Hypofractionated radiotherapy for refractory or relapsed aggressive B-cell lymphoma in the rituximab era.

BACKGROUND: Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. METHODS: We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. RESULTS: A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported. CONCLUSION: These data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.

Economic and clinical burden of chronic corticosteroid use in patients with Crohn[apos]s disease initiated on biologic or conventional therapies in the US: A retrospective claims study.

BACKGROUND: Chronic corticosteroid (CS) use is associated with complications, but estimates of the economic and clinical burden in patients with Crohn's disease (CD) are lacking. OBJECTIVE: To estimate the burden of chronic CS use in CD in the United States in terms of health care resource utilization (HRU), health care costs, and CS-related complications. METHODS: This was a retrospective study of adults with CD initiated on biologics or conventional therapies (index date). Patients from a deidentified insurance claims database (2004-2021) were classified as chronic CS users (>90 days of CS use) or nonchronic CS users based on a 12-month landmark period starting on the index date. Patient baseline characteristics were balanced, and outcomes (HRU, costs [2021 US dollars], and CS-related complications) 12 months after the landmark period were compared between CS groups using regressions with nonparametric bootstrap resampling to estimate confidence intervals and P values. RESULTS: Biologic initiators (mean age: 44 years, 55% female) included 3366 chronic and 3401 nonchronic CS users; conventional therapy initiators (mean age: 51 years, 59% female) included 3657 chronic and 3727 nonchronic CS users. Compared with nonchronic users, chronic users had significantly more inpatient days and outpatient visits (biologic initiators: 37% and 24% more, respectively; conventional therapy initiators: 36% and 17%, respectively; all P<0.05). Chronic users also had significantly higher mean all-cause total costs per-patient-per year (biologic: $72,967 vs. $63,100, mean cost difference [MCD] = $9867; conventional therapy: $40,144 vs. $26,426, MCD = $13,718; all P<0.001), as well as higher odds of infection (biologic: 14% higher; conventional therapy: 20% higher) and bone loss (63% and 41%, respectively) (all P<0.05). CONCLUSION: Chronic CS use in patients with CD is associated with a significant economic and clinical burden including higher HRU, health care costs, and prevalence of complications, suggesting unmet needs in the clinical management of this population.

Citric Acid Enhances the Activities of Astilbin on Psoriasis via Down-Regulation of P-Glycoprotein.

Astilbin (AS) has been confirmed to be an attractive candidate drug for psoriasis; however, the low oral absorption limits its further development and utilization. Herein, a simple method was discovered to solve this problem, which was combined with citric acid (CA). The efficiency was estimated by imiquimod (IMQ)-induced psoriasis-like mice, and the absorption was predicted by the Ussing chamber model, HEK293-P-gp cells were used to validate the target. Compared with the AS group, the combination with CA significantly reduced the PASI score and down-regulated the protein expression of IL-6 and IL-22, which showed that the combination of CA enhanced the anti-psoriasis effect of AS. Moreover, AS concentration in psoriasis-like mice plasma was significantly increased (3.90-fold) in the CA combined group, and the mRNA and protein levels of P-gp in the small intestine of the combined group were decreased by 77.95 and 30.00%, respectively. In addition, when combined with CA, AS absorption significantly increased while the efflux ratio decreased in vitro. Furthermore, CA significantly elevated the uptake of AS by 153.37% and decreased the protein expression of P-gp by 31.70% in HEK293-P-gp cells. These results indicated that CA enhanced the therapeutic efficacy of AS by improving its absorption via down-regulation of P-gp.

Low-temperature phenol-degrading microbial agent: construction and mechanism.

In this study, three cold-tolerant phenol-degrading strains, Pseudomonas veronii Ju-A1 (Ju-A1), Leifsonia naganoensis Ju-A4 (Ju-A4), and Rhodococcus qingshengii Ju-A6 (Ju-A6), were isolated. All three strains can produce cis, cis-muconic acid by ortho-cleavage of catechol at 12 â„ƒ. Response surface methodology (RSM) was used to optimize the proportional composition of low-temperature phenol-degrading microbiota. Degradation of phenol below 160 mg L-1 by low-temperature phenol-degrading microbiota followed first-order degradation kinetics. When the phenol concentration was greater than 200 mg L-1, the overall degradation trend was in accordance with the modified Gompertz model. The experiments showed that the microbial agent (three strains of low-temperature phenol-degrading bacteria were fermented separately and constructed in the optimal ratio) could completely degrade 200 mg L-1 phenol within 36 h. The above construction method is more advantageous in bio-enhanced treatment of actual wastewater. Through the construction of microbial agents to enhance the degradation effect of phenol, it provides a feasible scheme for the biodegradation of phenol wastewater at low temperature and shows good application potential.

The value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma staged with PET/CT.

BACKGROUND: Limited evidence supports the omission of routine bone marrow (BM) examination (biopsy and aspiration) in patients with nasal-type extranodal NK/T-cell lymphoma (ENKTCL). This study was aimed at assessing whether BM examination provides valuable information for positron emission tomography/computed tomography (PET/CT)-based staging in this patient population. PATIENTS AND METHODS: Patients newly diagnosed with ENKTCL who underwent initial staging with both PET/CT and BM examination between 2013 and 2020 were retrospectively identified in two Chinese institutions. Overall, 742 patients were included; the BM examination was positive in 67 patients. RESULTS: Compared with BM biopsy alone, the combination of BM biopsy and aspiration assessment did not afford any additional diagnostic value. No patient with a positive BM biopsy was found to have early-stage disease by PET/CT. BM biopsy or PET/CT led to upstaging from stage III to IV as a result of BM involvement in 21 patients. In 135 patients with distant organ involvement, BM involvement was associated with worse overall survival (OS) and progression-free survival (PFS) compared with the corresponding durations in patients without BM involvement (2-year OS: 35.9% vs. 60.4%, p < .001; PFS: 26% vs. 40.7%, p = .003). No difference in survival was noted between groups judged positive based on PET/CT and BM biopsy. CONCLUSION: Compared with aspiration, BM biopsy led to the detection of more BM lesions. Baseline PET/CT can be safely used to exclude BM involvement in early-stage disease. Overall, routine BM examination affords diagnostic or prognostic value over PET/CT in patients with advanced-stage nasal-type ENKTCL.

Comparative Study on Volatile Oils among Bupleuri radix Species and Habitats: Yields, Chemical Characterization and Antipyretic Activities.

Volatile oils from several Bupleuri radix (BR) are reported as potential sources of drugs. To provide evidence for the application of BR, the volatile oils from 19 batches of different species and habitats of BR including Bupleurum chinese DC. (BCD), Bupleurum scorzonerifolium Willd. (BSW), Bupleurum bicaule Helm (BBH), Bupleurum marginatum var. stenophyllum (Wolff) Shan et Y.Li (BMS), Bupleurum marginatum Wall.ex DC. (BMW) and Bupleurum falcatum L. (BFL) were investigated. The composition of BR volatile oils was determined by GC/MS. Samples were clustered by hierarchical cluster analysis (HCA). Fever was induced by Lipopolysaccharide (LPS), and antipyretic activities of BR volatile oils were evaluated with Chaihu injection (CI) as the positive control. The yields of volatile oils were among 360-5320 ppm. A total of 229 components were identified by GC/MS. Samples could be divided into 4 clusters by HCA. 4 representative samples, one for each cluster, were selected to further compare their antipyretic activities. For the highest content of volatile oil (5320 ppm) and the best activity, BSW has great potential for utilization.

A Comparison Study on Polysaccharides Extracted from Atractylodes chinensis (DC.) Koidz. Using Different Methods: Structural Characterization and Anti-SGC-7901 Effect of Combination with Apatinib.

For hundreds of years, Atractylodes chinensis (DC.) Koidz. (AK) has been widely used as a treatment for spleen and stomach diseases in China. The AK polysaccharides (AKPs) have been thought to be the important bioactive components. In this stud, the impacts of different extraction methods were analyzed. The differences between AKPs extracted by hot water extraction (HWE), AKPs extracted by ultrasonic extraction (UAE), and AKPs extracted by enzyme extraction (EAE) were compared in terms of yield, total carbohydrate content, molecular weight distribution, monosaccharide composition, and synergistic activity of the AKPs with apatinib were determined. The results indicated that the yield of the polysaccharide obtained from HWE was higher than that of UAE and EAE. However, activity assays indicated that UAE-AKPs and HWE-AKPs enhanced apoptosis of human gastric cancer cells (SGC-7901) treated with apatinib and UAE-AKPs showed the strongest synergistic activities. This is also in agreement with the fact that UAE-AKPs have a smaller molecular weight, ß-configuration, and higher galactose content. These findings suggested that UAE is an efficient and environmentally friendly method for producing new polysaccharides from Atractylodes chinensis (DC.) Koidz. for the development of natural synergist and for the treatment of gastric cancer.

Comparative Characterization and Immunomodulatory Activities of Polysaccharides Extracted from the Radix of Platycodon grandiflorum with Different Extraction Methods.

Platycodon grandiflorum is an edible and medicinal plant, and polysaccharides are one of its important components. To further improve the utilization rate of P. grandiflorum, we investigated the effects of four different extraction methods, including hot water, ultrasonic-assisted, acid-assisted, and alkali-assisted extractions, on the polysaccharides, which were named PG-H, PG-U, PG-C, and PG-A. The findings indicated that the extraction method had a significant impact on the yield, characteristics, and immunoregulatory activity. We observed that the yields decreased in the following order: PG-H, PG-U, PG-C, and PG-A. Galacturonic acid, glucose, galactose, and arabinose were the most prevalent monosaccharides in the four PGs. However, their proportions varied. In addition, the difference between the content of glucose and galacturonic acid was more significant. PG-U had the highest glucose content, whereas PG-C had the lowest. Galacturonic acid content was highest in PG-A, while the lowest in PG-U. The molecular weight decreased in the order of PG-U, PG-H, PG-C, and PG-A; the particle size was in the order of PG-U, PG-A, PG-H, and PG-C. Moreover, the extraction method had a great impact on immunoregulatory activity. The ability to stimulate the immune function of macrophages was as follows: PG-A > PG-C > PG-U > PG-H. The results indicated that PGs, with lower molecular weights and higher GalA content, exhibited better immune-stimulating activity. And more important the AAE method was a good way to extract polysaccharides from Platycodon grandiflorum for use as a functional product and immunological adjuvant.

(+/-)-Borneol Reverses Mitoxantrone Resistance against P-Glycoprotein.

P-Glycoprotein (Pgp) is a main factor contributing to multidrug resistance and the consequent failure of chemotherapy. Overcoming Pgp efflux is a strategy to improve the efficacy of drugs. (+)-Borneol (BNL1) and (-)-borneol (BNL2) interfere and inhibit Pgp, and thus, the accumulation of drugs increases in cells. However, it is not clear yet how they play the inhibitory effect against Pgp. In this work, the effect and molecular mechanism of borneol enantiomers in reversing mitoxantrone (MTO) resistance against Pgp were explored by in vitro and in silico approaches. Chemosensitizing potential tests showed that BNLs could enhance the efficacy of MTO in MES-SA/MX2 cells, and BNL2 exhibited a stronger potential. The protein expression of Pgp was decreased to some extent by the administration of BNLs. Molecular docking revealed that BNLs could reduce the binding affinity between MTO and Pgp. The results were consistent with the chemosensitizing potential test and were supported by molecular dynamics (MD) simulations. Molecular docking also suggested that BNLs preferred to bind in the drug-binding pocket rather than the nucleotide-binding domain of inward-facing Pgp. The occupied space of BNLs had an evident distance from that of MTO, which was further verified by the conformational analysis after MD simulations. The decomposition of binding free energies revealed the key amino acid residues (GLN195, SER196, TRP232, PHE343, SER344, GLY346, and GLN347) for BNLs to reverse MTO resistance. The results provide an insight into the mechanism through which BNLs reduce the MTO resistance against inward-facing Pgp in the drug-binding pocket through noncompetitive inhibition.

First-line immunotherapy versus targeted therapy in patients with BRAF-mutant advanced melanoma: a real-world analysis.

Aim: To compare effectiveness of nivolumab + ipilimumab (NIVO + IPI) versus BRAF + MEK inhibitors (BRAFi + MEKi) in patients with BRAF-mutant advanced melanoma in the real-world setting. Materials & methods: This study used the Flatiron Health electronic medical record database. Results: After adjusting for differences in baseline characteristics, NIVO + IPI was associated with a 32% reduction in risk of death versus BRAFi + MEKi. At a mean follow-up of 15-16 months, 64% of NIVO + IPI patients and 43% of BRAFi + MEKi patients were alive; subsequent therapy was administered to 33 and 41% of patients, respectively. After first-line NIVO + IPI, 20% of patients died before subsequent therapy, whereas 32% died after first-line BRAFi + MEKi. Conclusion: In this real-world study, patients treated with first-line NIVO + IPI showed significant survival benefit versus those receiving first-line BRAFi + MEKi.

Second-harmonic generation of single-mode Laguerre-Gaussian beams with an improved quasi-phase-matching method.

In the second-harmonic generation processes involving Laguerre-Gaussian (LG) beams, the generated second-harmonic wave is generally composed of multiple modes with different radial quantum numbers. To generate single-mode second-harmonic LG beams, a type of improved quasi-phase-matching method is proposed. The Gouy phase shift has been considered in the optical superlattice designing and an adjustment phase item is introduced. By changing the structure parameters, each target mode can be phase-matched selectively, whose purity can reach up to 95%. The single LG mode generated from the optical superlattice can be modulated separately and used as the input signals in the mode division multiplexing system.

A Phase II Trial of Concurrent Temozolomide and Hypofractionated Stereotactic Radiotherapy for Complex Brain Metastases.

PURPOSE: Complex brain metastases (BMs), such as large lesions, lesions within or close to eloquent locations, or multiple recurrent/progressive BMs, remain the most challenging forms of brain cancer because of decreased intracranial control rates and poor survival. In the present study, we report the results from a single institutional phase II trial of concurrent temozolomide (TMZ) with hypofractionated stereotactic radiotherapy (HFSRT) in patients with complex brain metastases, including assessment of its feasibility and toxicity. PATIENTS AND METHODS: Fifty-four patients with histologically proven primary cancer and complex BMs were enrolled between 2010 and 2015. All the patients were treated with concurrent HFSRT and TMZ (administrated orally at a dosage of 75 mg/m2 per day for at least 20 days). The primary endpoint was overall survival (OS). RESULTS: The median follow-up time was 30.6 months. The local control rates at 1 and 2 years were 96% and 82%, respectively. The median OS was 17.4 months (95% confidence interval [CI], 12.6-22.2), and the OS rates at 1 and 2 years were 65% (95% CI, 52%-78%) and 33% (19%-47%). Only six patients (15.8%) died of intracranial disease. The median brain metastasis-specific survival was 46.9 months (95% CI, 35.5-58.4). Treatment-related grade 3-4 adverse events were rare and included one grade 3 hematological toxicity and two grade 3 liver dysfunctions. CONCLUSION: Treatment using HFSRT concurrent with TMZ was well tolerated and could significantly extend OS compared with historical controls in complex BMs. Large randomized clinical trials are warranted. Trial registration ID: NCT02654106. IMPLICATIONS FOR PRACTICE: The treatment using hypofractionated stereotactic radiotherapy concurrent with temozolomide appeared to be safe and could significantly extend overall survival compared with historical control in complex brain metastases. Large randomized clinical trials are warranted to verify our results.

Adherence, persistence, glycaemic control and costs among patients with type 2 diabetes initiating dulaglutide compared with liraglutide or exenatide once weekly at 12-month follow-up in a real-world setting in the United States.

AIMS: To evaluate adherence, persistence, glycaemic control and costs at 12-month follow-up for patients initiating dulaglutide versus liraglutide or exenatide once weekly. MATERIALS AND METHODS: The present retrospective observational claims study included patients with type 2 diabetes (T2D) and ≥ 1 pharmacy claim for dulaglutide, liraglutide or exenatide once weekly from the HealthCore Integrated Research Database. Adherence was defined as proportion of days covered ≥80%, and persistence was measured by time to discontinuation of index therapy. Change from baseline in glycated haemoglobin (HbA1c) concentration was assessed in a subset with pre- and post-index HbA1c results. Propensity scores were used to match the cohorts. RESULTS: The baseline characteristics were balanced for the matched cohorts, dulaglutide versus liraglutide (n = 2471) and dulaglutide versus exenatide once weekly (n = 1891). Among those initiating dulaglutide there was a significantly higher proportion of adherent patients compared with the groups initiating liraglutide (51.2% vs. 38.2%; P < 0.001) and exenatide once weekly (50.7% vs. 31.9%; P < 0.001). At 12 months, 55% of patients in the dulaglutide group versus 43.8% in the liraglutide group (P < 0.001), and 54.9% in the dulaglutide versus 34.4% in the exenatide once-weekly group (P < 0.001) were persistent. The dulaglutide group had a significantly greater reduction in HbA1c than the liraglutide group (-34.24 vs. -31.94 mmol/mol; P = 0.032), and a greater, but nonsignificant, reduction in HbA1c than the exenatide once-weekly group (-34.46 vs. -31.94 mmol/mol; P = 0.056). The diabetes-related total costs were not significantly different between the dulaglutide and the liraglutide group ($16,174 vs. $16,694; P = 0.184), and were significantly higher for dulaglutide than for exenatide once weekly ($15,768 vs. $14,615; P = 0.005). CONCLUSIONS: Adherence and persistence are important considerations in patient-centric treatment selection for patients with T2D. Higher adherence and persistence for dulaglutide compared with liraglutide or exenatide once weekly are relevant criteria when choosing glucagon-like peptide-1 receptor agonist treatment for patients with T2D.

Nearly Diffraction-Free Nonlinear Imaging of Irregularly Distributed Ferroelectric Domains.

Second-harmonic generation is used experimentally for the nonlinear imaging of two-dimensional irregular domain structures. Analytical solutions and simulation results for the Fresnel distribution of domain walls are obtained. The results show that the domain wall plays an important role in the imaging process and the corresponding diffraction effect is greatly suppressed (we call it a nearly diffraction-free effect), thus providing a simple way to realize high-resolution imaging for ferroelectric domains.

Time-reversed and reciprocal second-harmonic generation with pump depletion.

The time-reversed second-harmonic generation in one-dimensional nonlinear photonic crystals has been theoretically studied without the undepleted pump approximation. A simple criterion has been deduced which determines the energy flow. Based on it, two kinds of structures with different symmetries are presented to realize the nonlinear time reversal effect. A completely reciprocal nonlinear response is also found in the same process. Furthermore, a multi-section-cascaded structure is proposed to realize the nonlinear time reversal at any given position.

Vinegar amount in the process affected the components of vinegar-baked Radix Bupleuri and its hepatoprotective effect.

BACKGROUND: Bupleuri Radix (in Chinese Chaihu), the dried roots of Bupleurum Chinense DC, is a traditional Chinese medicine widely used to treat fever, hepatitis, jaundice, nephritis, dizziness. When baked with vinegar, its effect is more focused on liver related disease. This paper was undertaken to determine the best vinegar amount in the processing and explore its key efficacy components. METHODS: Hepatoprotective effects of Radix Bupleuri after processing with different amount of vinegar (1:5, 2:5, 3:5) were investigated on liver hurt rats, and the change of constituents were analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). RESULTS: With the increasing amount of vinegar, the hepatoprotective effects of vinegar-baked Radix Bupleuri (VBRB) and the content of saikosaponin b2 increased. CONCLUSION: These results suggested that vinegar amount in the process affected the pharmacological effect of VBRB significantly and saikosaponin b2 may be the key efficacy component of it.

Formula PSORI-CM01 eliminates psoriasis by inhibiting the expression of keratinocyte cyclin B2.

BACKGROUND: Psoriasis is a chronically recurrent inflammatory skin disease, modern medicine could achieve good therapeutic effect, but these treatments led to recurrence of the psoriasis, more severe symptoms due to damaging skin barrier. Traditional Chinese medicine is a useful alternative therapies. The purpose of this study was to explore the mechanism of PSORI-CM01, a Chinese medicine formula for psoriasis therapy, in eliminating psoriasis by studying its effects on inhibiting epidermal hyperplasia. METHODS: Imiquimod induced psoriasis-form mice model was used to determine the efficacy of PSORICM-01 by assessing the improvement of hyperplasia in epidermal and dermal skin, cyclin B2 expression in skin was detected by immunochemistry. Human keratinocyte cell line HaCaT stimulated by LPS or not was used to research molecular mechanisms of PSORIMCM-01 as in vitro model. The inhibition of proliferation of HaCaT was determined by MTT assay, BrdU assay and real-time cell analysis (RTCA). Cell cycle distribution was detected by flow cytometry. Real-Time PCR and western blot analysis was performed to quantify the mRNA and protein expression levels, respectively. The ability of PSORICM-01 to inhibit proliferation of cyclin B2 overexpressed HaCaT cell were also investigated. RESULTS: PSORI-CM01 significantly inhibited epidermal hyperplasia in IMQ mice lesion skin, and reduced expression of epidermis cyclin B2. Serum containing PSORI-CM01 dramatically inhibited keratinocyte HaCaT cell proliferation, no matter stimulated by LPS or not. FACS analysis showed ability of PSORICM-01 to arrest cell cycle in the G2/M phase. Additionally, PSORI-CM01 significant downregulated mRNA and protein expression of cyclin B2, and over-expression of cyclin B2 antagonized the anti-proliferative effect of PSORI-CM01 on HaCaT cells. CONCLUSIONS: PSORI-CM01 inhibits epidermal hyperplasia in imiquimod-induced mouse psoriasis-form model and reduces keratinocyte proliferation in vitro. Our results indicate that PSORI-CM01 may possess therapeutic potential for psoriasis by inhibiting keratinocyte proliferation through downregulation of cyclin B2.

Two new γ-pyrone glucosides from Paeonia albiflora.

Two new γ-pyrone glucosides, along with three known compounds, were isolated from the roots of Paeonia albiflora, and their structures were elucidated by spectral experiments, chemical analysis, and comparison with literature data. The structures of the new compounds were established as 2-(hydroxymethyl)-4-oxo-4H-pyran-3-yl-6-O-α-L-rhamnopyranosyl-ß-D-glucopyranoside (1), and 2-(hydroxymethyl)-4-oxo-4H-pyran-3-yl-6-O-galloyl-ß-D-glucopyranoside (2). The inhibitory activity on the release of TNF-α of compounds 1-5 was evaluated in vitro. This is the first report of the presence of γ-pyrone glucoside in P. albiflora.

Identification and quantitative characterization of PSORI-CM01, a Chinese medicine formula for psoriasis therapy, by liquid chromatography coupled with an LTQ Orbitrap mass spectrometer.

PSORI-CM01 is a Chinese medicine formula prepared from medicinal herbs and used in China for the treatment of psoriasis. However, the chemical constituents in PSORI-CM01 have not been clarified yet. In order to quickly define the chemical profiles and control the quality of PSORI-CM01 preparations, ultra-high liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole Orbitrap mass spectrometry (UHPLC-ESI-LTQ/Orbitrap-MS) was applied for simultaneous identification and quantification of multiple constituents. A total of 108 compounds, including organic acids, phenolic acids, flavonoids, and terpenoids, were identified or tentatively deduced on the base of their retention behaviors, MS and MSn data, or by comparing with reference substances and literature data. In addition, an optimized UHPLC-ESI-MS method was established for the quantitative determination of 14 marker compounds in different dosage forms of PSORI-CM01 preparations. The validation of the method, including spike recoveries, linearity, sensitivity (LOQ), precision, and repeatability, was carried out and demonstrated to be satisfied the requirements of quantitative analysis. This is the first report on the comprehensive determination of chemical constituents in PSORI-CM01 preparations by UHPLC-ESI-LTQ/Orbitrap mass spectrometry. The results suggested that the established methods would be a powerful and reliable analytical tool for the characterization of multi-constituents in complex chemical system and quality control of TCM preparations.

Effect of saikosaponins and extracts of vinegar-baked Bupleuri Radix on the activity of ß-glucuronidase.

In Traditional Chinese Medicine, liver targeting is usually achieved by coadministration with Vinegar-baked Radix Bupleuri (VBRB), but the mechanism is unclear. In this paper, the influence of VBRB on the activity of ß-glucuronidase was investigated and compared with that of saikosaponins. The activity of ß-glucuronidase was measured by microplate reader using a 4-nitrophenyl-ß-d-glucuronide substrate. The change of 4-nitrophenol content was used to characterize the activity of ß-glucuronidase. Bupleurum chinenes were found to be the inhibitor of ß-glucuronidase. The inhibition rate of Bupleurum chinenes extracts BC1 (high molecular weight polysaccharides), BC2 (ethanol soluble/water insoluble component), BC3 (extracted by n-butanol, soluble in water), and BC4 (low molecular weight water soluble parts) on the activity of ß-glucuronidase was found to be 45.15%, 33.94%, 24.94%, and 34.54%, respectively, after 1 h incubation, with BC1 showing the highest inhibition rate. In contrast, the saikosaponins were demonstrated to be the promoter of ß-glucuronidase, with promotion rates of 333.56%, 217.04%, 247.87%, 149.75%, and 92.50% for saikosaponin standard samples A, B, B2, C, and D, respectively, (p<0.05). In conclusion, inhibiting the activity of ß-glucuronidase might be one of the reasons why VBRB could influence drug distribution upon its coadministration with other drugs. Since saikosaponins and VBRB extracts have opposite effect, more attention should be paid to the content of saikosaponins in the extracts upon its application.