Selection and application of aptamers for p-hydroxybenzyl hydrogen sulfite after Gastrodia elata Bl. fumigated with sulfur.

Gastrodia elata Bl. is a widely used traditional Chinese medicine known for its medicinal properties. However, during the drying process, G. elata is often fumigated with sulfur to prevent corrosion and improve its appearance. Sulfur-fumigation can result in a reduction in the effective components of the herb and can also be hazardous to human health due to the remaining sulfur dioxide. Sulfur-fumigation of G. elata poses a significant challenge to both end-users and researchers. The detection of p-hydroxybenzyl hydrogen sulfite (p-HS) is a useful tool in determining whether G. elata has been fumigated with sulfur. Unfortunately, the current method for detecting p-HS is costly and requires sophisticated instruments. Therefore, there is a need to develop a more cost-effective and user-friendly method for the detection of p-HS. This study utilized the Capture-SELEX technique to screen high-affinity aptamers for p-HS, which were subsequently characterized by isothermal titration calorimetry (ITC). An aptamer sequence (seq 6) with a high affinity of Kd = 26.5 µM was obtained following 8 rounds of selection against p-HS. With the aptamer serving as the recognition element and gold nanoparticles as the colorimetric indicator, a simple and efficient colorimetric sensor was developed for the specific detection of p-HS. This detection method exhibited a limit of detection of 1 µg/ml, while the p-HS recoveries demonstrated a range of between 88.5 % and 105 % for samples of G. elata obtained in the market. In summary, the aptamer exhibited a high affinity for p-HS, and the sensor developed through the use of a colloidal gold detector based on nucleic acid aptamer can be utilized for rapid detection of sulfur-fumigated G. elata. With these findings, this research paper provides valuable scientific insights and highlights significant potential for future studies in this area.

Lack of evolutionary convergence in multiple primary lung cancer suggests insufficient specificity of personalized therapy.

Multiple primary lung cancer (MPLC) is an increasingly prevalent subtype of lung cancer. According to recent genomic studies, the different lesions of a single MPLC patient exhibit functional similarities that may reflect evolutionary convergence. We perform whole-exome sequencing for a unique cohort of MPLC patients with multiple samples from each lesion found. Using our own and other relevant public data, evolutionary tree reconstruction reveals that cancer driver gene mutations occurred at the early trunk, indicating evolutionary contingency rather than adaptive convergence. Additionally, tumors from the same MPLC patient are as genetically diverse as those from different patients, while within-tumor genetic heterogeneity is significantly lower. Furthermore, the aberrant molecular functions enriched in mutated genes for a sample show a strong overlap with other samples from the same tumor, but not with samples from other tumors or other patients. Overall, there is no evidence of adaptive convergence during the evolution of MPLC. Most importantly, the similar between-tumor diversity and between-patient diversity suggest that personalized therapies may not adequately account for the genetic diversity among different tumors in an MPLC patient. To fully exploit the strategic value of precision medicine, targeted therapies should be designed and delivered on a per-lesion basis.

[Efficacy of Oral Cyclophosphamide for Treatment of Refractory T-cell Large Granular Lymphocytic Leukemia Accompanied with Pure Erythrocyte Aplastic Anemia].

OBJECTIVE: To explore the clinical effects of oral small dose of cyclophosphamide (CTX) in the treatment of T-cell large granular lymphocytic leukemia (T-LGLL) accompanied with pure red cell aplasia (PRCA). METHODS: The clinical features, characteristics of laboratory examinations and the process of oral small dose of CTX treatment after the ineffective treatment of cyclosporine A combining with prednisone in 1 case of T-LGLL with PRCA were reported and discussed with related references. RESULTS: The elderly female patient had indolent process, mainly presenting with anemia and significant low hyperplasia of bone marrow erythrocyte cells. Peripheral blood smear showed mainly with characteristic large granular lymphocytic morphology. The results of immunophenotypic analyses and genetic reassortment were compatible with T-LGLL. No effects were shown after 5 months of cyclosporine A combining with prednisone treatment and the patient still needed recurrent blood transfusion. CTX was prescribed as a second-line medication and the dose was 100 mg/d. Hemoglobin could returned to normal level and the efficacy remained for 1 year even after the medication was stopped. CONCLUSION: T-LGLL accompanied with PRCA is a rare disease and oral small dose CTX can be an effective therapeutic regimen.

Anthracycline dose optimisation in patients with diffuse large B-cell lymphoma: a multicentre, phase 3, randomised, controlled trial.

BACKGROUND: Anthracycline dose optimisation in the treatment of diffuse large B-cell lymphoma has rarely been tested. We aimed to find out whether R-CEOP70 was non-inferior to R-CHOP50 with less cardiotoxicity, and whether R-CEOP90 had a superior efficacy to R-CHOP50 or R-CEOP70 with acceptable toxic effects. METHODS: In this multicentre, phase 3, randomised, controlled study (NHL-001), patients with newly diagnosed diffuse large B-cell lymphoma or follicular lymphoma grade 3B were enrolled from 20 centres of the Multicenter Hematology-Oncology Programs Evaluation System in China. Young patients (16-60 years) were randomly assigned 1:1:1 (block size of six) to six courses of R-CHOP50, R-CEOP70, or R-CEOP90, and older patients (61-80 years) were assigned 1:1 (block size of four) to R-CHOP50 or R-CEOP70. Patients were randomly assigned using computer-assisted permuted-block randomisation. Investigators and patients were not masked to treatment assignment. In the R-CHOP50 group, patients were given rituximab 375 mg/m2 intravenously on day 0, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 (maximum dose 2 mg) intravenously on day 1, and prednisone 60 mg/m2 (maximum dose 100 mg) orally from day 1-5; in the R-CEOP70 group, epirubicin 70 mg/m2 replaced doxorubicin; and in the R-CEOP90 group, high dose epirubicin 90 mg/m2 replaced doxorubicin. All patients received two additional courses of rituximab 375 mg/m2 intravenously every 21 days. Consolidation radiotherapy was given to patients with bulky disease at diagnosis or residual disease at the end of treatment. The primary endpoint was 2-year progression-free survival. The non-inferiority margin for R-CEOP70 versus R-CHOP50 was defined by hazard ratio [HR] as the upper limit of its 95% CI being no greater than 1·50. Analysis of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01852435. FINDINGS: From May 15, 2013, to March 16, 2016, a total of 648 patients were enrolled, including 404 (62%) young patients (R-CHOP50 [n=135], R-CEOP70 [n=134], or R-CEOP90 [n=135]), and 244 (38%) older patients (R-CHOP50 [n=122] or R-CEOP70 [n=122]). Four patients were excluded from the study for consent withdrawal and one patient for misdiagnosis before treatment. The 2-year progression-free survival in the R-CHOP50 group was 72·5% (95% CI 66·6-77·6) and in the R-CEOP70 group was 72·4% ([66·5-77·5]; HR 1·00 [0·73-1·38]; p=0·99). The non-inferiority was met and adverse events were similar between the two groups. Fewer patients in the R-CEOP70 group (14 [13%] of 110) presented with over 10% decrease in left ventricular ejection fraction (LVEF) than those in the R-CHOP50 group (31 [29%] of 108) at 3 years after remission. For young patients, the 2-year progression-free survival in the R-CEOP90 group was 88·8% (82·1-93·1) and was significantly improved compared with the R-CHOP50 group (75·9% [67·7-82·3]; 0·44 [0·25-0·76]; p=0·0047) and the R-CEOP70 group (77·4% [69·4-83·7%]; 0·49 [0·27-0·86]; p=0·017). Grade 3-4 neutropenia occurred more frequently in the R-CEOP90 group (97 [72%] of 134) than in the R-CHOP50 group (87 [65%] of 133) and R-CEOP70 group (84 [63%] of 133) in young patients but without further increase of clinically significant infections. Fewer patients in the R-CEOP70 group (7 [11%] of 66) and in the R-CEOP90 group (10 [13%] of 79) presented with more than 10% decrease in LVEF than those in the R-CHOP50 group (17 [26%] of 66) at 3 years after remission. INTERPRETATION: R-CEOP70 could serve as an alternative regimen to R-CHOP50 with mild long-term cardiotoxicity. Young patients with diffuse large B-cell lymphoma might benefit from high-dose epirubicin. Epirubicin is an alternative drug to doxorubicin in regular R-CHOP with mild long-term cardiotoxicity. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program, Shanghai Commission of Science and Technology, Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support, Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine, Clinical Research Plan of Shanghai Hospital Development Center, and Chang Jiang Scholars Program.

[Effects of IFN-γ on Pulmonary GVHD after Allo-Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To explore the effects of IFN-γ on pulmonary GVHD after hematopoietic stem cell transplantation (HSCT). METHODS: The mouse GVHD models were established by using C57BL/6J, B6D2F1 mice and different HSCT. According to HSCT modes, the mice were divided into 3 groups: syngeneic HSCT group(C57BL/6J→C57BL/6J), allogeneic HSCT group (C57BL/6J→B6D2F1) and IFN-γ -/- allogeneic HSCT group (IFN-γ -/-→C57BL/6J→B6D2F1). The survival time, GVHD clinical seore, pulmonary pathologic changes in 3 groups were compared and analyzed, and the total cell count in BALF and IFN-γ level in serum were detected in 3 groups after transplantation. RESULTS: The mice in syngeneic HSCT group all survived at day 42 after transplantation without GVHD symptoms in lung, the GVHD clinical score was low. The mice in allogeneic HSCT group survived at day 24 after transplantation (survial rate >50%), the GVHD clinical score was higher than that in syngeneic HSCT group, the pathologic changes in lung did not serious, though the GVHD presentation was observed, but the olveola bleeding and lymphocyte infiltration in lung tissue were observed at day 28 after transplantation. The mice in IFN-γ -/- allogeneic HSCT group all died of lethal GVHD within 14 days after transplantation, the GVHD clinical score reached to 6.7± 0.83 at 1st week after tansplantation, which was significantly higher than that in syngeneic and allogeneic HSCT groups. At 1st week after transplantation, the serious GVHD pathological changes occured in lung tissue, total cell count in BALF significanty increased, compared with syngeneic and allogeneic HSCT groups, but IFN-γ level in serum was significantly lower than that in syngeneic and allogeneic HSCT groups (P<0.05). CONCLUSION: Donor-derived IFN-γ plays an important immunoprotective role for lung tissue after HSCT.