A pumpless liver-on-a-chip for drug hepatotoxicity analysis.

This study presents the development and validation of an innovative microfluidic liver-on-a-chip device utilizing gravity-driven perfusion for the evaluation of drug hepatotoxicity. This research involved the construction of a hydrogel-based coculture chip that integrates liver parenchymal and stellate cells within a tri-channel configuration. The assembly and operation of the liver-on-a-chip and its accompanying custom rocker were straightforward. The cells in the chip maintained high viability and continuously synthesized liver albumin over extended culture durations. Acetaminophen (APAP), a hepatic injury-inducing drug, was utilized as a positive control in hepatic toxicity assays on the chip. The liver chip exhibited hepatotoxic responses comparable to those observed in 2D models. Furthermore, in this study we evaluated the effects of two plant-derived natural compounds, aristolochic acid I (AA) and its analog aristolactam AII (AL), in both 2D cell models and the liver-on-a-chip system. AA, known for its hepatorenal toxicity, was observed to cause hepatotoxicity in both the 2D models and on the chip. The flow cytometry and mRNA sequencing results confirmed the propensity of these compounds to induce liver cell apoptosis. Notably, AL, previously considered nontoxic, provoked a significant decrease in the hepatic functionality marker albumin exclusively in the liver chip but not in 2D models, indicating the liver chip's enhanced sensitivity to toxic substances. In summary, this pumpless liver-on-a-chip is a simple yet powerful tool for drug hepatotoxicity studies.

Modulating the Gut Microbiota and Metabolites with Traditional Chinese Medicines: An Emerging Therapy for Type 2 Diabetes Mellitus and Its Complications.

Currently, an estimated 537 million individuals are affected by type 2 diabetes mellitus (T2DM), the occurrence of which is invariably associated with complications. Glucose-lowering therapy remains the main treatment for alleviating T2DM. However, conventional antidiabetic agents are fraught with numerous adverse effects, notably elevations in blood pressure and lipid levels. Recently, the use of traditional Chinese medicines (TCMs) and their constituents has emerged as a preferred management strategy aimed at curtailing the progression of diabetes and its associated complications with fewer adverse effects. Increasing evidence indicates that gut microbiome disturbances are involved in the development of T2DM and its complications. This regulation depends on various metabolites produced by gut microbes and their interactions with host organs. TCMs' interventions have demonstrated the ability to modulate the intestinal bacterial microbiota, thereby restoring host homeostasis and ameliorating metabolic disorders. This review delves into the alterations in the gut microbiota and metabolites in T2DM patients and how TCMs treatment regulates the gut microbiota, facilitating the management of T2DM and its complications. Additionally, we also discuss prospective avenues for research on natural products to advance diabetes therapy.

[Characteristics of resting energy expenditure and evaluation of prediction formulas in young men with different body mass indexes].

OBJECTIVE: To compare the resting energy expenditure (REE) characteristics among young men with different body mass indexes (BMI). METHODS: Thirty young men [average age was (26.93±4.16) years] were enrolled in this study. They underwent resting metabolism tests in the Department of Sports Medicine of Peking University Third Hospital from December 2017 to June 2021. The resting metabolic rate (RMR) was measured by indirect calorimetry, the body composition was measured by bioresistance antibody component analyzer. The REE characteristics were analyzed, and 11 predictive equations were used to estimate RMR and compared with the measured value. The differences were analyzed by paired t-test and intra-class correlation coefficient (ICC). RESULTS: The RMR of the overall 30 young men was (1 960.17±463.11) kcal/d (1 kcal=4.186 8 kJ). Including (1 744.33±249.62) kcal/d in those with normal BMI, which was significantly lower than that in those who were overweight or obese [(2 104.06± 520.32) kcal/d, P < 0.01], but the weight-corrected RMR in those with normal BMI was significantly higher than that in those who were overweight or obese [(24.02±2.61) kcal/(kg·d) vs. (19.98±4.38) kcal/(kg·d), P < 0.01]. The RMR was significantly and positively correlated with body weight, adiposity, lean body mass, body surface area, and extracellular fluid in the subjects with diffe-rent BMI (all P < 0.05). The predicted values of the 11 prediction equations were not in good agreement with the measured values (all ICC < 0.75), with relatively high agreement between the predicted and measured values of the World Health Organization (WHO) equation in overweight obese young men (ICC=0.547, P < 0.01). CONCLUSION: There were significant differences in RMR among young men with different BMI, and the RMR after weight correction should be considered for those who were overweight or obese. The consistency between the predicted values of different prediction equations and the actual measured values of RMR was relatively poor, and it is recommended to accurately measure RMR by indirect calorimetry. For overweight or obese young men, the WHO prediction equation can be considered to calculate RMR, but it is necessary to establish an RMR prediction equation applicable to different BMI populations.

Tailoring the Position of Ester Group on N-Alkyl Chains of Benzotriazole-based Small Molecule Acceptors for High-Performance Organic Solar Cells.

Side chain engineering plays a vital role in exploring high-performance small molecule acceptors (SMAs) for organic solar cells (OSCs). In this work, we designed and synthesized a series of A-DA'D-A type SMAs by introducing different N-substituted alkyl and ester alkyl side chains on benzotriazole (BZ) central unit and aimed to investigate the effect of different ester substitution positions on photovoltaic performances. All the new SMAs with ester groups exhibit lower the lowest unoccupied molecular orbital (LUMO) energy levels and more blue-shifted absorption, but relatively higher absorption coefficients than alkyl chain counterpart. After blending with the donor PM6, the ester side chain-based devices demonstrate enhanced charge mobility, reduced amorphous intermixing domain size and long-lived charge transfer state compared to the alkyl chain counterpart, which are beneficial to achieve higher short-circuit current density (Jsc ) and fill factor (FF), simultaneously. Thereinto, the PM6 : BZ-E31 based device achieves a higher power conversion efficiency (PCE) of 18.33 %, which is the highest PCE among the OSCs based on the SMAs with BZ-core. Our work demonstrated the strategy of ester substituted side chain is a feasible and effective approach to develop more efficient SMAs for OSCs.

Stabilized Carbon-Centered Radical-Mediated Carbosulfenylation of Styrenes: Modular Synthesis of Sulfur-Containing Glycine and Peptide Derivatives.

Sulfur-containing amino acids and peptides play critical roles in organisms. Thiol-ene reactions between the thiol residues of L-cysteine and the alkenyl fragments in the designed coupling partners serve as primary tools for constructing C─S bonds in the synthesis of unnatural sulfur-containing amino acid derivatives. These reactions are favored due to the preference for hydrogen transfer from thiol to ß-sulfanyl carbon radical intermediates. In this paper, the study proposes utilizing carbon-centered radicals stabilized by the capto-dative effect, generated under photocatalytic conditions from N-aryl glycine derivatives. The aim is to compete with the thiol hydrogen, enabling radical C─C bond formation with ß-sulfanyl carbon radicals. This protocol is robust in the presence of air and water, offers significant potential as a modular and efficient platform for synthesizing sulfur-containing amino acids and modifying peptides, particularly with abundant disulfides and styrenes.

Reductive Radical-Polar Crossover Enabled Carboxylative Alkylation of Aryl Thianthrenium Salts with CO2 and Styrenes.

Carboxylic functionalities are among the pivotal groups in bioactive molecules and in the synthesis of new lead compounds because of their unique character in the formation of hydrogen bonds and the possibility of constructing molecular complexes via amide couplings. We adopt the reductive radical-polar crossover strategy to introduce carboxyalkyl groups into arenes with styrenes and CO2 via thianthrenium salts. This protocol exhibits excellent potential as a straightforward and modular platform for site-selective carboxylative derivation of bioactive molecules.

Engineered M2 macrophage-derived extracellular vesicles with platelet membrane fusion for targeted therapy of atherosclerosis.

Atherosclerosis is featured as chronic low-grade inflammation in the arteries, which leads to the formation of plaques rich in lipids. M2 macrophage-derived extracellular vesicles (M2EV) have significant potential for anti-atherosclerotic therapy. However, their therapeutic effectiveness has been hindered by their limited targeting capability in vivo. The objective of this study was to create the P-M2EV (platelet membrane-modified M2EV) using the membrane fusion technique in order to imitate the interaction between platelets and macrophages. P-M2EV exhibited excellent physicochemical properties, and microRNA (miRNA)-sequencing revealed that the extrusion process had no detrimental effects on miRNAs carried by the nanocarriers. Remarkably, miR-99a-5p was identified as the miRNA with the highest expression level, which targeted the mRNA of Homeobox A1 (HOXA1) and effectively suppressed the formation of foam cells in vitro. In an atherosclerotic low-density lipoprotein receptor-deficient (Ldlr-/-) mouse model, the intravenous injection of P-M2EV showed enhanced targeting and greater infiltration into atherosclerotic plaques compared to regular extracellular vesicles. Crucially, P-M2EV successfully suppressed the progression of atherosclerosis without causing systemic toxicity. The findings demonstrated a biomimetic platelet-mimic system that holds great promise for the treatment of atherosclerosis in clinical settings.

Identification and quantification of micro-nano-plastics in polypropylene-bottled injections.

Micro-nano-plastic (MNP) particles (p) in the environment can enter the human body and pose a potential threat to human health. However, it is unknown whether these substances are present in polypropylene (PP) plastic-bottled injections, which are used as high-frequency intravenous infusions to treat diseases. Therefore, the objective of this study was to identify and quantify insoluble MNP particles in 16 batches of injectable formulations within the validity period. Primarily, ethylene-propylene copolymer or P(E-P) micro-plastic (MP) particles (2-10 µm, 216 p/mL) were identified by micro-Raman spectroscopy, and nano-particles (<50 nm, 2.1 × 104 p/mL) similar to PP containing only carbon were detected by scanning electron microscopy-energy-dispersive X-ray spectroscopy (photoelectron). Furthermore, P(E-P) MP particles (1 × 103 to 1 × 105 ng/L) from the injections were enriched on the GF-B filter, and PP or P(E-P) nano-plastic (NP) particles (1 × 103 to 4 × 104 ng/L) enriched on the alumina film were detected by pyrolysis-gas chromatography/mass spectrometry. Finally, the total insoluble particles in injections were 6 × 104 to 1 × 107 p/mL (0.02-100 µm). Our findings are the first to identify and quantify MNPs in PP-bottled injections. Considering that they can enter the blood circulation, so whether cause disease remains to be investigated.

Effects of concentrate feeding sequence on VFA production, and cecal microbiota of Dezhou donkeys by metagenomic technology.

Microorganisms residing in the cecum of donkeys are crucial for physiological processes, nutrient metabolism, and immune function. Feeding methods can affect the dynamic balance of animal gut microbiota, thereby affecting indicators such as volatile fatty acids. This study explores suitable feeding methods to promote actual production by changing the feeding order of concentrate. Fifteen Dezhou donkeys with similar age and weight profiles were randomly divided into three groups with the concentrate feeding sequence: fiber-to-concentrate (FC), concentrate-to-fiber (CF), and total mixed ration (TMR). The experiment spanned a duration of 82 days. The analyses conducted were primarily aimed at determining the effects of feeding on gut microbes, primarily using metagenomic sequencing techniques. The experimental findings revealed that the levels of valeric acid were notably higher in the CF and TMR groups compared to the FC group (p < 0.05). These results suggest that the feeding sequence exerts a certain impact on the microbial composition within the cecum of Dezhou donkeys. At the phylum level, the predominant microbiota consisted of Firmicutes and Bacteroidetes, with the CF group displaying a higher relative abundance of Firmicutes compared to both the FC and TMR groups. At the genus level, Prevotella, Bacteroides, and Fibrobacter were the dominant bacterial genera identified in cecum. The functional gene annotation analysis indicated a significantly lower abundance of lacZ (K01190), Por/nifJ (K03737), and ppdK (K01006) genes in CF group relative to the FC and TMR groups (p < 0.05), highlighting their roles in galactose metabolism and glycolysis, respectively. Moreover, the CF group exhibited a higher concentration of antibiotic resistance genes (tetO and tet44) in the gut microbiota compared to the TMR and FC groups (p < 0.05), underscoring the presence of numerous antibiotic resistance genes within the phyla Bacteroidetes, Firmicutes, and Proteobacteria. In conclusion, different precision feed sequences significantly impact the levels of volatile fatty acids in Dezhou fattening donkeys, modify the composition and functional genes of the cecal microbiota, and elucidate the microbial mechanisms influenced by the feeding sequence on the growth and metabolism. These insights are anticipated to provide a foundation for the rational design of precision feed sequences in practical agricultural settings.

Artificial Phages with Biocatalytic Spikes for Synergistically Eradicating Antibiotic-Resistant Biofilms.

Antibiotic-resistant pathogens have become a global public health crisis, especially biofilm-induced refractory infections. Efficient, safe, and biofilm microenvironment (BME)-adaptive therapeutic strategies are urgently demanded to combat antibiotic-resistant biofilms. Here, inspired by the fascinating biological structures and functions of phages, the de novo design of a spiky Ir@Co3O4 particle is proposed to serve as an artificial phage for synergistically eradicating antibiotic-resistant Staphylococcus aureus biofilms. Benefiting from the abundant nanospikes and highly active Ir sites, the synthesized artificial phage can simultaneously achieve efficient biofilm accumulation, extracellular polymeric substance (EPS) penetration, and superior BME-adaptive reactive oxygen species (ROS) generation, thus facilitating the in situ ROS delivery and enhancing the biofilm eradication. Moreover, metabolomics found that the artificial phage obstructs the bacterial attachment to EPS, disrupts the maintenance of the BME, and fosters the dispersion and eradication of biofilms by down-regulating the associated genes for the biosynthesis and preservation of both intra- and extracellular environments. The in vivo results demonstrate that the artificial phage can treat the biofilm-induced recalcitrant infected wounds equivalent to vancomycin. It is suggested that the design of this spiky artificial phage with synergistic "penetrate and eradicate" capability to treat antibiotic-resistant biofilms offers a new pathway for bionic and nonantibiotic disinfection.

The emerging therapies are reshaping the first-line treatment for advanced hepatocellular carcinoma: a systematic review and network meta-analysis.

Background: Given the superior performance of various therapies over sorafenib in advanced hepatocellular carcinoma (HCC) and the absence of direct comparisons, it is crucial to explore the efficacy of these treatments in phase III randomized clinical trials. Objectives: The goal is to identify which patients are most likely to benefit significantly from these emerging therapies, contributing to more personalized and informed clinical decision-making. Design: Systematic review and network meta-analysis. Data sources and methods: PubMed, Embase, ClinicalTrials.gov, and international conference databases have been searched from 1 January 2010 to 1 December 2023. Results: After screening, 17 phase III trials encompassing 18 treatments were included. In the whole-population network meta-analysis, the newly first-line tremelimumab plus durvalumab (Tre + Du) was found to be comparable with atezolizumab plus bevacizumab (Atezo + Beva) in providing the best overall survival (OS) benefit [hazard ratio (HR) 1.35, 95% confidence interval (CI): 0.93-1.92]. Concerning OS benefits, sintilimab plus bevacizumab biosimilar (Sint + Beva), camrelizumab plus rivoceranib (Camre + Rivo), and lenvatinib plus pembrolizumab (Lenva + Pemb) appear to exhibit similar effects to Tre + Du and Atezo + Beva. In the context of progression-free survival, Atezo + Beva seemed to outperform Tre + Du (HR: 0.66 CI: 0.49-0.87), while the effects are comparable to Sint + Beva, Camre + Rivo, and Lenva + Pemb. Upon comparison between Asia-Pacific and non-Asia-Pacific cohorts, as well as between hepatitis B virus (HBV)-infected and non-HBV-infected populations, immune checkpoint inhibitor (ICI)-based treatments seemed to exhibit heightened efficacy in the Asia-Pacific group and among individuals with HBV infection. However, combined ICI-based therapies did not show more effectiveness than molecular-targeted drugs in patients without macrovascular invasion and/or extrahepatic spread. As for grades 3-5 adverse events, combined therapies showed comparable safety to sorafenib and lenvatinib. Conclusion: Compared with sorafenib and lenvatinib, combination therapies based on ICIs significantly improved the prognosis of advanced HCC and demonstrated similar safety. At the same time, the optimal treatment approach should be tailored to individual patient characteristics, such as etiology, tumor staging, and serum alpha-fetoprotein levels. With lower incidence rates of treatment-related adverse events and non-inferior efficacy compared to sorafenib, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI-combined therapies. Trial registration: PROSPERO, CRD42022288172.

Lay summary/Key points The efficiency of various systemic therapies in advanced HCC patients with specific characteristics remains to be explored. This study revealed that the efficacy of ICI combined therapies is influenced by factors such as tumor staging, etiology, patient demographics, and more. Additionally, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI combined therapies. Complementing to recent guidelines, this study indicated that several critical factors needed to be took into consideration for patients with advanced HCC.

Enhancing aortic valve drug delivery with PAR2-targeting magnetic nano-cargoes for calcification alleviation.

Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells. Accordingly, we develop a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide for dual-active targeting drug delivery. We show that the nanocarriers effectively deliver XCT790-an anti-calcification drug-to the calcified aortic valve under extra magnetic field navigation. We demonstrate that the nano-cargoes consequently inhibit the osteogenic differentiation of valvular interstitial cells, and alleviate aortic valve calcification and stenosis in a high-fat diet-fed low-density lipoprotein receptor-deficient (Ldlr-/-) mouse model. This work combining PAR2- and magnetic-targeting presents an effective targeted drug delivery system for treating calcific aortic valve disease in a murine model, promising future clinical translation.

The Research Field of Meat Preservation: A Scientometric and Visualization Analysis Based on the Web of Science.

Meat plays a significant role in human diets, providing a rich source of high-quality protein. With advancements in technology, research in the field of meat preservation has been undergoing dynamic evolution. To gain insights into the development of this discipline, the study conducted an analysis and knowledge structure mapping of 1672 papers related to meat preservation research within the Web of Science Core Collection (WOSCC) spanning from 2001 to 2023. And using software tools such as VOSviewer 1.6.18 and CiteSpace 5.8.R3c allowed for the convenient analysis of the literature by strictly following the software operation manuals. Moreover, the knowledge structure of research in the field of meat preservation was synthesized within the framework of "basic research-technological application-integration of technology with fundamental research," aligning with the research content. Co-cited literature analysis indicated that meat preservation research could be further categorized into seven collections, as well as highlighting the prominent role of the antibacterial and antioxidant properties of plant essential oils in ongoing research. Subsequently, the future research direction and focus of the meat preservation field were predicted and prospected. The findings of this study could offer valuable assistance to researchers in swiftly comprehending the discipline's development and identifying prominent research areas, thus providing valuable guidance for shaping research topics.

Clinical observation of electroacupuncture combined with training to improve motor function and serum brain injury markers in patients with ischemic stroke / 针灸推拿医学（英文版）

Objective:To observe the effect of electroacupuncture(EA)combined with routine language and motor training on limb and language function,depression,and serum brain injury markers in patients with ischemic stroke. Methods:A total of 86 patients with ischemic stroke were selected and divided into an observation group and a control group using the random drawing method,with 43 cases in each group.Both groups received routine stroke treatments.The control group was additionally treated with routine language and motor training,and the observation group was additionally treated with EA treatment on the basis of the intervention of the control group.Changes in the limb function score,language function score,depression score,and brain injury marker protein were compared between the two groups,and the treatment safety of the two groups was evaluated. Results:The Fugl-Meyer assessment scale scores of both groups were higher than those before treatment(P<0.05),and the Fugl-Meyer assessment scale score of limb function of the observation group was higher than that of the control group(P<0.05).The language function score of the observation group was higher than that of the control group after treatment(P<0.05).The Montgomery-Asberg depression rating scale(MADRS)scores of the observation group were lower than those of the control group after treatment(P<0.05).The levels of brain injury markers heart-type fatty acid-binding protein(H-FABP),glial fibrillary acidic protein(GFAP),and annexin a7(ANXA7)of the observation group were lower than those of the control group(P<0.05).The incidence rate of adverse reactions in the two groups was 14.0%and 9.3%,respectively,with no statistically significant difference between the groups(P>0.05). Conclusion:EA combined with language and motor training is effective in the treatment of ischemic stroke.It can promote the recovery of limb motor function and language function,inhibit the occurrence of depression,and reduce the levels of brain injury markers,with good safety.

Role of Lyn kinase in imatinib-resistant chronic myelogenous leukemia / 中国实验血液学杂志

This study was aimed to explore the role of Lyn kinase in imatinib-resistant CML. Lyn, BCR/ABL fusion gene and chromosomes were detected in 76 CML patients being divided into imatinib-resistant, newly diagnosed and effective groups, and then the expression of Lyn was compared and the relationship between Lyn and clinical characteristics, BCR/ABL fusion gene and chromosomes were analyzed. The results indicated that all the 76 CML patients and 10 normal persons expressed Lyn. Lyn expression in imatinib-resistant patients was significantly higher than that in normal persons, newly diagnosed patients and imatinib-effective patients (P < 0.05). However, there was no statistically significant difference between newly diagnosed patients, effective patients and normal persons (P > 0.05). Lyn expression had no significant correlation with median age, sex, median hemoglobin level, and median platelet level, percentage of peripheral blasts, spleen size (P > 0.05). The Lyn expression was related with the higher count of peripheral blood leukocytes at new diagnosis (P < 0.05). There was no obvious relationship between Lyn and BCR/ABL levels (P > 0.05). There was 1 case with chromosome abnormality in t(6;22) and t(2;9) in 10 imatinib-resistant CML patients, coexisting with Ph chromosome. Ph chromosome only existed in the remanent 9 cases of CML. It is concluded that both the CML patients and normal persons express Lyn. Lyn is over-expressed in imatinib-resistant CML. The increased Lyn expression is closely related with higher WBC count.

Expression of DNA-dependent protein kinase catalytic subunit in adult acute leukemia and its significance / 中国实验血液学杂志

This study was aimed to explore the expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in adult acute leukemia and its correlation with clinical characteristics, karyotype and prognosis. Indirect immunofluorescent cytometry was used to detect the expression of DNA-PKcs in bone marrow mononuclear cells of 105 patients with acute leukemia before chemotherapy and 41 of them after 2 cycles of chemotherapy. Cytogenetic data were obtained from 26 of them by R band karyotypic analysis. The results showed that the expression of DNA-PKcs was correlated with higher WBC count level in peripheral blood (p < 0.05), but was not obviously associated with median age, gender, percentage of bone marrow blasts, clinical classification, median hemoglobin level and median platelet count (p > 0.05). The middle and strong positive expression of DNA-Pkcs in non-remission group was significantly higher than that in remission group (p < 0.05). The positive rate of DNA-PKcs in abnormal chromosome group was significantly higher than that in chromosome normal group (p < 0.05). It is concluded that the DNA-PKcs expression level is closely related with the increased WBC count, and the expression of DNA-PKcs is correlated also with karyotype and clinical prognosis in adult acute leukemia.

Expression of angiotensin-II type 1 receptor at1 mRNA in myeloid leukemia / 中国实验血液学杂志

This study was aimed to explore the expression level of angiotensin-II type 1 receptor (AT1) mRNA in bone marrow of myeloid leukemic patients, and its correlation with the proportion of leukemia cells in samples and Hb, WBC, Plt counting in peripheral blood. 51 samples, including 36 AML, 7 CML, and 8 samples of non-malignant hematological diseases as control group were collected. The expression of at1 mRNA was detected by real time-PCR; the expression levels of at1 gene in AML and CML groups were relatively quantitatively analyzed by using 2(-ΔΔCT) and were compared with control group. The results showed that the expression levels of at1 mRNA in AML, CML and control groups were 0.038 ± 0.076, 0.033 ± 0.039, 0.281 ± 0.366, respectively. at1 gene expression in the myeloid leukemic group was significantly lower than that in the control group. The expression level of at1 mRNA in AML was negatively correlated with the proportion of leukemia cells and positively with Hb level in peripheral blood. It is concluded that at1 gene may play a minor role in leukaemogenesis, however, may promote erythropoiesis.

Therapeutic effect of priming induction regimen of CAG for newly diagnosed acute myeloid leukemia in elderly patients / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the clinical efficacy and toxicity of priming induction regimen of CAG for newly diagnosed acute myeloid leukemia (AML) in elderly patients.@*METHODS@#Seventy-five patients with newly diagnosed AML were divided into 2 groups: 34 were treated with priming induction regimen CAG and the other 41 were treated with 2 classic routine chemotherapy regimens including pirarubicin+cytarabine (TA) and homoharringtonine+cytarabine (HA). All patients had a 14 day interval between the 2 courses of chemotherapy.@*RESULTS@#The complete remission rate after 2 courses of induction therapy in patients with the priming induction regimen CAG and the total efficacy rate was significantly higher than that of the routine chemotherapy patients(67.6% vs. 39%; 82.4% vs. 56.1%). Patients with unfavorable karyotypes had poor chemotherapy efficacy. The 3-year disease-free-survival (DFS) time was longer in patients with AML treated with priming induction regimen CAG than in patients treated with 2 classic routine chemotherapy regimens. Except for the muscular soreness, the hematological and non-hematological side effects in the CAG priming induction group were significantly fewer than those in the routine chemotherapy group.@*CONCLUSION@#The priming induction regimen of CAG has a significantly higher complete remission rate and an efficacy rate, fewer side effects, milder chemotherapy intensity and is more sensitive to chemotherapeutic drugs than those of the routine chemotherapy. It can shorten the duration of agranulocytosis and decrease infectious complications and increase the sensitivity of leukemia blast cells to chemotherapeutic drugs.

Clinical significance of NF-kappaB continual activity and expression of WT1 and MDR1 in acute nonlymphocytic leukemia / 中国实验血液学杂志

The study was aimed to explore the NF-kappaB continual activity and the expression of WT1 and MDR1 in acute non-lymphocytic leukemia (ANLL) patients, and to investigate if the three factors affect the curative effect of ANLL together as to provide some theoretical basis for finding new measures to improve the curative effect of refractory ANLL. The bone marrow samples of 45 ANLL patients was collected. 45 patients including 20 primary ANLL patients (A group) and 25 refractory ANLL patients. Refractory ANLL patients were divided into 2 sub-groups (B, C groups). The primary patients who was no effect after more than two courses of treatment were taken as group B, and the patients with more than two relapses were taken as group C. At the same time, 15 patients with simple iron deficiency anemia were collected as negative control. The NF-kappaB continual activity was measured by using electrophoretic mobility shift assay (EMSA) and the expressions of WT1, MDR1 were detected by reverse transcriptase polymerase chain reaction (RT-PCR). The results showed that the activity of NF-kappaB and the expressions of WT1, MDR1 were not detected in 15 samples of simply iron deficiency anemia subjects. The NF-kappaB continual activity, the expression levels of WT1 and MDR1 in the refractory group were significantly higher than that in primary group (P<0.001). But the NF-kappaB continual activity, the expression of WT1 gene and MDR1 gene were not significantly different between group B and group C (P>0.05). By assaying the relativity between the them the NF-kappaB continual activity and the expression of WT1 or MDR1 had positive correlation in ANLL patients. It is concluded that the NF-kappaB continual activity, the overexpression of WT1 and MDR1 may be one of the reasons causing poor curative effect in acute non-lymphocytic leukemia. The NF-kappaB continual activity and the expression of WT1, MDR1, all show positive correlation in ANLL patients.

Effect of recombinant human interleukin 11 on the platelet after hematopoietic stem cell transplantation in patients with leukemia / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect and toxicity profile of recombinant human interleukin 11(rhIL-11) on the platelet after hematopoietic stem cell transplantation in patients with leukemia.@*METHODS@#Twenty-four patients with acute or chronic leukemia treated by allogeneic peripheral blood stem cell transplantation (PBSCT) were randomly divided into a test group and a control group. The patients in the test group were treated with rhIL-11 since the 13th day after PBSCT (1.5mg/d),while the control group were given symptomatic treatment.@*RESULTS@#The average time for the platelet to recover to the level of 20 x 10(9)/L was 20.8 days in the test group, and 26.0 days in control group respectively, there was significant difference (P<0.01). The average time for the platelet to recover to the level of 50 x 10(9)/L was 25.7 days in the test group, and 32.3 days in the control group respectively, there was also significant difference (P<0.01). The average time for the platelet transfusion was 2.2 in the test group, 4.1 in the control group, and there was significantly different (P<0.01). The average number of megakaryocytes was 12.2 in the test group, 4.8 in the control group on 30th day after the transplantation,and there was significant difference(P<0.01). The main side effects of rhIL-11 were nausea, vomit, debility, headache, dizzy and pain of injection site, and the degree was all Iapproximately II grade.@*CONCLUSION@#rhIL-11 has definite recuperative effect on the recovery of the platelet after PBSCT. There is little side effect, and it can be accepted.