Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen （NSAA） is still widely used in treating metastatic castration-resistant prostate cancer （mCRPC）, especially in undevel...Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen （NSAA） is still widely used in treating metastatic castration-resistant prostate cancer （mCRPC）, especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate （Abi） remains uncertain, in the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA （from bicalutamide to flutamide） before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival （PSA-PFS, 5.5 vs 5.6 months, P = 0.967）, radiographic progression-free survival （rPFS, 12.8 vs 13.4 months, P = 0.508）, overall survival （OS, not reached vs 30.6 months, P = 0.606）, or PSA-response rate （71.4% [15121] vs 60.6% [40166], P = 0.370）. This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors＇ decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.展开更多
Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on l...Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.展开更多
Background:It remains unclear what the antiviral therapy affects disease-free survival(DFS) and overall survival(OS)of patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) at different tumor stag...Background:It remains unclear what the antiviral therapy affects disease-free survival(DFS) and overall survival(OS)of patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) at different tumor stages and baseline HBV DNA levels.In this study,we analyzed the association of antiviral treatment with DFS and OS based on the stratification of baseline HBV DNA load in early-stage(stages Ⅰ and Ⅱ) HCC patients.Methods:We included 445 patients with early-stage HBV-related HCC who underwent curative resection,and then classified them into four subgroups based on baseline HBV DNA load and antiviral therapy stratification.The KaplanMeier and Cox regression analyses were performed to determine the association of clinical characteristics with survival.Results:The median follow-up period was 74 months.For all patients,cumulative OS rates in the antiviral group were significantly higher than those in the non-antiviral group(log-rank test,P = 0.023),whereas no significant differences in DFS rates were observed.High baseline HBV DNA level was a risk factor associated with short DFS and OS in all patients.In patients with baseline HBV DNA levels ≥2000 lU/mL,antiviral treatment was significantly associated with prolonged DFS and OS(log-rank test,P = 0.041 and 0.001,respectively).In patients with HBV DNA levels <2000 lU/mL or undetectable,antiviral treatment did not show a significant benefit in prolonging DFS and OS.Conclusions:High baseline HBV DNA levels are associated with poor prognosis in the patients with early-stage HCC,and the antiviral treatment could generate survival benefits for the patients.Therefore,antiviral treatment should be given for these patients.However,the effect of antiviral treatment on the patients with low viral load remains unclear,and further investigation is warranted.展开更多
Cystatin-C(Cys-C)has been reported as a valuable prognostic biomarker in various malignancies.However,its effect on upper tract urothelial carci noma(UTUC)patie nts has not bee n investigated before.Thus,to explore th...Cystatin-C(Cys-C)has been reported as a valuable prognostic biomarker in various malignancies.However,its effect on upper tract urothelial carci noma(UTUC)patie nts has not bee n investigated before.Thus,to explore the impact of Cys-C on survival outcomes in patients undergoing radical nephroureterectomy(RNU),a total of 538 patients with UTUC who underwent RNU between 2005 and 2014 in our center(West China Hospital,Chengdu,China)were included in this study.Kaplan-Meier method and Cox regressi on an a lyses were performed to assess the relationship betwee n Cys-C and survival outcomes using SPSS versi on 22.0.The cutoff value of Cys-C was set as 1.4 mg I1 using the receiver operating characteristic(ROC)curves and Youden index.The mean age of patients included was 66.1±11.1 years,and the media n follow-up durati on was 38(interquartile ran ge:19-56)mon ths.Overall,162(30.1%)patients had elevated Cys-C,and they were much older and had worse renal function than those with Cys-C<1.4 mg I^-1(both P<0.001).Meanwhile,Kaplan-Meier analysis revealed that the group with elevated Cys-C had worse cancer-specific survival(CSS,P=0.001),disease recurrence-free survival(RFS,P=0.003),and overall survival(OS,P<0.001).Multivariable Cox analysis suggested that the elevated Cys-C was identified as an independent prognostic predictor of CSS(hazard ratio[HR]:1.997,95%confidential interval[CI]:1.331-2.996),RFS(HR:1.429,95%CI:1.009-2.023),and OS(HR:1.989,95%CI:1.366-2.896).In conclusion,our result revealed that the elevated preoperative serum Cys-C was significantly associated with worse outcomes in UTUC patients undergoing RNU.展开更多
Introduction:Most hepatocellular carcinomas(HCC) develop in a background of underlying liver disease including chronic hepatitis B.However,the effect of antiviral therapy on the long-term outcome of patients with hepa...Introduction:Most hepatocellular carcinomas(HCC) develop in a background of underlying liver disease including chronic hepatitis B.However,the effect of antiviral therapy on the long-term outcome of patients with hepatitis B virus(HBV)-related HCC treated with chemoembolization is unclear.This study aimed to evaluate the survival benefits of anti-HBV therapy after chemoembolization for patients with HBV-related HCC.Methods:A total of 224 HCC patients who successfully underwent chemoembolization were identified,and their survival and other relevant clinical data were reviewed.Kaplan-Meier and Cox regression analyses were performed to validate possible effects of antiviral treatment on overall survival(OS).Results:The median survival time(MST) was 15.9(95%confidence interval[CI],9.5-27.7) months in the antiviral group and 9.6(95%CI,7.8-13.7) months in the non-antiviral group(log-rank test,P = 0.044).Cox multivariate analysis revealed that antiviral treatment was a prognostic factor for OS(P = 0.008).Additionally,a further analysis was based on the stratification of the TNM tumor stages.In the subgroup of early stages,MST was significantly longer in the antiviral-treatment group than in the non-antiviral group(61.8 months[95%CI,34.8 months to beyond the follow-up period]versus 26.2[95%CI,14.5-37.7]months,P= 0.012).Multivariate analysis identified antiviral treatment as a prognostic factor for OS in the early-stage subgroup(P = 0.006).However,in the subgroup of advanced stages,MST of the antiviral-treated group was comparable to that of the non-antiviral group(8.4[95%CI,5.2-13.5]months versus 7.4[95%CI,5.9-9.3]months,P = 0.219).Multivariate analysis did not indicate that antiviral treatment was a significant prognostic factor in this subgroup.Conclusion:Antiviral treatment is associated with prolonged OS time after chemoembolization for HCC,especially in patients with early-stage tumors.展开更多
AIM:To compare the clinical performance of a real-time PCR assay with the COBAS Amplicor Hepatitis B Virus (HBV) Monitor test for quantitation of HBV DNA in serum samples. METHODS: The reference sera of the Chinese Na...AIM:To compare the clinical performance of a real-time PCR assay with the COBAS Amplicor Hepatitis B Virus (HBV) Monitor test for quantitation of HBV DNA in serum samples. METHODS: The reference sera of the Chinese National Institute for the Control of Pharmaceutical and Biological Products and the National Center for Clinical Laboratories of China, and 158 clinical serum samples were used in this study. The linearity, accuracy, reproducibility, assay time, and costs of the real-time PCR were evaluated and compared with those of the Cobas Amplicor test. RESULTS: The intra-assay and inter-assay variations of the real-time PCR ranged from 0.3% to 3.8% and 1.4% to 8.1%, respectively. The HBV DNA levels measured by the real-time PCR correlated very well with those obtained with the COBAS Amplicor test (r = 0.948). The real-time PCR HBV DNA kit was much cheaper and had a wider dynamic range. CONCLUSION: The real-time PCR assay is an excellent tool for monitoring of HBV DNA levels in patients with chronic hepatitis B.展开更多
AIM To investigate whether the preoperative neutrophil-tolymphocyte ratio(NLR) could predict the prognosis of hepatocellular carcinoma(HCC) patients with portal/hepatic vein tumor thrombosis(PVTT/HVTT) after hepatecto...AIM To investigate whether the preoperative neutrophil-tolymphocyte ratio(NLR) could predict the prognosis of hepatocellular carcinoma(HCC) patients with portal/hepatic vein tumor thrombosis(PVTT/HVTT) after hepatectomy.METHODS The study population included 81 HCC patients who underwent hepatectomy and were diagnosed with PVTT/HVTT based on pathological examination. The demographics, laboratory analyses, and histopathology data were analyzed.RESULTS Overall survival(OS) and disease-free survival(DFS) were determined in the patients with a high(> 2.9) and low(≤ 2.9) NLR. The median OS and DFS duration in the high NLR group were significantly shorter than those in the low NLR group(OS: 6.2 mo vs 15.7 mo, respectively, P = 0.007; DFS: 2.2 mo vs 3.7 mo, respectively, P = 0.039). An NLR > 2.9 was identified as an independent predictor of a poor prognosis of OS(P = 0.034, HR = 1.866; 95%CI: 1.048-3.322) in uni-and multivariate analyses. Moreover, there was a significantly positive correlation between the NLR and the Child-Pugh score(r = 0.276, P = 0.015) and the maximum diameter of the tumor(r = 0.435, P < 0.001). Additionally, the NLR could enhance the prognostic predictive power of the CLIP score for DFS in these patients. CONCLUSION The preoperative NLR is a prognostic predictor after hepatectomy for HCC patients with PVTT/HVTT. NLR > 2.9 indicates poorer OS and DFS.展开更多
Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a re...Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a retrospective,single-center trial.Between April 3,2017 and July 2,2018,104 patients with Child-Pugh A and advanced HCC received either 400 mg of sorafenib orally twice daily plus HAIC with oxaliplatin(oxaliplatin 85 mg/m^2,every 3 weeks via repetitive catheterization)(n=46,soraOXA group)or 400 mg of only sorafenib orally twice daily(n=58,sorafenib group).Overall survival,progression-free survival,objective response rate,and treatment-related adverse events were compared.Results:The median overall survival was 9.37 months(95%CI,7.05-11.68)in the soraOXA group versus 4.8 months(95%CI,2.98-6.62)in the sorafenib group(HR 0.46[95%CI,0.29-0.72];P<0.001).The soraOXA group also showed a higher objective response rate(16[34.8%]vs 1[1.7%];P<0.001)and a longer progressionfree survival rate(5.5 months[95%CI,2.32-8.68]vs 2.4 months[95%CI,1.65-3.15],HR 0.54[95%CI,0.36-0.81],P=0.003)than the sorafenib group.There was no significant difference in the overall incidence of any grade adverse events,grade 3/4 adverse events,serious adverse events,or incidence of treatment termination due to adverse events between the two groups.Conclusion:Compared with sorafenib alone,sorafenib plus HAIC with oxaliplatin showed favorable treatment outcomes in patients with advanced HCC.The merits of this approach need to be established with a prospective trial.展开更多
BACKGROUND Cervical spine pyogenic infection(CSPI)is a rare and challenging form of spinal infection that is typically caused by pyogenic bacteria and primarily affects the cervical vertebral bodies and surrounding ti...BACKGROUND Cervical spine pyogenic infection(CSPI)is a rare and challenging form of spinal infection that is typically caused by pyogenic bacteria and primarily affects the cervical vertebral bodies and surrounding tissues.Given its nonspecific symptoms,such as fever and neck pain,early diagnosis is crucial to prevent severe complications,including spinal cord injury.We report a previously unreported case of acute CSPI arising from chronic paronychia,exploring its diagnostic and therapeutic challenges through a review of the current literature.CASE SUMMARY The presented case involved a 15-year-old man with CSPI caused by Staphylococcus aureus,which led to complications including bacteremia and a paronychiaassociated abscess.Acute pyogenic infection was initially diagnosed by typical symptoms and blood culture.Fever improved after antibiotic treatment while developing progressive limbs dysfunction.Six days after admission,the patient underwent anterior cervical debridement+autogenous iliac bone graft fusion+plate internal fixation and received 12 weeks of antibiotic treatment after the operation.Re-examination 3 years postoperatively showed that the patient had stable cervical fixation,no significant neck pain or upper limb abnormalities,and normal urinary function.CONCLUSION Early imaging findings,laboratory markers,and timely antibiotic treatment are crucial for CSPI management,preventing complications and facilitating recovery.展开更多
Background: Mucosal-associated invariant T(MAIT) cells are systemically depleted in human immunodeficiency virus type 1(HIV-1) infected patients and are not replenished even after successful combined antiretroviral th...Background: Mucosal-associated invariant T(MAIT) cells are systemically depleted in human immunodeficiency virus type 1(HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy(cART).This study aimed to identify the mechanism underlying MAIT cell depletion.Methods: In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.Results: Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4+ T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D(GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12(IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro.Conclusions: Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients,which could potentiate disease progression and poor immune reconstitution.展开更多
Although converting the greenhouse gasses carbon dioxide(CO_(2))into solar fuels is regarded as a convenient means of solar energy storage,the intrinsic mechanism on how the high chemical inertness linear CO_(2)molecu...Although converting the greenhouse gasses carbon dioxide(CO_(2))into solar fuels is regarded as a convenient means of solar energy storage,the intrinsic mechanism on how the high chemical inertness linear CO_(2)molecules is activated and converted on a semiconductor oxide is still elusive.Herein,by creating the oxygen vacancies on the typical hexagonal tungsten oxide(WO3),we realize the continuous photoinduced CO_(2)reduction to selectively produce CO under light irradiation,which was verified by isotope labeling experiment.Detailed oxygen vacancies evolution investigation indicates that light irradiation can simultaneously induce the in-situ formation of oxygen vacancies on hexagonal WO3,and the oxygen vacancies promote the adsorption and activation of CO_(2)molecules,leading to the CO_(2)reduction to CO on the hexagonal WO3via an oxygen vacancies-involved process.Besides,the existence of water further promotes the formation of CO_(2)reduction intermediate,further promote the CO_(2)photoreduction.Our work provides insight on the mechanism for converting CO_(2)into CO under light irradiation.展开更多
We utilize high-resolution resonant angle-resolved photoemission spectroscopy(ARPES)to study the band structure and hybridization effect of the heavy-fermion compound Ce2 IrIn8.We observe a nearly flat band at the bin...We utilize high-resolution resonant angle-resolved photoemission spectroscopy(ARPES)to study the band structure and hybridization effect of the heavy-fermion compound Ce2 IrIn8.We observe a nearly flat band at the binding energy of 7 meV below the coherent temperature Tcoh^40 K,which characterizes the electrical resistance maximum and indicates the onset temperature of hybridization.However,the Fermi vector and the Fermi surface volume have little change around Tcoh,which challenges the widely believed evolution from a hightemperature small Fermi surface to a low-temperature large Fermi surface.Our experimental results of the band structure fit well with the density functional theory plus dynamic mean-field theory calculations.展开更多
Photodynamic therapy(PDT)has significant advantages in treating primary tumors.However,the hypoxic tumor microenvironment hinders the generation of sufficient reactive oxygen species during PDT to effectively kill tum...Photodynamic therapy(PDT)has significant advantages in treating primary tumors.However,the hypoxic tumor microenvironment hinders the generation of sufficient reactive oxygen species during PDT to effectively kill tumor cells,further greatly limiting the applications of PDT in cancer treatment.Herein,we reported a temperature/pH dual controlled drug delivery system LPC@PCN@PDA/Fe^(3+)-AS1411 based on a porous coordination network(PCN(Mn))coated with polydopamine(PDA)and modified with an aptamer AS1411.β-lapachone(LPC)was loaded inside the PCN(Mn)framework,and Fe^(3+)was attached to the surface of the PDA coating.These nanoparticles(NPs)exhibited excellent multimodal cancer therapeutic effects and tumor targeting ability with their photo-and chemodynamic properties.The therapeutic effect can be enhanced by the production of sufficient oxygen by the internal hydrogen peroxide,which improves the photodynamic effect of the photosensitizer PCN(Mn)and the chemotherapy effect ofβ-lapachone.Notably,the conversion of Fe^(2+)to Fe^(3+)in the tumor cells exerts the Fenton effect,which generates hydroxyl radicals that cause lipid peroxidation in tumor cells and induce apoptosis,thus enhancing the chemodynamic therapeutic effect.In vitro and in vivo experiments revealed that the NPs demonstrated specific tumor targeting,excellent inhibition effect on tumor growth,and biocompatibility.Together,our findings can help develop an intelligent multifunctional therapeutic nanoplatform for cancer therapy.展开更多
The electronic structure of iron-pnictide compound superconductor Ba_2Ti_2Fe_2As_4O, which has metallic intermediate Ti_2O layers, is studied using angle-resolved photoemission spectroscopy. The Ti-related bands show ...The electronic structure of iron-pnictide compound superconductor Ba_2Ti_2Fe_2As_4O, which has metallic intermediate Ti_2O layers, is studied using angle-resolved photoemission spectroscopy. The Ti-related bands show a‘peak-dip-hump＇ line shape with two branches of dispersion associated with the polaronic states at temperatures below around 120 K. This change in the spectra occurs along with the resistivity anomaly that was not clearly understood in a previous study. Moreover, an energy gap induced by the superconducting proximity effect opens in the polaronic bands at temperatures below T_c（~21 K）. Our study provides the spectroscopic evidence that superconductivity coexists with polarons in the same bands near the Fermi level, which provides a suitable platform to study interactions between charge, lattice and spin freedoms in a correlated system.展开更多
BACKGROUND Trastuzumab constitutes the fundamental component of initial therapy for patients with advanced human epidermal growth factor receptor 2(HER-2)-positive gastric cancer(GC).However,the efficacy of this treat...BACKGROUND Trastuzumab constitutes the fundamental component of initial therapy for patients with advanced human epidermal growth factor receptor 2(HER-2)-positive gastric cancer(GC).However,the efficacy of this treatment is hindered by substantial challenges associated with both primary and acquired drug resistance.While S-phase kinase associated protein 2(Skp2)overexpression has been implicated in the malignant progression of GC,its role in regulating trastuzumab resistance in this context remains uncertain.Despite the numerous studies investigating Skp2 inhibitors among small molecule compounds and natural products,there has been a lack of successful commercialization of drugs specifically targeting Skp2.AIM To discover a Skp2 blocker among currently available medications and develop a therapeutic strategy for HER2-positive GC patients who have experienced progression following trastuzumab-based treatment.METHODS Skp2 exogenous overexpression plasmids and small interfering RNA vectors were utilized to investigate the correlation between Skp2 expression and trastuzumab resistance in GC cells.Q-PCR,western blot,and immunohistochemical analyses were conducted to evaluate the regulatory effect of thioridazine on Skp2 expression.A cell counting kit-8 assay,flow cytometry,a amplex red glucose/glucose oxidase assay kit,and a lactate assay kit were utilized to measure the proliferation,apoptosis,and glycolytic activity of GC cells in vitro.A xenograft model established with human GC in nude mice was used to assess thioridazine's effectiveness in vivo.RESULTS The expression of Skp2 exhibited a negative correlation with the sensitivity of HER2-positive GC cells to trastuzumab.Thioridazine demonstrated the ability to directly bind to Skp2,resulting in a reduction in Skp2 expression at both the transcriptional and translational levels.Moreover,thioridazine effectively inhibited cell proliferation,exhibited antiapoptotic properties,and decreased the glucose uptake rate and lactate production by suppressing Skp2/protein kinase B/mammalian target of rapamycin/glucose transporter type 1 signaling pathways.The combination of thioridazine with either trastuzumab or lapatinib exhibited a more pronounced anticancer effect in vivo,surpassing the efficacy of either monotherapy.CONCLUSION Thioridazine demonstrates promising outcomes in preclinical GC models and offers a novel therapeutic approach for addressing trastuzumab resistance,particularly when used in conjunction with lapatinib.This compound has potential benefits for patients with Skp2-proficient tumors.展开更多
Although photocatalytic water splitting has excellent potential for converting solar energy into chemical energy,the challenging charge separation process and sluggish surface catalytic reactions significantly limit p...Although photocatalytic water splitting has excellent potential for converting solar energy into chemical energy,the challenging charge separation process and sluggish surface catalytic reactions significantly limit progress in solar energy conversion using semiconductor photocatalysts.Herein,we demonstrate a feasible strategy involving the surface assembly of cobalt oxide species(CoO_(x))on a visible-light-responsive Cd_(0.9)Zn_(0.1)S(CZS)photocatalyst to fabricate a hierarchical CZS@CoO_(x) heterostructure.The unique hierarchical structure effectively accelerates the directional transfer of photogenerated charges,reducing charge recombination through the smooth interfacial heterojunction between CZS and CoO_(x),as evidenced by photoluminescence(PL)spectroscopy and various electrochemical characterizations.The surface cobalt species on the CZS material also act as efficient cocatalysts for photocatalytic hydrogen production,with activity even higher than that of noble metals.The well-defined CZS@CoO_(x) heterostructure not only enhances the interfacial separation of photoinduced charges,but also improves surface catalytic reactions.This leads to superior photocatalytic performances,with an apparent quantum efficiency of 20%at 420 nm for visible-light-driven hydrogen generation,which is one of the highest quantum efficiencies measured among noble-metal-free photocatalysts.Our work presents a potential pathway for controlling complex charge separation and catalytic reaction processes in photocatalysis,guiding the practical development of artificial photocatalysts for successful transformation of solar to chemical energy.展开更多
基金This work was supported by the National Natural Science Foundation of China （NSFC 81672547, 81402110, and 81272820） Science and Technology Support Program of Sichuan Province （2015SZ0142） and the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University.
文摘Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen （NSAA） is still widely used in treating metastatic castration-resistant prostate cancer （mCRPC）, especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate （Abi） remains uncertain, in the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA （from bicalutamide to flutamide） before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival （PSA-PFS, 5.5 vs 5.6 months, P = 0.967）, radiographic progression-free survival （rPFS, 12.8 vs 13.4 months, P = 0.508）, overall survival （OS, not reached vs 30.6 months, P = 0.606）, or PSA-response rate （71.4% [15121] vs 60.6% [40166], P = 0.370）. This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors＇ decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.
基金supported by the National Natural Science Foundation of China(No.81625017 and No.81572385)the Fundamental Research Funds for the Central Universities of China(No.16ykjc36)
文摘Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.
基金supported by project grants from the National Natural Science Foundation of China(no.81201603 for Dr.XML)the Guangdong Natural Science Funds(No.S2012010009631 for Dr.XML)the International Program for Ph.D.Candidates from Sun Yat-sen University(for Dr.JLC)
文摘Background:It remains unclear what the antiviral therapy affects disease-free survival(DFS) and overall survival(OS)of patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) at different tumor stages and baseline HBV DNA levels.In this study,we analyzed the association of antiviral treatment with DFS and OS based on the stratification of baseline HBV DNA load in early-stage(stages Ⅰ and Ⅱ) HCC patients.Methods:We included 445 patients with early-stage HBV-related HCC who underwent curative resection,and then classified them into four subgroups based on baseline HBV DNA load and antiviral therapy stratification.The KaplanMeier and Cox regression analyses were performed to determine the association of clinical characteristics with survival.Results:The median follow-up period was 74 months.For all patients,cumulative OS rates in the antiviral group were significantly higher than those in the non-antiviral group(log-rank test,P = 0.023),whereas no significant differences in DFS rates were observed.High baseline HBV DNA level was a risk factor associated with short DFS and OS in all patients.In patients with baseline HBV DNA levels ≥2000 lU/mL,antiviral treatment was significantly associated with prolonged DFS and OS(log-rank test,P = 0.041 and 0.001,respectively).In patients with HBV DNA levels <2000 lU/mL or undetectable,antiviral treatment did not show a significant benefit in prolonging DFS and OS.Conclusions:High baseline HBV DNA levels are associated with poor prognosis in the patients with early-stage HCC,and the antiviral treatment could generate survival benefits for the patients.Therefore,antiviral treatment should be given for these patients.However,the effect of antiviral treatment on the patients with low viral load remains unclear,and further investigation is warranted.
基金the National Key Research and Development Program of China(Grant No.SQ2017YFSF090096)the Prostate Cancer Foundation Young Investigator Award 2013,the National Natural Science Foundation of China(Grant No.81300627,81370855,81702536,and 81770756)+1 种基金the Science and Technology Department of Sichuan Province(Grant No.2014JY0219 and 2017HH0063)Young Investigator Award of Sichuan University 2017.The funders had no role in patient selection,data extraction,statistical analysis or interpretation,writing of this article,or the decision to publish.
文摘Cystatin-C(Cys-C)has been reported as a valuable prognostic biomarker in various malignancies.However,its effect on upper tract urothelial carci noma(UTUC)patie nts has not bee n investigated before.Thus,to explore the impact of Cys-C on survival outcomes in patients undergoing radical nephroureterectomy(RNU),a total of 538 patients with UTUC who underwent RNU between 2005 and 2014 in our center(West China Hospital,Chengdu,China)were included in this study.Kaplan-Meier method and Cox regressi on an a lyses were performed to assess the relationship betwee n Cys-C and survival outcomes using SPSS versi on 22.0.The cutoff value of Cys-C was set as 1.4 mg I1 using the receiver operating characteristic(ROC)curves and Youden index.The mean age of patients included was 66.1±11.1 years,and the media n follow-up durati on was 38(interquartile ran ge:19-56)mon ths.Overall,162(30.1%)patients had elevated Cys-C,and they were much older and had worse renal function than those with Cys-C<1.4 mg I^-1(both P<0.001).Meanwhile,Kaplan-Meier analysis revealed that the group with elevated Cys-C had worse cancer-specific survival(CSS,P=0.001),disease recurrence-free survival(RFS,P=0.003),and overall survival(OS,P<0.001).Multivariable Cox analysis suggested that the elevated Cys-C was identified as an independent prognostic predictor of CSS(hazard ratio[HR]:1.997,95%confidential interval[CI]:1.331-2.996),RFS(HR:1.429,95%CI:1.009-2.023),and OS(HR:1.989,95%CI:1.366-2.896).In conclusion,our result revealed that the elevated preoperative serum Cys-C was significantly associated with worse outcomes in UTUC patients undergoing RNU.
基金partly supported by the Foundation for the Outstanding Young Scholar Award(Dr.Xiang-Ming Lao) from Sun Yat-sen University Cancer Center
文摘Introduction:Most hepatocellular carcinomas(HCC) develop in a background of underlying liver disease including chronic hepatitis B.However,the effect of antiviral therapy on the long-term outcome of patients with hepatitis B virus(HBV)-related HCC treated with chemoembolization is unclear.This study aimed to evaluate the survival benefits of anti-HBV therapy after chemoembolization for patients with HBV-related HCC.Methods:A total of 224 HCC patients who successfully underwent chemoembolization were identified,and their survival and other relevant clinical data were reviewed.Kaplan-Meier and Cox regression analyses were performed to validate possible effects of antiviral treatment on overall survival(OS).Results:The median survival time(MST) was 15.9(95%confidence interval[CI],9.5-27.7) months in the antiviral group and 9.6(95%CI,7.8-13.7) months in the non-antiviral group(log-rank test,P = 0.044).Cox multivariate analysis revealed that antiviral treatment was a prognostic factor for OS(P = 0.008).Additionally,a further analysis was based on the stratification of the TNM tumor stages.In the subgroup of early stages,MST was significantly longer in the antiviral-treatment group than in the non-antiviral group(61.8 months[95%CI,34.8 months to beyond the follow-up period]versus 26.2[95%CI,14.5-37.7]months,P= 0.012).Multivariate analysis identified antiviral treatment as a prognostic factor for OS in the early-stage subgroup(P = 0.006).However,in the subgroup of advanced stages,MST of the antiviral-treated group was comparable to that of the non-antiviral group(8.4[95%CI,5.2-13.5]months versus 7.4[95%CI,5.9-9.3]months,P = 0.219).Multivariate analysis did not indicate that antiviral treatment was a significant prognostic factor in this subgroup.Conclusion:Antiviral treatment is associated with prolonged OS time after chemoembolization for HCC,especially in patients with early-stage tumors.
文摘AIM:To compare the clinical performance of a real-time PCR assay with the COBAS Amplicor Hepatitis B Virus (HBV) Monitor test for quantitation of HBV DNA in serum samples. METHODS: The reference sera of the Chinese National Institute for the Control of Pharmaceutical and Biological Products and the National Center for Clinical Laboratories of China, and 158 clinical serum samples were used in this study. The linearity, accuracy, reproducibility, assay time, and costs of the real-time PCR were evaluated and compared with those of the Cobas Amplicor test. RESULTS: The intra-assay and inter-assay variations of the real-time PCR ranged from 0.3% to 3.8% and 1.4% to 8.1%, respectively. The HBV DNA levels measured by the real-time PCR correlated very well with those obtained with the COBAS Amplicor test (r = 0.948). The real-time PCR HBV DNA kit was much cheaper and had a wider dynamic range. CONCLUSION: The real-time PCR assay is an excellent tool for monitoring of HBV DNA levels in patients with chronic hepatitis B.
文摘AIM To investigate whether the preoperative neutrophil-tolymphocyte ratio(NLR) could predict the prognosis of hepatocellular carcinoma(HCC) patients with portal/hepatic vein tumor thrombosis(PVTT/HVTT) after hepatectomy.METHODS The study population included 81 HCC patients who underwent hepatectomy and were diagnosed with PVTT/HVTT based on pathological examination. The demographics, laboratory analyses, and histopathology data were analyzed.RESULTS Overall survival(OS) and disease-free survival(DFS) were determined in the patients with a high(> 2.9) and low(≤ 2.9) NLR. The median OS and DFS duration in the high NLR group were significantly shorter than those in the low NLR group(OS: 6.2 mo vs 15.7 mo, respectively, P = 0.007; DFS: 2.2 mo vs 3.7 mo, respectively, P = 0.039). An NLR > 2.9 was identified as an independent predictor of a poor prognosis of OS(P = 0.034, HR = 1.866; 95%CI: 1.048-3.322) in uni-and multivariate analyses. Moreover, there was a significantly positive correlation between the NLR and the Child-Pugh score(r = 0.276, P = 0.015) and the maximum diameter of the tumor(r = 0.435, P < 0.001). Additionally, the NLR could enhance the prognostic predictive power of the CLIP score for DFS in these patients. CONCLUSION The preoperative NLR is a prognostic predictor after hepatectomy for HCC patients with PVTT/HVTT. NLR > 2.9 indicates poorer OS and DFS.
基金supported by National Key R&D Program of China(2017YFA0505803)National Natural Science Foundation of China(No.81625017,No.81572385)National Science and Technology Major Project of China(2018ZX10302205).
文摘Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a retrospective,single-center trial.Between April 3,2017 and July 2,2018,104 patients with Child-Pugh A and advanced HCC received either 400 mg of sorafenib orally twice daily plus HAIC with oxaliplatin(oxaliplatin 85 mg/m^2,every 3 weeks via repetitive catheterization)(n=46,soraOXA group)or 400 mg of only sorafenib orally twice daily(n=58,sorafenib group).Overall survival,progression-free survival,objective response rate,and treatment-related adverse events were compared.Results:The median overall survival was 9.37 months(95%CI,7.05-11.68)in the soraOXA group versus 4.8 months(95%CI,2.98-6.62)in the sorafenib group(HR 0.46[95%CI,0.29-0.72];P<0.001).The soraOXA group also showed a higher objective response rate(16[34.8%]vs 1[1.7%];P<0.001)and a longer progressionfree survival rate(5.5 months[95%CI,2.32-8.68]vs 2.4 months[95%CI,1.65-3.15],HR 0.54[95%CI,0.36-0.81],P=0.003)than the sorafenib group.There was no significant difference in the overall incidence of any grade adverse events,grade 3/4 adverse events,serious adverse events,or incidence of treatment termination due to adverse events between the two groups.Conclusion:Compared with sorafenib alone,sorafenib plus HAIC with oxaliplatin showed favorable treatment outcomes in patients with advanced HCC.The merits of this approach need to be established with a prospective trial.
基金Supported by the Guangxi University of Chinese Medicine Doctoral Startup Research Fund Project,No.2018BS065Department of Traditional Chinese Orthopedics,Guangxi International Zhuang Medicine Hospital,No.[2021]33.
文摘BACKGROUND Cervical spine pyogenic infection(CSPI)is a rare and challenging form of spinal infection that is typically caused by pyogenic bacteria and primarily affects the cervical vertebral bodies and surrounding tissues.Given its nonspecific symptoms,such as fever and neck pain,early diagnosis is crucial to prevent severe complications,including spinal cord injury.We report a previously unreported case of acute CSPI arising from chronic paronychia,exploring its diagnostic and therapeutic challenges through a review of the current literature.CASE SUMMARY The presented case involved a 15-year-old man with CSPI caused by Staphylococcus aureus,which led to complications including bacteremia and a paronychiaassociated abscess.Acute pyogenic infection was initially diagnosed by typical symptoms and blood culture.Fever improved after antibiotic treatment while developing progressive limbs dysfunction.Six days after admission,the patient underwent anterior cervical debridement+autogenous iliac bone graft fusion+plate internal fixation and received 12 weeks of antibiotic treatment after the operation.Re-examination 3 years postoperatively showed that the patient had stable cervical fixation,no significant neck pain or upper limb abnormalities,and normal urinary function.CONCLUSION Early imaging findings,laboratory markers,and timely antibiotic treatment are crucial for CSPI management,preventing complications and facilitating recovery.
基金supported by the Peking University Clinical Scientist Program Special(BMU2019LCKXJ013)the National Natural Science Foundation Innovation Research Group Project(81721002)+2 种基金the Sanming Project of Medicine Project in Shenzhen(SZSM201612014)the Yunnan Applied Basic Research Projects-Union Foundation by Yunnan Provincial Department of Science and Technology and Kunming Medical University(202001AY070001-154)the Scientific Research Fund of Education Department of Yunnan Province(2021J0297)。
文摘Background: Mucosal-associated invariant T(MAIT) cells are systemically depleted in human immunodeficiency virus type 1(HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy(cART).This study aimed to identify the mechanism underlying MAIT cell depletion.Methods: In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.Results: Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4+ T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D(GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12(IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro.Conclusions: Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients,which could potentiate disease progression and poor immune reconstitution.
基金supported by National Natural Science Foundation of China(No.22088102)supported by National Natural Science Foundation of China(No.22090033)+1 种基金the support from Youth Innovation Promotion Association of Chinese Academy of SciencesDalian Institute of Chemical Physics,CAS。
文摘Although converting the greenhouse gasses carbon dioxide(CO_(2))into solar fuels is regarded as a convenient means of solar energy storage,the intrinsic mechanism on how the high chemical inertness linear CO_(2)molecules is activated and converted on a semiconductor oxide is still elusive.Herein,by creating the oxygen vacancies on the typical hexagonal tungsten oxide(WO3),we realize the continuous photoinduced CO_(2)reduction to selectively produce CO under light irradiation,which was verified by isotope labeling experiment.Detailed oxygen vacancies evolution investigation indicates that light irradiation can simultaneously induce the in-situ formation of oxygen vacancies on hexagonal WO3,and the oxygen vacancies promote the adsorption and activation of CO_(2)molecules,leading to the CO_(2)reduction to CO on the hexagonal WO3via an oxygen vacancies-involved process.Besides,the existence of water further promotes the formation of CO_(2)reduction intermediate,further promote the CO_(2)photoreduction.Our work provides insight on the mechanism for converting CO_(2)into CO under light irradiation.
基金Supported by the National Key Research and Development Program of China under Grant Nos 2016YFA0401000,2015CB921300,2016YFA0300303,2016YFA0401002 and 2017YFA0303103the National Natural Science Foundation of China under Grant Nos 11674371,11774401 and 11874330+4 种基金the Strategic Priority Research Program(B)of the Chinese Academy of Sciences under Grant No XDB07000000the Beijing Municipal Science and Technology Commission under Grant No Z171100002017018the Hundred-Talent Program(type C)of the Chinese Academy of Sciencesthe Sino-Swiss Science and Technology Cooperation under Grant No IZLCZ2-170075the Swiss National Science Foundation under Grant No 200021-159678
文摘We utilize high-resolution resonant angle-resolved photoemission spectroscopy(ARPES)to study the band structure and hybridization effect of the heavy-fermion compound Ce2 IrIn8.We observe a nearly flat band at the binding energy of 7 meV below the coherent temperature Tcoh^40 K,which characterizes the electrical resistance maximum and indicates the onset temperature of hybridization.However,the Fermi vector and the Fermi surface volume have little change around Tcoh,which challenges the widely believed evolution from a hightemperature small Fermi surface to a low-temperature large Fermi surface.Our experimental results of the band structure fit well with the density functional theory plus dynamic mean-field theory calculations.
基金supported by the National Natural Science Foundation of China(No.62071413)the Hebei Natural Science Foundation of China(Nos.C2019203556 and F2020203056)the Natural Science Foundation of Hebei Province for Innovation Group Project,China(No.C2022203003)。
文摘Photodynamic therapy(PDT)has significant advantages in treating primary tumors.However,the hypoxic tumor microenvironment hinders the generation of sufficient reactive oxygen species during PDT to effectively kill tumor cells,further greatly limiting the applications of PDT in cancer treatment.Herein,we reported a temperature/pH dual controlled drug delivery system LPC@PCN@PDA/Fe^(3+)-AS1411 based on a porous coordination network(PCN(Mn))coated with polydopamine(PDA)and modified with an aptamer AS1411.β-lapachone(LPC)was loaded inside the PCN(Mn)framework,and Fe^(3+)was attached to the surface of the PDA coating.These nanoparticles(NPs)exhibited excellent multimodal cancer therapeutic effects and tumor targeting ability with their photo-and chemodynamic properties.The therapeutic effect can be enhanced by the production of sufficient oxygen by the internal hydrogen peroxide,which improves the photodynamic effect of the photosensitizer PCN(Mn)and the chemotherapy effect ofβ-lapachone.Notably,the conversion of Fe^(2+)to Fe^(3+)in the tumor cells exerts the Fenton effect,which generates hydroxyl radicals that cause lipid peroxidation in tumor cells and induce apoptosis,thus enhancing the chemodynamic therapeutic effect.In vitro and in vivo experiments revealed that the NPs demonstrated specific tumor targeting,excellent inhibition effect on tumor growth,and biocompatibility.Together,our findings can help develop an intelligent multifunctional therapeutic nanoplatform for cancer therapy.
基金Supported by the National Basic Research Program of China under Grant Nos 2013CB921700,2015CB921300 and2015CB921301the National Natural Science Foundation of China under Grant Nos 11234014,11622435,11274362,11674371 and11474340+1 种基金the National Key Research and Development Program of China under Grant Nos 2016YFA0300300,2016YFA0300600,2016YFA0401000 and 2016YFA0400902the Open Large Infrastructure Research of Chinese Academy of Sciences,and the Pioneer Hundred Talents Program(Type C)of Chinese Academy of Sciences
文摘The electronic structure of iron-pnictide compound superconductor Ba_2Ti_2Fe_2As_4O, which has metallic intermediate Ti_2O layers, is studied using angle-resolved photoemission spectroscopy. The Ti-related bands show a‘peak-dip-hump＇ line shape with two branches of dispersion associated with the polaronic states at temperatures below around 120 K. This change in the spectra occurs along with the resistivity anomaly that was not clearly understood in a previous study. Moreover, an energy gap induced by the superconducting proximity effect opens in the polaronic bands at temperatures below T_c（~21 K）. Our study provides the spectroscopic evidence that superconductivity coexists with polarons in the same bands near the Fermi level, which provides a suitable platform to study interactions between charge, lattice and spin freedoms in a correlated system.
基金Supported by Youth Fund of National Natural Science Foundation of China,No.81803575,No.31902287Kaifeng Science and Technology Development Plan Project,No.2203008+2 种基金Key Specialized Research and Promotion Project of Henan Province in 2023,No.232102311205Henan Medical Science and Technology Research Program Project,No.LHGJ20210801College Students Innovation and Entrepreneurship Training Program of Henan University,No.20231022007.
文摘BACKGROUND Trastuzumab constitutes the fundamental component of initial therapy for patients with advanced human epidermal growth factor receptor 2(HER-2)-positive gastric cancer(GC).However,the efficacy of this treatment is hindered by substantial challenges associated with both primary and acquired drug resistance.While S-phase kinase associated protein 2(Skp2)overexpression has been implicated in the malignant progression of GC,its role in regulating trastuzumab resistance in this context remains uncertain.Despite the numerous studies investigating Skp2 inhibitors among small molecule compounds and natural products,there has been a lack of successful commercialization of drugs specifically targeting Skp2.AIM To discover a Skp2 blocker among currently available medications and develop a therapeutic strategy for HER2-positive GC patients who have experienced progression following trastuzumab-based treatment.METHODS Skp2 exogenous overexpression plasmids and small interfering RNA vectors were utilized to investigate the correlation between Skp2 expression and trastuzumab resistance in GC cells.Q-PCR,western blot,and immunohistochemical analyses were conducted to evaluate the regulatory effect of thioridazine on Skp2 expression.A cell counting kit-8 assay,flow cytometry,a amplex red glucose/glucose oxidase assay kit,and a lactate assay kit were utilized to measure the proliferation,apoptosis,and glycolytic activity of GC cells in vitro.A xenograft model established with human GC in nude mice was used to assess thioridazine's effectiveness in vivo.RESULTS The expression of Skp2 exhibited a negative correlation with the sensitivity of HER2-positive GC cells to trastuzumab.Thioridazine demonstrated the ability to directly bind to Skp2,resulting in a reduction in Skp2 expression at both the transcriptional and translational levels.Moreover,thioridazine effectively inhibited cell proliferation,exhibited antiapoptotic properties,and decreased the glucose uptake rate and lactate production by suppressing Skp2/protein kinase B/mammalian target of rapamycin/glucose transporter type 1 signaling pathways.The combination of thioridazine with either trastuzumab or lapatinib exhibited a more pronounced anticancer effect in vivo,surpassing the efficacy of either monotherapy.CONCLUSION Thioridazine demonstrates promising outcomes in preclinical GC models and offers a novel therapeutic approach for addressing trastuzumab resistance,particularly when used in conjunction with lapatinib.This compound has potential benefits for patients with Skp2-proficient tumors.
文摘Although photocatalytic water splitting has excellent potential for converting solar energy into chemical energy,the challenging charge separation process and sluggish surface catalytic reactions significantly limit progress in solar energy conversion using semiconductor photocatalysts.Herein,we demonstrate a feasible strategy involving the surface assembly of cobalt oxide species(CoO_(x))on a visible-light-responsive Cd_(0.9)Zn_(0.1)S(CZS)photocatalyst to fabricate a hierarchical CZS@CoO_(x) heterostructure.The unique hierarchical structure effectively accelerates the directional transfer of photogenerated charges,reducing charge recombination through the smooth interfacial heterojunction between CZS and CoO_(x),as evidenced by photoluminescence(PL)spectroscopy and various electrochemical characterizations.The surface cobalt species on the CZS material also act as efficient cocatalysts for photocatalytic hydrogen production,with activity even higher than that of noble metals.The well-defined CZS@CoO_(x) heterostructure not only enhances the interfacial separation of photoinduced charges,but also improves surface catalytic reactions.This leads to superior photocatalytic performances,with an apparent quantum efficiency of 20%at 420 nm for visible-light-driven hydrogen generation,which is one of the highest quantum efficiencies measured among noble-metal-free photocatalysts.Our work presents a potential pathway for controlling complex charge separation and catalytic reaction processes in photocatalysis,guiding the practical development of artificial photocatalysts for successful transformation of solar to chemical energy.
