Research progress on the nucleoside/nucleotide-loaded nanomedicines / 浙江大学学报·医学版

Nucleoside drugs play an essential role in treating major diseases such as tumor and viral infections, and have been widely applied in clinics. However, the effectiveness and application of nucleoside drugs are significantly limited by their intrinsic properties such as low bioavailability, lack of targeting ability, and inability to enter the cells. Nanocarriers can improve the physiological properties of nucleoside drugs by improving drug delivery efficiency and availability, maintaining drug efficacy and system stability, adjusting the binding ability of the carrier and drug molecules, as well as modifying specific molecules to achieve active targeting. Starting from the design strategy of nucleoside drug nanodelivery systems, the design and therapeutic effect of these nanomedicines are described in this review, and the future development directions of nucleoside/nucleotide-loaded nanomedicines are also discussed.

Quality evaluation of Galli Gigerii Endothelium Corneum based on HPLC fingerprints and content determination of nucleosides / 中国中药杂志

Galli Gigerii Endothelium Corneum(GGEC), the dried gizzard membrane of Gallus gallus domesticus is a Chinese medicinal material commonly used for digestion. However, due to the particularity of texture and composition, its active ingre-dients have not been clarified so far, and there is also a lack of quality evaluation indicators. In this study, UPLC-Q-TOF-MS was used to analyze the chemical components from the water extract of GGEC, and ten nucleosides were identified for the first time. HPLC fingerprints of the water extracts of GGEC were established and the content of seven nucleosides was determined. The fingerprint similarities of 40 batches of GGEC samples ranged from 0.765 to 0.959, indicating that there were great differences among the GGEC products processed with different methods. In addition, SPSS 22.0 and SIMCA 14.1 were used for hierarchical cluster analysis(HCA) and principal component analysis(PCA) on the 19 common peaks of the HPLC fingerprints of GGEC, and the 40 batches of samples were divided into three categories: raw GGEC, fried GGEC and vinegar-processed GGEC. Eight differential components in GGEC were marked by orthogonal partial least squares discrimination analysis(OPLS-DA), two of which were adenine and thymine. The results of content determination showed that the total content of the seven nucleosides in raw GGEC, fried GGEC and vinegar-processed GGEC were 182.5-416.8, 205.3-368.7, and 194.2-283.0 μg·g~(-1), respectively. There were significant differences in the content of hypoxanthine, thymine and thymidine among the GGEC products processed with different methods(P<0.05), which were graded in the order of fried GGEC>vinegar-processed GGEC>raw GGEC. This suggested that the content of hypoxanthine, thymine and thymidine tended to increase during the frying process, and the variation range might be related to the degree of heat exposure. The established methods in this study were simple and reproducible, and could be used for qualitative and quantitative analysis of GGEC and its processed pro-ducts. This study also provided reference for the establishment of quality standards of GGEC with chemical components as control index.

Eficacia y seguridad de Molnupiravir para el tratamiento de COVID-19: actualización enero 2022 / Eficacia y seguridad de Molnupiravir para el tratamiento de COVID-19: nueva actualización 2022

INTRODUCCIÓN: El virus SARS-CoV-2, sigue presentando múltiples variantes, el espectro de la enfermedad es amplio e incluye desde cuadros leves y autolimitados hasta neumonía atípica severa y progresiva, falla multiorgánica y muerte. Actualmente, existen vacunas eficaces para prevenir COVID-19, y se están desarrollando otras más nuevas para la prevención del COVID-19 grave, asimismo algunos medicamentos muestran resultados promisorios para prevenir y combatir esta enfermedad. Sin embargo, se carece de fármacos antivirales eficaces para combatir esta enfermedad. Aunque algunos de los medicamentos han recibido recientemente una autorización de uso de emergencia (EUA) para COVID-19, todos estos agentes farmacéuticos deben administrarse en entornos hospitalarios. Este documento fue elaborado para actualizar la evidencia científica disponible respecto a la eficacia y seguridad de Molnupiravir en el tratamiento de COVID-19. OBJETIVO: El objetivo de este documento es actualizar la evidencia científica disponible respecto a la eficacia y seguridad de Molnupiravir en el tratamiento de COVID-19, mejorando los desenlaces de los pacientes, y/o previniendo la enfermedad COVID-19 causada por el virus SARS-CoV-2. MÉTODOS: En la SNT N° 08-2021: E

Eficacia y Seguridad de Molnupiravir para el tratamiento de COVID-19 / Efficacy and Safety of Molnupiravir for the treatment of COVID-19

ANTECEDENTES: El presente informe se realiza a solicitud del Viceministerio de Salud Pública del Ministerio de Salud, y tiene como objetivo identificar la evidencia disponible respecto a la eficacia y seguridad de Molnupiravir en el tratamiento de COVID-19. MÉTODOS: Se realizó una búsqueda en la plataforma Living Overview of the Evidence (L·OVE) de la Fundación Epistemonikos que consulta 10 bases de datos incluyendo Medline, EMBASE, LILACS, medRxiv (un servidor de distribución de manuscritos aún no publicados, sin certificación de revisión por pares) entre otros. La búsqueda se realizó el 13/08/2021. Los detalles de la metodología de búsqueda utilizada por L.OVE se encuentra disponible en: https://app.iloveevidence.com/loves/5e6fdb9669c00e4ac072701d?population=5e7fce7e3d05156b5f5e 032a§ion=methods&classification=all. Adicionalmente se consultó el Registro Cochrane Central de Ensayos Controlados (CENTRAL) y Clinicaltrials.gov de los Institutos de Salud Pública de Estados Unidos (NIH) para identificar los ensayos en curso. La pregunta PICO abordada es: ¿Cuál es la eficacia y seguridad de Molnupiravir para el tratamiento de COVID-19? Ensayos clínicos controlados que reporten la eficacia y seguridad para al menos uno de los desenlaces de interés. Idioma: inglés o español. Se excluyeron estudios preclínicos, series de casos, reportes de casos, reportes breves y cartas al editor. RESULTADOS: La búsqueda sistemática identificó 34 artículos, a la lectura de título y resumen fueron seleccionados 11, solo 3 respondían a la pregunta PICO. Características de los estudios incluidos: Se identificaron 03 estudios que cumplieron con los criterios de selección: 2 ensayos clínicos en fase I y uno en fase II. Dentro de los resultados, 2 de los reportes corresponden a manuscritos no publicados ni certificados por una revisión por pares, lo que implica que éstos podrían modificar sus resultados y/o conclusiones en sucesivas versiones hasta su publicación y no es posible garantizar que respondan satisfactoriamente la revisión por pares y sean finalmente publicados. CONCLUSIONES: Se identificaron 3 estudios, dos ensayos clínicos de fase I y uno de fase II. Dos ensayos evalúan la seguridad y tolerabilidad de una dosis de Molnupiravir comparada con placebo o cuidado estándar para ser usada en otra fase. Los estudios de fase I, reportan la incidencia de eventos adversos evaluados para el uso de Molnupiravir en dosis desde 200 hasta 800 mg vía oral. Sin embargo, recomiendan la dosis de 800 para futuros estudios. Un estudio de fase II, sugiere el uso de Molnupiravir para reducir la replicación del virus en etapas tempranas de la enfermedad, siendo que en el grupo en el que se presentaron mejores resultados fue con la dosis de 800 mg en solo 55 participantes comparado con 62 participantes en el grupo de 400 mg, 23 en el grupo de 200 mg y 62 en el grupo placebo. No existe evidencia sobre la eficacia o efectividad del uso de Molnupiravir para el tratamiento profiláctico, o terapéutico contra COVID-19, pues los ensayos clínicos desarrollados aún se encuentran en fases iniciales para determinar la dosis adecuada con mejores resultados clínicos.

Qualitative and quantitative analysis of nucleosides and nucleobases in Phylloporia ribis by UPLC-Q-TOF-MS and HPLC / 中国中药杂志

The dried fruit body of Phylloporia ribis(Hymenochaetaceae), which prefers to live on the stumps of Lonicera japonica(Caprifoliaceae), has a variety of activities, whereas its pharmacodynamic material basis is not completely clear and there are few reports on its quality control and evaluation. In this study, an UPLC-Q-TOF-MS method was used to analyze the nucleosides and nucleobases in P. ribis and a HPLC method was established for simultaneous determination of 10 nucleosides and nucleobases. MS and MS/MS data were acquired in positive ion mode. Based on the data comparison of the sample and the reference substance, the literature data and the compound databases of ChemSpider and PubChem, 18 nucleosides and nucleobases were identified qualitatively from the water extract of P. ribis for the first time. After optimization, the HPLC was performed using a Welch Ultimate AQ C_(18) column(4.6 mm×250 mm, 5 μm) by gradient elution with acetonitrile and water as mobile phase, the flow rate of 1.0 mL·min~(-1), the detection wavelength of 260 nm, and the column temperature of 30 ℃. Through the investigation of the extraction method, solvent and time, it was determined that the test solution should be obtained by cold water extraction for 18 h. At the present HPLC conditions, 10 components of uracil, cytidine, hypoxanthine, uridine, thymine, inosine, guanosine, 2'-deoxyinosine, 2'-deoxyguanosine and thymidine could be well separated(R > 1.5) and showed good linearity(r > 0.999 9) in the concentration ranges of 0.247-24.7, 0.283-28.3, 0.273-27.3, 0.256-25.6, 0.257-25.7, 0.318-31.8, 0.245-24.5, 0.267-26.7, 0.250-25.0 and 0.267-26.7 mg·L~(-1), respectively. The average reco-veries of 10 components were 95.78%-104.5%, and the RSDs were 2.2%-5.2%(n=6). The contents of 10 nucleosides and nucleobases in different samples of P. ribis varied greatly, which were 0.021-0.122, 0.004-0.029, 0.014-0.226, 0.009-0.442, 0.003-0.014, 0.002-0.146, 0.007-0.098, 0-0.054, 0.005-0.069, 0.004-0.081 and 0.072-1.28 mg·g~(-1) for uracil, cytidine, hypoxanthine, uridine, thymine, inosine, guanosine, 2'-deoxyinosine, 2'-deoxyguanosine, thymidine and total 10 components, respectively. These results demonstrated that the components had significant differences in the internal quality, and good quality control was needed to ensure the medical efficacy. This study provides a scientific basis for the discovery of pharmacodynamic ingredients, quality control and evaluation of P. ribis.

Regional differences of nucleosides and amino acids in Elaphuri Davidiani Cornu / 中国中药杂志

In order to reveal the regional characteristics of nucleosides and amino acids in Elaphuri Davidiani Cornu,39 samples of Elaphuri Davidiani Cornu collected from 4 different regions were analyzed by UPLC-QTRAP ~®/MS2 method followed by orthogonal partial least-squares discrimination analysis( OPLS-DA) and cluster analysis( CA). The results showed all the samples contained abundant nucleosides and amino acids,with the total content of 45. 09 μg·g~(-1) and 634. 80 μg·g-1,respectively. The samples presented significant regional differences in the contents of individual components,and the main differential components included Ura,Hpro,Thr,Glu,G5 P,2'-dG,Adeno,Met,Ade,Gln,Orni,Phe,2'-dA,Hit,Lys,and Ile. Among them,Ura,Met,Glu,and Ile had the highest content in the samples from Dafeng in Jiangsu,Qinhu in Jiangsu,Beijing,and Shishou in Hubei,respectively. OPLS-DA and CA demonstrated that all the samples of Elaphuri Davidiani Cornu could be divided into three categories,reflecting the regional characteristics. The results indicated that the accumulation of nucleosides and amino acids in Elaphuri Davidiani Cornu was closely related to its habitat,providing a useful reference for the research on the quality formation,quality evaluation and control,as well as the comprehensive utilization of Elaphuri Davidiani Cornu. The findings suggested that the content factors of Ura,Met,Glu,and Ile could be included into the quality standard system of Elaphuri Davidiani Cornu as the characteristics of medicinal materials from different regions.

Nucleosides-based identification model for Fritillariae Cirrhosae Bulbus / 中国中药杂志

A high performance liquid chromatography( HPLC) method was established for the fast,and precise determination of ten nucleosides in Fritillariae Cirrhosae Bulbus and its counterfeits. Then multivariate statistical analyses,such as clustering analysis,principal component analysis( PCA),and Fisher' s linear discriminant analysis( LDA),were conducted to establish a discriminant function model for an integrated analysis. The results indicated that data acquisition time of a single sample was shortened within 16 min by the HPLC method. In the range of 5-1 000 mg·kg~(-1),the mass concentrations of all nucleosides exhibited good linear relationships with the corresponding peak areas( R2> 0. 999). The spiked recoveries were in the range of 93. 83%-108. 9% with RSDs of0. 12%-1. 3%( n = 5). The limit of quantitation( LOQ) was 0. 98-4. 13 mg·kg~(-1). As revealed by the clustering analysis,Fritillariae Cirrhosae Bulbus and the counterfeits could be discriminated into two clusters based on the content of nucleosides. Fisher's LDA could achieve this discrimination,while PCA dimension reduction failed. The accuracy of the discriminant function model established on the screened characteristic indicators reached 97. 5%. The present study proposed a new identification method of Fritillariae Cirrhosae Bulbus with one-dimensional indicators,which is simple,accurate,and reliable. It can provide a scientific basis for further optimizing the identification techniques for Fritillariae Cirrhosae Bulbus and inspiration for quality control strategy development of Chinese medicinal materials.

Development of an eco-friendly and fast HPLC method for quantitative analysis of four nucleosides in Cordyceps and related products / 中国天然药物

An eco-friendly and fast HPLC method was developed for the determination of adenosine, inosine, guanosine and uridine in Cordyceps and related products (fermented mycelia of Hirsutella sinensis andPaecilomyces hepiali). The sample was ultrasonically extracted using 0.5% phosphoric acid solutions for 2.5 min. Sample separation was performed on a Poroshell SB-Aq column (50 mm × 4.6 mm, 2.7 μm) using eco-friendly mobile phase consisting of formic acid and ammonium formate aqueous solution at a flow rate of 1.0 mL·min

Low-level viremia in nucleoside analog-treated chronic hepatitis B patients / 中华医学杂志(英文版)

Low-level viremia (LLV) was defined as persistent or intermittent episodes of detectable hepatitis B virus (HBV) DNA (<2000 IU/mL, detection limit of 10 IU/mL) after 48 weeks of antiviral treatment. Effective antiviral therapies for chronic hepatitis B (CHB) patients, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), have been shown to inhibit the replication of HBV DNA and prevent liver-related complications. However, even with long-term antiviral therapy, there are still a number of patients with persistent or intermittent LLV. At present, the research on LLV to address whether adversely affect the clinical outcome is limited, and the follow-up treatment for these patients is open to question. At the same time, the mechanism of LLV is not clear. In this review, we summarize the incidence of LLV, the association between LLV and long-term outcomes, possible mechanisms, and management strategies in these patient populations.

Simultaneous determination of multiple bioactive constituents in Abelmoschi Corolla by UFLC-QTRAP-MS/MS / 中国中药杂志

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 38 active components in Abelmoschi Corolla, including flavonoids, organic acids, nucleosides and amino acids, so as to investigate the effects of different harvesting and processing methods on multi-active components in Abelmoschi Corolla. The chromatographic separation was performed on a XBridg®C_(18) column(4.6 mm×100 mm, 3.5 μm) with(0.1% formic acid water) methanol-acetonitrile(1∶1) as the mobile phase for gradient elution at 30 ℃. The flow rate was 0.5 mL·min~(-1). The components were detected in a multiple-reaction monitoring(MRM) mode. The gray relational analysis(GRA) was used to comprehensively evaluate the multiple active components of Abelmoschi Corolla at different harvesting times and drying temperatures. The results showed that 38 components had a good linearity with correlation coefficients all above 0.999 0. The method featured a good precision, repeatability and stability with the relative stan-dard deviations(RSDs) of less than 5.0%. Recoveries ranged from 98.06% to 104.4% with RSD between 0.22% and 4.9%. The results of GRA indicated that a better quality in the samples collected on September 9 th. Samples dried at 90 ℃ had a better quality. The established method is accurate and reliable, and can be used to assess the internal quality of Abelmoschi Corolla. This study can provide basic materials for determining appropriate harvesting time and processing method of Abelmoschi Corolla.

Recomendaciones en el tratamiento actual de la infección crónica por el virus de la hepatitis B / Current recommendations for the treatment of chronic hepatitis B infection

La infección crónica por el virus de la hepatitis B (VHB) se considera un problema de salud pública mundial. Se estima que al menos dos mil millones de personas han estado expuestas al VHB, y a pesar de una vacuna efectiva, 300 millones de personas están infectadas crónicamente a nivel mundial. Aunque el virus no es directamente citopático, la infección puede desencadenar cirrosis hepática y aun, carcinoma hepatocelular (CHC). El ADN circular cerrado covalentemente (ADNccc) en el núcleo de los hepatocitos y la incapacidad del sistema inmunitario para eliminar la infección crónica por el virus son los mecanismos más importantes de la infección por VHB. Las diferentes entidades, como la Asociación Europea para el Estudio del Hígado (EASL) y la Asociación Americana para el Estudio de las Enfermedades Hepáticas (AASLD), ponen a disposición las pautas para el manejo de esta enfermedad. A pesar de los avances en el tratamiento de la infección crónica por el VHB, en particular con el desarrollo de los análogos de los nucleótidos/ nucleósidos, quedan aún muchos interrogantes. Las investigaciones continúan para el desarrollo de nuevas opciones de tratamiento enfocadas principalmente en evitar que la suspensión de la terapia conlleve a un incremento de la carga viral, con el consecuente aumento del riesgo de progresión de la enfermedad hepática, y un eventual CHC.

Chronic hepatitis B virus (HBV) infection is considered a global public health problem. It is estimated that at least two billion people have been exposed to HBV, and despite an effective vaccine, 300 million people are chronically infected worldwide. Although the virus is not directly cytopathic, the infection can trigger liver cirrhosis and even hepatocellular carcinoma (HCC). Covalently closed circular DNA (cccDNA) in the nucleus of hepatocytes and the inability of the immune system to eliminate chronic virus infection are the most important mechanisms of chronic HBV infection. Different entities, such as the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), provide guidelines for the management of this disease. Despite advances in the treatment of chronic HBV infection, including the development of nucleotide and nucleoside analogs, many questions remain. Research continues for the development of new treatment options focused mainly on avoiding a relapse on viral load after therapy discontinuation, with an increased risk of liver disease progression, and an eventual CHC.

Simultaneous determination and analysis of amino acids and nucleosides in Dendrobium by UHPLC-QTRAP-MS/MS / 中国中药杂志

By using multivariate statistical analysis to evaluate essential quality, and provide scientific basis for their comprehensive utilization, we established an UHPLC-QTRAP-MS/MS method for the fast, precise, efficient determination of 21 kinds of amino acids and 10 kinds of nucleosides in different species of Dendrobium. The analysis was performed on a Waters XBridge Amide column(2.1 mm×100 mm,3.5 μm) with elution by mobile phase of 0.2% formic acid in water-0.2% formic acid in acetonitrile at a flow rate of 0.2 mL·min~(-1) with the column temperature at 30 ℃. The target compounds were analyzed by the positive ion multiple reaction monitoring(MRM) mode. The comprehensive evaluation of different species of Dendrobium was carried out by PCA and TOPSIS analysis. All 21 kinds of amino acids and 10 nucleosides showed good linearity among certain concentration range(r>0.999), the RSDs of the stability, precision, and repeatability tests were less than 3.0%. The recovery rate was in the range from 93.31% to 107.5%, and RSD was in the range of 1.1%-3.7%. The comprehensive evaluation index obtained with PCA showed that D. huoshanense was significantly higher than others regarding amino acids and D. officinale has higher nucleosides than other species. The biggest C_i difference of TOPSIS was 68.7%, and comprehensive evaluation showed that D. huoshanense produced the highest comprehensive quality. The method is precise, fast and efficient and can provide reliable basis for further researches and intrinsic quality control of Dendrobium.

Important pharmacogenomic aspects in the management of HIV/AIDS

In managing HIV/AIDS with highly active antiretroviral agents, the historical therapeutic aim remains to maintain the plasma concentrations at a level above the half maximal inhibitory concentration (IC50) required for 50% inhibition in viral replication.Concentration dependent toxicity is often observed in patients with elevated drug exposure and high peak plasma levels in lieu of accurately calculated drug dosages. Similarly lowplasmaconcentrationsarefrequently witnessed in individuals receiving adequate dosage regimens. Pharmacogenetic variations in drug metabolizing enzymes may contribute to this phenomenon.Over the last decade, knowledge about the role of pharmacogenetics in the treatment and prediction of ARV plasma levels have increased significantly. However, the extent of these genetic variations remain largely unknown in the South African population,which has sparked a renewed enthusiasm forlocalpharmacogenetic studies

Comparative study for freeze-drying and sun-drying on multi-index ingredients of Cordyceps sinensis / 中国中药杂志

The aim of this paper was to compare the influence of freeze-drying and sun-drying on six main nucleosides and nucleobases of Cordyceps sinensis by HPLC. Hypoxanthine,xanthine,uridine,inosine,guanosine and adenosine were reference substances. HPLC analysis was performed on a GL Inertsustain AQ-C_(18) column( 4. 6 mm×250 mm,5 μm),with mobile phase consisting of water( A)-acetonitrile( B) at the flow rate of 1. 0 mL·min~(-1)( 0-10 min,0-1% B; 10-65 min,1%-3% B). The detection wavelength was 260 nm,the column temperature was controlled at 30 ℃,and the injection volume was 5 μL. The linear ranges of hypoxanthine,xanthine,uridine,inosine,guanosine and adenosine were 1. 025-20. 50( r = 0. 999 8),0. 545-10. 90( r = 0. 999 9),4. 051-81. 02( r = 0. 999 8),4. 044-80. 88( r= 0. 999 9),2. 075-41. 50( r= 0. 999 9),4. 032-80. 64( r = 0. 999 9) mg·L~(-1),respectively. The average recoveries of them( n = 6)were as follows: 102. 3%( RSD 2. 1%),101. 1%( RSD 2. 4%),97. 80%( RSD 1. 7%),101. 8%( RSD 1. 8%),98. 90%( RSD2. 0%) and 98. 10%( RSD 1. 4%),respectively. Each sample was processed by freeze-drying and sun-drying so as to compare the difference between the two drying methods. The contents of six index ingredients were significantly different between freeze-drying and sun-drying sample of C. sinensis. The total contents of six index ingredients in sun-drying sample were higher than that in the corresponding freeze-drying sample. This research results provide the scientific basis for the drying methods and quality evaluation of C. sinensis.

Analysis of chemical components in Cordyceps by online gradient extraction-HPLC / 中国中药杂志

Online gradient extraction-high performance liquid chromatography( HPLC) method was developed for simultaneous determination of high and low polar components in Cordyceps. The sample powder of Cordyceps was uniformly mixed with diatomaceous earth,packed into extraction tank,and installed into the HPLC system. Online gradient extraction was conducted with mobile phase at 70 ℃. The separation was performed on Zorbax SB-AQ( 4. 6 mm×150 mm,5 μm) column with 0. 1% formic acid solution-methanol as the mobile phase for gradient elution at 1. 0 mL·min~(-1). The column temperature was 30 ℃,and detection wavelength was set at 260 nm. The results showed that the high and low polar components in Cordyceps could be simultaneously extracted and separated by the developed method. Meanwhile,six high polar compounds( uracil,uridine,thymine,inosine,guanosine and adenosine) and one low polar compound( ergosterol) were identified by comparison with the reference peaks. The established method is rapid,stable and environment friendly,which is helpful to improve the quality evaluation level for Cordyceps.

An expert consensus for the adjustment of treatment strategies in patients with chronic hepatitis B treated with non-first-line nucleos(t)ide analogues / 中华肝脏病杂志

Oral nucleos(t)ide analogues (NAs) is one of the main and efficient way for the treatment of chronic hepatitis B (CHB). Considering the antiviral potency and drug resistance of domestic and foreign guidelines, NAs are divided into first-line and non-first-line drugs. "An Expert Consensus for the Adjustment of Treatment Strategies in Patients with Chronic Hepatitis B Treated with Non-first-line Nucleos(t)ide Analogues," is mainly aimed at those patients who are currently using non-first-line NAs drugs. In addition, how to standardize the adjustment to first-line NAs drugs of choice, which can strengthen the effectiveness of initial antiviral treatment to obtain better antiviral efficacy, and improve patient compliance, coinciding with the avoidance of occurrence of serious drug adverse reactions in patients with CHB is presented.

Stimultaneous determination of multiple bioactive constituents in Panacis Japonici Rhizoma processed by different methods and grey relational analysis / 中国中药杂志

A method, for determination of saponins, amino acids and nucleosides in Panacis Japonici Rhizoma of ultra fast liquid chromatography with triple quadrupole linear ion trap mass spectrometry (UFLC-QTRAP-MS/MS), was established to investigate the effect of different processing methods on the target components of Panacis Japonici Rhizoma. The chromatographic separation was performed on a XBridgeC₁₈(4.6 mm×100 mm, 3.5 μm) at 30 °C with a gradient elution of 0.1% formic acid solution-0.1% formic acid acetonitrile, and the flow rate was 0.8 mL·min⁻¹, using multiple-reaction monitoring (MRM) mode. The grey relational analysis was adopted for the analysis of different processing samples. The results showed that the thirty-three constituents were in a good linear range and the correlation coefficient was greater than 0.999 0; the precision, repeatability and stability were good; the average recovery rates were between 95.33% and 101.8%, and the relative standard deviations were less than 5%. The result of grey relational analysis showed that the complete rhizomes without peeling, which were adopted for the microwave dried method, had the best quality. The established method was accurate and reliable, which could be used to appraise the quality of Panacis Japonici Rhizoma. Our study may lay the way for the processing method of Panacis Japonici Rhizoma in optimization,normalization and standardization.

Influence of Treg cells and HBV genotype on sustained response and drug resistance in the treatment with nucleoside drugs

We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV) genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group. The lamivudine group received treatment continuously, and then patients were categorized into non-resistance group and resistance group. Compared with the suboptimal response and resistance groups for lamivudine, CD4+CD25+/CD3+ levels were higher in the response and non-resistance groups (t=4.372, P=0.046; t=7.262, P=0.017). In the non-resistance group, CD8+CD28-/CD3+ frequency was lower than in the resistance group (t=5.527, P=0.037). Virus load and hepatitis B E antigen (HBeAg)-positive rate were significantly lower than in the response and resistance group (t=2.164, P=0.038; X2=4.239, P=0.040; t=2.015, P=0.044; X2=16.2, P=0.000). Incidence of drug resistance was high in patients with virogene type C. For the virological response to entecavir, CD8+CD28-/CD3+ level was significantly lower than that of the suboptimal response group (t=6.283, P=0.036). Response and suboptimal response groups were compared in CD3+, CD4+, CD8+, CD4+CD25+/CD3+ and virus genotype, and differences were not statistically significant (P>0.05). Baseline regulatory T cells including CD4+CD25+/CD3+ and CD8+CD28-/CD3+ frequencies have a relationship with the incidence of rapid virological response and the resistance to nucleoside drugs. Patients with HBV genotype C receiving lamivudine more often underwent drug resistance. Antiviral efficacy and the resistance to lamivudine were closely correlated with baseline factors; the same cannot be found for entecavir.

Nucleos(t)ide antiviral agents for preventing mother-to-child transmission of hepatitis B virus: an interpretation of relevant international guidelines / 中华肝脏病杂志

A high maternal viral load is the most important factor affecting immunoprophylaxis against mother-infant transmission of HBV. The application of antiviral drugs in pregnant women with a high serum HBV DNA level (>10(6)~10(7) IU/ml) during the second and third trimesters can reduce the prenatal serum HBV DNA level and significantly increase the success rate of blocking mother-infant transmission in neonates. This article interprets the contents related to antiviral therapy for pregnant women carrying HBV with the purpose of blocking mother-infant transmission of HBV in the guidelines published by Asian Pacific Association for the Study of the Liver, European Association for the Study of the Liver, National Institute for Health and Care Excellence, Korean Association for the Study of the Liver, and World Health Organization.

Efficacy of Tenofovir-based Rescue Therapy for Patients with Drug-resistant Chronic Hepatitis B / 대한소화기학회지

BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) plays a pivotal role in the management of drug-resistant chronic hepatitis B. However, it remains unclear whether TDF-nucleoside analogue combination therapy provides better outcomes than TDF monotherapy. This study aimed to compare the efficacy of TDF monotherapy with that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B. METHODS: This retrospective cohort study included 76 patients receiving TDF-based rescue therapy for more than 12 months. Suboptimal response was defined as serum HBV-DNA level of >60 IU/mL during prior rescue therapy. Multi-drug resistance was defined as the presence of two or more drug resistance-related mutations confirmed by mutation detection assay. The relationship between baseline characteristics and virologic response (HBV DNA <20 IU/mL) at 12 months were evaluated using logistic regression analysis. RESULTS: Fifty-five patients (72.4%) were suboptimal responders to prior rescue therapy, and 26 (34.2%) had multi-drug resistance. Forty-two patients (55.3%) received combination therapy with nucleoside analogues. Virologic response at 12 months was not significantly different between the TDF monotherapy group and TDF-nucleoside analogue combination therapy group (p=0.098). The serum HBV DNA level was reduced to -4.49+/-1.67 log10 IU/mL in the TDF monotherapy group and to -3.97+/-1.69 log10 IU/mL in the TDF-nucleoside analogue combination therapy group at 12 months (p=0.18). In multivariate analysis, female sex (p=0.032), low baseline HBV-DNA level (p=0.013), and TDF monotherapy (p=0.046) were predictive factors for virologic response at 12 months. CONCLUSIONS: TDF monotherapy showed similar efficacy to that of TDF-nucleoside analogue combination therapy in patients with drug-resistant chronic hepatitis B.