_(3)O_(4) assemblies are characterized by x-ray diffraction,scanning electron microscopy,and transmission electron microscopy.Moreover,the prepared Fe_(3)O_(4) assemblies are used as a magnetic heat treatment agent,and their heating efficiency is investigated.Compared to solid assembly,hollow lichee-like Fe_(3)O_(4) assembly exhibits a higher specific absorption rate of 116.53 W/g and a shorter heating time,which is ascribed to its higher saturation magnetization,larger initial particle size,and the unique hierarchical hollow structure.Furthermore,the magnetothermal effect is primarily attributed to Neel relaxation.Overall,we propose a facile and convenient approach to enhance the heating efficiency of magnetic nanoparticles by forming hollow hierarchical assemblies.

食管放线菌感染1例

背景食管放线菌病是一种罕见的食管感染性疾病,常见症状包括吞咽困难和吞咽痛,这些症状通常是非特异性的,易导致误诊或延迟诊断.病例简介85岁女性,有9年的吞咽困难症状,加重9 d.她合并了高血压病、慢性阻塞性肺疾病及脑梗塞病史.胃镜发现食管多发溃疡并狭窄,后续组织病理报告确诊为食管放线菌病.抗菌治疗临床缓慢改善.结论食管放线菌病临床表现非特异性,组织病理学是目前临床确诊放线菌感染的主要检查方法.高效抗生素长期治疗,本病预后良好.

ACS合并AHF患者治疗中RAAS抑制剂对CI-AKI发病的影响

目的探讨肾素血管紧张素醛固酮系统(RAAS)抑制剂在急性冠状动脉综合征(ACS)合并急性心力衰竭(AHF)患者经皮冠状动脉介入术(PCI)中对比剂致急性肾损伤(CI-AKI)中的作用。方法回顾性分析成功行PCI手术ACS合并AHF患者504例,并于术后24~48 h内复查肾功能。分别按照有无CI-AKI及有无应用RAAS抑制剂进行分组,对比相关观察指标,并将差异有统计学意义的观察指标进行Logistics回归分析。结果504例患者中144例(28.6%)患者发生CI-AKI。CI-AKI组RAAS抑制剂使用比例、高血压、糖尿病患病率与非CI-AKI组比较,差异有统计学意义(P<0.05)。CI-AKI组反映心脏功能超声指标LVEF、LVEDD、PAP、NT-proBNP、hs-CRP及Hcy水平与非CI-AKI组比较,差异有统计学意义(P<0.05)。将上述指标引入Logistic回归分析发现,应用RAAS抑制剂对CI-AKI影响消失。而高血压、NT-proBNP、Hcy、hs-CRP、LVEF、PAP仍为心力衰竭患者CI-AKI发生高危因素。结论对ACS合并AHF患者需行PCI治疗患者,常规应用RAAS抑制剂并不增加CI-AKI发生风险。

免疫检查点抑制剂的毒副作用及其管理

免疫检查点抑制剂是针对相应免疫检查点的一些单抗类药物,发挥阻断肿瘤细胞对免疫细胞的抑制作用.基于免疫治疗特有的作用机制,其相关性毒副反应不同于其他癌症疗法,机体的所有器官均可累及,以皮肤、胃肠道、肝脏、内分泌和肺部毒性为多见,通常是轻微、可逆的,但严重的毒副反应可危及生命.因此,加强对其相关性不良事件的管理,减少中重度毒副反应的发生,对于提高免疫治疗的疗效至关重要.本文汇总各临床指南和最新研究,分别从临床表现和管理措施两个方面对抗细胞毒性T淋巴细胞相关抗原4单抗和抗程序性死亡受体1及其配体1单抗在治疗中的常见毒副作用进行综述,为临床更有效地处理免疫相关毒性事件提供参考.

Exosomes derived from human induced pluripotent stem cell-derived neural progenitor cells protect neuronal function under ischemic conditions

Compared with other stem cells,human induced pluripotent stem cells-derived neural progenitor cells(iPSC-NPCs)are more similar to cortical neurons in morphology and immunohistochemistry.Thus,they have greater potential for promoting the survival and growth of neurons and alleviating the proliferation of astrocytes.Transplantation of stem cell exosomes and stem cells themselves have both been shown to effectively repair nerve injury.However,there is no study on the protective effects of exosomes derived from iPSC-NPCs on oxygen and glucose deprived neurons.In this study,we established an oxygen-glucose deprivation model in embryonic cortical neurons of the rat by culturing the neurons in an atmosphere of 95%N2 and 5%CO2 for 1 hour and then treated them with iPSC-NPC-derived exosomes for 30 minutes.Our results showed that iPSC-NPC-derived exosomes increased the survival of oxygen-and glucose-deprived neurons and the level of brain-derived neurotrophic factor in the culture medium.Additionally,it attenuated oxygen and glucose deprivation-induced changes in the expression of the PTEN/AKT signaling pathway as well as synaptic plasticity-related proteins in the neurons.Further,it increased the length of the longest neurite in the oxygen-and glucose-deprived neurons.These findings validate the hypothesis that exosomes from iPSCNPCs exhibit a neuroprotective effect on oxygen-and glucose-deprived neurons by regulating the PTEN/AKT signaling pathway and neurite outgrowth.This study was approved by the Animal Ethics Committee of Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,China(approval No.SRRSH20191010)on October 10,2019.

Prognostic values of interim and post-therapy ^(18)F-FDG PET/CT scanning in adult patients with Burkitt's lymphoma

Background:The prognostic values of interim and post-therapy fluorine-18-fluorodeoxyglucose(^(18)F-FDG) positron emission tomography(PET) and PET/computed tomography(CT) scanning have been confirmed in several subtypes of lymphoma.However,its prognostic value in Burkitt's lymphoma has not been clearly defined.The aim of the present study was to assess the prognostic value of PET/CT scanning during different treatment processes of Burkitt's lymphoma.Methods:A total of 29 adult patients with newly diagnosed Burkitt's lymphoma were retrospectively involved in this study;of them,23 patients underwent baseline PET/CT,15 patients underwent mid-therapy PET/CT after 1-4 cycles of chemotherapy,and 17 patients underwent post-therapy PET/CT after all planned first-line chemotherapy cycles.Mid-therapy and post-therapy PET/CT results(positive vs.negative) were visually interpreted according to the criteria of the International Harmonization Project.The reduction in the maximum standardizes uptake values(ASUVmax)of 25%,50%,and 75%were regarded as cutoff points.Overall survival(OS) and progression-free survival(PFS) were regarded as the major endpoints.Results:The median OS and PFS were 27.6 months(range 6.5-78.3 months) and 27.2 months(range 3.0-78.3 months),respectively.The median SUVmax of the baseline PET/CT was 18.3(range 1.6-35.9),whereas the median SUVmax of the mid-therapy and post-therapy PET/CT decreased to 4.0(range 0-17.6) and 3.0(range 0-14.5),respectively.The patients' Eastern Cooperative Oncology Group(ECOG) scores(<2 vs.≥2) were significantly associated with the baseline PET/CT SUVmax.The mid-therapy and post-therapy PET/CT results(positive vs.negative) showed no significant association with OS or PFS.The optimal cutoff ASUVmax from the baseline to the post-therapy PET/CT that could predict a change in OS in patients with Burkitt's lymphoma was 50%(P = 0.019).Conclusions:^(18)F-FDG uptake was intense in Burkitt's lymphoma,and there was a significant reduction in SUVmax during the interim and post-therapy PET/CT procedures.A ASUVmax of greater than 50%was a favorable cutoff point to predict the OS of Burkitt's lymphoma patients.

Bone marrow mesenchymal stem cells transplantation promotes the release of endogenous erythropoietin after ischemic stroke

This study investigated whether bone marrow mesenchymal stem cell（BMSC） transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 106 human BMSCs（h BMSCs） were injected into the tail vein. Fourteen days later, we found that h BMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor（s EPOR） was injected into the lateral ventricle, and on the next 13 consecutive days. s EPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the h BMSCs ＋ s EPOR group than in the h BMSCs ＋ heat-denatured s EPOR group. The adhesive-removal test result and the modified Neurological Severity Scores（m NSS） were lower in the h BMSCs ＋ s EPOR group than in the heat-denatured s EPOR group. The adhesive-removal test result and m NSS were similar between the h BMSCs ＋ heat-denatured s EPOR group and the h BMSCs ＋ s EPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke.

Broadband and high efficiency terahertz metasurfaces for anomalous refraction and vortex beam generation

The applications of metasurfaces are currently a highly active research field due to their extraordinary ability to manipulate electromagnetic waves. The ultra-thin characteristics of metasurfaces allow the miniaturization and integration of metasurface devices. However, these devices work typically under a low efficiency and narrow bandwidth condition. In this work, we design eight multilayered unit cells with similar amplitudes and a phase interval of π/4, which convert the polarization states of the terahertz(THz) waves between two orthogonal directions. The average cross-polarized transmission amplitudes of these cells are all around 0.9 in an ultra-broad frequency range from 0.5 THz to 1.4 THz. Furthermore,unit cells are used to construct both an ultra-thin anomalous refraction metalens and a vortex phase plate. Our simulation results show that the anomalous refraction for the transmitted linear polarization component is comparable to the theoretical prediction, and the maximum error is determined to be below 4.8%. The vortex phase plate can also generate an ideal terahertz vortex beam with a mode purity of 90% and more. The distributions of longitudinal electric field, intensity, and phase illustrate that the generated vortex beam has excellent propagation characteristics and a weak divergence. Simulations of the two types of metasurface devices, based on the eight unit cells, exhibit very high efficiencies in a wide bandwidth. Our research will assist in the improvement in the practical applications of metasurfaces. It also provides a reference for the design of high efficiency and broadband devices that are applied to other frequency ranges.

The interactive effects of nitrogen addition and increased precipitation on gross ecosystem productivity in an alpine meadow

The ecological consequences of precipitation change and increased atmospheric nitrogen(N)deposition have profound impacts on ecosystem CO2 exchange in grassland ecosystems.Water and N can largely influence grassland productivity,community composition and ecosystem functions.However,the influences of water and N addition on the ecosystem CO2 exchange of alpine grassland ecosystems remain unclear.A field manipulative experiment with water and N additions was conducted in an alpine meadow on the Tibetan Plateau over 4 years with contrasting precipitation patterns.There were four treatments:control(Ctrl),N addition(N),water addition(W)and N and water addition(NW),each replicated three times.N addition,but not water addition,increased gross ecosystem productivity(GEP),plant biomass,community cover and community-weighted mean height.The responses of ecosystem CO2 exchange to water and N addition varied between the wet and dry years.Water addition had a positive effect on net ecosystem carbon exchange(NEE)due to a larger increase in GEP than in ecosystem respiration(ER)only in the dry year.On the contrary,N addition significantly enhanced ecosystem CO2 exchange only in the wet year.The increased GEP in N addition was attributed to the larger increase in NEE than ER.Moreover,N addition stimulated NEE mainly through increasing the cover of dominant species.Our observations highlight the important roles of precipitation and dominant species in regulating ecosystem CO2 exchange response to global environmental change in alpine grasslands.