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.

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.

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.

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.

Qualitative and quantitative analysis of Rhizoma Smilacis glabrae by ultra high performance liquid chromatography coupled with LTQ OrbitrapXL hybrid mass spectrometry.

Rhizoma Smilacis glabrae, a traditional Chinese medicine (TCM) as well as a functional food, has been commonly used for detoxification treatments, relieving dampness and as a diuretic. In order to quickly define the chemical profiles and control the quality of Smilacis glabrae, ultra high performance 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 its bioactive constituents. A total of 56 compounds, including six new compounds, were identified or tentatively deduced on the basis of their retention behaviors, mass spectra, or by comparison with reference substances and literature data. The identified compounds belonged to flavonoids, phenolic acids and phenylpropanoid glycosides. In addition, an optimized UHPLC-ESI/LTQ-Orbitrap-MS method was established for quantitative determination of six marker compounds from five batches. The validation of the method, including linearity, sensitivity (LOQ), precision, repeatability and spike recoveries, was carried out and demonstrated to be satisfied the requirements of quantitative analysis. The results suggested that the established method would be a powerful and reliable analytical tool for the characterization of multi-constituent in complex chemical system and quality control of TCM.

[Pharmacokinetic study on peoniflorin, astilbin, rosmarinic acid, isofraxidin and liquiritin in rat blood after oral administration of shaolin xiaoyin tablets].

To establish a method for the determination of astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin contained in Shaolin Xiaoyin tablets, in order to lay a foundation for designing late-stage dosage forms and clinical medication schemes. In this paper, efforts were made to establish a method for the determination of the blood concentration of the five components and study the in vivo pharmacokinetics in rats. The blood concentration was determined by HPLC. Phenomenex C18 column (4.6 mm x 250 mm, 5 microm) was adopted and eluted with methanol-acetonitrile-0.05% formic acid, the flow rate was 0.8 mL x min(-1), and the wavelength was 275 nm. The samples were processed by the solid phase extraction method. After oral administration of Shaoling Xiaoyin tablets, the rat bloods were collected at different time points to determine the blood concentrations. The experimental results showed that the baseline separation could be adopted for the five components, and astilbin, peoniflorin, rasmarinci acid, isofraxidin and liquiritin showed good linear relations within ranges of 2.48-248, 0.213 6-21.36, 0.531-53.1, 0.704-70.4, 0.253-25.3 mg x L(-1). All the five components could be absorbed in blood and excreted quickly. The method established in this paper is rapid and accurate, and could be used for in vivo analysis on preparations containing similar components. The main components in Shaoling Xiaoyin tablets could be absorbed and excreted quickly, and thus suitable to be made into sustained release tablets. Common preparations are required to be taken for 4-6 times a day.

Determination of isofraxidin and astilbin by HPLC in rat plasma and its application after orally administration the extract of Sarcandra glabra.

Sarcandra glaber is a common traditional Chinese medicine used to treat psoriasis and other infectious diseases, isofraxidin and astilbin are the main components of it. In order to study the pharmacokinetics of Sarcandra glabra, an HPLC method for simultaneous determination of isofraxidin and astilbin in rat plasma was established. Plasma samples were prepared using solid phase extraction method. C(18) column with a guard was used, mobile phase was consisted of A (methanol) and B (0.1% aqueous acetic acid) with gradient elution as follows: 0 - 4min, A: 35%, B: 65%; 4 - 10min, A: 35% - 45%, B: 65% - 55%; 10 - 20min, A: 45%, B: 55%. The flow rate was 1.2 mL/min from 0 to 4 min, 1.0 mL/min from 4 to 20 min. The detection wavelength was 300 nm. A linear correlation between drug amount and peak area was established for isofraxidin in the range of 20-320 ng and for astilbin in the range of 19-304 ng. The recovery was over 68% for both compounds, the accuracy was within 8%, and the inter-day and intra-day precisions were all less than 8%. The pharmacokinetics of isofraxidin and astilbin was studied after orally administration the extract of Sarcandra glabra.

Determinants and Assembly Mechanism of Bacterial Community Structure in Ningxia Section of the Yellow River.

The Yellow River is a valuable resource in the Ningxia Hui Autonomous Region and plays a vital role in local human activities and biodiversity. Bacteria are a crucial component of river ecosystems, but the driving factors and assembly mechanisms of bacterial community structure in this region remain unclear. Herein, we documented the bacterial community composition, determinants, co-occurrence pattern, and assembly mechanism for surface water and sediment. In comparison to sediment, the bacterioplankton community showed significant seasonal variation, as well as less diversity and abundance. The network topology parameters indicated that the sediment bacterial network was more stable than water, but the bacterioplankton network had higher connectivity. In this lotic ecosystem, CODMn, Chl a, and pH affected the structure of the bacterioplankton community, while TP was the primary factor influencing the structure of the sediment bacterial community. The combined results of the neutral community model and the phylogenetic null model indicate that Bacterial communities in both habitats were mainly affected by stochastic processes, with ecological processes dominated by ecological drift for bacterioplankton and dispersal limitation for sediment bacteria. These results provide essential insights into future research on microbial ecology, environmental monitoring, and classified management in the Ningxia section of the Yellow River.

A Preliminary Study of Bacterioplankton Community Structure in the Taiyangshan Wetland in Ningxia and Its Driving Factors.

The Taiyangshan Wetland, a valuable wetland resource in the arid zone of central Ningxia, is critical for flood storage and drought resistance, climate regulation, and biodiversity protection. Nevertheless, the community structure and diversity of bacterioplankton in the Taiyangshan Wetland remains unclear. High-throughput sequencing was used to analyze the differences in bacterioplankton structure and major determinants in the Taiyangshan Wetland from April to October 2020. The composition and diversity of the bacterioplankton community varied significantly in different sampling periods but showed negligible differences across lake regions. Meanwhile, the relative abundances of bacterioplankton Bacteroidetes, Actinobacteria, Firmicutes, Chloroflexi, Tenericutes, Epsilonbacteraeota, and Patescibacteria were significantly different in different sampling periods, while the relative abundances of Cyanobacteria in different lake regions were quite different. Network analysis revealed that the topological attributes of co-occurrence pattern networks of bacterioplankton were high, and bacterioplankton community compositions were complicated in the month of July. A mantel test revealed that the bacterioplankton community in the entire wetland was affected by water temperature, electrical conductivity, dissolved oxygen, salinity, total nitrogen, ammonia nitrogen, chemical oxygen demand, fluoride, and sulfate. The bacterioplankton community structure was affected by ten environmental parameters (e.g., water temperature, dissolved oxygen, salinity, and permanganate index) in April, while the bacterioplankton community was only related to 1~2 environmental parameters in July and October. The bacterioplankton community structure in Lake Region IV was related to seven environmental parameters, including dissolved oxygen, pH, total nitrogen, and chemical oxygen demand, whereas the bacterioplankton community structures in the other three lake regions were related to two environmental parameters. This study facilitates the understanding of the bacterioplankton community in wetlands in arid areas and provides references to the evaluation of aquatic ecological management of the Taiyangshan Wetland.

Formula PSORI-CM01 inhibits the inflammatory cytokine and chemokine release in keratinocytes via NF-κB expression.

Psoriasis is a common chronic inflammatory disease in which T-helper 1(Th1) and T-helper 17(Th17) cells play an important role in its pathology. Formula PSORI-CM01 was a novel formulated Chinese medicine used for psoriasis therapy. It had been demonstrated previously that PSORI-CM01 and serum contained Formula PSORI-CM01 (PCM01CS) could improve psoriasis by inhibiting the epithelial hyperplasia, how PSORI-CM01 affects inflammatory cytokine and chemokine in dermis is still unknown. In this study we found PSORI-CM01 pre-treated 3days before IMQ painting could ameliorated IMQ-induced mice skin lesion as PASI score was apparently reduced. Th1 related cytokine IFN-γ and Th17 related cytokine IL-17/IL-22 was used to induce inflammatory models on human keratinocyte cell line HaCaT in vitro, respectively. PCM01CS significantly reduced IFN-γ induced mRNA expression of IL-6, IL-12 and CXCL-10, reduced IL-6 and CXCL-10 release into HaCaT supernatant. 20ng/ml IL-17/IL-22 co-stimulation significantly upregulated expression of IL-6, IL-8 and CCL20 mRNA expression in HaCaT cells, PCM01CS significantly inhibit these cytokines expression both in mRNA and in protein levels. Finally, PCM01CS could obviously inhibit nuclear NF-κB p65 expression which activated by IFN-γ and IL-17/IL-22 stimulation. Thus, our new findings reveal that Formula PSORI-CM01 may possess therapeutic action on psoriasis by inhibiting inflammatory within skin environments.

Clerosterol from vinegar-baked radix bupleuri modifies drug transport.

Vinegar-baked Radix Bupleuri (VBRB) is reportedly used to treat liver cancer when combined with traditional chemotherapy and data show that this combination may modify drug transport. We isolated clerosterol from VBRB and studied its effect on drug transporters in normal or transporter-overexpressing cells. Transporter activity was assayed using cellular substrate concentration and transporter expression with Western blot and RT-qPCR. Clerosterol decreased cisplatin uptake in BRL cells mainly through increasing Mrp2 gene expression. Clerosterol also decreased the uptake of colchicine in HEK 293 cells by increasing both Pgp and Mrp1 activity; in detail, it could increase Pgp protein but had marginal effects on Mrp1 protein and gene expression. Further study showed clerosterol increased OCT2 activity in HEK293-Pgp cells by increasing OCT2 protein and mRNA. Clerosterol could suppress Pgp overexpression but not by regulating protein and gene expression. And clerosterol had marginal effects on Mrp2 and Mrp1 activity in Mrp2- and Mrp1-overexpressing HEK293 cells. Thus, Clerosterol may be an active constituent of VBRB and may work against cancer multidrug resistance by inhibiting Pgp activity.

Five new diarylheptanoids from the rhizomes of Curcuma kwangsiensis and their antiproliferative activity.

Five new diarylheptanoids (1-5), along with nine known ones (6-14), were isolated from the rhizomes of Curcuma kwangsiensis. Their structures were established on the basis of spectroscopic analyses. Compounds 1-3 were cyclic diarylheptanoids rarely discovered from C. kwangsiensis. Of all the isolated compounds, compound 4 showed moderate antiproliferative activity on HH and HaCaT cells.

Liver targeting effect of vinegar-baked Radix Bupleuri on rhein in rats.

Vinegar-baked Radix Bupleuri (VBRB) is usually used to focus other drugs effect on liver in traditional Chinese medicine (TCM). However, no sufficient scientific data are available to support this concept. In this paper, the liver targeting enhancing effect of VBRB on rhein was investigated. 432 of rats were divided into two large groups according to the dose of rhein, low dose group of rhein (LDGR) and high dose group of rhein (HDGR). In each group, the rats were further divided into four subgroups, rhein control and rhein co-administered with three different doses of VBRB peroral. Concentrations of rhein and its metabolite in different tissues were determined by HPLC. Compared to the control group, VBRB significantly increased the distribution of both rhein and its metabolite in liver and meanwhile decreased their distribution in other tissues, indicating a strong liver targeting enhancing effect. This liver targeting effect of VBRB depended on the dose of VBRB and rhein. Low and high dose of VBRB had a more strong effect than medium dose in HDGR; high dose of rhein was more sensitive than low dose of rhein (P<0.05). Rhein existed in two forms after peroral administration in vivo. It was found that the liver targeting effect of VBRB was more remarkable with the native form of rhein compared to its derivative form. The results of this paper demonstrated that co-administration with VBRB is a simple and efficiencient method for liver targeting therapy, and the meridine guide theory of TCM was credible.