Precision targeting in hepatocellular carcinoma:Exploring ligandreceptor mediated nanotherapy

Hepatocellular carcinoma(HCC)is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality.Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages,but it is often ineffective and suffers from problems such as multidrug resistance,rapid drug clearance,nonspecific targeting,high side effects,and low drug accumulation in tumor cells.In response to these limitations,recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC.This review focuses on recent advances in nanoparticle-based targeted drug delivery systems,with special attention to various receptors overexpressed on HCC cells.These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC.We comprehensively summarize the current understanding of these receptors,their role in nanoparticle targeting,and the impact of such targeted therapies on HCC.By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies,more effective and precise treatment of HCC can be achieved.

Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro

BACKGROUND Prohibitin 1(PHB1)has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed,and it participates in a variety of essential cellular functions,including apoptosis,cell cycle regulation,prolifera-tion,and survival.Emerging evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma(HCC).However,the role of PHB1 in HCC is controversial.AIM To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in vitro.METHODS HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria;then,PHB1 levels in the sera and liver tissues of these participates were determined using ELISA,RT-PCR,and immunohistoche-mistry.Human HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA(shRNA-PHB1)for 24-72 h.Cell prolif-eration was analysed with an MTT assay.Cell cycle progression and apoptosis were analysed using flow cytometry(FACS).The mRNA and protein expression levels of the cell cycle-related molecules p21,Cyclin A2,Cyclin E1,and CDK2 and the cell apoptosis-related molecules cytochrome C(Cyt C),p53,Bcl-2,Bax,caspase 3,and caspase 9 were measured by real-time PCR and Western blot,respectively.RESULTS Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals,and decreased PHB1 was positively correlated with low differentiation,TNM stage III-IV,and alpha-fetoprotein≥400μg/L.Overexpression of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent manner.FACS revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced apoptosis.The proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compared with untreated control and empty vector-transfected cells.The percentage of apoptotic HepG2 cells that were transfected with pEGFP-PHB1 was 15.41%±1.06%,which was significantly greater than that of apoptotic control cells(3.65%±0.85%,P<0.01)and empty vector-transfected cells(4.21%±0.52%,P<0.01).Similar results were obtained with SMMC-7721 cells.Furthermore,the mRNA and protein expression levels of p53,p21,Bax,caspase 3,and caspase 9 were increased while the mRNA and protein expression levels of Cyclin A2,Cy-clin E1,CDK2,and Bcl-2 were decreased when PHB1 was overexpressed in human HCC cells.However,when PHB1 was upregulated in human HCC cells,Cyt C expression levels were increased in the cytosol and decreased in the mitochondria,which indicated that Cyt C had been released into the cytosol.Conversely,these effects were reversed when PHB1 was knocked down.CONCLUSION PHB1 inhibits human HCC cell viability by arresting the cell cycle and inducing cell apoptosis via activation of the p53-mediated mitochondrial pathway.

Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies

The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to be diagnosed at an early stage,and it rapidly progresses to an advanced stage,resulting in poor treatment and prognosis.Fusobacterium nucleatum(F.nucleatum)is a gram-negative,sporefree anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal,esophageal,gastric,and pancreatic cancers via various intricate mechanisms.Recent development in novel research suggests that F.nucleatum may function as a biomarker in GI malignancies.Detecting the abundance of F.nucleatum in stool,saliva,and serum samples of patients may aid in the diagnosis,risk assessment,and prognosis monitoring of GI malignancies.This editorial systematically describes the biological roles and mechanisms of F.nucleatum in GI malignancies focusing on the application of F.nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F.nucleatum and GI tumors-related research.

Application of buried auricular point combined with Wenjing Sanhan prescription in arteriosclerosis obliterans patients with resting pain

BACKGROUND Research on the combined use of ear acupoint embedding beans and warming meridians with cold-dispersing formulas for alleviating resting pain in patients with arteriosclerosis obliterans(ASO)remains limited.AIM To explore the therapeutic efficacy of auricular point embedding beans combined with Wenjing Sanhan prescription in alleviating resting pain in patients with lower-limb ASO.METHODS A total of 100 patients with ASO experiencing resting pain who were treated at our hospital from January 2022 to January 2023 were enrolled.They were randomly allocated into two groups using a double-blind approach.The control group was treated using a warming meridian with a cold-dispersing formula,while the study group received additional treatment with ear acupoint embedding beans.The clinical efficacy,ankle-brachial artery pressure ratio,hemorheological indicators,and traditional Chinese medicine symptom scores were compared between the two groups.RESULTS The clinical efficacy rate in the study group was significantly higher(94.00%)than that in the control group(72.00%,P<0.05).Moreover,the ankle-brachial artery pressure ratio was significantly higher in the study group after treatment(P<0.05).Hemorheological parameters,including whole blood viscosity,plasma viscosity(1.83±0.11)mPa/s,fibrinogen levels(3.30±0.21)g/L,platelet adhesion rate(49.87%±10.51%),and erythrocyte aggregation index(1.79±0)were improved in the study group compared to the control group.In addition,the scores for decreased skin temperature(1.41±0.26),intermittent claudication(1.30±0.20),and resting pain(1.23±0.31)were significantly lower in the study group than those in the control group(all P<0.05).The level of oxidative stress in the study group also exhibited significant improvement(P<0.05),and the levels of inflammatory factors were considerably lower than those in the control group.CONCLUSION The combination of ear point embedding beans and Wenjing Sanhan prescription demonstrates promising clinical efficacy in alleviating resting pain associated with ASO.

Application of traditional Chinese medicine acupoint needle embedding combined with emotional nursing in patients with gynecological malignant tumors

BACKGROUND Few relevant literature reports on applying acupoint press-needle embedding combined with emotional nursing in patients with a gynecological malignant tumor.AIM To explore the effect of traditional Chinese medicine acupoint needle embedding combined with emotional nursing on chemotherapy-related nausea and vomiting(CINV),cancer-related fatigue(CRF)and psychological state in patients with gynecological malignant tumors.METHODS Retrospective analysis of the clinical information of 84 patients with gynecological malignant tumors treated in our hospital from August 2020 to December 2022 Led to the development of an observation group(n=42)and a control group(n=42)based on various nursing approaches.Ondansetron hydrochloride injection was administered to the individuals in the control group.However,the observation group received emotional nursing based on the control group and acupoint pressneedle embedding of traditional Chinese medicine.Patients in both groups received the chemotherapy regimen of paclitaxel liposome+carbo-platin/cisplatin.For four weeks,both groups intervened.The CINV grade,quality of life,CRF,psychological status and sleep quality scores of the two groups before and RESULTS After intervention,the degree of CINV in the observation group was significantly better than that in the control group.After intervention,the scores of each dimension and total score of FLIE scale were significantly higher than those in the control group.After intervention,the scores of each dimension and total score of Piper Fatigue Scale were significantly lower than those in the control group(P<0.05).After intervention,the scores of avoidance and yield dimensions in the observation group were significantly lower than those in the control group,and the scores of confrontation dimension were significantly higher than those in the control group(P<0.05).After intervention,the sleep quality score of the observation group was significantly lower than that of the control group,and the Karnofsky Performance Status scale score was significantly higher than that of the control group(P<0.05).CONCLUSION The acupuncture point needle embedding of traditional Chinese medicine combined with emotional nursing can further reduce the incidence of chemotherapy-related nausea and vomiting in patients with gynecological malignant tumors,improve the quality of life and the degree of CRF,alleviate the bad psychological state,adopt a positive way to face the disease and treatment,and improve the quality of sleep and quality of life.

HBV相关肝病患者外周血T细胞及细胞因子水平研究

背景乙型肝炎病毒(hepatitis B virus,HBV)相关慢性肝病患者外周血T细胞及细胞因子水平与患者免疫功能状态密切相关,不同疾病程度的HBV相关肝病患者的T细胞、细胞因子水平及与肝病阶段的相关性值得进一步探究.目的探究不同阶段HBV相关慢性肝病患者外周血T细胞亚群计数、细胞因子变化特点及关联性.方法本研究为一项观察性研究,共纳入慢性乙型肝炎(chronic hepatitis B,CHB)患者65例,肝硬化失代偿期(decompensated cirrhosis,DCC)患者122例,肝细胞癌(hepatocellular carcinoma,HCC)患者109例,收集患者一般信息、病史、治疗情况及实验室检查结果、Child-Paugh分级及HCC患者肿瘤巴塞罗那分期,分析各项指标,尤其是T细胞亚群计数及细胞因子的组间差异及特征.结果HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞水平与Child分级A到C呈负相关.HCC患者CD8^(+)T细胞绝对计数显著低于DCC[240(150-379)cells/μLvs 277(154-435)cells/μL,P<0.05]及CHB[240(150-379)cells/μL vs 452(269-706)cells/μL,P<0.001]患者.白细胞介素(interleukin,IL)-6、IL-8、肿瘤坏死因子(tumor necrosis factor,TNF)-α在HCC组均最高.DCC、HCC患者Child-Paugh分级越差,CD3^(+)、CD8^(+)T细胞水平越低,IL-6水平越高.HCC患者CD3^(+)、CD8^(+)T细胞水平随着肿瘤巴塞罗那分期由A到D呈下降趋势,IL-6呈上升趋势.且肝硬化、HCC患者CD3^(+)(r=-0.340,P<0.001)、CD8^(+)(r=-0.353,P<0.001)T细胞水平与IL-6升高水平呈显著负相关.结论HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞计数与Child分级(由A到C)呈负相关,且IL-6水平与CD8^(+)T细胞计数存在负相关关系.

Hepatitis B cure:Current situation and prospects

Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and international CHB management guidelines.Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens.These regimens incorporate either nucleos(t)ide analogs,immunomodulatory agents such as pegylated interferonα,or a strategic combination of both,sequentially or concurrently administered.Despite these advancements in the clinical handling of hepatitis B,achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes.These include,but are not limited to,the emergence of antiviral resistance,incomplete immune recovery,and the persistence of covalently closed circular DNA.Moreover,the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure.This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.

Predictors of portal vein thrombosis after splenectomy in patients with cirrhosis

BACKGROUND Portal vein thrombosis(PVT)is a commonthsn complication after splenectomy in patients with cirrhosis.However,the predictors of postoperative PVT are not known.AIM To investigate the predictors of PVT after splenectomy in patient with cirrhosis.METHODS A total of 45 patients with cirrhosis who underwent splenectomy were consecutively enrolled from January 2017 to December 2018.The incidence of PVT at 1 months,3 months,and 12 months after splenectomy in patients with cirrhosis was observed.The hematological indicators,biochemical and coagulation parameters,and imaging features were recorded at baseline and at each observation point.The univariable,multivariable,receiver operating characteristic curve and timedependent curve analyses were performed.RESULTS The cumulative incidence of PVT was 40.0%,46.6%,and 48.9%at 1 months,3 months,and 12 months after splenectomy.Multivariable analysis showed that portal vein diameter(PVD)≥14.5 mm and monthsdel end-stage liver disease(MELD)score>10 were independent predictors of PVT at 1 months,3 months,and 12 months after splenectomy(P<0.05).Time-dependent curve showed that the cumulative incidence of PVT was significantly different between patients with MELD score≤10 and>10(P<0.05).In addition,the cumulative incidence of PVT in the PVD≥14.5 mm group was significantly higher than that in the PVD<14.5 mm group(P<0.05).CONCLUSION Wider PVD and MELD score>10 were independent predictors of PVT at 1 months,3 months,and 12 months after splenectomy in patient with cirrhosis.

Caffeic acid phenethyl ester up-regulates antioxidant levels in hepatic stellate cell line T6 via an Nrf2-mediated mitogen activated protein kinases pathway

AIM To investigate the antioxidant effect of caffeic acid phenethyl ester (CAPE) in hepatic stellate cell-T6 (HSC-T6) cells cultured in vitro and the potential mechanisms. METHODS HSC-T6 cells were cultured in vitro and treated with various concentrations of CAPE for 24, 48 and 72 h, respectively. Cell proliferation was investigated using the MTT assay, and cell ultrastructural alterations were observed by transmission electron microscopy. Flow cytometry was employed to investigate the effects of CAPE on apoptosis and the levels of reactive oxygen species in HSC-T6 cells cultured in vitro. An enzyme immunoassay instrument was used to evaluate antioxidant enzyme expression. The effect on alpha-smooth muscle actin was shown using immunofluorescence. Gene and protein levels of Nrf2, related factors, and mitogen activated protein kinases (MAPKs), in HSC-T6 cells were detected using RT-PCR and Western blot, respectively. RESULTS CAPE inhibited the proliferation and activation of HSC-T6 cells cultured in vitro. CAPE increased the antioxidant levels and the translocation of Nrf2 from the cytoplasm to the nucleus in HSC-T6 cells. Moreover, the phosphorylation of MAPKs in cells decreased in response to CAPE. Interestingly, CAPE-induced oxidative stress in the cells was significantly attenuated by pretreatment with MAPKs inhibitors. CONCLUSION CAPE inhibits cell proliferation and up-regulates the antioxidant levels in HSC-T6 cells partly through the Nrf2-MAPKs signaling pathway.

Caffeic acid phenethyl ester inhibits liver fibrosis in rats

AIM: To investigate the hepatoprotective effects and antioxidant activity of caffeic acid phenethyl ester(CAPE) in rats with liver fibrosis. METHODS: A total of 75 male Sprague-Dawley rats were randomly assigned to seven experimental groups: a normal group(n = 10), a vehicle group(n = 10), a model group(n = 15), a vitamin E group(n = 10), and three CAPE groups(CAPE 3, 6 and 12 mg/kg, n = 10, respectively). Liver fibrosis was induced in rats by injecting CCl4 subcutaneously, feeding with high fat forage, and administering 30% alcohol orally for 10 wk. Concurrently, CAPE(3, 6 and 12 mg/kg) was intraperitoneally administered daily for 10 wk. After that, serum total bilirubin(TBil), aminotransferase(ALT) and aspartate aminotransferase(AST) levels were measured to assess hepatotoxicity. To investigate antioxidant activity of CAPE, malondialdehyde(MDA), glutathione(GSH) levels, catalase(CAT) and superoxide dismutase(SOD) activities in liver tissue were determined. Moreover, the effect of CAPE on α-smooth muscle actin(α-SMA), a characteristic hallmark of activated hepatic stellate cells(HSCs), and NF-E2-related factor 2(Nrf2), a key transcription factor for antioxidant systems, was investigated by immunohistochemistry. RESULTS: Compared to the model group, intraperitoneal administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats(P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE groups were markedly lower than that in the model group(P < 0.05 and P < 0.001, respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH levels, as well as CAT and SOD activities in liver fibrosis rats compared to the model group(P < 0.05). Moreover, CAPE effectively inhibited α-SMA expression while increasing Nrf2 expression compared to the model group(P < 0.01). CONCLUSION: The protective effects of CAPE against liver fibrosis may be due to its ability to suppress the activation of HSCs by inhibiting oxidative stress.

Real life efficacy and safety of direct-acting antiviral therapy for treatment of patients infected with hepatitis C virus genotypes 1, 2and 3 in northwest China

BACKGROUND Regimens involving direct-acting antiviral agents(DAAs)are recommended for the treatment of infection with hepatitis C virus(HCV)genotypes 1,2 and 3.But real-world data is still not enough,especially in Asia.AIM To investigate the efficacy and safety of DAA-based regimens in a real-life setting in China.METHODS This study included 366 patients infected with HCV genotypes 1,2 and 3,with or without cirrhosis,who were observed between May 2015 and December 2018.They were treated with ledipasvir and sofosbuvir(SOF)(genotype 1)with or without ribavirin(RBV),SOF and RBV(genotype 2),or SOF and daclatasvir(genotype 3),with or without RBV,for 12 or more wk.The participants’sustained virological responses(SVR)at post-treatment week 12(SVR12)was the primary endpoint.The occurrence of adverse events and drug-drug interactions were recorded.RESULTS In the 366 patients,genotype 1(59.0%)was the most common genotype,followed by genotypes 2(34.4%)and 3(6.6%).Liver cirrhosis was diagnosed in 154(42.1%)patients.Fifty(13.7%)patients were treatment-experienced.Intention-to-treat analysis revealed that SVR12 was 86.3%(316/366).For modified intention-totreat analysis,SVR12 was achieved in 96.6%of overall patients(316/327),96.3%in patients with genotype 1,97.5%in those with genotype 2,and 95.0%in those with genotype 3.Most of the treatment failures were due to lack of follow-up(3cases had non-responses,1 had virological breakthrough,11 relapsed and 36 did not participate in the follow-up).There was no significant difference in SVR between different genotypes and liver statuses(P<0.05).Patients with lower alanine aminotransferase levels at baseline who achieved an end of treatment response were more likely to achieve SVR12(P<0.05).High SVR was observed regardless of age,gender,liver status,alpha-fetoprotein,HCV RNA levels or history of antiviral therapy(P>0.05 for all).The cumulative hepatocellular carcinoma occurrence and recurrence rate after using the DAAs was 0.9%.Most of the adverse events were mild.We found two cases of special adverse events.One case involved facial and bilateral lower extremity edema,and the other case showed an interesting change in lipid levels while on medication.No severe adverse events were noted.CONCLUSION The DAA-based regimens tested in this study have excellent effectiveness and safety in all patients infected with HCV genotypes 1,2 and 3,including those with cirrhosis.

乙肝临床治愈:欣喜与期待

慢性乙型肝炎(chronic hepatitis B,CHB)患者实现临床治愈代表患者获得了持久的病毒学抑制和免疫学控制,是目前国内外CHB防治指南的理想治疗目标.临床实践证明,以核苷(酸)类似物(nucleus(t)ide analogs,NAs)或免疫调节剂(如聚乙二醇干扰素α)序贯或联合治疗的优化方案针对部分优势人群取得了令人欣喜的结果,但在临床上乙肝治愈欣喜的同时仍有相当多的患者还不能实现临床治愈的目标,要达到较好的治疗效果诸多难题仍需要跨越.本文就乙肝临床治愈目前的研究进展与存在问题做一简要述评.

Constraints on axion-like particles with different magnetic field models from the PKS 2155–304 energy spectrum

Axion-like particles(ALPs) are a promising kind of dark matter candidate particle that are predicted to couple with photons in the presence of magnetic fields. The oscillations between photons and ALPs traveling in the magnetic fields have been used to constrain ALP properties. In this work, we obtain some new constraints on the ALP mass ma and the photon-ALP coupling constant g with two different magnetic field models through TeV photons from PKS 2155–304. The first is the discrete-Φ model in which the magnetic field has the orientation angle Φ that changes discretely and randomly from one coherent domain to the next, and the second is the linearly-continuous-Φ model in which the magnetic field orientation angle Φ varies continuously across neighboring coherent domains. For the discrete-Φ model, we can obtain the best constraints on the ALP mass m1 = ma/(1 neV)= 0.1 and on the photon-ALP coupling constant g11= g/(10^-11 GeV^-1)= 5. The reasonable range of the ALP mass m1 is 0.08 ~ 0.2 when g11 = 5,and the only reasonable value of the photon-ALP coupling constant is g11 = 5 when m1 = 0.1. For the linearly-continuous-Φ model, we can obtain the best constraints on the ALP mass m1 = 0.1 and on the photon-ALP coupling constant g11 = 0.7. The reasonable range of the ALP mass m1 is 0.05 ~ 0.4 when g11= 0.7, and the reasonable range of the photon-ALP coupling constant g11 is 0.5 ~ 1 when m1 = 0.1.All of the results are consistent with the upper bound(g < 6.6 × 10^-11 GeV^-1, i.e., g11 < 6.6) set by the CAST experiment.

Tuning the thermal conductivity of strontium titanate through annealing treatments

Strontium titanate（SrTiO3） is a promising n-type material for thermoelectric applications. However, its relatively high thermal conductivity limits its performance in efficiently converting heat into electrical power through thermoelectric effect.This work shows that the thermal conductivity of SrTiO3 can be effectively reduced by annealing treatments, through an integrated study of laser flash measurement, scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray absorption fine structure, and first-principles calculations. A phonon scattering model is proposed to explain the reduction of thermal conductivity after annealing. This work suggests a promising means to characterize and optimize the material for thermoelectric applications.

Eighty-year-old man with rare chronic neutrophilic leukemia caused by CSF3R T618I mutation:A case report and review of literature

BACKGROUNDChronic neutrophilic leukemia (CNL) is a rare bone marrow proliferative tumorand a heterogeneous disorder. In 2016, the World Health Organization includedactivating mutations in the CSF3R gene as one of the diagnostic criteria, withCSF3R T618I being the most common mutation. The disease is often accompaniedby splenomegaly, but no developmental abnormalities and significant reticularfibrosis, and no Ph chromosome and BCR-ABL fusion gene. So, it is difficult todiagnose at the first presentation in the absence of classical symptoms. Herein wedescribe a rare CNL patient without splenomegaly whose initial diagnostic cluewas neutrophilic hyperactivity.CASE SUMMARYThe patient is an 80-year-old Han Chinese man who presented with one month offatigue and fatigue aggravation in the last half of the month. He had nosplenomegaly, but had persistent hypofibrinogenemia, obvious skin bleeding, andhemoptysis, and required repeated infusion of fibrinogen therapy. After manyrelevant laboratory examinations, histopathological examination, and sequencinganalysis, the patient was finally diagnosed with CNL [CSF3R T618I positive:c.1853C>T (p.T618I) and c.2514T>A (p.C838)].CONCLUSIONThe physical examination and blood test for tumor-related genes are insufficientto establish a diagnosis of CNL. Splenomegaly is not that important, buthyperplasia of interstitial neutrophil system and activating mutations in CSF3Rare important clues to CNL diagnosis.

Theoretical Prediction of Superconductivity in Boron Kagome Monolayer:MB3(M=Be,Ca,Sr)and the Hydrogenated CaB3

Using first-principles calculations, we predict a new type of two-dimensional(2D) boride MB3(M = Be,Ca, Sr), constituted by boron kagome monolayer and the metal atoms adsorbed above the center of the boron hexagons. The band structures show that the three MB3compounds are metallic, thus the possible phononmediated superconductivity is explored. Based on the Eliashberg equation, for BeB3, CaB3, and SrB3, the calculated electron–phonon coupling constants λ are 0.46, 1.09, and 1.33, and the corresponding superconducting transition temperatures Tc are 3.2, 22.4, and 20.9 K, respectively. To explore superconductivity with higher transition temperature, hydrogenation and charge doping are further considered. The hydrogenated CaB3, i.e.,HCaB3, is stable, with the enhanced λ of 1.39 and a higher Tc of 39.3 K. Moreover, with further hole doping at the concentration of 5.8 × 1011hole/cm2, the Tc of HCaB3can be further increased to 44.2 K, exceeding the Mc Millan limit. The predicted MB3and HCaB3provide new platforms for investigating 2D superconductivity in boron kagome lattice since superconductivity based on monolayer boron kagome lattice has not been studied before.

Strong-coupling superconductivity with Tc above 70 K in Be-decorated monolayer T-graphene

Using first-principles calculations,we predict a new type of two-dimensional(2D)beryllium(Be)-decorated T-graphene named BeC_(2),where Be atoms are inserted into C–C bonds linking the carbon tetrarings of T-graphene.The band structure shows that BeC_(2)is metallic,thus,the possible phonon-mediated superconductivity is explored based on the Eliashberg equation.The calculated electron-phonon coupling(EPC)constantλis up to 4.07,and the corresponding superconducting critical temperature(Tc)is 72.1 K,approaching the liquid nitrogen temperature.The reason for the high Tc is the strong EPC.And it is proved to be an anisotropic single-gap superconductor by analyzing the superconducting gap?kof BeC_(2).The electronic susceptibility calculation shows strong nesting effect in BeC_(2).Since rare 2D superconductors show such a strong EPC constantλwhich originates from the coupling between electrons in C-pzorbital and in-plane vibrations of Be and C atoms,the predicted BeC_(2)provides a new platform for investigating strong EPC 2D superconductor.

终末期肝病合并真菌感染诊治的热点与难点

终末期肝病(end-stage liver disease,ESLD)患者由于住院时间长、免疫功能调节失衡、多合并有细菌感染且常因行侵袭性操作等原因,在临床上合并真菌感染并不少见.由于其表现不典型不易早期发现,ESLD一旦合并真菌感染往往诱发或者加重疾病进展、病死率增加.因此,本文主要就近年来有关ESLD患者合并真菌感染的流行病学、危险因素、临床表现及处理方法等热点及难点问题的研究进展进行阐述,以供临床医生参考.

Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen≤1500 IU/mL:An observational study

BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.

Cytokeratin 8 is increased in hepatitis C virus cells and its ectopic expression induces apoptosis of SMMC7721 cells

AIM:To investigate cytokeratin 8(CK8)overexpression during hepatitis C virus(HCV)infection and its pathogenesis,and the effect of ectopic CK8 expression on hepatoma cell lines.METHODS:We successfully established an in vitro HCV cell culture system(HCVcc)to investigate the different expression profiles of CK8 in Huh-7-HCV and Huh-7.5-HCV cells.The expression of CK8 at the mRNA level was determined by real-time polymerase chain reaction(RT-PCR).The expression of CK8 at the protein level was evaluated by Western blotting.We then constructed a eukaryotic expression combination vector containing the coding sequence of human full length CK8 gene.CK8cDNA was amplified by reverse transcription-PCR and inserted into pEGFP-C1 and the positive clone pEGFPCK8 was obtained.After confirming the sequence,the recombinant plasmid was transfected into SMMC7721cells with lipofectamine2000 and CK8 expression was detected using inverted fluorescence microscopy,RTPCR and Western blotting.Besides,we identified biological function of CK8 on SMMC7721 cells,including cell proliferation,cell cycle and apoptosis detection.RESULTS:RT-PCR showed that the expression level of CK8 in Huh-7-HCV and Huh-7.5-HCV cells was 2.88and 2.95 times higher than in control cells.Western blot showed that CK8 expression in Huh-7-HCV and Huh-7.5-HCV cells was 2.53 and 3.26 times higher than that in control cells,respectively.We found that CK8at mRNA and protein levels were both significantly increased in HCVcc.CK8 was up-regulated in SMMC7721cells.CK8 expression at the mRNA level was significantly upregulated in SMMC7721/pEGFP-CK8 cells.CK8expression in SMMC7721/pEGFP-CK8 cells was 2.69times higher than in SMMC7721 cells,and was 2.64times higher than in SMMC7721/pEGFP-C1 cells.CK8expression at the protein level in SMMC7721/pEGFPCK8 cells was 2.46 times higher than in SMMC7721cells,and was 2.29 times higher than in SMMC7721/pEGFP-C1 cells.Further analysis demonstrated that forced expression of CK8 slowed cell growth and induced apoptosis of SMMC7721 cells.CONCLUSION:CK8 up-regulation might have a functional role in HCV infection and pathogenesis,and could be a promising target for the treatment of HCV infection.