Overexpression of SCN5A overcomes ABC transporter-mediated multidrug resistance in acute myeloid leukemia through promoting apoptosis.

BACKGROUND: This study aimed to explore the effect and mechanism of SCN5A overcoming ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR) in acute myeloid leukemia (AML) through promoting apoptosis. RESEARCH DESIGN AND METHODS: The tissues derived from AML patients were divided into Sensitive group and Resistance group according to the presence of drug-resistance. Human AML cell line HL-60 and drug-resistant strain HL-60/ADR were divided into HL-60/ADR-vector group, HL-60/ADR-SCN5A group, HL-60-vector group and HL-60-SCN5A group. RT-qPCR was used to detect the mRNA expression level of SCN5A; MTT assay to assess the survival rate and proliferation level of cells; flow cytometry to determine the apoptosis level; and western blot to check the levels of SCN5A, P-glycoprotein (P-gp), MDR protein 1 (MRP1), MDR gene 1 (MDR1), breast cancer resistance protein (BCRP), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) proteins in cells. RESULTS: SCN5A expressed lowly in drug-resistant AML tissues and cells. Up-regulation of SCN5A inhibited MDR in HL-60 cells, enhanced the chemosensitivity of HL-60/ADR, and increased the apoptosis levels of HL-60 and HL-60/ADR cells. However, over-expression of SCN5A inhibited the expression of MDR-related proteins. CONCLUSIONS: SCN5A may overcome ABC transporter-mediated MDR in AML through enhancing the apoptosis and inhibiting the expression of MDR proteins.

Sanhuang Xiexin Decoction Ameliorates TNBC By Modulating JAK2-STAT3 and Lipid Metabolism.

OBJECTIVE: To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism. METHODS: The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice. RESULTS: Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice. CONCLUSION: SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.

Acupotomy Contributes to Suppressing Subchondral Bone Resorption in KOA Rabbits by Regulating the OPG/RANKL Signaling Pathway.

Subchondral bone lesions, as the crucial inducement for accelerating cartilage degeneration, have been considered as the initiating factor and the potential therapeutic target of knee osteoarthritis (KOA). Acupotomy, the biomechanical therapy guided by traditional Chinese meridians theory, alleviates cartilage deterioration by correcting abnormal mechanics. Whether this mechanical effect of acupotomy inhibits KOA subchondral bone lesions is indistinct. This study aimed to investigate the effects of acupotomy on inhibiting subchondral bone resorption and to define the possible mechanism in immobilization-induced KOA rabbits. After KOA modeling, 8 groups of rabbits (4w/6w acupotomy, 4w/6w electroacupuncture, 4w/6w model, and 4w/6w control groups) received the indicated intervention for 3 weeks. Histological and bone histomorphometry analyses revealed that acupotomy prevented both cartilage surface erosion and subchondral bone loss. Further, acupotomy suppressed osteoclast activity and enhanced osteoblast activity in KOA subchondral bone, showing a significantly decreased expression of tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinases-9 (MMP-9), and cathepsin K (Ctsk) and a significantly increased expression of osteocalcin (OCN); this regulation may be mediated by blocking the decrease in osteoprotegerin (OPG) and the increase in NF-κB receptor activated protein ligand (RANKL). These findings indicated that acupotomy inhibited osteoclast activity and promoted osteoblast activity to ameliorate hyperactive subchondral bone resorption and cartilage degeneration in immobilization-induced KOA rabbits, which may be mediated by the OPG/RANKL signaling pathway. Taken together, our results indicate that acupotomy may have therapeutic potential in KOA by restoring the balance between bone formation and bone resorption to attenuate subchondral bone lesions.

Halobaculum halophilum sp. nov. and Halobaculum salinum sp. nov., isolated from salt lake and saline soil.

Two halophilic archaeal strains, Gai3-2T and NJ-3-1T, were isolated from salt lake and saline soil samples, respectively, collected in PR China. The 16S rRNA gene sequences of the two strains were 97.5% similar to each other. Strains Gai3-2T and NJ-3-1T had the highest sequence similarities to 'Halobonum tyrrellense' G22 (96.7 and 97.8%, respectively), and displayed similarities of 91.5-93.5% and 92.3-94.7%, respectively, to Halobaculum members. Phylogenetic analysis revealed that the two strains formed different branches and clustered tightly with 'H. tyrrellense' G22 and Halobaculum members. The average nucleotide identity (ANI), in silico DNA-DNA hybridization (isDDH) and amino acid identity (AAI) values between the two strains were 83.1, 26.9 and 77.9%, respectively, much lower than the threshold values proposed as a species boundary. These values between the two strains and 'H. tyrrellense' G22 (ANI 77.9-78.2%, isDDH 22.5-22.6% and AAI 68.8-69.3%) and Halobaculum members (ANI 77.53-77.63%, isDDH 21.8-22.3% and AAI 68.4-69.4%) were almost identical, and much lower than the recommended threshold values for species delimitation. These results suggested that strains Gai3-2T and NJ-3-1T represent two novel species of Halobaculum. Based on phenotypic, chemotaxonomic and phylogenetic properties, strains Gai3-2T (=CGMCC 1.16080T=JCM 33550T) and NJ-3-1T (=CGMCC 1.16040T=JCM 33552T) represent two novel species of the genus Halobaculum, for which the name Halobaculum halophilum sp. nov. and Halobaculum salinum sp. nov. are proposed.

Hypoxia-inducible factor-1α-mediated upregulation of CD99 promotes the proliferation of placental mesenchymal stem cells by regulating ERK1/2.

BACKGROUND: As human placenta-derived mesenchymal stem cells (hP-MSCs) exist in a physiologically hypoxic microenvironment, various studies have focused on the influence of hypoxia. However, the underlying mechanisms remain to be further explored. AIM: The aim was to reveal the possible mechanisms by which hypoxia enhances the proliferation of hP-MSCs. METHODS: A hypoxic cell incubator (2.5% O2) was used to mimic a hypoxic microenvironment. Cell counting kit-8 and 5-ethynyl-20-deoxyuridine incorporation assays were used to assay the proliferation of hP-MSCs. The cell cycle was profiled by flow cytometry. Transcriptome profiling of hP-MSCs under hypoxia was performed by RNA sequencing. CD99 mRNA expression was assayed by reverse transcription-polymerase chain reaction. Small interfering RNA-mediated hypoxia-inducible factor 1α (HIF-1α) or CD99 knockdown of hP-MSCs, luciferase reporter assays, and the ERK1/2 signaling inhibitor PD98059 were used in the mechanistic analysis. Protein expression was assayed by western blotting; immunofluorescence assays were conducted to evaluate changes in expression levels. RESULTS: Hypoxia enhanced hP-MSC proliferation, increased the expression of cyclin E1, cyclin-dependent kinase 2, and cyclin A2, and decreased the expression of p21. Under hypoxia, CD99 expression was increased by HIF-1α. CD99-specific small interfering RNA or the ERK1/2 signaling inhibitor PD98059 abrogated the hypoxia-induced increase in cell proliferation. CONCLUSION: Hypoxia promoted hP-MSCs proliferation in a manner dependent on CD99 regulation of the MAPK/ERK signaling pathway in vitro.

Successful treatment of mycobacterial infection associated hemophagocytic lymphohistiocytosis with etoposide and anti-tuberculous therapy: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome. CASE PRESENTATION: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide. CONCLUSION: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.

[Heritability of obesity in children aged 30-36 months and an analysis of single nucleotide polymorphisms at four loci in Xi'an, China].

OBJECTIVE: To study the heritability of obesity in children aged 30-36 months in Xi'an, China, as well as the role of four single nucleotide polymorphisms (SNPs) associated with body mass index in the susceptibility to obesity in children. METHODS: Random sampling was performed to select 1 637 children, aged 30-36 months, from four communities of Xi'an from March 2017 to December 2018. Physical assessment was performed for these children, and a questionnaire survey was conducted for parents. Then the Falconer regression method was used to calculate the heritability of childhood obesity. Venous blood samples were collected from 297 children who underwent biochemical examinations, among whom there were 140 children with obesity/overweight (obesity/overweight group) and 157 with normal body weight (normal body weight group). The MassARRAY RS1000 typing technique was used to detect CDKAL1 gene rs2206734, KLF9 gene rs11142387, PCSK1 gene rs261967, and GP2 gene rs12597579. The distribution of alleles and genotypes was compared between the obesity/overweight and normal body weight groups. An unconditional logistic regression model was used to investigate the benefits of dominant and recessive genetic models. RESULTS: For the 1 637 children, the heritability of obesity from the parents was 83%±8%, and the heritability from mother was slightly higher than that from father (86%±11% vs 78%±12%). There were significant differences in the distribution of rs2206734 alleles and genotypes and rs261967 genotypes between the obesity/overweight and normal body weight groups (P<0.0125). The children carrying T allele at rs2206734 had a significantly higher risk of obesity than those carrying CC (OR=0.24, P<0.0125), and the children carrying GG at rs261967 had a significantly higher risk of obesity than those carrying A allele (OR=4.11, P<0.0125). CONCLUSIONS: Genetic factors play an important role in the pathogenesis of obesity in children, and the SNPs of CDKAL1 rs2206734 and PCSK1 rs261967 are associated with the susceptibility to obesity in children aged 30-36 months in Xi'an.

Design, synthesis and antitumor activity of aromatic urea-quinazolines.

Background: Gefitinib and sorafenib have been proved effective for the treatment of cancers in clinical practice for years. Materials & methods: We intended to integrate the structural features of gefitinib and sorafenib and construct structurally unique 7-aromatic ureido-4-anilinoquinazolines. Results: Most of the targets exhibited promising antitumor activities. 8u showed excellent antitumor activities against the three tested cell lines (IC50, 0.81-2.49 µM). The enzymatic, apoptosis assay of 8u were also performed to study their preliminary action of mechanism. Conclusion: 8u deserve further research as antitumor agents.

[Influence of pre-pregnancy parental body mass index, maternal weight gain during pregnancy, and their interaction on neonatal birth weight].

OBJECTIVE: To investigate the influence of pre-pregnancy parental body mass index (BMI), maternal weight gain during pregnancy, and their interaction on neonatal birth weight. METHODS: A total of 1 127 pregnant women who underwent regular prenatal examinations and full-term singleton delivery in the First Hospital of Xi'an Jiaotong University from January 2017 to October 2018 were enrolled. The data on their pre-pregnancy BMI, maternal weight gain during pregnancy, pre-pregnancy BMI of the husband, and neonatal birth weight were collected. The interaction between pre-pregnancy parental BMI and maternal weight gain during pregnancy was analyzed, and their correlation with neonatal birth weight was analyzed. RESULTS: Among the 1 127 full-term neonates, the detection rates of low birth weight neonates and macrosomia were 2.22% (25/1 127) and 3.82% (43/1 127) respectively. There were significant differences in pre-pregnancy parental BMI and maternal weight gain during pregnancy among the low birth weight, normal birth weight, and macrosomia groups (P<0.05). Neonatal birth weight was positively correlated with pre-pregnancy parental BMI and maternal weight gain during pregnancy (r=0.097-0.322, P<0.05). Low maternal weight before pregnancy increased the risk of low birth weight (RR=4.17, 95%CI: 1.86-9.38), and maternal overweight/obesity before pregnancy (RR=3.59, 95%CI: 1.93-6.67) and excessive weight gain during pregnancy (RR=3.21, 95%CI: 1.39-7.37) increased the risk of macrosomia. No interaction between pre-pregnancy maternal BMI and maternal weight gain during pregnancy was observed. CONCLUSIONS: Pre-pregnancy parental BMI and maternal weight gain during pregnancy are related to neonatal birth weight, and there is no interaction between pre-pregnancy maternal BMI and maternal weight gain during pregnancy.

[Effect of needle knife intervention on tensile mechanics of femoral quadriceps tendon in rabbits with knee osteoarthritis].

OBJECTIVE: To observe the effects of acupotomy intervention on the behavior, morphology and tensile mechanics of knee osteoarthritis (KOA) rabbits, and to explore the biomechanical effects of acupotomy on KOA. METHODS: Twenty-four New Zealand male rabbits were randomly divided into four groups: normal group, model group, electroacupuncture group and needle-knife group, with 6 rabbits in each group. In each model group, rabbit KOA model was established by fixing Videman's left hind limb in straight position for 6 weeks. In the electroacupuncture group, rats were treated left on Liang Qiu, Xue Hai, Nei Xi Yan and Wai Xi Yan 3 times a week for 3 weeks. In the acupotomology group, the left quadriceps femoris tendon was released with acupotomology, and the treatment was once a week for 3 weeks. Behavioral tests were performed using Lequesne MG knee joint evaluation method one week after the end of modeling and one week after the end of treatment, and HE staining and mechanical tests were performed one week after the end of treatment. RESULTS: Behavioral observation before treatment showed that there were significant differences in local pain, gait response, joint activity and joint swelling between the normal group and the model group(P<0.05), while there was no significant difference among the model group, electro-acupuncture group and needle-knife group(P>0.05). After treatment, the results showed that there were significant differences in local pain, gait response, joint activity and joint swelling among model group, electro-acupuncture group and needle-knife group compared with normal group(P<0.05); In local pain, the electro-acupuncture group was lower than the model group, and there was no significant difference(P>0.05); there was significant difference between needle knife group and model group(P<0.05); there was no significant difference between electro-acupuncture group and needle-knife group(P>0.05). In gait change, there was significant difference between model group and electro-acupuncture group(P<0.05); there was no significant difference between needle-knife group and model group(P>0.05). In joint activity, there was significant difference between electro-acupuncture group and model group(P<0.05). In joint swelling, compared with model group, there was significant difference on electro-acupuncture group and electro-knife group(P<0.01), but there was no significant difference between the electro-acupuncture group and the needle-knife group(P>0.05). Mechanics: Compared with the blank group, the ultimate load of the model group decreased significantly(P<0.01), the ultimate load of the electro-acupuncture group decreased(P>0.05), and the ultimate load of the needle-knife group increased(P>0.05). Compared with the model group, the ultimate load of the electro-acupuncture group increased significantly(P<0.05), and the ultimate load of the needle-knife group increased significantly (P<0.01). Compared with the electro-acupuncture group, the ultimate load of the needle-knife group increased(P>0.05). Compared with the blank group, the maximum displacement of the model group decreased significantly(P<0.01), and the maximum displacement of the electro-acupuncture group and the needle-knife group decreased(P>0.05). Compared with the model group, the maximum displacement of the electro-acupuncture group increased(P>0.05), and the maximum displacement of the needle-knife group increased significantly(P<0.05). Compared with the electro-acupuncture group, the maximum displacement of the needle-knife group increased(P>0.05). There was no significant difference in stiffness among groups(P>0.05). CONCLUSIONS: Acupotomy intervention can significantly change the behavior and morphology, significantly improve the mechanical properties of quadriceps femoris tendon stretch, and exert its biomechanical effects to achieve the purpose of treating KOA.

Polymorphism in rs2229783 of the Alpha 1(XI) Collagen Gene Is Associated with Susceptibility to but not Severity of Kashin-Beck Disease in a Northwest Chinese Han Population.

A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. The purpose of this study was to explore whether genomic polymorphisms in the alpha 1(XI) collagen gene (COL11A1) were associated with the risk and severity of Kashin-Beck disease (KBD). Twenty-two single nucleotide polymorphisms (SNPs) in COL11A1 were genotyped in 274 KBD cases and 249 healthy controls using the Sequenom MassARRAY system. The expression of type XI collagen (COL11A) in the knee articular cartilage of 22 KBD patients and 21 controls was analyzed by immunohistochemistry. Our results showed that the frequency distribution of genotypes of the rs2229783 polymorphism in COL11A1 was significantly different between the KBD and control groups (P = 0.0003). Moreover, the expression level of COL11A in cartilage was significantly lower in the KBD group than in the controls (t = 2.637, P = 0.02). However, no association was found between the rs2229783 and the severity of KBD, suggesting a role of COL11A1 in the susceptibility to but not the severity of KBD.

Effects of Connexin 43 Inhibition in an Ovalbumin-induced Mouse Model of Asthma.

Connexion 43 (Cx43), a gap junction protein, is expressed abundantly in the airway and has been implicated in the pathogenesis of asthma. However, the effects of blocking Cx43 in asthma remain unclear. We investigated the therapeutic effects of two specific Cx43 inhibitors (Gap26 and Gap27) on the development of allergic airway disease in mice. Allergic asthma was induced in BALB/c mice by sensitization and challenge with ovalbumin (OVA). Different doses of Cx43 inhibitors were administered by aerosol inhalation 1 h after OVA challenge on days 21 and 23. Airway hyperresponsiveness (AHR), lung pathology, mucus production, and inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were examined. We found that Gap26 significantly inhibited OVA-induced AHR, inflammatory cell infiltration surrounding the bronchia, mucus production, inflammatory cells and cytokines in BALF, and OVA-specific IgE in the serum in a dose-dependent manner. Gap27 showed effects similar to those of Gap26 in inhibiting inflammatory cytokine production in BALF. We conclude Cx43 inhibitor inhalation alleviates asthma featuresin mice and may be a promising therapy for clinical asthma.

Phosphodiesterase 4 Inhibitor Roflumilast Protects Rat Hippocampal Neurons from Sevoflurane Induced Injury via Modulation of MEK/ERK Signaling Pathway.

BACKGROUND/AIMS: Sevoflurane, a commonly used volatile anesthetic, recently has been found has neurotoxicity in the central nervous system of neonatal rodents. This study aimed to reveal whether phosphodiesterase 4 (PDE-4) inhibitor roflumilast has protective functions in sevoflurane-induced nerve damage. METHODS: Hippocampal neurons were isolated from juvenile rats, and were exposed to sevoflurane with or without roflumilast treatment. Cell viability and apoptosis were respectively assessed by CCK-8 and flow cytometry. Western blot analysis was performed to detect the protein expressions of apoptosis-related factors, and core factors in MEK/ERK and mTOR signaling pathways. RESULTS: Toxic effects of sevoflurane on hippocampal neurons were observed, as cell viability was reduced, apoptotic cell rate was increased, Bcl-2 was down-regulated, and Bax, cleaved caspase-3 and -9 were up-regulated after 1% sevoflurane exposure for 16 h. Sevoflurane exhibited a temporarily (less than 16 h) inhibitory effect on MEK/ERK pathway, but has no impact on mTOR pathway. Roflumilast promoted the release of cAMP and down-regulated the protein expression of PDE-4. Roflumilast (1 µM) alone has no impact on viability and apoptosis of hippocampal neurons. However, roflumilast increased cell viability and deceased apoptosis in sevoflurane-injured neurons. Besides, roflumilast could recover sevoflurane-induced deactivation of MEK/ERK pathway. CONCLUSION: To conclude, this study demonstrated a neuroprotective role of roflumilast in sevoflurane-induced nerve damage. Roflumilast promoted hippocampal neurons viability, and reduced apoptosis possibly via modulation of MEK/ERK signaling pathway.

Clerodens E-J, antibacterial caffeic acid derivatives from the aerial part of Clerodendranthus spicatus.

Six new caffeic acid derivatives, Clerodens E-J (1-6) were isolated from the aerial part of Clerodendranthus spicatus. Their structures were elucidated by extensive spectroscopic analysis, including NMR, MS, and ECD data. Compound 1 showed moderate antibacterial activities against drug-resistant strains of bacteria in vitro.

Exploring Genome-wide DNA Methylation Profiles Altered in Kashin-Beck Disease Using Infinium Human Methylation 450 Bead Chips.

To understand how differentially methylated genes (DMGs) might affect the pathogenesis of Kashin-Beck disease (KBD). Genome-wide methylation profiling of whole blood from 12 matched KBD and controls pairs was performed using a high-resolution Infinium 450 K methylation array. In total, 97 CpG sites were differentially methylated in KBD compared to the normal controls; of these sites, 36 sites were significantly hypermethylated (covering 22 genes) and 61 sites were significantly hypomethylated (covering 34 genes). Of these genes, 14 significant pathways were identified, the most significant P value pathway was type I diabetes mellitus pathway and pathways associated with autoimmune diseases and inflammatory diseases were included in this study. Subsequently, 4 CpG sites in HLA-DRB1 were validated using bisulfite sequencing polymerase chain reaction (BSP) in articular cartilage, and the results showed significant differences in the methylation status between KBD and controls, consistent with the results of the high-resolution array. These results suggested that differences in genome-wide DNA methylation exist between KBD and the controls, and the biological pathways support the autoimmune disease and inflammatory disease hypothesis of KBD.

Bioactive equivalence of combinatorial components identified in screening of an herbal medicine.

PURPOSE: To identify bioactive equivalent combinatorial components (BECCs) in herbal medicines. The exact composition of effective components in herbal medicines is often elusive due to the lack of adequate screening methodology. Herein, we propose a hypothesis that BECCs accounting for the whole efficacy of original herbal medicines could be discovered from a complex mixture of constituents. METHODS: We developed a bioactive equivalence oriented feedback screening method and applied it to discover the BECCs from an herbal preparation Cardiotonic Pill (CP). The operations include chemical profiling of CP, followed by an iterative loop of determining, collecting and evaluating candidate BECCs. RESULTS: A combination of 18 compounds was identified as BECCs from CP, which accounts for 15.0% (w/w) of original CP. We have demonstrated that the BECCs were as effective as CP in cell models and in a rat model of myocardial infarction. CONCLUSIONS: This work answers the key question of which are real bioactive components for CP that have been used in clinic for many years, and provides a promising approach for discovering BECCs from herbal medicines. More importantly, the BECCs could be extended to improve quality control of herbal products and inspire an herbal medicines based discovery of combinatorial therapeutics.

[Clinical investigation of homoharringtonine in combination with all-transretinoic acid and arsenic trioxide for acute promyelocytic leukemia].

OBJECTIVE: To study the clinical outcome, adverse effect and treatment cost of homoharringtonine (HHT) in combination with all-trans retinoic acid (ATRA) and arsenic trioxide (AS2O3) for newly diagnosed with patients acute promyelocytic leukemia (APL). METHODS: Clinical data of treatment of newly diagnosed patients with APL in experimental group (HHT + ATRA + AS2O3, n = 14) and control group \[Idarubicin (IDA) + ATRA + AS2O3, n = 21\] were analyzed retrospectively. The therapeutic effects, side effects and costs during induction therapy were compared between the two groups. RESULTS: (1) The complete remission (CR) rate were 92.9% (13/14) and 95.2% (20/21) in experimental group and control group, respectively. The time to achieve CR were (28.1 ± 3.8) and (31.7 ± 4.2) days, respectively (P > 0.05). The negative rate of PML-RARα fusion gene at the time of CR were 76.9% (10/13) and 75.0% (15/20), respectively, and that in CR patient at the end of the first cycle treatment were 100.0% (13/13) and 95.0% (19/20), respectively (P > 0.05). (2) 5-year overall survival (OS) rate were (92.6 ± 0.6)% and (89.9 ± 0.5)%, respectively (P > 0.05), 5-year disease free survival (DFS) rate were 100.0% and (86.8 ± 0.6)%, respectively (P > 0.05). (3) During induction therapy, the incidence of infection in experimental and control group were 23.1% (3/13), 60.0% (12/20), respectively (P < 0.05). The amount of platelet transfusion were (54.7 ± 29.6) and (76.5 ± 25.6) units, respectively (P > 0.05), and that of fresh frozen plasma were (1157.1 ± 238.4) and (1423.5 ± 324.6) ml, respectively (P > 0.05). The total medical costs (excluding HHT and IDA) in experimental and control group were (36074.9 ± 1245.6) and (50564.5 ± 3658.4)CNY, respectively (P < 0.05). CONCLUSION: HHT in combination with ATRA and AS2O3 regimen for newly diagnosed APL has a better efficacy, a higher long-term survival rate, and a lower costs, which is one of the reasonable choice.