Treatment of myelofibrosis with refractory anemia with luspatercept: a multicenter Chinese study.

Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44-80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4-16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance.

[Research advances of chemical constituents and analytical methods of Citri Reticulatae Pericarpium Viride and Citri Reticulatae Pericarpium].

Citri Reticulatae Pericarpium Viride(CRPV) and Citri Reticulatae Pericarpium(CRP) are two commonly used Chinese medicinal materials. They have the same origin while are harvested in different seasons and have different clinical effects. They contain similar chemical components, like flavonoids, terpenes, volatile oils, and alkaloids. Although it has been demonstrated that differential components exist between them, there is still a lack of systematic comparison. Many studies have reported the chemical composition and quality evaluation of CRPV and CRP, including the characterization of flavonoids, alkaloids, and volatile oils via thin-layer chromatography, high-performance liquid chromatography, gas chromatography, infrared spectroscopy, and ultraviolet spectroscopy. A few studies have explored the differences between CRPV and CRP. In this paper, we systematically summarized the reported chemical composition, analytical methods, and quality evaluation of CRPV and CRP in recent ten years, aiming to facilitate the research on the pharmacodynamic material basis, quality evaluation, and standard improvement of CRPV and CRP.

Endoscopic ultrasound features of rectal melanoma: A case report and review of literature.

BACKGROUND: Rectal mucosal melanoma is a rare and highly aggressive disease. Common symptoms include anal pain, an anal mass, or bleeding. As such, the disease is usually detected on rectal examination of patients with other suspected anorectal diseases. However, due to its rarity and nonspecific symptoms, melanoma of the rectal mucosa is easily misdiagnosed. CASE SUMMARY: This report describes the case of a 58-year-old female patient who presented with a history of blood in her stool for the prior one or two months, without any identifiable cause. During colonoscopy, a bulge of approximately 2.2 cm × 2.0 cm was identified. Subsequently, the patient underwent endoscopic ultrasound (EUS) to characterize the depth of invasion of the lesions. EUS suggested a hypoechoic mucosal mass with involvement of the submucosal layer and heterogeneity of the internal echoes. Following surgical intervention, the excised tissue samples were examined and confirmed to be rectal malignant melanoma. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION: This case shows that colonoscopy with EUS and pathological examination can accurately diagnose rare cases of rectal mucosal melanoma.

Exogenous plant growth regulator alleviate the adverse effects of U and Cd stress in sunflower (Helianthus annuus L.) and improve the efficacy of U and Cd remediation.

Plant growth regulators (PGRs) are widely used in agricultural activities and have the potential to improve plant growth and plant tolerance against metal stress. PGR-assisted phytoextraction is now an effective and inexpensive method for enhancing the plant removal of toxic metals from soil. In this study, we conducted experiments to determine the effects of PGR treatments on soil uranium (U) and cadmium (Cd) removal by sunflowers as well as their stress response to U and Cd contamination. We found that the plant growth was inhibited by combined U and Cd stress in sunflowers compared with that of the control; however, the application of exogenous PGR had reduced the combined U and Cd stress by stimulating photosynthesis, decreasing the levels of active oxygen and lipid peroxidation, and enhancing the activity of the antioxidant defence systems. Exogenous PGR also increased the uptake of U and Cd by sunflowers and therefore, improved their U and Cd remediation efficiency. Moreover, indoleacetic acid (IAA) was the most effective PGR at removing U and Cd in the soil; the U and Cd removal efficiency was 484.21% and 238.85% higher in the 500 mg L-1 IAA application compared with that of the control without PGR application, respectively. Furthermore, none of the PGR treatments significantly influenced the available U and Cd contents in soil. Our results, therefore, may provide some detailed understanding on the technologies for the sustainable remediation of U and Cd contaminated soil by the combination of PGR treatments and phytoextraction.

Phytoremediation of cadmium (Cd) and uranium (U) contaminated soils by Brassica juncea L. enhanced with exogenous application of plant growth regulators.

This investigation was made to examine the role of indole-3-acetic acid (IAA), gibberellin A3 (GA3), 6-Benzylaminopurine (6-BA), and 24-epibrassinolide (EBL) in improving stress tolerance and phytoremediation of the cadmium (Cd) and uranium (U) by mustard (Brassica juncea L.). The optimum concentrations of IAA, GA3, 6-BA, and EBL were determined based on plant biomass production, metal uptake, translocation, and removal efficiency. The biomass and total chlorophyll content decreased under Cd and U stress. Nevertheless, the application of IAA, GA3, and 6-BA significantly (p < 0.05) increased the growth and total chlorophyll content of mustard. The malondialdehyde (MDA) and H2O2 content of mustard were enhanced under Cd and U stress, but they were significantly (p < 0.05) decreased in plant growth regulators (PGRs) treatments (except for EBL). PGRs treatments increased activities of antioxidant enzymes such as superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase, thus reducing the oxidative stress. Furthermore, the shoot uptake of Cd and U of IAA and EBL treatments was significantly (p < 0.05) higher than that of other treatments. IAA and EBL also have more significant effects on the translocation and remediation of Cd and U compared to GA3 and 6-BA. The removal efficiency of Cd and U reached the maximum in the 500 mg L-1 IAA treatment, which was 330.77% and 118.61% greater than that in the control (CK), respectively. These results suggested that PGRs could improve the stress tolerance and efficiency of phytoremediation using B. juncea in Cd- and U- contaminated soils.

[Expression of DLK1 gene in acute leukemias and its function in erythroid differentiation of K562 cell line].

OBJECTIVE: To determine the expression of DLK1 gene in acute leukemias (AL) and its function in erythroid differentiation of K562 cells. METHODS: We detected the expression of DLK1 gene in 65 different acute leukemia categories (a test group) and 34 normal bone marrow controls (a control group) with RT-PCR. DLK1 protein in 20 out of the 65 AL patients and 13 of the 34 controls was assayed by Western blot. The K562 cell line was induced to erythroid differentiation by hemin. We observed the relationship between its expression and erythroid differentiation. RESULTS: Both leukemia cells and normal marrow cells expressed DLK1. The expression of DLK1 mRNA in patients in the test group was higher than that in the control group (P=0.018), while there was no significance between acute lymphoblastic leukemia and acute myelogenous leukemia (P>0.05).The expression of DLK1 mRNA in the test group at onset had no relation with the WBC and platelet count in the total peripheral blood, and the same was true for blast cell rates in bone marrow cells.The level of DLK1 protein in the test group was higher than that in the control group, which was consistent with the mRNA expression (P=0.042). The expression of DLK1 mRNA decreased gradually with K562 cells towards hemin-induced erythroid differentiation. CONCLUSION: DLK1 gene may be involved in leukemia,but the mRNA level of DLK1 has no relation with some clinical characteristics of AL patients at onset. DLK1 may inhibit the erythroid differentiation of K562 cells.

Effect of biodegradable chelators on induced phytoextraction of uranium- and cadmium- contaminated soil by Zebrina pendula Schnizl.

This study investigated the effect of ethylenediamine-N,N'-disuccinic acid (EDDS), oxalic acid (OA), and citric acid (CA) on phytoextraction of U- and Cd-contaminated soil by Z. pendula. In this study, the biomass of tested plant inhibited significantly following treatment with the high concentration (7.5 mmol·kg-1) EDDS treatment. Maximum U and Cd concentration in the single plant was observed with the 5 mmol·kg-1 CA and 7.5 mmol·kg-1 EDDS treatment, respectively, whereas OA treatments had the lowest U and Cd uptake. The translocation factors of U and Cd reached the maximum in the 5 mmol·kg-1 EDDS. The maximum bioaccumulation of U and Cd in the single plants was 1032.14 µg and 816.87 µg following treatment with 5 mmol·kg-1 CA treatment, which was 6.60- and 1.72-fold of the control groups, respectively. Furthermore, the resultant rank order for available U and Cd content in the soil was CA > EDDS > OA (U) and EDDS > CA > OA (Cd). These results suggested that CA could greater improve the capacity of phytoextraction using Z. pendula in U- and Cd- contaminated soils.

The role of lenvatinib in the era of immunotherapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) frequently presents as advanced stage with poor prognosis and high mortality. Systemic treatment is the treatment of choice for advanced disease. In 2007, the first multi-kinase inhibitor (MKI) sorafenib was approved and shown to modestly prolong overall survival (OS). The progress of systemic therapy has been slow afterwards until 2018 when lenvatinib, another MKI, was shown to be non-inferior to sorafenib on median OS as the first-line therapy for HCC. Since then, remarkable progress has been achieved on the treatment of advanced HCC, including the development of second-line targeted treatment, including regorafenib, cabozantinib and ramucirumab from 2017 to 2019. A growing focus has been placed on immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4. These ICIs have proven their potency in treating HCC as both initial and subsequent line of therapy. At present, both regimens of atezolizumab combined with bevacizumab, as well as the combination of tremelimumab and durvalumab, are recommended as the first-line treatments based on positive phase III clinical trials. With the advancement of ICIs, it is anticipated that the role of MKIs in the treatment of HCC will evolve. In this article, lenvatinib, one of the most commonly used MKIs in HCC, is chosen to be reviewed.

Chiral separation methods and the applications in the study of chiral components of traditional Chinese medicines / 药学学报

Chirality is one of the fundamental properties of nature, and most of the important molecules in living organisms contain chiral structures. The efficacy and safety of drugs are often closely related to the chiral structure of compounds, however, there are relatively more studies on synthetic characterization, pharmacology, and toxicology of chiral small molecule chemical drugs, but relatively less studies on chiral compounds contained in natural drugs such as traditional Chinese medicines. Chiral separation, as the basis of chiral research, has a pivotal position in the study of chiral compounds. In this paper, we systematically describe the separation methods of chiral compounds from the classification of chiral splitting methods based on chromatographic and non-chromatographic methods, as well as chromatographic packing materials, chiral additives and chiral derivatization, and review the chiral compounds in natural drugs such as traditional Chinese medicines reported in the past ten years, in order to provide references for the splitting and evaluating the activity of chiral compounds, and the improvement of quality standards of traditional Chinese medicines.

Desorption electrospray ionization-mass spectrometry in the analysis of natural medicines / 药学学报

Desorption electrospray ionization mass spectrometry (DESI-MS) is a newly emerging in-situ ionization mass spectrometry analysis technology. The ionization process occurs in an open ambient environment at atmospheric pressure, and has the characteristics of simple sample pretreatment, quick and sensitive analysis, and is widely used in biomedicine, pharmaceutical analysis, food safety, environmental monitoring, and material characterization. Natural medicines, such as Chinese herbal medicines, contain a variety of chemical components. Extraction, separation, identification, and in vitro and in vivo efficacy evaluation of natural medicines, especially research on active ingredients with significant efficacy, have received long-term attention. The development of DESI-MS technology provides many new opportunities for direct and rapid analysis of active ingredients in natural medicines. This article briefly introduces the principles, characteristics, influencing factors, and technical progress of DESI-MS technology, and systematically summarizes progress in the research and application of this technology to natural medicines such as Chinese herbal medicines and other plant samples with pharmacological activity. The future application prospects in this field are further presented.

The role of circulating adiponectin in prostate cancer: a meta-analysis.

PURPOSE: Emerging evidence suggests that adiponectin may play a protective role in tumor progression and prognosis. However, available evidence in prostate cancer is conflicting. Therefore, we carried out a meta-analysis to evaluate the role of circulating adiponectin and prostate cancer. METHODS AND RESULTS: An extensive search was performed on Google, PubMed, Elsevier Science and Springer from the date of the inception of those services to December 2013. Eleven studies with 2,504 patients and 3,565 controls concerning this association were included in our analysis. Standard mean difference (SMD) with 95% confidence intervals (95% CIs) was used to estimate this association. The pooled analysis showed that circulating adiponectin concentrations were lower in patients with prostate cancer than controls, with a pooled SMD of -0.893 µg/mL (95% CI, -1.345 to -0.440, p=0.000). Dose-response relationships between concentrations of adiponectin and risk of prostate cancer were evaluated. We found that decreased concentrations of adiponectin were associated with a significantly greater risk of prostate cancer (p for nonlinearity = 0.043). CONCLUSIONS: The results of our analysis indicated that concentration of adiponectin in cancer patients was significantly lower than in controls. Thus, adiponectin may serve as a potential biomarker for early diagnosis of this disease. We also found that decreased concentration of adiponectin was associated with a significantly greater risk of prostate cancer. However, more studies in future, especially larger, prospective studies, are needed to confirm this association with underlying biological mechanisms.

Preparation of melanin from Catharsius molossus L. and preliminary study on its chemical structure.

A great deal of melanin was found in the waste alkali liquor produced by extraction of chitin from Catharsius molossus L. Discarding the lye could harm the environment and cause waste of resources. In this paper, melanin from C. molossus L. was recovered through acid precipitation and purified by pepsin and so on. The purity, chemical composition and structure of the prepared melanin were explored by UV-visible absorption spectroscopy, Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, high resolution (13)C Cross polarization magic angle spinning nuclear magnetic resonance spectroscopy pyrolysis gas chromatography mass spectrometry, X ray diffraction, X ray fluorescence, matrix-assisted laser desorption/ionization time of flight tandem mass spectrometry, thermal analysis, and so on. The results showed that the purity of the prepared melanin was higher than the commercial standard melanin and it was a kind of nanoaggregates composed of a large quantity of 5,6-dihydroxyindole eumelanin and a small amount of phaeomelanin. In addition, the prepared melanin was irregular in shape and its structure could be divided into three levels: advanced structure maintained by polypeptides, substructure maintained by the ferric ion and microstructure. In particular, the smallest structural unit showed the graphite-like layered structure containing five layers linked by non-covalent bonds and each layer mainly consisted of 5,6-dihydroxyindole and its derivatives, which might be connected to each other through various chemical bonds.