Safety evaluation of ceftazidime/avibactam based on FAERS database.

OBJECTIVE: To explore adverse event (AE) signals of Ceftazidime/avibactam (CZA) based on the FDA Adverse Event Reporting System (FAERS) database. METHODS: AE reports primarily associated with CZA were retrieved from the FAERS database from the second quarter of 2015 to the second quarter of 2023. Signal detection was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods. RESULTS: A total of 750 AEs reports with CZA as the preferred suspected drug were obtained, identifying 66 preferred terms (PTs) involving 24 system organ classes (SOCs). Besides, the AEs already mentioned in the drug label, this study also revealed some new, clinically valuable potential AEsignals, such as Cholestasis (n = 14, ROR 29.39, PRR 29.15, IC 3.34, EBGM 29.11), Drug-induced liver injury (n = 8, ROR 9.05, PRR 9.01, IC 2.25, EBGM 9.01), Hepatocellular injury (n = 7, ROR 13.90, PRR 13.84, IC 2.41, EBGM 13.63), Haemolytic anaemia (n = 5, ROR 24.29, PRR 24.22, IC 2.42, EBGM 40.53), etc. Additionally, AE signals with higher intensity were identified, such as Hypernatraemia (n = 5, ROR 40.73, PRR 40.61, IC 2.31, EBGM 24.19), Toxic epidermal necrolysis (n = 4, ROR 11.58, PRR 11.55, IC 1.89, EBGM 11.54). Therefore, special vigilance for these potential AEs is warranted when using CZA clinically. CONCLUSION: This study highlights the potential AEs and risks associated with the clinical use of CZA, particularly the risks related to Cholestasis, Drug-induced liver injury, Haemolytic anaemia, Hypernatraemia, and Toxic epidermal necrolysis.

FeNi (oxy)hydroxides embedded with high-valence Mo atoms: A efficient and robust water oxidation electrocatalyst.

The incorporation of high-valence transition metal atoms into FeNi (oxy)hydroxides may be a promising strategy to regulate the intrinsic electronic states, thereby reducing the thermodynamic barrier and accelerating oxygen evolution reaction (OER). Here, a high-valence Mo atoms doping route is proposed by an efficient self-reconstruction strategy to prepare MoFeNi (oxy)hydroxides for efficient alkaline OER. By using borides (MoNiB) as sacrificial template and Mo source, FeNi (oxy)hydroxides nanoflakes embedded with high-valence Mo atoms (MoFeNi) is successfully synthesized, which can modulate the electron coordination to improve the intrinsic catalytic activity. Remarkably, the obtained MoFeNi exhibits extremely low overpotential (η100 = 252 mV and η500 = 288 mV) and small Tafel slope (18.35 mV dec-1). The robust catalyst can run stably for hours at 500 mA cm-2. Characterization results and theoretical calculations confirmed that the addition of high-valence Mo effectively modulated the intrinsic electronic structure of metal sites and optimized the adsorption/desorption energy of the intermediates, accelerating OER reactions kinetics. By coupling MoFeNi anode with Pt/C cathode, anion exchange membrane (AEM) electrolyser can operate stably at 500 mA cm-2 with about less than 2.2 V. This research introduces a novel approach to develop ideal electrocatalysts through the incorporation of high-valence molybdenum species.

Bimetallic metal-organic framework-derived bamboo-like N-doped carbon nanotube-encapsulated Ni-doped MoC nanoparticles for water oxidation.

Molybdenum carbide materials with unique electronic structures have received special attention as water-splitting catalysts, but their structural stability in the alkaline water electrolysis process is not satisfactory. This study reports an in situ pyrolysis method for preparing NiMo-based metal-organic framework (MOF)-derived chain-mail oxygen evolution reaction (OER) electrocatalysts and bamboo-like N-doped carbon nanotube (NCNT)-encapsulated Ni-doped MoC nanoparticles (NiMoC-NCNTs). The NCNTs can provide chain mail shells to protect the inner highly reactive Ni-doped MoC cores from electrochemical corrosion by the alkaline electrolyte and regulate their catalytic properties through charge redistribution. Benefiting from high N-doping with abundant pyridinic moieties and abundant active sites of the periodic bamboo-like nodes, the as-prepared NiMoC-NCNTs display an outstanding activity for the OER with an overpotential of 310 mV at 10 mA cm-2 and a superior long-term stability of 50 h. Density functional theory calculations reveal that the excellent electrocatalytic activity of NiMoC-NCNTs comes from the electron transfer from NiMoC nanoparticles to NCNTs, resulting in a decrease in the local work function at the carbon surface and optimized free efficiencies of OER intermediates on C sites. This work provides an effective approach to improve the structural stability of fragile catalysts by equipping them with carbon-based chain.

Comparative analysis of the effectiveness difference of SARS-COV-2 mRNA vaccine in different populations in the real world: A review.

Coronavirus disease 2019 (COVID-19) has ravaged the world since December 2019. Up to now, it is still prevalent around the world. Vaccines are an important means to prevent the spread of COVID-19 and reduce severe disease and mortality. Currently, different types of novel coronavirus vaccines are still being developed and improved, and the relevant vaccines that have been approved for marketing have been widely vaccinated around the world. As vaccination coverage continues to grow, concerns about the efficacy and safety of vaccines after real-world use have grown. Some clinical studies have shown that vaccine effectiveness is closely related to antibody response after vaccination. Among them, the advantages of COVID-19 messenger ribonucleic acid (mRNA) vaccine, such as better adaptability to variant strains and better immune response ability, have attracted great attention. However, different populations with different genders, ages, previous COVID-19 infection history, underlying diseases and treatments will show different antibody responses after mRNA vaccination, which will affect the protection of the vaccine. Based on this, this paper reviews the reports related severe acute respiratory syndrome Coronavirus 2 mRNA vaccines, and summarizes the effectiveness of vaccines in different populations and different disease states and looked forward to the precise vaccination strategy of the vaccine in the future.

Optimized Electronic Modification of S-Doped CuO Induced by Oxidative Reconstruction for Coupling Glycerol Electrooxidation with Hydrogen Evolution.

Glycerol (electrochemical) oxidation reaction (GOR) producing organic small molecule acid and coupling with hydrogen evolution reaction is a critical aspect of ensuring balanced glycerol capacity and promoting hydrogen generation on a large scale. However, the development of highly efficient and selective non-noble metal-based GOR electrocatalysts is still a key problem. Here, an S-doped CuO nanorod array catalyst (S-CuO/CF) constructed by sulfur leaching and oxidative remodeling is used to drive GOR at low potentials: It requires potentials of only 1.23 and 1.33 V versus RHE to provide currents of 100 and 500 mA cm-2, respectively. Moreover, it shows satisfactory comprehensive performance (at 100 mA cm-2, Vcell = 1.37 V) when assembled as the anode in asymmetric coupled electrolytic cell. Furthermore, we propose a detailed cycle reaction pathway (in alkaline environment) of S-doped CuO surface promoting GOR to produce formic acid and glycolic acid. Among them, the C-C bond breaking and lattice oxygen deintercalation steps frequently involved in the reaction pathway are the key factors to determine the catalytic performance and product selectivity. This research provides valuable guidance for the development of transition metal-based electrocatalysts for GOR and valuable insights into the glycerol oxidation cycle reaction pathway.

Human cytomegalovirus glycoprotein B genotypic distributions and viral load in symptomatic infants.

INTRODUCTION: HCMV infection is widespread in humans. This retrospective study aimed to explore the relationship between human cytomegalovirus (HCMV) glycoprotein B (gB) genotype distribution, viral load, and the demographic and clinical features of symptomatic infants. The detection rate of HCMV in blood and urine samples was also compared. METHODOLOGY: Retrospective data from 265 infants who underwent urine HCMV DNA testing were analyzed. The viral load and gB genotype were detected in 91 HCMV positive infants by quantitative fluorescence polymerase chain reaction (PCR) and DNA sequencing, respectively. RESULTS: The positive rate of HCMV infection was 46.04% (122/265) in all infants, and increased rapidly with age. Among the 91 infants investigated, liver function abnormality was the most common diagnosis (34/91, 37.36%), followed by pneumonia (21/91, 23.07%). Sequence analysis of gB yielded two genetic subtypes: the most prevalent gB3 (47/91, 51.65%), followed by gB1 (44/91, 48.35%). The gB3 HCMV infection was more prevalent in infants aged 0-2 months than in infants aged 3-12 months (χ2 = 4.38, p = 0.0364). The data showed that ALT and AST levels were significantly higher in the anti-HCMV IgM+IgG- group than in the anti-HCMV IgM+IgG+ and IgM-IgG+ groups. In addition, this study showed that the detection rate of HCMV DNA in the blood was significantly lower than that in the urine (χ2 = 6.7131, p = 0.0096). CONCLUSIONS: This study presents the HCMV infection status of infants and its relationship with their demographic characteristics and clinical manifestations. In addition, this study suggests that urinary PCR is the most appropriate assay for detecting HCMV infections.

Imipenem cilastatin sodium-associated thrombocytopenia in an older patient: A case report and literature review.

Imipenem cilastatin sodium, as a member of a new generation of ß-lactam antibiotics, has a broad spectrum of antibacterial activity and a very wide range of application. Thrombocytopenia has been reported as a rare adverse event in several studies of patients treated with imipenem cilastatin sodium. In this study, we present a case of thrombocytopenia associated with imipenem cilastatin sodium in an older patient. The 78-year-old male patient with pulmonary infection was initiated on anti-infection therapy with imipenem cilastatin sodium. On the 9th day after imipenem cilastatin sodium administration, the patient experienced a sudden and dramatic decrease in platelet count. Similarly, on the 4th day after the re-administration of imipenem cilastatin sodium for anti-infection therapy, the patient's platelet count showed a remarkable downward trend again. A time correlation between the drug therapy and the occurrence of platelet reaction was found. The patient's platelet count gradually returned to the normal level on the 6th day after the first drug withdrawal and the 13th day after the second drug withdrawal, respectively. Considering the widespread use of imipenem cilastatin sodium, healthcare providers should improve the notification of thrombocytopenia associated with imipenem cilastatin sodium.

Tigecycline-associated acute pancreatitis in a child with pulmonary cystic fibrosis: A case report and literature review.

Tigecycline is a tetracycline-class antibacterial indicated for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections, and community-acquired bacterial pneumonia. It has a broad-spectrum antibacterial activity. It has identified gastrointestinal side-effects, particularly nausea and vomiting. With the increasing clinical use of tigecycline, its associated acute pancreatitis has been frequently reported in adults. However, cases of tigecycline-induced acute pancreatitis have rarely been described in children. In this study, we report a case of acute pancreatitis caused by the use of tigecycline in a child with pulmonary cystic fibrosis. In this case, abdominal pain, nausea, and vomiting occurred on the 5th day after the use of tigecycline. Elevated pancreatic enzymes occurred, and abdominal computed tomography findings were compatible with pancreatitis. After 2 weeks of discontinuation of tigecycline, the pancreatic enzyme level decreased to normal, and the symptoms of abdominal pain, nausea, and vomiting disappeared completely. In conclusion, we hope to improve the clinical awareness of children with tigecycline-associated pancreatitis, so as to reduce the probability of adverse reactions through the analysis of this case.

Baricitinib, a drug with potential effect to prevent SARS-COV-2 from entering target cells and control cytokine storm induced by COVID-19.

In December 2019, a novel coronavirus pneumonia (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suddenly broke out in China and rapidly spread all over the world. Recently, a cell surface protein, known as angiotensin-converting enzyme II (ACE2), has been identified to be involved in receptor-mediated endocytosis for SARS-CoV-2 entry to the cells. Many studies have reported the clinical characteristics of COVID-19: sudden deterioration of disease around 1-2 weeks after onset; much lower level of lymphocytes, especially natural killer (NK) cells in peripheral blood; extremely high pro-inflammatory cytokines and C reactive protein (CRP). About 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression. Currently, there are no specific drugs for COVID-19 and the cytokine storm it causes. Baricitinib intracellularly inhibits the proinflammatory signal of several cytokines by suppressing Janus kinase (JAK) JAK1/JAK2. It has been demonstrated clinical benefits for the patients with rheumatoid arthritis (RA), active systemic lupus erythematosus and atopic dermatitis with good efficacy and safety records. Baricitinib is expected to interrupt the passage and intracellular assembly of SARS-CoV-2 into the target cells mediated by ACE2 receptor, and treat cytokine storm caused by COVID-19. Several clinical trials are currently investigating the drug, and one of which has been completed with encouraging results. In this paper, we will elaborate the role of cytokine storm mediated by JAK-STAT pathway in severe COVID-19, the possible mechanisms of baricitinib on reducing the viral entry into the target cells and cytokine storm, the key points of pharmaceutical care based on the latest research reports, clinical trials progress and drug instruction from the US FDA, so as to provide reference for the treatment of severe COVID-19.

Erratum: Fungal infection in lung transplant recipients in perioperative period from one lung transplant center.

[This corrects the article DOI: 10.21037/jtd.2019.03.18.].

Fungal infection in lung transplant recipients in perioperative period from one lung transplant center.

BACKGROUND: This study aimed to analyze the distribution and prophylaxis strategy of pathogens causing fungal infection in lung transplant recipients from cardiac-brain dead donors in the perioperative period to provide evidence for antifungal prophylaxis and treatment in lung transplant recipients. METHODS: This retrospective study evaluated 194 lung transplant recipients from January 2015 to December 2016. Fungal pathogens were isolated and identified from respiratory tract cultures before and after transplantation in the perioperative period. The galactomannan (GM) testing of bronchoalveolar lavage fluid (BALF) might facilitate the diagnosis of Aspergillus infection. Data were statistically analyzed using SPSS 19.0. RESULTS: A total of 31 cases of fungal strains isolated from the 194 recipients were identified prior to lung transplantation, and the positive rate was 16.0% (31/194). A total of 27 cases of isolated fungal strains in the 194 recipients were identified, and the positive rate after lung transplantation was 13.9% (27/194) in the perioperative period. A total of 54 cases with positive fungal infection (27.8%) were detected before and after lung transplantation. Overall, 10.3% (20/194) of the lung transplant recipients developed fungal infection in the observation period. The most common fungal pathogens were filamentous fungi and Candida albicans. CONCLUSIONS: Our data suggested that fungi were frequently isolated before and after transplantation from respiratory samples. However, the incidence of invasive fungal infection in lung transplant recipients in the perioperative period was relatively low. Targeted antifungal prophylaxis and treatment should be applied on the basis of the fungal distribution status of different individuals.

An Extracellular Matrix-Mimicking Hydrogel for Full Thickness Wound Healing in Diabetic Mice.

An extracellular matrix-mimicking hydrogel is developed consisting of a hyaluronan-derived component with anti-inflammatory activity, and a gelatin-derived component offering adhesion sites for cell anchorage. The in situ-forming hyaluronan-gelatin (HA-GEL) hydrogel displays a sponge-like microporous morphology. Also, HA-GEL shows a rapid swelling pattern reaching maximum weight swelling ratio within 10 min, while at the equilibrium state, fully swollen hydrogels display an exceedingly high water content with ≈2000% of the dry gel weight. Under typical 2D cell culture conditions, murine 3T3 fibroblasts adhere to, and proliferate on top of the HA-GEL substrates, which demonstrate that HA-GEL provides a favorable microenvironment for cell survival, adhesion, and proliferation. In vivo healing study further demonstrates HA-GEL as a viable and effective treatment option to improve the healing outcome of full thickness wounds in diabetic mice by effectively depleting the inflammatory chemokine monocyte chemoattractant protein-1 in the wound bed.

HBsAg spontaneous seroclearance in a cohort of HBeAg-seronegative patients with chronic hepatitis B virus infection.

Loss of hepatitis B surface antigen (HBsAg) is considered to reflect the resolution of a hepatitis B virus (HBV) infection. Patient characteristics and various seromarkers were evaluated to characterize factors predicting spontaneous HBsAg loss in a cohort of HBeAg-seronegative patients with presumed chronic HBV infection. Relationships between seromarkers and HBsAg loss were assessed annually and after 6 years using binary logistic regression. Among the 634 participants, 117 (18.45%) cleared HBsAg after 6 years, with a 3.08% annual seroclearance rate. Baseline HBsAg levels and platelet (PLT) counts were predictors of HBsAg seroclearance. The HBsAg level predicted HBsAg seroclearance better than the PLT count (area under the receiver operating characteristic curve (AUROC): HBsAg, 0.965 (95%CI, 0.947-0.980) versus PLT count, 0.617 (95%CI, 0.561-0.669); P < 0.001). A cutoff HBsAg level of 10 IU/ml at baseline predicted spontaneous HBsAg seroclearance at 6 years with a diagnostic accuracy of 93.4%, a sensitivity of 87.2%, a specificity of 94.8%, a positive predictive value of 79.1%, and a negative predictive value of 97.0%. HBsAg seroclearance may occur more commonly than expected. A serum HBsAg level <10 IU/ml and PLT count were accurate predictors of clearance.

Glucocorticoid Receptor ß Acts as a Co-activator of T-Cell Factor 4 and Enhances Glioma Cell Proliferation.

We previously reported that glucocorticoid receptor ß (GRß) regulates injury-mediated astrocyte activation and contributes to glioma pathogenesis via modulation of ß-catenin/T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity. The aim of this study was to characterize the mechanism behind cross-talk between GRß and ß-catenin/TCF in the progression of glioma. Here, we reported that GRß knockdown reduced U118 and Shg44 glioma cell proliferation in vitro and in vivo. Mechanistically, we found that GRß knockdown decreased TCF/LEF transcriptional activity without affecting ß-catenin/TCF complex. Both GRα and GRß directly interact with TCF-4, while only GRß is required for sustaining TCF/LEF activity under hormone-free condition. GRß bound to the N-terminus domain of TCF-4 its influence on Wnt signaling required both ligand- and DNA-binding domains (LBD and DBD, respectively). GRß and TCF-4 interaction is enough to maintain the TCF/LEF activity at a high level in the absence of ß-catenin stabilization. Taken together, these results suggest a novel cross-talk between GRß and TCF-4 which regulates Wnt signaling and the proliferation in gliomas.

Glucocorticoid receptor ß regulates injury-mediated astrocyte activation and contributes to glioma pathogenesis via modulation of ß-catenin/TCF transcriptional activity.

Astrocytes react to central nervous system (CNS) injury and participate in gliotic responses, imparting negative, as well as positive effects on axonal regeneration. Despite the considerable biochemical and morphological changes astrocytes undergo following insult, and the known influence of steroids on glial activation, details surrounding glucocorticoid receptor expression and activity are lacking. Such mechanistic information is essential for advancing and enhancing therapies in the treatment of CNS injuries. Using an in vitro wound-healing assay, we found glucocorticoid receptor ß (GRß), not GRα, is upregulated and acts as a regulator of gliosis after injury. In addition, our results suggest that GRß interacts with ß-catenin and is a necessary component for proliferation and migration in both injured astrocytes and glioma cells. Further analysis indicated GRß/ß-catenin interaction as a key modulator of astrocyte reactivity through sustained Wnt/ß-catenin/TCF signaling in its dominant-negative effect on GRα mediated trans-repression by a GSK-3ß-independent manner. These findings expand our knowledge of the mechanism of GRß action in promoting astrocyte proliferation and migration following injury and in glioma. This information furthers our understanding the function of glucocorticoid receptor in CNS injury and disease, as well as in the basic biochemical responses astrocytes undergo in response to injury and glioma pathogenesis.

Glutamine synthetase functions as a negative growth regulator in glioma.

Our recent study demonstrated that glutamine synthetase (GS) may not only serve as a glutamate-converting enzyme in glial cells, but may also function as a regulator of astrocyte migration after injury. In this report, we showed that GS expression increased in cultured rat C6 glioma cells that underwent long-term serially propagation. The stable overexpression of GS in C6 glioma cells resulted in growth arrest and motility suppression; however the stable knockdown of GS resulted in motility enhancement. In correlation with cell aggregation, N-cadherin levels increased at sites of cell-cell contact in C6 cells overexpressing GS, and decreased in C6 cells with stable GS knockdown; total N-cadherin expression levels remained unchanged in these cells. In addition, levels of p21, a potent cyclin-dependent kinase inhibitor, increased, while cyclin D1 levels decreased in C6 cells overexpressing GS. Our additional studies showed that N-cadherin-mediated cell-cell contacts were implicated in GS-induced cell growth arrest and impairment of cell migration, as evidenced by the inhibition of GS on cell growth and motility by the neutralizing anti-N-cadherin monoclonal antibody (GC-4 mAb). Collectively, these observations suggest a novel mechanism of growth regulation by GS that involves N-cadherin mediated cell-cell contact.

Antigenic heterogeneity of the NS3 proteins in hepatitis C virus genotypes 1 and 6.

OBJECTIVE: To investigate the effect of sequence variability between different genotypes of hepatitis C virus (HCV) on the antigenic properties of the NS3 proteins, and to evaluate the significance of the proteins in the serological diagnosis. METHODS: The recombinant expression plasmids of pET/NS3-1 and pET/NS3-6 were constructed with the NS3 region fragments from HCV genotypes 1 and 6, respectively. The antigenic reactivity of the recombinant NS3 proteins was determined. The NS3 nucleotide sequences were aligned with 6 HCV full-length strains representing different genotypes. RESULTS: The two recombinant NS3 proteins were generated and enzyme immunoassay tests were developed. The positive rates of anti-NS3 were 61.2 and 58.8% by using the NS3 antigens from HCV genotypes 1 and 6, respectively. This difference had no statistical significance (p > 0.05). However, it was interesting that 16 samples gave a discordant result for different genotype NS3 antigens.The two partial NS3 sequences shared approximately 63.9-79.9% identity with the different genotype strains. CONCLUSION: The primary structure of the HCV NS3 region is highly variable. Thus, sequence variability has a profound effect on the antigenic properties of the NS3 regions, and the antigenic differences should be taken into account for the development of more effective diagnostic tests.

[Study on the correlation of GCS and MDR1 genes in inducing multidrug resistance in human K562/A02 cell line].

OBJECTIVE: To investigate the correlation of glucosylceramide synthase (GCS) gene and multidrug resistance 1 (MDR1) gene in inducing multidrug resistance in human multidrug-resistant K562/A02 cell line, and search for a novel strategy for reversing multidrug resistance of leukemia cells. METHODS: The expression levels of GCS and MDR1 mRNA in K562 and K562/A02 cells were assayed by RT-PCR. siRNAs targeting the GCS and MDR1 gene were transfected into K562/A02 cells with liposome, respectively. The differential expression of GCS and MDR1 mRNAs, as well as their correlation, were detected by RT-PCR and real time quantitative-PCR(QPCR). RESULTS: The expression level of GCS and MDR1 mRNA was dramatically lower in drug-sensitive K562 cells compared with the K562/A02 cells. The GCS mRNA was inhibited by 73%(59%-82%) and MDR1 mRNA expression was down regulated by 67% (38%-82%) in K562/A02 cells after being transfected with GCS siRNA. The expression level of MDR1 mRNA was inhibited by 81%(63%-91%) and GCS mRNA expression had no apparent change in K562/A02 cells treated with MDR1 small interference RNA(siRNA). CONCLUSION: Positive correlation was detected between the expression of GCS and MDR1 mRNA in K562/A02 cells and MDR1 mRNA expression was down regulated after silencing the GCS gene expression.

GCS induces multidrug resistance by regulating apoptosis-related genes in K562/AO2 cell line.

We have previously shown that the expression of glucosylceramide synthase (GCS) gene in drug-resistant K562/AO2 human leukemia cell was higher than that in drug-sensitive K562 cell, and the sensitivity to adriamycin of K562/AO2 cell was enhanced by inhibiting GCS. It is concluded that the overexpression of GCS gene is one of the reasons which lead to multidrug resistance (MDR) of leukemia cell. Meanwhile, we also found that higher expression of Bcl-2 gene and protein were exhibited in K562/AO2 cell compared with K562 cell. Basing on this, we hypothesized that the high expression of GCS gene which results in MDR of leukemia cell is correlated with Bcl-2 signal transduction. In order to validate the hypothesis, the inhibition of GCS gene in K562/AO2 cell was observed by using chemical suppressor PPMP and siRNA targeted at GCS, and applying RT-PCR and flow cytometry, the expression levels of apoptosis-related gene Bcl-2 and Bax were analyzed before and after inhibiting GCS gene in K562/AO2 cell. The results demonstrated that the gene and protein of Bcl-2 in K562/AO2 cell were both down-regulated significantly after GCS gene being inhibited; however, the Bax mRNA expression had no apparent change in different groups. This suggested that GCS gene may contributed to MDR of human leukemia cell K562/AO2 by Bcl-2 signal transduction.