Disruption of DNA-PKcs-mediated cGAS retention on damaged chromatin potentiates DNA damage-inducing agent-induced anti-multiple myeloma activity.

BACKGROUND: Targeting DNA damage repair factors, such as DNA-dependent protein kinase catalytic subunit (DNA-PKcs), may offer an opportunity for effective treatment of multiple myeloma (MM). In combination with DNA damage-inducing agents, this strategy has been shown to improve chemotherapies partially via activation of cGAS-STING pathway by an elevated level of cytosolic DNA. However, as cGAS is primarily sequestered by chromatin in the nucleus, it remains unclear how cGAS is released from chromatin and translocated into the cytoplasm upon DNA damage, leading to cGAS-STING activation. METHODS: We examined the role of DNA-PKcs inhibition on cGAS-STING-mediated MM chemosensitivity by performing mass spectrometry and mechanism study. RESULTS: Here, we found DNA-PKcs inhibition potentiated DNA damage-inducing agent doxorubicin-induced anti-MM effect by activating cGAS-STING signaling. The cGAS-STING activation in MM cells caused cell death partly via IRF3-NOXA-BAK axis and induced M1 polarization of macrophages. Moreover, this activation was not caused by defective classical non-homologous end joining (c-NHEJ). Instead, upon DNA damage induced by doxorubicin, inhibition of DNA-PKcs promoted cGAS release from cytoplasmic chromatin fragments and increased the amount of cytosolic cGAS and DNA, activating cGAS-STING. CONCLUSIONS: Inhibition of DNA-PKcs could improve the efficacy of doxorubicin in treatment of MM by de-sequestrating cGAS in damaged chromatin.

Estimating the remaining atmospheric environmental capacity using a single-box model in a high pollution risk suburb of Chengdu, China.

The atmospheric pollution has been the public attention in recent years. In order to better coordinate economic development and atmospheric environmental management, China introduced the concept of atmospheric environmental capacity (AEC). The remaining atmospheric environmental capacity (RAEC) calculated by existing atmospheric pollution sources and AEC is an important basis for regional development and environmental protection. The RAEC of the high-pollution risk suburb of Chengdu in 2015 was estimated by the single-box model and analyzed on multiple time scales. The results show that the RAEC of SO2 and NO2 in this region is 3299 t/a and 2849 t/a, respectively under the annual time scale. However, in the daily time scale, the RAEC of NO2 is negative for 3 days, that is, there are 3 days with serious air pollution. Therefore, it is not appropriate to plan the industrial area only by relying on annual RAEC. Especially, RAEC displays inter-seasonal and monthly variability. On the one hand, in plain areas with low wind speed and little change in wind direction, achieving the prediction of atmospheric mixing layer height could give early warning of atmospheric pollution events. On the other hand, different management measures are taken on different time scales. On a long timescale, the regional energy structure should be optimized. On seasonal and monthly time scales, the production plans should be adapted to RAEC. On the daily time scale, it mainly deals with the serious atmospheric pollution accident timely.

Ginkgetin inhibits proliferation of human leukemia cells via the TNF-α signaling pathway.

Ginkgetin is known to be an anticancer agent in many studies. However, its effectiveness in treating chronic myeloid leukemia [corrected] remains unknown. The present study aimed to evaluate the effects of ginkgetin on the growth of the K562 cell line. The MTT assay was employed to examine the proliferation of K562, and a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining was conducted to detect the apoptotic rates. Furthermore, changes of tumor necrosis factor-α (TNF-α) were detected by Western blot analysis. Ginkgetin inhibited the proliferation of K562 cells in a dose- and time-dependent manner. Concentrations of ginkgetin required to induce 50% death of K562 at 24, 48 and 72 h were 38.9, 31.3 and 19.2 µM, respectively. Moreover, treatment of ginkgetin increased K562 apoptosis in vitro along with increased levels of TNF-α. Interestingly, anti-TNF-α antibody prevented ginkgetin-induced K562 cell apoptosis and growth inhibition via deactivation of caspase-8, caspase-9 and caspase-3. Concomitantly, downregulation of TNF-α by etanercept in vivo attenuated ginkgetin-induced inhibitory effects on the tumor growth in an xenograft mouse model. Our results indicate that ginkgetin effectively inhibits K562 cell proliferation, and TNF-α plays a key role in ginkgetin-induced cell apoptosis.

[Efficacy and Safety of Plerixafor Combined with G-CSF for Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization in Lymphoma Patients].

OBJECTIVE: To investigate the efficacy and safety of plerixafor combined with granulocyte colony-stimulating factor (G-CSF) in mobilizing peripheral blood hematopoietic stem cells in patients with lymphoma. METHODS: The clinical data of lymphoma patients who received autologous hematopoietic stem cell mobilization using plerixafor combined with G-CSF from January 2019 to December 2021 were retrospectively analyzed. The patients received 3 kinds of mobilization regimens: front-line steady-state mobilization, preemptive intervention, and recuse mobilization. The acquisition success rate, excellent rate of collection, and incidence of treatment-related adverse reaction were counted. The influence of sex, age, disease remission status, bone marrow involvement at diagnosis, chemotherapy lines, number of chemotherapy, platelet count and number of CD34+ cells on the day before acquisition in peripheral blood on the collection results were analyzed to identify the risk factors associated with poor stem cell collection. RESULTS: A total of 43 patients with lymphoma were enrolled, including 7 cases who received front-line steady-state mobilization, 19 cases who received preemptive intervention, and 17 cases who received recuse mobilization. The overall acquisition success rate was 58.1% (25/43) after use of plerixafor combined with G-CSF, and acquisition success rate of front-line steady-state mobilization, preemptive intervention, and recuse mobilization was 100%, 57.9%(11/19), and 41.2%(7/17), respectively. The excellent rate of collection was 18.6%(8/43). A total of 15 patients experienced mild to moderate treatment-related adverse reactions. The number of CD34+ cells < 5 cells/µl in peripheral blood on the day before collection was an independent risk factor affecting stem cell collection. CONCLUSIONS: Plerixafor combined with G-CSF is a safe and effective mobilization regimen for patients with lymphoma. The number of CD34+ cells in peripheral blood on the day before collection is an predictable index for the evaluation of stem cell collection.

A novel risk model for predicting early relapse in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem-cell transplantation.

Relapse remains the leading cause of death in acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem-cell transplantation (allo-HSCT), limiting the efficacy of allo-HSCT. Thus, the ability to identify high-risk patients in a manner that permits early intervention has the potential to improve survival outcomes. We retrospectively enrolled 414 younger patients (aged 14-60 years) with AML who received allo-HSCT between January 2014 and May 2020. From June 2020 to June 2021, 110 consecutive patients were included prospectively in the validation cohort. The primary outcome was early relapse (relapse within 1 year). The cumulative incidence of early relapse after allo-HSCT was 11.8%. The overall survival rate for patients who relapsed within 1-year was 4.1% at 3 years after relapse. After multivariable adjustment, statistically significant associations between primary resistance, pre-transplantation measurable residual disease, DNMT3A mutation, or white blood cell count at diagnosis and early relapse were observed. An early relapse prediction model was developed based on these factors and the model performed well. Patients deemed to have a high risk or a low risk of early relapse had early relapse rates of 26.2% and 6.8%, respectively (P < 0.001). The prediction model could be used to help identify patients at risk for early relapse and to guide personalized relapse prevention.

Treatment and outcome patterns of patients with Waldenström's macroglobulinemia: a large, multicenter retrospective review in China.

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets <100 × 109/L, serum albumin <3.5 g/dl, ß2 microglobulin concentration ≥4 mg/L and LDH ≥250 IU/L predicted poor OS. In summary, our study showed that frontline treatment choices for WM are widely heterogeneous. We validated most of the established prognostic factors in the rIPSS (age >65 years, LDH ≥250 IU/L, ALB <3.5 g/dl and ß2 microglobulin ≥4 mg/L) together with PLT ≤ 100 × 109/L indicate a poor prognosis for patients with WM.

Evaluation methods for the efficacy of neoadjuvant chemotherapy for breast cancer.

With the widespread clinical application of neoadjuvant chemotherapy, it has become an essential part of combination therapy for patients with breast cancer. However, a rapid, accurate, and effective approach for assessing the therapeutic efficacy of neoadjuvant chemotherapy is unavailable. Routine physical examinations cannot provide effective clinical evaluation. Although imaging techniques play an important role in evaluating the therapeutic effect of neoadjuvant chemotherapy, this is limited because it only detects morphologic changes. Blood oxygen detection for breast diseases is an emerging diagnostic technique that has distinctive merit in assessing the efficacy of chemotherapy. Biologic markers are becoming more important in assessing the effect of neoadjuvant chemotherapy for patients with breast cancer. This review summarizes the principles and the current applied practice of these approaches to evaluate the effect of neoadjuvant chemotherapy for patients with breast cancer.

Simplified MIPI-B prognostic stratification method can predict the outcome well-retrospective analysis of clinical characteristics and management of newly-diagnosed mantle cell lymphoma patients from China.

Mantle cell lymphoma (MCL) is an invasive B-cell lymphoma with significant individual differences. Currently, MCL international prognostic index (MIPI) score and tumor cell proliferation index Ki-67 have been proved to be the most important prognostic factors. But the prognostic effect of these factors in Asian population is uncertain. This study aimed to analyze the disease characteristics and prognostic factors of Chinese MCL patients.A total of 83 cases of newly-diagnosed MCL patients diagnosed by the Department of Pathology of our hospital between January 1, 2011, and May 31, 2016, were enrolled. The disease characteristics, treatment effects, and outcomes of the patients were collected and analyzed.According to our analysis, MCL cases accounted for 6.2% of non-Hodgkin lymphoma (NHL) cases and mainly occurred in elderly males. But the proportion of patients at stage IV by Ann Arbor staging system and high-risk group by simplified-MIPI (s-MIPI) were significantly lower than that among European patients. Immunochemotherapy containing rituximab was significantly more effective than chemotherapy (overall response rate, [ORR]: 88.5% vs 65.2%, P = .021) and significantly prolonged patient survival (progression free survival [PFS]: 45.5 m vs 16.2 m, P = .001; overall survival [OS]: 58.3 m vs 22.8 m, P = .001). The multivariate analysis showed that the B symptoms, s-MIPI and administration of immunochemotherapy were independent prognostic factors that affected PFS and OS of the patients. s-MIPI and B symptom make up s-MIPI-B stratification method, by which patients in low-risk group of s-MIPI without B symptom were classified as low-risk, patients in high-risk group of s-MIPI and patients in low-risk group of s-MIPI with B symptom as high-risk, the rest as middle-risk. 3-year PFS of the 3 groups were 74.9%, 43.4% and 16.1%, respectively (P = .001). 3-year OS were 84.4%, 62.2%, 27.6% (P <.001).Chinese MCL was male predominance. We have a minor proportion of late-stage and high-risk patients compared to European patients. Immunochemotherapy was proved to significantly improve the prognosis of MCL patients. B symptoms, s-MIPI, and administration of rituximab independently influenced the outcome. s-MIPI-B prognostic stratification method may better predict the prognosis of Asian MCL patients. Still, further confirmation in larger populations is needed.

Breast cancer resistance protein expression and 5-fluorouracil resistance.

OBJECTIVE: To filtrate breast cancer resistance protein (BCRP)-mediated resistant agents and to investigate clinical relationship between BCRP expression and drug resistance. METHODS: MTT assay was performed to filtrate BCRP-mediated resistant agents with BCRP expression cell model and to detect chemosensitivity of breast cancer tissue specimens to these agents. A high performance liquid chromatography (HPLC) assay was established, and was used to measure the relative dose of intracellular retention resistant agents. RT-PCR and immunohistochemistry (IHC) were employed to investigate the BCRP expression in breast cancer tissue specimens. RESULTS: MTT assay showed that the expression of BCRP increased with the increasing resistance of 5-fluorouracil (5-Fu) (P<0.05, n=3) in the cell model, while HPLC assay indicated that the intracellular retention dose of 5-Fu was significantly correlated with the expression of BCRP (r=-0.897, P<0.05, n=3). A total of 140 breast cancer tissue specimens were collected. BCRP-positive expression was detected in forty-seven specimens by both RT-PCR and IHC. As shown by MTT assay subsequently, the resistance index (RI) of 47 BCRP-positive breast cancer tissue specimens to 5-Fu was 7-12 times as high as that of adjacent normal tissue samples. BCRP expression was related to 5-Fu resistance (R2=0.8124, P<0.01). CONCLUSION: Resistance to 5-Fu can be mediated by BCRP. Clinical chemotherapy for breast cancer patients can be optimized based on BCRP-positive expression.

Clinical and histopathological features of chronic hepatitis B virus infected patients with high HBV-DNA viral load and normal alanine aminotransferase level: A multicentre-based study in China.

BACKGROUND: The aim of this study is to reveal the clinical and histopathological features of HBsAg-positive and HBeAg-positive chronic hepatitis B infected patients with high level of HBV DNA, from 17 hospitals and medical centres in China, with alanine aminotransferase levels within the lower region of normal range versus those with levels within the upper region of normal range and to investigate the clinical risk factors for the requirement of treatment through the examination of liver biopsy. METHODS: Liver biopsy was performed on high level of HBV DNA of 455 patients with HBsAg-positive and HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase level. Liver necroinflammation and fibrosis were graded per the Knodell histological activity index and Ishak's fibrosis score, respectively. Univariate analysis of the clinical parameters versus necroinflammation and fibrosis was carried out. RESULTS: Of the subjects in this multicentre-based study, 5.49% and 10.11% had significant necroinflammation with Knodell histological activity index ≥ 9 and hepatic fibrosis stages with Ishak scores ≥ 3, respectively. The subjects were stratified into three age groups (30-39, 40-49 and ≥ 50 years), and our data clearly suggested that age, particularly in the age group over 50, was an independent predictor of liver necroinflammation and fibrosis. Lower HBV-DNA viral levels were found in patients with Knodell histological activity index ≥ 9 or advanced fibrosis (Ishak scores ≥ 3). CONCLUSION: Our results showed that histological changes in liver tissues were observed in a significant proportion of patients with persistently normal alanine aminotransferase level. According to the data evaluation results, liver biopsy is advisable for HBeAg-positive chronic hepatitis B infected patients aged older than 40 and high HBV-DNA viral load in China.

Effects of continuous renal replacement therapy on serum cytokines, neutrophil gelatinase-associated lipocalin, and prognosis in patients with severe acute kidney injury after cardiac surgery.

The aim of our study was to evaluate the effect of continuous renal replacement therapy (CRRT) on serum cytokines, neutrophil gelatinase-associated lipocalin (NGAL), and prognosis in patients with severe acute kidney injury (AKI) following cardiac surgery. A total number of 153 patients with severe AKI following cardiac surgery were treated with CRRT. They were divided into the survival and non-survival groups. Clinical data from these two groups before and after CRRT were recorded and analyzed. It was found that the number of impaired organs, MODS and APACHE II scores were significantly higher in the non-survival group than those in the survival group before CRRT. After CRRT, MODS and APACHE II scores decreased significantly. The post-CRRT levels of serum TNF-α and IL-6 were significantly decreased. After CRRT, serum NGAL decreased in the two groups, but the levels were higher in the non-survival group than those in the survival group. MODS and APACHE II scores could be used to evaluate the severity of AKI in patients after cardiac surgery. CRRT is an effective treatment for these patients and high levels of TNF-α, IL-6, and NGAL are associated with a poor prognosis in these patients.

Clinical research on navel application of Shehuang Paste combined with Chinese herbal colon dialysis in treatment of refractory cirrhotic ascites complicated with azotemia.

AIM: To explore the efficacy and mechanism of a novel therapeutic method of traditional Chinese medicine in patients with refractory cirrhotic ascites complicated with azotemia. METHODS: Seventy-five cases of refractory cirrhotic ascites complicated with azotemia were randomly divided into 3 groups: comprehensive treatment (n = 29), simple treatment (n = 24), and control (n = 22). The basic treatment methods were the same in all groups, including liver protecting medicines, diuretics and supportive drugs. The control group underwent only the basic treatment. Shehuang Paste (SHP) was applied to the navels of the two treatment groups once a day for 30 d. Colon dialysis with Chinese herbs was administered to the comprehensive treatment group once every two days. Before and after treatment, we measured abdominal circumference, BUN, Cr, serum Na+, urine Na+/K+, liver function, endotoxin content, NO, and ET-1. Color Doppler ultrasonography was conducted to measure the portal vein blood flow. RESULTS: The total effective rate for ascites was 72.4% in the comprehensive treatment group, 45.8% in the simple treatment, contrasting with 18.2% in the controls. Between the two treatment groups and the controls, there were significant differences in the effective rates (P < 0.01, and P < 0.05). There was also a significant difference (P < 0.05) between the two treatment groups. Measurements of Cr and BUN showed higher values for the treatment groups, with the comprehensive better than the simple group (P < 0.05). Sera Na, urine Na/K were different, P < 0.01 between pre- and post-treatment in the comprehensive group, and P < 0.05 in the simple group. The treatment groups' endotoxin content was also significantly reduced (P < 0.01, and P < 0.05), with the comprehensive group better than the simple group (P < 0.05). Portal vein blood flow and NO content significantly reduced (P < 0.05), as did ET-1 content (P < 0.01). There were no significant changes in the control group (P > 0.05). The comprehensive treatment group's pre- and post-treatment portal vein and splenic vein blood flows showed a positive correlation to NO, ET-1 and endotoxin contents. CONCLUSION: When treating refractory cirrhotic ascites complicated with azotemia, Shehuang Paste combined with Chinese herbal dialysis is better than Shehuang Paste alone for ascites resolution, azotemia, and endotoxin elimination. However, both methods on their own were also effective for reducing portal and splenic vein blood flow, and lowering the contents of NO, ET-1 in the two treatment groups.

[Correlation between hepatic immunological markers and virus genotype in patients with chronic hepatitis C].

OBJECTIVE: To investigate the hepatic expression of immunological markers relevant to a cytotoxic response in relation to viral genotype. METHODS: The frozen liver biopsies were obtained from 28 HF genotyped patients and made the sections stained. The morphometry was used to analyze the major histocompatibility complex class I (MHC-I), CD8, beta(2)-microglobulin (beta(2) -mG), HFE and CD68 in the stained sections. Biopsy data of response to therapy with interferon were available in 18 cases. RESULTS: CD8+ was usually clustered together and localized in portal tracts and sinusoids, and seen to interact with MHC I positive lining cells. MHC-I and beta(2) -mG were expressed mainly in endothelial and Kupffer cells. HFE was expressed in most round and dendritic CD68+ cells. Patients with virus genotype 3a had higher hepatic MHC-I and HFE expression, and a better sustained response to interferon (IFN) therapy than patients without. CONCLUSION: The MHC-I expression in the liver of patient with chronic hepatitis C virus infection seems to relate to viral-genotype. The hepatic MHC-I and HFE expression are higher in patients with virus genotype 3a than that in patients with non-3a genotype.

[Study on unrelated donor allogeneic bone marrow transplantation with Bu-CY2 conditioning regimen for myelodysplastic syndrome].

OBJECTIVE: To evaluate the efficacy and safety of Bu-CY(2) conditioning regimen on allogeneic bone marrow transplantation (BMT) with unrelated donor for myelodysplastic syndrome. METHODS: Six patients received chemotherapy regimen of busulfan (Bu) and cyclophosphamide (CY) before allogeneic BMT (Bu 4 mg . kg(-1) . d(-1), -7 d - -4 d, CY 60 mg . kg(-1) . d(-1), -3 d - -2 d). Mycophenolate mofetil combined with cyclosporin A and methotrexate was used for prevention of acute graft-versus-host disease after transplantation. Lipo prostaglandin E(1)was used in prophylactic regimen for hepatic veno-occlusive disease. RESULT: Neutrophil count began to be higher than 0.5 x 10(9)/Lat the 18th day after BMT. Platelet count began to be higher than 20 x 10(9)/Lat the 21st day after BMT. Disease-free survival in the six patients was 27 months. CONCLUSION: Bu-CY(2) conditioning regimen on allogeneic bone marrow transplantation with unrelated donor is an effective therapy for patients with myelodysplastic syndrome.

Acute myeloid leukemia of a primary hepatic carcinoma patient after liver transplantation: a case report and literature review.

Living donor liver transplantation (LDLT) is an important means to treat end-stage liver disease. Although effective immunosuppressant medication greatly assists the survival of patients, it is likely to promote infections and cancer. Acute leukemia (AL) is a rare complication after LDLT and up to now only 1 case of post-transplantation AL has occurred in our liver transplantation center after more than 1,600 LDLT interventions since 1993. In the present report, we describe a rare case of subsequent acute myeloid leukemia (AML), 27 months after LDLT and review the literature of this infrequent complication.

Hypovitaminosis D is associated with endothelial dysfunction in patients with non-dialysis chronic kidney disease.

OBJECTIVE: Cardiovascular events are highly prevalent in chronic kidney disease (CKD). Hypovitaminosis D and vascular endothelial dysfunction are risk factors for cardiovascular morbidity and mortality and they both are common in CKD patients. This study aimed to investigate the association between hypovitaminosis D and endothelial dysfunction in non-dialysis CKD patients. METHODS: In 117 non-dialysis CKD patients, we assessed endothelial function by brachial artery flow-mediated dilation (FMD), soluble vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin. 25-hydroxyvitamin D [25(OH)D] was measured by electrochemiluminescence immunoassay. RESULTS: Brachial artery FMD was lower in vitamin D-deficient and -insufficient versus vitamin D-sufficient groups, with the lowest value observed in the vitamin D-deficient group. Conversely, sVCAM-1 and sE-selectin were higher in vitamin D-deficient and -insufficient groups versus vitamin D-sufficient, and the highest value was observed in the vitamin D-deficient group. There was a positive association between FMD and 25(OH)D (r = 0.556, p < 0.001) and negative correlations between both sVCAM-1 (r = -0.549, p < 0.001) and sE-selectin (r = -0.360, p < 0.001) and 25(OH)D. These associations remained significant after adjusting for confounders. CONCLUSIONS: Hypovitaminosis D is associated with endothelial dysfunction in non-dialysis CKD patients. Further studies are needed to confirm whether vitamin D supplementation can improve endothelial function and reduce cardiovascular events in these patients.

Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years.

Invasive fungal infection (IFI) is a growing cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively reviewed the records of 408 patients undergoing allo-HSCTs during the period November 1998 to December 2009, analyzed the incidence and risk factors of IFI, and examined the impact of IFI on overall survival. A total of 92 (22.5%) episodes suffered proven or probable IFI (4 patients were proven, 88 patients were probable). Candida was the most common pathogen for early IFI, and mold was the most frequent causative organism for late IFI. A prior history of IFI, human leukocyte antigen (HLA) mismatch, long-time neutropenia, and acute graft-versus-host-disease (GVHD) were risk factors for early IFI. A prior history of IFI, corticosteroid therapy, cytomegalovirus (CMV) disease, and chronic GVHD were risk factors for late IFI. IFI-related mortality was 53.26%. The 12-year overall survival (OS) rate for IFI was significantly lower than that of patients without IFI (41.9% vs. 63.6%, P<0.01).

Metformin displays anti-myeloma activity and synergistic effect with dexamethasone in in vitro and in vivo xenograft models.

Epidemiologic studies and meta-analyses have suggested that patients with type 2 diabetes mellitus (T2DM) have a higher incidence of malignancies, including myeloma. Metformin is a widely prescribed antidiabetic drug. Recently, researchers have shown that metformin has direct anticancer activity against many tumor cell lines, mainly through activating AMP-activated protein kinase (AMPK) or reducing the blood insulin level. In the present study, we investigated whether metformin exerts an anti-myeloma effect in in vitro and in vivo xenograft models and explored the underlying mechanism. We found that metformin can inhibit proliferation of MM cells by inducing apoptosis and cell cycle arrest in the G0/G1 phase. Western blot showed that metformin activated caspase 3, caspase 9, PARP-1, Bak, and p21 and inactivated Mcl-1, HIAP-1, cyclin D1, CDK4, and CDK6. Metformin inhibited the expression of insulin growth factor-I receptor (IGF-IR), and phosphatidyl inositol 3-kinase (PI3K), protein kinase B (PKB/AKT) and the downstream mammalian target of rapamycin (mTOR). IGF-I blocked metformin-induced MM cell apoptosis and reactivation of the PI3K/AKT/mTOR signaling pathway. Metformin also demonstrated synergistic activity with dexamethasone but not bortezomib to eradicate MM cells in vitro and in vivo, especially in MM.1S cells. We conclude that metformin inhibits MM cell proliferation through the IGF-1R/PI3K/AKT/mTOR signaling pathway. Metformin and dexamethasone combination therapy may be an option for MM treatment.

Moxa-stick suffumigation for disinfecting air in hematology and hematopoietic stem cell transplantation wards with class 100 laminar flow.

OBJECTIVE: To evaluate the effect of moxa-stick suffumigation in the hematology and hematopoietic stem cell transplantation (HSCT) wards with luminar flow. METHODS: The plate exposure method was used to measure the effect of air-disinfection of moxa-stick suffumigation in hematology and HSCT wards. The yearly average qualified rates of air sampling in HSCT wards were evaluated from 2007 to 2010. To further investigate the disinfecting effect of moxa-stick suffumigation, the colony counts of common pathogens (including Staphylcoccus aureus and Pseudomonas aeruginosa) before and after moxa-stick suffumigation were compared. RESULTS: The mean air quality rates of the HSCT wards with class 100 laminar flow were all above 90.0% (91.2%-96.2%) from 2007 to 2010. Moxa-stick suffumigation effectively decreased the presence of bacteria in the hematology ward's air (P<0.01). The most notable effect was the drastic reduction in the colony counts of Staphylococcus aureus and Pseudomonas aeruginosa on the blood plates exposed to air treated with moxa-stick suffumigation (77.1±52.9 cfu/m(2) vs 196.1±87.5 cfu/m(2), P<0.01; and 100.2±35.3 cfu/m(2) vs 371.5±35.3 cfu/m(2), P<0.01). CONCLUSION: Moxa-stick suffumigation proved to be a reliable and effective airdisinfection method for hematology and HSCT wards, and hence, it should be employed extensively.