All-dielectric super-lattice metasurfaces with fivefold spatial resolution enhancement for structured illumination microscopy.

Structured illumination microscopy (SIM) is a promising imaging technique for high-resolution imaging with a wide field of view. Although a periodic nanostructure is a versatile platform for engineering the spatial frequency of structured illumination patterns in SIM, challenges remain, including artifacts from Fourier space gaps. We designed an all-dielectric super-lattice metasurface (ADSLM) to generate structured illumination patterns with enhanced spatial frequency and broadened spatial frequency coverage with no intermediate frequency gaps. Our numerical simulations reveal that ADSLM-based image reconstruction is capable of producing high-contrast, artifact-free images, resulting in enhanced spatial resolution up to 5.7-fold for coherent SIM at 450 nm. Our results show that the ADSLM-SIM technique may facilitate high-resolution imaging using CMOS-compatible substrates, offering potential for compact miniaturized imaging applications.

The epidemiology of varicella and effectiveness of varicella vaccine in Ganyu, China: a long-term community surveillance study.

BACKGROUND: The real-world data of long-term protection under moderate vaccination coverage is limited. This study aimed to evaluate varicella epidemiology and the long-term effectiveness under moderate coverage levels in Ganyu District, Lianyungang City, Jiangsu Province. METHODS: This was a population-based, retrospective birth cohort study based on the immunization information system (IIS) and the National Notifiable Disease Surveillance System (NNDSS) in Ganyu District. Varicella cases reported from 2009 to 2020 were included to describe the epidemiology of varicella, and eleven-year consecutive birth cohorts (2008-2018) were included to estimate the vaccine effectiveness (VE) of varicella by Cox regression analysis. RESULTS: A total of 155,232 native children and 3,251 varicella cases were included. The vaccination coverage was moderate with 37.1%, correspondingly, the annual incidence of varicella infection increased 4.4-fold from 2009 to 2020. A shift of the varicella cases to older age groups was observed, with the peak proportion of cases shifting from 5-6 year-old to 7-8 year-old. The adjusted effectiveness of one dose of vaccine waned over time, and the adjusted VE decreased from 72.9% to 41.8% in the one-dose group. CONCLUSIONS: The insufficient vaccination coverage (37.1%) may have contributed in part to the rising annual incidence of varicella infection, and a shift of varicella cases to older age groups occurred. The effectiveness of one dose of varicella vaccine was moderate and waned over time. It is urgent to increase varicella vaccine coverage to 80% to reduce the incidence of varicella and prevent any potential shift in the age at infection in China.

A Generalized Polymer Precursor Ink Design for 3D Printing of Functional Metal Oxides.

Three-dimensional-structured metal oxides have myriad applications for optoelectronic devices. Comparing to conventional lithography-based manufacturing methods which face significant challenges for 3D device architectures, additive manufacturing approaches such as direct ink writing offer convenient, on-demand manufacturing of 3D oxides with high resolutions down to sub-micrometer scales. However, the lack of a universal ink design strategy greatly limits the choices of printable oxides. Here, a universal, facile synthetic strategy is developed for direct ink writable polymer precursor inks based on metal-polymer coordination effect. Specifically, polyethyleneimine functionalized by ethylenediaminetetraacetic acid is employed as the polymer matrix for adsorbing targeted metal ions. Next, glucose is introduced as a crosslinker for endowing the polymer precursor inks with a thermosetting property required for 3D printing via the Maillard reaction. For demonstrations, binary (i.e., ZnO, CuO, In2O3, Ga2O3, TiO2, and Y2O3) and ternary metal oxides (i.e., BaTiO3 and SrTiO3) are printed into 3D architectures with sub-micrometer resolution by extruding the inks through ultrafine nozzles. Upon thermal crosslinking and pyrolysis, the 3D microarchitectures with woodpile geometries exhibit strong light-matter coupling in the mid-infrared region. The design strategy for printable inks opens a new pathway toward 3D-printed optoelectronic devices based on functional oxides.

Evaluation of the Roche MagNA Pure 96 nucleic acid extraction platform for the SPF10 line probe assay system.

OBJECTIVE: To evaluate the MagNA Pure 96 (MP96) nucleic acid extraction system as an alternative for cervical specimen processing for human papillomavirus (HPV) genotyping detection by reverse hybridization line probe assay (LiPA-25), compared to the well-established extraction system MagNA Pure LC 2.0 (MPLC). METHODS AND RESULTS: A total of 200 cervical samples preserved in ThinPrepCyt® solution were extracted by MP96 and MPLC, respectively, and then purified nucleic acids were amplified using the SPF10 PCR primer set. Amplification products were subjected to SPF10-DNA enzyme immunoassay (DEIA) and LiPA-25. The concordance between different extraction methods in this study was reflected in the comparison of the results of the DEIA and LiPA-25. Agreement of HPV-positive results (DEIA) was 97.5% (Kappa = 0.932). Pair-wise analyses of either HPV grouping (any HPV genotypes, any high-risk HPV genotypes, any low-risk HPV genotypes, any nonavalent vaccine-targeted HPV, and any non-vaccine-targeted oncogenic HPV genotypes) identified >95% agreement (all Kappa > 0.900). For the two extraction methods, there was no statistical difference (chi-square test: P = 0.690) for single versus multiple genotypes, and concordant, compatible, and discordant genotypes were observed in 87.0%, 9.5%, and 3.5% of 200 samples, respectively. CONCLUSION: HPV genotyping results of the MPLC system and the MP96 system showed a high degree of concordance. Combined with the advantages of high-throughput and anti-contamination of MP96, the MP96 extraction system could be more suitable for the testing of samples in future studies.

Safety of hepatitis E vaccination for pregnancy: a post-hoc analysis of a randomized, double-blind, controlled phase 3 clinical trial.

Special attention has been paid to Hepatitis E (HE) prophylaxis for pregnant women due to poor prognosis of HE in this population. We conducted a post-hoc analysis based on the randomized, double-blind, HE vaccine (Hecolin)-controlled phase 3 clinical trial of human papillomavirus (HPV) vaccine (Cecolin) conducted in China. Eligible healthy women aged 18-45 years were randomly assigned to receive three doses of Cecolin or Hecolin and were followed up for 66 months. All the pregnancy-related events throughout the study period were closely followed up. The incidences of adverse events, pregnancy complications, and adverse pregnancy outcomes were analysed based on the vaccine group, maternal age, and interval between vaccination and pregnancy onset. During the study period, 1263 Hecolin receivers and 1260 Cecolin receivers reported 1684 and 1660 pregnancies, respectively. The participants in the two vaccine groups showed similar maternal and neonatal safety profiles, regardless of maternal age. Among the 140 women who were inadvertently vaccinated during pregnancy, the incidences of adverse reactions had no statistical difference between the two groups (31.8% vs 35.1%, p = 0.6782). The proximal exposure to HE vaccination was not associated with a significantly higher risk of abnormal foetal loss (OR 0.80, 95% CI 0.38-1.70) or neonatal abnormality (OR 2.46, 95% CI 0.74-8.18) than that to HPV vaccination, as did distal exposure. Significant difference was not noted between pregnancies with proximal and distal exposure to HE vaccination. Conclusively, HE vaccination during or shortly before pregnancy is not associated with increased risks for both the pregnant women and pregnancy outcomes.

The impact of the digital economy on Chinese enterprise innovation based on intermediation models with financing constraints.

The digital economy has become an important driving force for the steady development of China's economy, and enterprise innovation is a key element for an enterprise's survival and development. This paper constructs a mathematical model to measure the scale of digital economic development and the efficiency of enterprise innovation. It builds a fixed effects model and mediated effects model to study the effect of the development of the digital economy on enterprise innovation based on data from 30 provinces from 2012 to 2020. The results show that (1) there is a significant positive effect of the digital economy on enterprise innovation with an impact coefficient of 0.028, and the economic meaning of the coefficient is that for every 1-point increase in the digital economy index, the ratio of R&D capital expenditures to the enterprise's operating income increases by 0.028% points. This finding remains significant in the robustness test. (2) A further test of the mediating effect finds that the digital economy can drive enterprise innovation by reducing financing constraints. (3) In the regional heterogeneity analysis, it is found that the effect of the digital economy in promoting enterprise innovation is more prominent in the central region, and the impact coefficients are 0.04, 0.06, 0.025, and 0.024 for the eastern, central, western, and northeastern regions, respectively. Taking the central region as an example, the economic meaning of the coefficient is that for every 1-point increase in the digital economy index, the ratio of R&D capital expenditures to the enterprise's operating income increases by 0.06% points. The findings of this paper are of practical significance to enterprises in enhancing their innovation capabilities and promoting the high-quality development of China's economy.

Mid-infrared silicon metasurfaces for near-field enhancement of molecular fingerprints.

Mid-infrared dielectric metasurfaces are promising fundamental building blocks for integrated sensing with high sensitivity, compositional selectivity, and low loss. We have designed and fabricated a silicon metasurface with resonance properties in the 4∼5 µm mid-infrared region and a volume enhancement of up to 9 times. Benchmark FTIR characterizations of solutions of tungsten hexacarbonyl molecules showed a detection limit of 1 mg/mL without the usage of surface enrichment treatment. We further rationalize the detection limit of the molecules-nanostructure open interface with volume field enhancement analysis. Our results show that mid-infrared silicon metasurfaces may be a suitable platform for potential integration with microfluidic for in vivo detection.

Head-to-head comparison of genotyping of human papillomavirus by real-time multiplex PCR assay using type-specific primers and SPF10-PCR-based line probe assay.

The SPF10-polymerase chain reaction (PCR)-based line probe assay (LiPA-25) with high analytical sensitivity and specificity for human papillomavirus (HPV) genotyping in clinical samples has been widely used in vaccine and epidemiologic studies. A real-time multiplex PCR assay using type-specific primers (Hybribio-23) with low workload and cost has been developed recently. The study aimed to compare the performance of LiPA-25 and Hybribio-23 in selected 1731 cervical swab and 117 tissue samples, with a focus on 20 common HPV types (14 high-risk: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68/73; 6 low-risk: 6, 11, 42, 43, 44, and 53). The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 1296 (74.9%) swab samples were identified as HPV-positive by Hybribio-23 or LiPA-25, of which 814 (62.8%) samples exhibited concordant, 358 (27.6%) showed additional or fewer types (compatible), and 124 (9.6%) were discordant. In addition, the two assays showed a perfect agreement for 20 HPV-combined detection (κ = 0.838) and 17 individual HPV types (all κ > 0.800), a good agreement for HPV31 (κ = 0.792) and 43 (κ = 0.696), and a moderate agreement for HPV42 (κ = 0.504). Hybribio-23 was significantly more sensitive for HPV58, 59, 68/73, 42, 43, and 44, and less sensitive for HPV35 and 66 than LiPA-25 (McNemar's test: all p < 0.05). For 117 HPV-positive tissue specimens, the identification of genotypes was 85.2% identical, 12.2% compatible, and only 2.6% discordant. The agreement for HPV31 (κ = 0.786), 68/73 (κ = 0.742), and HPV53 (κ = 0.742) was good, while for other types (all κ > 0.853) and 20 HPV-combined detection (κ = 0.936) was perfect (all p > 0.05). In conclusion, Hybribio-23 and LiPA-25 are comparable. Hybribio-23 could be used for the detection and genotyping of HPV in cervical samples for epidemiological and vaccine studies worldwide.

Light-Induced Phase Segregation Evolution of All-Inorganic Mixed Halide Perovskites.

Light-induced phase segregation in mixed halide perovskites is a major roadblock for commercialization of optoelectronics utilizing these materials. We investigate the phenomenon in a model material system consisting of only surfaces and the bulk of a single-crystalline-like microplate. We utilize environmental in-situ time-dependent photoluminescence spectroscopy to observe the bandgap evolution of phase segregation under illumination. This enables analysis of the evolution of the iodide-rich phase composition as a function of the environment (i.e., surface defects) and carrier concentration. Our study provides microscopic insights into the relationship among photocarrier generations, surface structural defects, and subsequently iodide ion migrations that result in the complex evolution of phase segregation. We elucidate the significance of surface defects with respect to the evolution of phase segregation, which may provide new perspectives for modulating ion migration by engineering of defects and carrier concentrations.

Head-to-head comparison of genotyping of human papillomavirus by GP5+/6+-PCR-based reverse dot blot hybridization assay and SPF10-PCR-based line probe assay.

The SPF10-PCR-based line probe assay (LiPA-25) for human papillomavirus (HPV) genotyping with high analytical sensitivity and specificity was widely used in HPV vaccine clinical trials and epidemiologic studies. In the study, we aimed to compare a novel GP5+/6+-PCR-based reverse dot blot hybridization assay (Yaneng-23) with LiPA-25. The performance of two assays was evaluated in 1735 cervical swab and 117 tissue samples, with a focus on 19 common HPV types (14 high-risk: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68/73; 5 low-risk: 6, 11, 42, 43, and 53). A total of 1197 (69.0%) swab samples were identified as HPV-positive by two assays. Of these, 878 (73.4%) samples displayed absolute agreement (concordant), 255 (21.3%) showed additional or fewer types (compatible), and the remaining 64 (5.3%) samples were discordant. Additionally, the two assays showed an excellent strength of agreement for 19 HPV-combined detection (κ = 0.886) and 17 individual HPV types (all κ > 0.800), and displayed a good agreement for HPV39 (κ = 0.780) and 42 (κ = 0.699). Yaneng-23 was more sensitive than LiPA-25 for HPV58, 59, 68/73, 42, 43 and 53 (McNemar's test: all p < 0.05), while LiPA-25 was more sensitive for HPV31, 39, 52, and 66 than Yaneng-23 (all p < 0.05). In 113 HPV-positive tissue specimens, the identification of genotypes was 82.3% identical and 17.7% compatible. The agreement between the tests for HPV45 (κ = 0.796) and 51 (κ = 0.742) was good, and for other types (all κ > 0.843) and 19 HPV-combined detection (κ = 0.929) was perfect (all p > 0.05). In conclusion, Yaneng-23 and LiPA-25 are comparable. Yaneng-23 could be used for the detection and genotyping of HPV in cervical samples for epidemiological and vaccine studies worldwide.

Using Patient-Derived Xenograft (PDX) Models as a 'Black Box' to Identify More Applicable Patients for ADP-Ribose Polymerase Inhibitor (PARPi) Treatment in Ovarian Cancer: Searching for Novel Molecular and Clinical Biomarkers and Performing a Prospective Preclinical Trial.

(1) The accuracy of patient-derived xenografts (PDXs) in predicting ADP-ribose polymerase inhibitor (PARPi) efficacy in ovarian cancer was tested, novel biomarkers were investigated, and whether PARPis could replace platinum-based chemotherapy as a first-line therapy was explored. (2) PDXs were reconstructed for 40 patients with ovarian cancer, and niraparib, olaparib and paclitaxel, and carboplatin (TC) sensitivity tests were conducted. Whole exon sequencing and homologous recombination deficiency (HRD) scores were performed, and patient clinical information was collected. The molecular biomarkers were identified by reverse-transcription quantitative PCR and immunoblotting. (3) Niraparib and olaparib sensitivity were tested in 26 patients and showed high consistency. Approximately half of BRCA wild-type, HRD-negative, and platinum-resistant patients may benefit from PARPis. AKT1 enrichment indicated PARPi resistance; high KRAS expression indicated PARPi sensitivity. CA125 below 10 U/mL during chemotherapy has a sensitivity and specificity similar to platinum sensitivity in predicting PARPi efficacy. Niraparib and TC sensitivity tests were performed on 23 patients, and TC showed a better response in this preclinical trial. (4) PDX can indicate individualized PARPi efficacy. Decreased CA125 levels and KRAS and ATK1 expression levels may be novel biomarkers. The preclinical evidence does not support the implementation of PARPis as the first-line treatment in an unselected population.

Optical Visualization of Photoexcitation Diffusion in All-Inorganic Perovskite at High Temperature.

All-inorganic halide perovskites are promising candidates for optoelectronic and photovoltaic devices because of their good thermal stability and remarkable optoelectronic properties. Among those properties, carrier transport properties are critical as they inherently dominate the device performance. The transport properties of perovskites have been widely studied at room and lower temperatures, but their high-temperature (i.e., tens of degrees above room temperature) characteristics are not fully understood. Here, the photoexcitation diffusion is optically visualized by transient photoluminescence microscopy (TPLM), through which the temperature-dependent transport characteristics from room temperature to 80 °C are studied in all-inorganic CsPbBr3 single-crystalline microplates. We reveal the decreasing trend of diffusion coefficient and the almost unchanged trend of diffusion length when heating the sample to high temperature. The phonon scattering in combination with the variation of effective mass is proposed for the explanation of the temperature-dependent diffusion behavior.

Large-cohort humanized NPI mice reconstituted with CD34+ hematopoietic stem cells are feasible for evaluating preclinical cancer immunotherapy.

Cancer immunotherapy has achieved impressive therapeutic effects in many cancers, while only a small subset of patients benefit from it and some patients even have experienced severe toxicity. It is urgent to develop a feasible large-cohort humanized mouse model to evaluate the pre-clinical efficacy and safety of cancer immunotherapy. Furthermore, developing potentially effective combination therapy between cancer immunotherapy and other therapies also needs humanized mouse model to adequately mimic clinical actual setting. Herein, we established a humanized mouse model engrafted with less human CD34+ HSCs than ever before and then evaluated reconstitution efficiency and the profiles of human immune cells in this humanized mouse model. Also, this humanized mouse model was used to evaluate the preclinical efficacy and safety of cancer immunotherapy. For each batch of CD34+ HSCs humanized mouse model, a relatively-large cohort with over 25% human CD45+ cells in peripheral blood was established. This humanized mouse model could efficiently reconstitute human innate and adaptive immune cells. This humanized mouse model supported patient-derived xenograft tumor growth and tumor infiltration of PD-1+ human T cells. Furthermore, therapeutic efficacy, re-activation of tumor-infiltrated T cells, and side effects of checkpoint blockade therapy could be monitored in this humanized mouse model. Human T cells from this humanized mouse model were successfully engineered with CD19-CAR. CD19 CAR-T cells could effectively deplete B cells and suppress tumor growth of acute lymphoblastic leukemia in vivo in this humanized mouse model. This humanized mouse model also could be used to demonstrate the efficacy of bispecific antibodies, such as anti-CD19/CD3. Overall, our work provides a feasible large-cohort humanized mouse model for evaluating a variety of cancer immunotherapy approaches including checkpoint inhibitors, adoptive cell therapy, and bispecific antibody therapy, and demonstrates that human T cells from this humanized mouse model possess anti-tumor activities in vitro and in vivo.

A potent and protective human neutralizing antibody targeting a novel vulnerable site of Epstein-Barr virus.

Epstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection.

Dispersion Mapping in 3-Dimensional Core-Shell Photonic Crystal Lattices Capable of Negative Refraction in the Mid-Infrared.

Engineering of the dispersion properties of a photonic crystal (PhC) opens a new paradigm for the design and function of PhC devices. Exploiting the dispersion properties of PhCs allows control over wave propagation within a PhC. We describe the design, fabrication, and experimental observation of photonic bands for 3D PhCs capable of negative refraction in the mid-infrared. Band structure and equifrequency contours were calculated to inform the design of 3D polymer-germanium core-shell PhCs, which were fabricated using two-photon lithography direct laser writing and sputtering. We successfully characterized a polymer-Ge core-shell lattice and mapped its band structure, which we then used to calculate the PhC refraction behavior. An analysis of wave propagation revealed that this 3D core-shell PhC refracts light negatively and possesses an effective negative index of refraction in the experimentally observed region. These results suggest that architected nanolattices have the potential to serve as new optical components and devices across infrared frequencies.

Bending and precipitate formation mechanisms in epitaxial Ge-core/GeSn-shell nanowires.

Core-shell Ge/GeSn nanowires provide a route to dislocation-free single crystal germanium-tin alloys with desirable light emission properties because the Ge core acts as an elastically compliant substrate during misfitting GeSn shell growth. However, the uniformity of tin incorporation during reduced pressure chemical vapor deposition may be limited by the kinetics of mass transfer to the shell during GeSn growth. The balance between Sn precursor flux and available surfaces for GeSn nucleation and growth determines whether defects are formed and their type. On the one hand, when the Sn precursor delivery is insufficient, local variations in Sn arrival rate at the nanowire surfaces during GeSn growth produce asymmetries in shell growth that induce wire bending. This inhomogeneous elastic dilatation due to the varying composition occurs via deposition of Sn-poor regions on some of the {112} sidewall facets of the nanowires. On the other hand, when the available nanowire surface area is insufficient to accommodate the arriving Sn precursor flux, Sn-rich precipitate formation results. Between these two extremes, there exists a regime of growth conditions and nanowire densities that permits defect-free GeSn shell growth.

Patient-Derived Xenografts Are a Reliable Preclinical Model for the Personalized Treatment of Epithelial Ovarian Cancer.

To generate robust patient-derived xenograft (PDX) models for epithelial ovarian cancer (EOC), analyze the resemblance of PDX models to the original tumors, and explore factors affecting engraftment rates, fresh cancer tissues from a consecutive cohort of 158 patients with EOC were collected to construct subcutaneous PDX models. Paired samples of original tumors and PDX tumors were compared at the genome, transcriptome, protein levels, and the platinum-based chemotherapy response was evaluated to ensure the reliability of the PDXs. Univariate and multivariate analyses were used to determine the factors affecting the engraftment rates. The engraftment success rate was 58.23% (92/158) over 3-6 months. The Ki-67 index and receiving neoadjuvant chemotherapy can affect the engraftment rate in primary patients. The PDX models generated in this study were found to retain the histomorphology, protein expression, and genetic alteration patterns of the original tumors, despite the transcriptomic differences observed. Clinically, the PDX models demonstrated a high degree of similarity with patients in terms of the chemotherapy response and could predict prognosis. Thus, the PDX model can be considered a promising and reliable preclinical tool for personalized and precise treatment.

Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat.

Knockout of the ubiquitously expressed miRNA-17∼92 cluster in mice produces a lethal developmental lung defect, skeletal abnormalities, and blocked B lymphopoiesis. A shared target of miR-17∼92 miRNAs is the pro-apoptotic protein BIM, central to life-death decisions in mammalian cells. To clarify the contribution of miR-17∼92:Bim interactions to the complex miR-17∼92 knockout phenotype, we used a system of conditional mutagenesis of the nine Bim 3' UTR miR-17∼92 seed matches. Blocking miR-17∼92:Bim interactions early in development phenocopied the lethal lung phenotype of miR-17∼92 ablation and generated a skeletal kinky tail. In the hematopoietic system, instead of causing the predicted B cell developmental block, it produced a selective inability of B cells to resist cellular stress; and prevented B and T cell hyperplasia caused by Bim haploinsufficiency. Thus, the interaction of miR-17∼92 with a single target is essential for life, and BIM regulation by miRNAs serves as a rheostat controlling cell survival in specific physiological contexts.

Development of an UHPLC-MS/MS method for comparative pharmacokinetics of nine anthraquinones in rats and application to dosage conversion between different Semen Cassiae forms.

Semen Cassiae, called Juemingzi in Chinese, is widely used in clinic for alleviating constipation, improving eyesight and preventing hyperlipidemia. It can be used as medicine or food including many application forms, such as traditional pieces and ultrafine granular powder (UGP). In this paper, comparative pharmacokinetics of Semen Cassiae in different forms of traditional pieces and UGP were achieved to research the clinical dosage of UGP. Also, the scientific connotation of brewing way for traditional pieces of Semen Cassiae application in clinic was revealed. To achieve this purpose, a rapid, sensitive and reliable UHPLC-MS/MS method was developed for simultaneous determination of rhein, emodin, aloe-emodin, chrysophanol, physcion, aurantio-obtusin, chryso-obtusin, obtusifolin and obtusin in rat plasma. Multiple reaction monitoring mode via an electrospray ionization was applied for the quantitation of the analytes. The separation was carried out on an Agilent Extend-C18 column (100 mm × 2.1 mm, 1.8 µm) with an 8.0 min gradient elution using ultra-purify water and acetonitrile as mobile phase. The samples were prepared by liquid-liquid extraction with ethyl acetate. The development and validation of bioanalytical method were performed according to the latest "Bioanalytical Method Validation: Guidance for Industry" issued by FDA in 2018. Finally, the clinical dosage of UGP was concluded to be 1/4 of Semen Cassiae traditional pieces in oral administration way by comparing the pharmacokinetic parameters of UGP to that of traditional pieces in the aspect of mathematical statics using plus of AUC values.

Nine components pharmacokinetic study of rat plasma after oral administration raw and prepared Semen Cassiae in normal and acute liver injury rats.

In China, Semen Cassiae has long been used to protect liver, brighten eyes, and relieve constipation. Prepared Semen Cassiae is produced from raw Semen Cassiae by processing, the two forms of Semen Cassiae have different clinical applications. Pathological state is an important factor affecting the efficacy of drugs, the pharmacokinetic behavior of drugs could be significantly changed when people or animal were under different pathological state. To clarify the effect of processing mechanism and pathological state for pharmacokinetic behavior, the pharmacokinetics of nine components of raw and prepared Semen Cassiae under normal and acute liver injury rats were examined. The results showed that the bimodal phenomenon appeared on the plasma concentration-time profiles of obtusin, emodin, chrysophanol, aloe emodin and rhein. The Tmax of aurantio-obtusin, obtusin, chrysoobtusin, emodin, chrysophanol, aloe emodin, physcion in normal groups administrated prepared Semen Cassiae were shorter than those administrated raw Semen Cassiae. For the AUC0-t , aurantio-obtusin, obtusin, chrysoobtusin, chrysophanol, aloe emodin and physcione in model groups administrated prepared Semen Cassiae were significantly higher than other groups, unlike above components, rhein had poor absorption in model groups. The study would be useful for further studies on pharmacokinetics and clinical application of raw and prepared Semen Cassiae.