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Current evidence suggests that the mortality rate of intermediate-stage hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remains high. We aimed to investigate the safety and efficacy of double plasma molecular adsorption system (DPMAS) with sequential low-volume plasma exchange (LPE) treatment in intermediate-stage HBV-related ACLF. This prospective study recruited intermediate-stage HBV-related ACLF patients and was registered on ClinicalTrials.gov (NCT04597164). Eligible patients were randomly divided into a trial group and a control group. Patients in both groups received comprehensive medical treatment. Patients in the trial group further received DPMAS with sequential LPE. Data were recorded from baseline to Week 12. Fifty patients with intermediate-stage HBV-related ACLF were included in this study. The incidence of bleeding events and allergic reactions in the trial group was 12% and 4%, respectively, with no other treatment-related adverse events. The levels of total bilirubin and prothrombin time-international normalized ratio, and model for end-stage liver disease scores after each session of DPMAS with sequential LPE were significantly lower than those before treatment (all p < 0.05). The 12-week cumulative liver transplantation-free survival rates in the trial and control groups were 52% and 24%, respectively (p = 0.041). The 12-week cumulative overall survival rates in the trial and control groups were 64% and 36%, respectively (p = 0.048). The Kaplan-Meier survival analysis revealed significant differences in liver transplantation-free survival (p = 0.047) and overall survival (p = 0.038) between the trial and control groups. Cox regression analysis indicated that blood urea nitrogen (p = 0.038), DPMAS with sequential LPE (p = 0.048), and Chinese Group on the Study of Severe Hepatitis B-ACLF II score (p < 0.001) were significant risk factors for mortality. DPMAS with sequential LPE treatment is safe and effective for patients with intermediate-stage HBV-related ACLF.
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Insuficiencia Hepática Crónica Agudizada , Enfermedad Hepática en Estado Terminal , Hepatitis B Crónica , Hepatitis B , Humanos , Virus de la Hepatitis B , Intercambio Plasmático/efectos adversos , Insuficiencia Hepática Crónica Agudizada/terapia , Estudios Prospectivos , Enfermedad Hepática en Estado Terminal/complicaciones , Adsorción , Índice de Severidad de la Enfermedad , Hepatitis B/complicaciones , Hepatitis B/terapia , Pronóstico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/terapia , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the prognostic value of Model for End-Stage Liver Disease (MELD) score and Hepatic Encephalopathy (HE) for short-term prognosis of Hepatitis B virus-related Acute-on-Chronic Liver Failure (HBV-ACLF) patients treated with plasma exchange (PE). METHODS: A total of 108 patients with HBV-ACLF treated with PE were retrospectively enrolled between January 2014 to December 2020. Based on survival at 28 days, patients were divided into survival (N = 87) and death groups (N = 21). Clinical data and laboratory indicators were analyzed. RESULTS: Compared with the survival group, the death group was associated with higher ACLF grade and incidence of HE. The levels of total bilirubin, prothrombin time, creatinine, blood urea nitrogen, MELD score, and Chinese Group on the Study of Severe Hepatitis B-ACLF II (COSSH II) score were significantly higher in the death group than in the survival group (p < .05). Grade 1 ACLF and the MELD score after PE treatment at one week were independent risk factors for 28-day liver transplantation-free mortality (OR = 0.062, 95%CI: 0.005-0.768; OR = 1.328, 95%CI: 1.153-1.531). A MELD score at one week of at least 25.5 was associated with a poor short-term prognosis. Of note, HE was a strong independent risk factor for a decline in MELD score at one week. (OR = 11.815, 95%CI: 3.187-43.796, p < 0.001). CONCLUSION: We found patients with HE at admission and MELD score of at least 25.5 at one week after PE treatment had a poor short-term prognosis and should prompt preparation for liver transplantation. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565). Registered 13 May 2020.
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Insuficiencia Hepática Crónica Agudizada , Enfermedad Hepática en Estado Terminal , Encefalopatía Hepática , Hepatitis B , Insuficiencia Hepática Crónica Agudizada/etiología , Insuficiencia Hepática Crónica Agudizada/terapia , Enfermedad Hepática en Estado Terminal/complicaciones , Enfermedad Hepática en Estado Terminal/terapia , Encefalopatía Hepática/complicaciones , Encefalopatía Hepática/terapia , Hepatitis B/complicaciones , Virus de la Hepatitis B , Humanos , Intercambio Plasmático/efectos adversos , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The long-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is not well characterised. We assessed long-term outcomes and the associated risk factors of HBV-ACLF patients in southern China. METHODS: We retrospectively analysed clinical data, adverse events, and clinical endpoint events of HBV-ACLF patients treated at our department between January 2014 and December 2018. RESULTS: A total of 616 (52.3%) patients with cirrhosis and 561 (47.7%) patients without cirrhosis were included. In 973 (83%) patients, the disease was associated only with HBV, while 204 (17%) patients had two or more aetiological factors. The proportion of patients receiving antiviral treatment for HBV was low (20.3%). Further analyses indicated that patients without cirrhosis had a significantly lower 90-day liver transplantation-free mortality and higher 5-year survival rate than those with cirrhosis (59.5% vs. 27.6%; 62% vs. 36%; P < 0.05). Remarkably, self-withdrawal of nucleos(t)ide analog (NA) was an independent risk factor for short-term prognosis. Age, cirrhosis at admission, and platelet level were closely related to long-term prognosis of HBV-ACLF patients. CONCLUSION: The proportion of HBV-ACLF patients receiving antiviral treatment is very low in south China. Cirrhosis at admission has a significant effect on both short-term and long-term prognosis. No significant improvement in the short-term prognosis of HBV-ACLF patients was observed compared with previous studies. More comprehensive access to antiviral treatment and long-term surveillance of HBV patients are key imperatives to reduce the incidence of HBV-ACLF and improve the prognosis. Trial Registration The trial was registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565) on May 13, 2020: https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S0009OZY&selectaction=Edit&uid=U00036P1&ts=2&cx=27seqt.
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Insuficiencia Hepática Crónica Agudizada , Hepatitis B Crónica , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
To investigate mechanisms that TMEM2 activation inhibits hepatitis B virus (HBV) infection in hepatocarcinoma (HCC) cells, co-immunoprecipitation (Co-IP) and mass spectrometry were used in screening interacting proteins for TMEM2. Levels of casein kinase 2 subunit α3 (CSNK2A3) in HCC cells were found to be inhibited or overexpressed using siRNAs and pcDNA3.1-CSNK2A3, respectively. Effect of CSNK2A3 expression on cell proliferation was analyzed using MTS, while its effect on HBV infection was measured using ddPCR and IHC. Western blotting and JAK inhibitor ruxolitinib were also used to determine whether TMEM2-regulated CSNK2A3 expression and HBV infection were affected by JAK-STAT signaling. Co-IP and mass spectrometry results showed that CSNK2A3 interacts with TMEM2. Moreover, overexpression of CSNK2A3 significantly inhibited cell proliferation, while inhibition of CSNK2A3 promoted proliferation of HCC cells. In addition, overexpression of CSNK2A3 was observed to significantly enhance HBV infection, while siRNA knockdown of CSNK2A3 inhibited HBV infection. Notably, effect of CSNK2A3 overexpression on HBV infection was suppressed by TMEM2 overexpression. Further mechanistic analyses have revealed that TMEM2 could antagonize the effects of CSNK2A3 on cell proliferation and HBV infection via JAK-STAT pathway activation. In conclusion, TMEM2 has been determined to bind to CSNK2A3 to inhibit HBV infection via activation of the JAK-STAT pathway.
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Quinasa de la Caseína II/metabolismo , Epilepsia del Lóbulo Temporal/prevención & control , Hepatitis B/prevención & control , Janus Quinasa 1/metabolismo , Proteínas de la Membrana/metabolismo , Factores de Transcripción STAT/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Estudios de Casos y Controles , Quinasa de la Caseína II/genética , Epilepsia del Lóbulo Temporal/genética , Epilepsia del Lóbulo Temporal/metabolismo , Epilepsia del Lóbulo Temporal/patología , Hepatitis B/metabolismo , Hepatitis B/patología , Hepatitis B/virología , Virus de la Hepatitis B/fisiología , Humanos , Janus Quinasa 1/genética , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Proteínas de la Membrana/genética , PPAR gamma/genética , PPAR gamma/metabolismo , Factores de Transcripción STAT/genética , Células Tumorales CultivadasRESUMEN
Tenofovir alafenamide (TAF) has been available in China for a short time, little is known about its safety and efficacy in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). We conducted this study to further verify the safety and efficacy of TAF in these patients. Eighty-eight eligible subjects were included and divided into three groups: TAF group, TDF group and ETV group. Clinical and laboratory test results were collected and the survival status, virus suppression status and liver and renal function improvement were observed during follow-up. No drug-related adverse events were observed within a 48-week observation period. At week 48, the survival rates of the three groups were 56.5%, 78.3% and 59.5% (p = 0.262). HBV DNA undetectable rates were similar (80.0% vs.75.0% vs.84.6%, respectively, p = 0.863). Liver function improved in all the three groups over time. Compared with the other two groups, patients in the TAF group had a greater decrease in serum creatinine (CR) and an increase in estimated glomerular filtration rate (eGFR), especially at week 12. At week 48, the median changes of CR were -0.7 (IQR -3.0, 13.0) vs. 15.0 (IQR -3.0, 21.0) vs. 5.0 (IQR -9.0, 14.0), respectively (pâ¯=â¯0.334), while the median changes of eGFR were -2.12 (IQR -13.87, 1.44) vs. -10.43 (IQR -20.21, 3.18) vs. -5.31 (IQR -14.72, 5.44) ml/min/1.73 m2 , respectively (pâ¯=â¯0.592). In this real-world clinical study, TAF is as effective as TDF and ETV, and may be more beneficial in protecting renal function in the early stages of antiviral therapy.
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Insuficiencia Hepática Crónica Agudizada , Hepatitis B Crónica , Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Alanina , Antivirales/efectos adversos , Guanina/uso terapéutico , Virus de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Estudios Prospectivos , Tenofovir/análogos & derivados , Tenofovir/uso terapéutico , Resultado del TratamientoRESUMEN
Two-dimensional layered metal chalcogenides (LMCs) are widely used in battery anode materials, energy conversion, and semiconductor devices, because of their high energy storage characteristics, high thermoelectric characteristics, and large electron mobility. SnSe2 as a kind of LMC has strong nonlinear optical characteristics. However, its research on dissipative system dynamics as a saturable absorber has not been studied. In this work, we obtained SnSe2 nanosheets using lithium ion intercalation and we reported a passively mode-locked fiber laser with SnSe2 as a saturable absorber to achieve the dissipative soliton in a dissipative system. Due to the high third-order nonlinearity of SnSe2, the evolution of square wave pulses from 2 to 16 ns was obtained in a fiber ring cavity. Through adjusting the polarization state, the evolution phenomenon of soliton rain, the soliton rain phenomenon with a spectrum of dual-wavelengths, and a bound state harmonic phenomenon with a frequency of 313 MHz were obtained. Therefore, the strong nonlinear fiber laser based on SnSe2 provides a good platform for study the pulsation, explosion, rainfall and other phenomena.
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BACKGROUND: Because there is no reliable risk stratification tool for severe coronavirus disease 2019 (COVID-19) patients at admission, we aimed to construct an effective model for early identification of cases at high risk of progression to severe COVID-19. METHODS: In this retrospective multicenter study, 372 hospitalized patients with nonsevere COVID-19 were followed for > 15 days after admission. Patients who deteriorated to severe or critical COVID-19 and those who maintained a nonsevere state were assigned to the severe and nonsevere groups, respectively. Based on baseline data of the 2 groups, we constructed a risk prediction nomogram for severe COVID-19 and evaluated its performance. RESULTS: The training cohort consisted of 189 patients, and the 2 independent validation cohorts consisted of 165 and 18 patients. Among all cases, 72 (19.4%) patients developed severe COVID-19. Older age; higher serum lactate dehydrogenase, C-reactive protein, coefficient of variation of red blood cell distribution width, blood urea nitrogen, and direct bilirubin; and lower albumin were associated with severe COVID-19. We generated the nomogram for early identifying severe COVID-19 in the training cohort (area under the curve [AUC], 0.912 [95% confidence interval {CI}, .846-.978]; sensitivity 85.7%, specificity 87.6%) and the validation cohort (AUC, 0.853 [95% CI, .790-.916]; sensitivity 77.5%, specificity 78.4%). The calibration curve for probability of severe COVID-19 showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analyses indicated that nomogram conferred high clinical net benefit. CONCLUSIONS: Our nomogram could help clinicians with early identification of patients who will progress to severe COVID-19, which will enable better centralized management and early treatment of severe disease.
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Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/patología , Neumonía Viral/diagnóstico , Neumonía Viral/patología , Adulto , Área Bajo la Curva , Betacoronavirus/patogenicidad , COVID-19 , China , Infecciones por Coronavirus/virología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nomogramas , Pandemias , Neumonía Viral/virología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo , SARS-CoV-2RESUMEN
Previously, we identified rare missense mutations of complement component 2 (C2) to be associated with chronic hepatitis B (CHB) by exome sequencing. However, up to now, little is known about the role of C2 in CHB. In the present study, we aimed to perform preliminary exploration about the underlying role of C2 in CHB. Serum samples from 113 CHB patients and 30 healthy controls, and liver biopsy samples from 5 CHB patients and 3 healthy controls were obtained from the Third Affiliated Hospital of Sun Yat-sen University between January 2018 and January 2020. HepG2.2.15 and HepG2-NTCP cells infected with HBV were used to examine the influence of HBV infection on C2 expression. IFN-treated HepG2.2.15 cells were used to assess the effect of IFN on C2 expression. C2-overexpressing or C2-silencing HepG2.2.15 cells were constructed to evaluate the effect of C2 on HBV infection. Western blot and RT-qPCR were used to measure C2 expression in biopsy samples. HBeAg and HBsAg in culture medium and C2 of serum samples were measured by ELISA. HBV-DNA was measured by RT-qPCR. GSE84044, GSE54747 and GSE27555 were downloaded from GEO. C2 expression in liver tissue and serum was significantly lower in CHB patients compared to healthy controls, and significantly higher C2 expression was found in CHB patients with lower ALT, AST, Scheuer grade and stages compared to CHB patients with higher ALT, AST, Scheuer grades and Scheuer stage. Besides, HBV infection could decrease C2 expression by increasing expression of Sp1 and reducing expression of HDAC4. Moreover, C2 could enhance the anti-virus effect of IFN on HepG2.2.15 cells and also inhibit HBV replication in HepG2.2.15 cells by inhibition of p38-MAPK signalling pathway. In conclusion, HBV may promote viral persistence in CHB patients by inhibiting C2 expression.
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Virus de la Hepatitis B , Hepatitis B Crónica , Complemento C2 , ADN Viral , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , HumanosRESUMEN
PURPOSE: The purpose of this study was to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA) in urine and blood specimens, and anal and oropharyngeal swabs from patients with confirmed SARS-CoV-2 infection, and correlated positive results with clinical findings. METHODS: Patients with confirmed SARS-CoV-2 infections were included in this study. Patients' demographic and clinical data were recorded. Quantitative real-time polymerase chain reaction was used to detect SARS-CoV-2 RNA in urine and blood specimens, and anal and oropharyngeal swabs. The study is registered at ClinicalTrials.gov (No. NCT04279782, 19 February, 2020). RESULTS: SARS-CoV-2 RNA was present in all four specimen types, though not all specimen types were positive simultaneously. The presence of viral RNA was not necessarily predictive of clinical symptoms, for example, the presence of viral RNA in the urine did not necessarily predict urinary tract symptoms. CONCLUSIONS: SARS-CoV-2 can infect multiple systems, including the urinary tract. Testing different specimen types may be useful for monitoring disease changes and progression, and for establishing a prognosis.
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Canal Anal/virología , Líquidos Corporales/virología , COVID-19/diagnóstico , COVID-19/virología , Orofaringe/virología , SARS-CoV-2 , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , SARS-CoV-2/clasificación , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificaciónRESUMEN
Bismuthene with a similar layered lattice structure belonging to group VA is regarded as a kind of novel two-dimensional material and has excellent properties such as small indirect bandgap (less than 1 eV) and unique electronic properties, etc. Based on the large magnitude of third-order nonlinear susceptibility and high carrier motility, bismuthene can be considered as a promising material for various optoelectronics, electronics, and nonlinear optics. Compared with the mass research about the few-layer bismuthene, we focus on the characteristics and nonlinear optical properties of bismuthene nanosheets in this work. Bismuthene nanosheets present high modulation depth over 7.7%. The sheet-structured bismuthene as saturable absorbers (SAs) is a technically important issue in laser technology. Here, for the first time, it is demonstrated that bismuthene nanosheets can be served as an SA to readily generate a harmonic dual-wavelength mode-locked picosecond pulse in a highly nonlinear fiber laser. A harmonic mode-locked pulse order from 1st to 20th is obtained at the pump power from 43.2 to 201.5 mW. When the pump power is greater than 408 mW, a 52th harmonic dual-wavelength pulse (corresponding to the repetition of 208 MHz) has been obtained. This study demonstrates the bismuthene saturable absorption is an intrinsic property independent from the structural dimension. Our work attests the promise of bismuthene in optical communication, optical detecting, sensor systems, and material processing, etc.
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BACKGROUND/AIMS: Zinc finger antiviral protein (ZAP) has been reported to be expressed in hepatocellular carcinoma (HCC), and ZAP expression is associated with apoptotic signaling in cancer cells. This study aimed at investigating the expression of ZAP in HCC cells and its significance in clinical pathology. METHODS: Real-time quantitative PCR and western blot assays were employed to detect ZAP RNA and protein expression in normal human hepatocytes, HCC cells, and five primary HCC cell lines. Immunohistochemistry was performed to detect ZAP expression in 147 paraffin-embedded HCC tissues and adjacent normal tissues. The clinical significance of ZAP expression was analyzed in tissue samples from patients with or without infection by hepatitis B virus (HBV). RESULTS: ZAP expression in HCC cells and human primary HCC cell lines was significantly lower than that of normal human hepatocytes. Among 147 HCC samples, ZAP expression was lower in HCC tissues than in adjacent normal tissues for 107 (77.0%) samples. In patients with HCC and HBV infection, ZAP expression was related to pathological grade (P < 0.05); in HBV-negative patients with HCC, ZAP expression was associated with tumor size (P < 0.05) and clinical stage (P < 0.05). The overall survival time in patients with low ZAP expression was significantly shorter than survival times of those with high ZAP expression (P < 0.05), especially for patients with moderately to well-differentiated HCC (Grade 1-2) and HCC at stage T1 and T2 (P < 0.05). Cox multivariate analysis showed that ZAP expression was an independent predictor of survival of patients with HCC (P < 0.01). CONCLUSION: Low ZAP expression is closely associated with disease progression and poor prognosis for patients with HCC.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteínas de Unión al ARN/metabolismo , Adulto , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Línea Celular Tumoral , Supervivencia sin Enfermedad , Femenino , Hepatitis B/complicaciones , Antígenos de Superficie de la Hepatitis B/sangre , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
OBJECTIVE: Acute-on-chronic liver failure (ACLF) is a syndrome characterized by a high short-term mortality rate, and effective interventions are still lacking. This study aims to investigate whether the small molecule baicalein can mitigate ACLF and elucidate the molecular mechanisms. METHODS: The ACLF mouse model was induced through chronic liver injury using carbon tetrachloride, followed by acute inflammation induction with lipopolysaccharide (LPS). Baicalein was administered through intraperitoneal injection to explore its therapeutic effects. In vitro experiments utilized the iBMDM macrophage cell line to investigate the underlying mechanisms. Peripheral blood was collected from clinical ACLF patients for validation. RESULTS: In the LPS-induced ACLF mouse model, baicalein demonstrated a significant reduction in acute inflammation and liver damage, as evidenced by histopathological evaluation, liver function analysis, and inflammatory marker measurements. Transcriptomic analysis, coupled with molecular biology experiments, uncovered that baicalein exerts its effects in ACLF by activating the TrKB-CREB1 signaling axis to upregulate the surface expression of the TREM2 receptor on macrophages. This promotes M2 macrophage polarization and activates efferocytosis, thereby inhibiting inflammation and alleviating liver damage. Furthermore, we observed a substantial negative correlation between postoperative peripheral blood plasma soluble TREM2 (sTREM2) levels and inflammation, as well as adverse outcomes in clinical ACLF patients. CONCLUSION: Baicalein plays a protective role in ACLF by enhancing the surface expression of the TREM2 receptor on macrophages, leading to the suppression of inflammation, mitigation of liver damage, and a reduction in mortality. Additionally, plasma sTREM2 emerges as a critical indicator for predicting adverse outcomes in ACLF patients.
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Insuficiencia Hepática Crónica Agudizada , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Flavanonas , Macrófagos , Glicoproteínas de Membrana , Ratones Endogámicos C57BL , Receptores Inmunológicos , Transducción de Señal , Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Animales , Flavanonas/farmacología , Flavanonas/uso terapéutico , Humanos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Masculino , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Glicoproteínas de Membrana/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Lipopolisacáridos , Regulación hacia Arriba/efectos de los fármacos , Receptor trkB/metabolismo , Modelos Animales de Enfermedad , Persona de Mediana Edad , Femenino , Línea Celular , Adulto , Proteínas Tirosina Quinasas/metabolismo , Hígado/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacologíaRESUMEN
We demonstrate that layered violet phosphorus, an emerging 2D semiconductor, undergoes strong anisotropic third-harmonic generation (THG). Polarization dependence of in-plane THG presents a cruciate-flower-shaped curve. Through theoretical modeling of the in-plane THG response, done by considering crystalline symmetry of violet phosphorus, we successfully quantify four non-zero third-order nonlinear optical susceptibility tensor elements. From control experiments, the magnitude of third-order nonlinear optical susceptibility |χ3| is calculated to be about 4.0 × 10-19 m2 V-2, which is comparable to those of conventional 2D layered semiconductors. These results indicate that the layered violet phosphorus can serve as an ideal building block for nonlinear optical applications.
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BACKGROUND AND AIMS: For chronic hepatitis B (CHB) patients, there is still a need to improve hepatitis B surface antigen (HBsAg) clearance rates. This study aimed to assess the predictive effectiveness of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) for HBsAg clearance in HBeAg-negative CHB patients undergoing peginterferon (Peg-IFN)-based antiviral treatment. METHODS: This study encompassed 280 patients undergoing treatment with Peg-IFNα. Serum levels of sPD-1 and sPD-L1 were measured using ELISA kits at baseline, as well as at 12, 24 and 48 weeks. The primary endpoint of the study was the determination of HBsAg clearance at 48 weeks. Logistic regression analysis was employed to identify predictors of HBsAg clearance. RESULTS: The clearance group demonstrated significantly lower serum sPD-L1 levels compared to the non-clearance group. While both groups exhibited an increase in sPD-1 levels, only the clearance group showed a rise in sPD-L1 levels. Multivariate analysis identified sPD-L1 increase at 24 weeks, and HBsAg decline at 24 weeks as predictors for HBsAg clearance at 48 weeks. The combined use of these indicators showed a predictive performance for HBsAg clearance with an AUROC of 0.907 (95% CI: 0.861-0.953, p < 0.001). CONCLUSIONS: The study revealed an inverse relationship between the trends of sPD-1/sPD-L1 and HBsAg clearance during combined IFN and NAs treatment. Moreover, the magnitude of HBsAg reduction and sPD-L1 increase emerged as significant predictors for HBsAg clearance.
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Antivirales , Antígeno B7-H1 , Biomarcadores , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Hepatitis B Crónica , Interferón-alfa , Receptor de Muerte Celular Programada 1 , Humanos , Masculino , Femenino , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/sangre , Hepatitis B Crónica/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Adulto , Antígeno B7-H1/sangre , Antivirales/uso terapéutico , Biomarcadores/sangre , Interferón-alfa/uso terapéutico , Antígenos e de la Hepatitis B/sangre , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/sangre , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Polietilenglicoles/uso terapéutico , Valor Predictivo de las Pruebas , Resultado del Tratamiento , Proteínas Recombinantes/uso terapéutico , Adulto Joven , Virus de la Hepatitis B/inmunologíaRESUMEN
Background and Aims: To investigate the safety and efficacy of double plasma molecular adsorption system (DPMAS) with sequential low-dose plasma exchange (LPE) in treating early hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods: Clinical data of patients with HBV-ACLF were prospectively collected, including patients in a DPMAS with sequential LPE (DPMAS+LPE) group and those in a standard medical treatment (SMT) group. The primary endpoint was death or liver transplantation (LT) at 12 weeks of follow-up. Propensity-score matching was performed to control the effects of confounding factors on prognosis between the two groups. Results: After 2 weeks, total bilirubin, alanine aminotransferase, blood urea nitrogen levels, and Chinese Group on the Study of Severe Hepatitis B score, were significantly lower in the DPMAS+LPE group than those in the SMT group (p<0.05). After 4 weeks, laboratory parameters of the two groups were similar. The cumulative survival rate of the DPMAS+LPE group was significantly higher than that of the SMT group at 4 weeks (97.9% vs. 85.4%, p=0.027), but not at 12 weeks (85.4% vs. 83.3%, p=0.687). Cytokine levels were significantly lower in 12-week survival group than in the death-or-LT group (p<0.05). Functional enrichment analysis showed that downregulated cytokines were mainly involved in positive regulation of proliferation and activation of lymphocytes and monocytes, regulation of immune effect response, regulation of endotoxin response, and glial cell proliferation. Conclusion: DPMAS+LPE significantly improved the 4-week cumulative survival rate, and ameliorated the inflammatory response in patients. DPMAS+LPE may be a promising modality for patients with early HBV-ACLF.
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Acute-on-chronic liver failure (ACLF) is a major cause of liver-related death worldwide, but its key pathological features remain incompletely defined. This study aimed to reveal the molecular basis of hepatitis B virus-related ACLF (HBV-ACLF) by transcriptome sequencing of human liver tissue. A total of 18 human liver tissues from patients with different stages of HBV-related disease were collected for RNA sequencing, and liver tissues from patients and mouse models with ACLF were used for subsequent validation. Specifically, 6,853 differentially expressed genes (DEGs) and 5,038 differentially expressed transcripts were identified in patients with ACLF compared to patients with chronic hepatitis B (CHB) and normal controls (NCs). Investigation of functional by KEGG pathway enrichment analysis revealed prominent immune and metabolic dysregulation at the ACLF stage. We found that the key genes FGF19, ADCY8 and KRT17, which are related to immunometabolic disturbances, were significantly upregulated in the progression of ACLF. The three key genes were validated in human and mouse samples, indicating their prognostic and therapeutic potential in ACLF. In summary, our work reveals that immunometabolic disorder is involved in HBV-ACLF pathogenesis and indicates that FGF19, ADCY8 and KRT17 may be sensitive biomarkers for HBV-related ACLF.
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Background: The p.Ser267Phe mutation in the SLC10A1 gene can cause NTCP deficiency. However, the full clinical presentation of p.Ser267Phe homozygous individuals and its long-term consequences remain unclear. Hence, in the present study, we characterized the phenotypic characteristics of NTCP deficiency and evaluated its long-term prognosis. Methods: Ten NTCP p.Ser267Phe homozygous individuals were recruited and a comprehensive medical evaluation with a 5-year follow-up observation was performed. The phenotypic characteristics of NTCP deficiency were also demonstrated using an NTCP-global knockout mouse model. Results: During the 5-year follow-up observation of 10 NTCP p.Ser267Phe homozygous adults, we found that the most common phenotypic features of NTCP deficiency in adults were hypercholanemia, vitamin D deficiency, bone loss, and gallbladder abnormalities. The profile of bile acids (BAs) in the serum was significantly altered in these individuals and marked by both elevated proportion and concentration of primary and conjugated BAs. Moreover, the NTCP deficiency led to increased levels of serum BAs, decreased levels of vitamin D, and aggravated the osteoporotic phenotype induced by estrogen withdrawal in mice. Conclusions: Both mice and humans with NTCP deficiency presented hypercholanemia and were more prone to vitamin D deficiency and aggravated osteoporotic phenotype. Therefore, we recommend monitoring the levels of BAs and vitamin D, bone density, and abdominal ultrasounds in individuals with NTCP deficiency.
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Osteoporosis , Simportadores , Deficiencia de Vitamina D , Adulto , Animales , Ácidos y Sales Biliares , Humanos , Ratones , Transportadores de Anión Orgánico Sodio-Dependiente/genética , Osteoporosis/genética , Simportadores/genética , Vitamina DRESUMEN
OBJECTIVE: Kruppel-associated box (KRAB) proteins reportedly play a dual role in neoplastic transformation. At present, little is known about the function of the proteins encoded by the human pogo transposable element derived with KRAB domain (POGK) gene. Herein, we evaluated the prognostic significance of POGK expression in patients with hepatocellular carcinoma (HCC). METHODS: The data of HCC patients was downloaded from The Cancer Genome Atlas (TCGA) database. To determine the relationship between POGK and clinical features, logistic regression was applied. Cox regression and Kaplan-Meier analyses were used to evaluate the correlation between POGK and survival rates. Gene ontology (GO) analysis and Gene set enrichment analysis (GSEA) were conducted to identify the enriched pathways and functions associated with POGK. RESULTS: A total of 374 HCC patients were identified in TCGA. POGK was significantly upregulated in HCC and correlated with tumor status (p = 0.036), race (p = 0.025), weight (p = 0.002), body mass index (p = 0.033), histologic grade (p < 0.001), and alpha-fetoprotein (p < 0.001). High POGK expression in HCC patients correlated with a poor outcome in terms of overall survival (p = 0.0018), progression-free survival (p = 0.0087), relapse-free survival (p = 0.045), and disease-specific survival (p = 0.014), according to Kaplan-Meier analysis. Receiver operating characteristic curve analysis showed that the area under the curve of POGK expression for HCC diagnosis was 0.891. GSEA showed that high POGK expression might activate mitotic prometaphase, kinesins, homologous DNA pairing and strand exchange, MET activates PTK2 signaling pathway, G1 to S cell cycle control, Aurora B pathway, ncRNAs involved in WNT signaling pathway, hepatitis C, and ncRNAs involved in the STAT3 signaling pathway. POGK expression correlated with the abundance of adaptive and innate immunocytes in HCC. CONCLUSION: High expression of POGK has high diagnostic and prognostic values in patients with HCC. Moreover, POGK expression is correlated with immune infiltration in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Recurrencia Local de Neoplasia/genética , PronósticoRESUMEN
Background: The prevalence of zinc deficiency is high in patients with chronic liver disease, but few studies have hitherto explored the relationship between the serum zinc level and hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). This study aimed to assess the association between zinc deficiency and infectious complications, and model for end-stage liver disease (MELD) score in patients with HBV-related ACLF. Methods: Patients with HBV-related ACLF from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between January 2019 and December 2019 were retrospectively analysed in this study. Their demographic, clinical, and laboratory data were retrieved from the hospital information system and analysed. The Student's t-test was used for normally distributed continuous variables between two groups and the Chi-square test was used for categorical data. Univariate and multivariate logistic regression analyses were applied to identify independent parameters. Results: A total of 284 patients were included in this study, including 205 liver cirrhosis and 79 non-cirrhosis patients. The proportion of patients with zinc deficiency was the highest (84.5%), followed by subclinical zinc deficiency (14.1%) and normal zinc level (1.4%). Patients in the zinc deficiency group had a higher MELD score than the subclinical zinc deficiency or normal zinc group (P = 0.021). Age, total bilirubin, and serum zinc level were independent factors for infection (Ps < 0.05). The serum zinc level in patients without complications at admission was significantly higher than that in patients with complications (P = 0.004). Moreover, the serum zinc level in patients with prothrombin time activity (PTA) of <20% was significantly lower than that in patients with 20% ≤ PTA < 30% (P = 0.007) and that in patients with 30% ≤ PTA < 40% (P < 0.001). Conclusions: Zinc deficiency is common in patients with HBV-related ACLF. Zinc deficiency is closely associated with infectious complications and MELD score in patients with HBV-related ACLF.
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OBJECTIVES: Hepatitis B virus infection is an important public health problem. We analysed the cost-effectiveness of the first-line therapies, including nucleotide analogues (namely tenofovir alafenamide fumarate (TAF), tenofovir disoproxil fumarate (TDF) and entecavir) and pegylated interferon (Peg-IFN) for patients with chronic hepatitis B (CHB) in China. METHODS: A Markov model describing CHB disease progression was constructed to compare the cost-effectiveness of the first-line therapies, considering both satisfactory (HBeAg seroconversion) and optimal (HBsAg seroclearance) treatment goals. We examined the main outcomes, including cumulative lifetime cost per patient, incremental quality-adjusted life years (QALYs), incremental cost-effectiveness ratio and net monetary benefit. Uncertainty analysis was conducted to identify key influential parameters. RESULTS: Compared with the baseline strategy, Peg-IFN had the highest QALY gain for HBeAg-positive (HBeAg+) CHB patients achieving a satisfactory goal and an optimal goal (3.19 and 6.32 respectively), and TDF was the most cost-effective therapy for HBeAg-negative CHB patients ($1418/QALY) achieving a satisfactory goal. Among nucleotide analogues, TAF was the most-effective strategy and had higher acceptability to achieve an optimal goal in the Eastern region of China (under 1 x GDP per capita threshold). CONCLUSIONS: Among nucleotide analogues, TDF was the most cost-effective treatment in China for CHB patients to achieve satisfactory and optimal treatment goals, whereas TAF was cost-effective and more effective in the wealthier region. Peg-IFN was most cost-effective among HBeAg+ CHB patients to achieve both goals, with better clinical outcomes. Our findings also indicate the importance of regular monitoring during and after CHB treatment, and could inform treatment strategies in China and other countries.