Bortezomib-based chemotherapy for patients with Waldenström macroglobulinemia: a single-center experience.

Waldenström Macroglobulinemia (WM) is a rare type of non-Hodgkin lymphoma with no standard first-line treatment, and the disease is still incurable. This study evaluated the clinical efficacy, safety, and prognostic factors of bortezomib-based chemotherapy as initial treatment in WM patients. We retrospectively analyzed the clinical data collected from 44 newly diagnosed WM patients treated with bortezomib-based regimens at the Affiliated Hospital of Nantong University from December 2011 to June 2021. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). The median age was 67 years old, with an overall response rate (ORR) of 93.2%, complete response (CR) rate of 6.8%, and very good partial response (VGPR) rate of 29.5%. With a median follow-up of 39 months, the 2-year overall survival (OS) and 2-year PFS rates were 88.0% and 59.0%, respectively. By the last follow-up, eight patients (18.2%) had died. Univariate analysis showed patients with B symptoms, elevated LDH, international prognostic stage system of WM (IPSSWM) stage III, high Revised IPSSWM (R-IPSSWM) score, and those who did not achieve VGPR were associated with shorter PFS. And patients with B symptoms, with high R-IPSSWM score, and who do not achieve VGPR also had shorter OS than their counterparts. Multivariate analysis confirmed that failure to achieve VGPR was an independent adverse prognostic factor for OS and PFS. In conclusion, we showed that bortezomib-based chemotherapy effectively treated newly diagnosed patients with WM. However, combinations of drugs with different mechanisms are recommended for patients with a high tumor burden. In addition, deep remission can improve patients' survival.

A case report of IgG4-related respiratory disease with pleural effusion and a literature review.

RATIONALE: IgG4-related respiratory disease (IgG4-RRD) is a chronic autoimmune disease that affects the respiratory system and organs outside the respiratory system. This study explored the diagnosis and treatment of a case of IgG4-RRD with unilateral pleural effusion diagnosed using medical thoracoscopy, and provides an associated literature review. This report summarizes the clinical characteristics of IgG4-RRD involving the pleura to improve the diagnosis of this disease. PATIENT CONCERNS: A 39-year-old man presented with a 2-week history of cough and chest tightness. Both physical examination and imaging supported the presence of left pleural effusion. DIAGNOSIS: Medical electronic thoracoscopy was performed to obtain a pleural biopsy, which showed lymphoplasmacytic infiltration, 40 IgG4+ plasma cells per High Power Field (HPF) on microscopy, IgG4/IgG ratio >50%, phlebitis obliterans, and storiform fibrosis. The final diagnosis was IgG4-RRD. INTERVENTIONS AND OUTCOMES: The patient was treated with methylprednisolone, after which his symptoms improved, and he was discharged. Oral hormone therapy was continued outside the hospital. After 4 months, the patient returned to the hospital and his condition had improved significantly. LESSONS: Pleural involvement in IgG4-RRD is rare, and its diagnosis depends on pleural biopsy. Thoracoscopy usually reveals pleural thickening, pleural nodules, and milky white plaques.

[Molecular cytogenetic study of a case with ring chromosome 15].

OBJECTIVE: To explore the genetic basis for a patient featuring developmental delay. METHODS: The patient and her parents were subjected to G- and C-banded chromosomal karyotyping analysis. The proband was also analyzed by single nucleotide polymorphism microarray (SNP-array). The result was verified by using fluorescence quantitative PCR (qPCR). RESULTS: The proband's karyotype was ascertained as 46,XX, r(15)(p11.2q26.3)[92]/45,XX,-15[9]/46,XX, dic r(15)(p11.2q26.3;p11.2q26.3)[4]. SNP-array revealed that she has carried a de novo deletion at 15q26.3 (98 957 555-102 429 040) spanning approximately 3.4 Mb, which encompassed the IGF1R gene. qPCR has confirmed haploinsufficiency of exons 3, 10 and 20 of the IGF1R gene. Both of her parents had a normal karyotype. CONCLUSION: The abnormal phenotype of the proband may be attributed to the microdeletion at 15q26.3, in particular haploinsuffiency of the IGF1R gene and instability of the ring chromosome. Cytogenetic method combined with SNP-array and qPCR can efficiently delineate chromosomal aberrations and provide accurate information for clinical diagnosis and genetic counseling.

Circulating low CD4+/CD8+ ratio is associated with poor prognosis in Waldenstrom macroglobulinemia patients.

Waldenstrom macroglobulinemia (WM) is a rare type of non-Hodgkin lymphoma with great heterogeneity, and the data of peripheral blood T-lymphocyte subsets in WM are limited. This study aimed to investigate the clinical correlation and distribution of circulating T-lymphocyte subsets in newly diagnosed WM patients. We retrospectively searched medical records for 86 newly diagnosed WM patients. Comparisons of the absolute CD3+ T-lymphocyte count (ACD3C), CD4+ T-lymphocyte count (ACD4C), CD8+ T-lymphocyte count (ACD8C), and CD4+/CD8+ T-lymphocyte ratio (CD4+/CD8+) as continuous parameters in different groups were calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). Young patients (<65 years) had lower ACD8C levels and a higher CD4+/CD8+ ratio. And the lower level of ß2-microglobulin (<3 mg/L) was associated with a higher CD4+/CD8+ ratio. With a median follow-up of 25 months, the univariate survival analysis showed that CD4+/CD8+ ratio inversion (CD4+/CD8+<1.5) was associated with shorter OS and PFS, and multivariate analysis confirmed that inverted CD4+/CD8+ ratio could be an independent adverse prognostic factor for OS and PFS. Additionally, initial treatment with rituximab or bortezomib significantly improved the PFS and OS of CD4+/CD8+ inversion patients but did not affect normal CD4+/CD8+ patients. We show that low circulating CD4+/CD8+ ratio at diagnosis is an adverse prognostic factor in WM patients and that first-line therapy which included rituximab or bortezomib significantly improved PFS and OS for patients with CD4+/CD8+ ratio less than 1.5.

Effects of IFN-γ on the proliferation of 32D cells expressing Akt after IRF-1 gene silencing.

BACKGROUND: Interferon regulatory factor-1 (IRF-1) plays a critical role in the injury to stem and progenitor regions associated with aberrant interferon-gamma (IFN-γ) in aplastic anemia (AA). The present study aimed to investigate the effects of IFN-γ on murine myeloid precursor cells (32D cells) with wild-type and inactive-type protein kinase B (Akt) after IRF-1 gene silencing. METHODS: With treatment of four concentrations of IFN-γ, the 32D cell viability and inhibition rate were assayed by middle-time-spray (MTS). The apoptosis rate was determined by flow cytometry, and the expression of the phosphorylated signal transducer and activator of transcription 3 (p-Stat3) and the phosphorylated signal transducer and activator of transcription 5 (p-Stat5) was analyzed by Western blot. RESULTS: The results from real time PCR (RT-PCR) assays suggested that the relative expression level of IRF-1-mRNA in the knockdown group (KD) was lower than that of in the negative control (NC) and blank control (Ctrl). In addition, the silencing efficiency was >70%, which was further validated by Western blotting. At 48 h, the rate of proliferation of 32D cells of wild-type Akt was significantly higher than that of inactive-type Akt (0.918±0.005 vs. 0.503±0.003, P=0.008), while the apoptosis rate in wild-type was significantly lower than that of inactive Akt (1.46%±0.41% vs. 2.98%±0.32%, P=0.006). After reducing the expression of IRF-1 gene, the promotion of hematopoiesis was recovered, resulting from the high concentration of IFN-γ achieved by reducing the expression of p-Stat5 via the Akt signaling pathway. CONCLUSIONS: Taken together, these results suggested that IRF-1 plays a critical role in the pro-apoptotic effect of IFN-γ on the proliferation of hematopoietic progenitor cells. These findings could contribute to understanding the mechanisms underlying the conversion from IFN-γ-mediated inhibition to promotion of hematopoiesis.

Clinical Characteristics of Infections Caused by Streptococcus Anginosus Group.

This study aimed to investigate the clinical characteristics, distribution of different strains and risk factors of patients infected with Streptococcus anginosus group (SAG). In the population of 463 patients, the male-to-female ratio was 1.95:1, and the patient age ranged from 6 months to 103 years. There were 49 children (10.58%), 311 young and middle-aged adults (67.17%), and 103 elderly adults (22.25%). Approximately 45.4% had underlying conditions, which were mostly malignant tumors and diabetes. Of the 463 specimens, 254 were S. anginosus (54.86%), 173 were S. constellatus (37.37%), and 36 were S. intermedius (7.77%). According to the age distribution, the incidence peaked in the 35-54 year age group. Different sites of infection had statistically significant differences regarding the constituent ratios of these three species. Different age groups also exhibited statistically significant differences in constituent ratios of the pathogenic organisms, as well as organ infections. In our population, 269 were clinically cured, 184 reported satisfactory improvement, and 10 died. SAG, as an opportunistic pathogen, can induce pyogenic infections in patients of all ages and shows no significant gender predilection in any age group. The three pathogenic organisms had differences with respect to patient age and infections of body sites.

Increased serum IL-17 and decreased serum IL-10 and IL-35 levels correlate with the progression of COPD.

Purpose: This study aimed to measure the serum levels of interleukin (IL)-17, IL-10, and IL-35 in patients with stable chronic obstructive pulmonary disease (COPD) and disclose the correlations between their expression levels and clinical factors of patients. Methods: A total of 75 patients with stable COPD (47 males and 28 females) and 30 healthy controls (15 males and 15 females) were included in this study. The serum levels of IL-17, IL-10, and IL-35 were determined by enzyme-linked immunosorbent assay. The correlations between their expression levels and clinical factors of patients were determined using linear regression methods. Results: The serum level of IL-17 was upregulated in stable COPD, and increased IL-17 expression was positively correlated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading, modified Medical Research Council (mMRC) score, and long clinical history (P<0.05), but negatively correlated with the pulmonary function (P<0.05) of patients. The serum levels of IL-10 and IL-35 were downregulated in stable COPD, and decreased IL-10 and IL-35 levels negatively correlated with the smoking status, GOLD grading, mMRC score, and long clinical history (P<0.05), but positively correlated with the pulmonary function (P<0.05) of patients. Moreover, the level of IL-17 negatively correlated with IL-10 and IL-35, but IL-10 positively correlated with IL-35. Conclusion: The serum levels of IL-17, IL-10, and IL-35 correlated with the clinical factors of COPD, indicating that they can serve as indicators to estimate the progression of COPD.

[Application of next generation sequencing for the analysis of patients with spontaneous abortion].

OBJECTIVE: To assess the value of next generation sequencing (NGS) for the analysis of spontaneous abortion samples. METHODS: The NGS analysis was carried out on 85 chorionic villi samples (taken between 42 days to 12 weeks of gestation) for which conventional cell culture has failed or chromosomal karyotyping has yielded normal or uncertain result. RESULTS: Among 68 samples with a normal karyotype, the NGS analysis has identified 2 copy number variations (CNVs) and 2 chimeras. For 16 cases with failed cell culture, the NGS has identified 4 chromosomal abnormalities including 1 copy number variation and 3 numerical chromosomal aberrations. For 1 remaining case with uncertain karyotyping result, the NGS analysis has verified it as 46,XX,del(4) (p15.1p16.3).seq[GRCh37/hg19] (57 549 - 32 371 364)×1. CONCLUSION: The NGS analysis is capable of identifying novel CNVs in samples for which conventional cell culture may fail or karyotyping analysis may yield a normal result.

Erlotinib induces the human non-small-cell lung cancer cells apoptosis via activating ROS-dependent JNK pathways.

Although erlotinib (ERL) has drawn more and more attention toward its anticancer properties effect, the underlying mechanisms of ERL's anticancer properties effect remain unclear yet. So, the aim of this research was to explore the underlying anticancer mechanisms of ERL and to explore whether the reactive oxygen species (ROS)-dependent c-Jun N-terminal kinase (JNK) pathway contributed to the anticancer properties provided by ERL. In our study, we used MTT assay to detect the anticell growth ability of ERL on human non-small-cell lung cancer cell lines (A549). The extent of cell apoptosis was determined by Hoechst 33342 staining and fluorescence-activated cell sorter (FACS) assay. Then, DCFH-DA and JC-1 staining were used to monitor intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP), respectively. Finally, the effect of ERL on phosphorylation state of JNK protein and downstream apoptosis concerned proteins were detected by western blotting assay. Results showed that ERL significantly suppressed the growth and reproduction of A549 cells with the concentration rising up in vitro. Hoechst 33342 staining and FACS assay also confirmed the proapoptosis effect of ERL on A549 cells with the concentration rising up. Furthermore, exposure of A549 cells to ERL increased the intracellular ROS production. As expected, intracellular ROS activated the proapoptotic JNK signaling pathway and inhibited the activation of EFGR signaling pathway. Our results also revealed that ERL could induce cell-cycle arrest at G0/G1 period. Activation of JNK protein decreased MMP and downregulated content of antiapoptotic protein Bcl-2 concomitant with the upregulated content of proapoptotic protein Bax in A549 cells. In addition, c-Jun and cleaved caspase-3 were also activated by the phosphorylated JNK induced by ERL. All of these proapoptosis effect of ERL was reversed by administration of N-acetylcysteine (NAC), which performed as a ROS scavenger. Our results suggest that ERL induces A549 cells apoptosis via activating ROS-dependent JNK pathways in human non-small lung cancer cells that provide a new experimental foundation for cancer therapy.

Deep molecular response by IFN-α and dasatinib combination in a patient with T315I-mutated chronic myeloid leukemia.

The T315I mutation is especially challenging as it confers resistance to all first- and second-generation tyrosine kinase inhibitors. We present here a chronic myeloid leukemia patient harboring the T315I and E255V BCR-ABL1 mutation successfully achieved deep molecular response with a combined treatment of dasatinib and IFN-α. To our knowledge, this is the second case of a T315I-bearing chronic myeloid leukemia patient displaying satisfactory response to the combination therapy of dasatinib and IFN-α.

Two cases of endobronchial aspergilloma with lung cancer: a review the literature of endobronchial aspergilloma with underlying malignant lesions of the lung.

Endobronchial aspergilloma is a rare disease entity with pulmonary involvement of aspergillus. Few cases of endobronchial aspergilloma associated with malignant lesions have been reported in the literature. We present 2 more cases of endobronchial aspergilloma with underlying lung cancer. And summarize the published literatures to investigate the clinical manifestations, bronchoscopic characters, imaging performances in patients with endobronchial aspergilloma with underlying malignant lesions of the lung. A review of the literature reveals 8 cases of endobronchial aspergilloma with coexisting lung malignant lesions upon presentation. The medical details of the patients including age, sex, clinical symptoms, radiological manifestations bronchoscopic characters, diagnosis and treatment are summarized. Endobronchial aspergilloma is usually incidentally detected in patients with underlying lung disease. With the increasing popularity of flexible bronchoscopy, it is being recognized as a necrotic mass causing bronchial obstruction. We should be paid more attention to prevent misdiagnosis of combined endobronchial aspergilloma and lung malignant diseases.

Red and Processed Meat Consumption Increases Risk for Non-Hodgkin Lymphoma: A PRISMA-Compliant Meta-Analysis of Observational Studies.

The association between consumption of red and processed meat and non-Hodgkin lymphoma (NHL) remains unclear. We performed a meta-analysis of the published observational studies to explore this relationship.We searched databases in MEDLINE and EMBASE to identify observational studies which evaluated the association between consumption of red and processed meat and risk of NHL. Quality of included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale (NOS). Random-effects models were used to calculate summary relative risk (SRR) and the corresponding 95% confidence interval (CI).We identified a total of 16 case-control and 4 prospective cohort studies, including 15,189 subjects with NHL. The SRR of NHL comparing the highest and lowest categories were 1.32 (95% CI: 1.12-1.55) for red meat and 1.17 (95% CI: 1.07-1.29) for processed meat intake. Stratified analysis indicated that a statistically significant risk association between consumption of red and processed meat and NHL risk was observed in case-control studies, but not in cohort studies. The SRR was 1.11 (95% CI: 1.04-1.18) for per 100 g/day increment in red meat intake and 1.28 (95% CI: 1.08-1.53) for per 50 g/day increment in processed meat intake. There was evidence of a nonlinear association for intake of processed meat, but not for intake of red meat.Findings from our meta-analysis indicate that consumption of red and processed meat may be related to NHL risk. More prospective epidemiological studies that control for important confounders and focus on the NHL risk related with different levels of meat consumption are required to clarify this association.

[Systematic genetic analysis for a case with duplication 9p].

OBJECTIVE: To identify the genetic cause for a case with growth retardation and mental retardation. METHODS: After conventional peripheral blood karyotyping with G-banding, the abnormal chromosome was identified as suspicious 9p duplication by multiplex ligation dependent probe amplification (MLPA) . RESULTS: The proband's karyotype was suspicious 46,XY,der(9)t(9;14)(q13;q11.2), then the abnormal chromosome 9 was identified as 9p duplication with MLPA. The 9p duplication occurs because of a balanced chromosomal rearrangement between two chromosomes of 9 and 14 in the proband's father. CONCLUSION: 9p11.2-p24.3 duplication is the cause of abnormal phenotypes in the child patient. Cytogenetic methods combined with MLPA can efficiently identify abnormal chromosomes and provide accurate results for clinical diagnosis and treatment.

Establishment and characterization of a rare atypical chronic myeloid leukemia cell line NT-1.

Human leukemia cell lines are of great value in leukemia research. In this study, we established and described the biological characteristics of a rare atypical chronic myeloid (aCML) leukemia cell line (NT-1). Mononuclear cells were isolated from the bone marrow of a patient with atypical chronic myeloid leukemia (Ph(-)/bcr(-)/abl(-)), and were passaged by liquid culture. Cells were maintained without any cytokines for over 1 year, and named NT-1. This cell line was extensively characterized using morphological assays, flow cytometry, cytogenetic analysis, clonogenic culture, quantitative fluorescent PCR, short tandem repeating sequence PCR (STR-PCR) and array-CGH. Its tumorigenic capacity was also examined in nude mice. The NT-1 cell line had morphological features of chronic myeloid leukemia and major myeloid markers (CD13, CD33, CD11b). Additionally, NT-1 expressed progenitor cells and natural killer cell-related antigens such as CD34, CD117, CD56. Cytogenetic analysis initially demonstrated two abnormalities: 47, xx, +8 and 47, xx, +8 accompanied by t(5;12)(q31;p13) translocation. The one-year passage process did not alter the karyotype. NT-1 cells maintained the same morphology, immunophenotyping and cytogenetic features as primary leukemia cells, which was strongly supported by STR-PCR results. Neither Epstein-Barr virus nor mycoplasma was detected in the NT-1 line. In addition, NT-1 cells showed high tumorigenic capacity in nude mice. NT-1 is a new atypical chronic myeloid leukemia cell line with the +8 and t(5,12) translocation, and exhibits high tumorigenicity in nude mice. This new cell line provides a useful tool for the study of leukemogenesis.

[Sorting of side population cells from multiple myeloma cell lines and analysis of their biological characteristics].

This study was aimed to sort the side population (SP) cells from human multiple myeloma cell lines, then detect the biological characteristics of those SP cells. After Hoechst33342 staining, intracellular Hoechst33342 fluorescence staining differences of myeloma cell lines observed by the fluorescence microscopy. The fluorescence-activated cell sorting (FACS) technology was used to isolate SP cells and main population (MP) cells; proliferative capacity in vitro was determined by cell growth curve; the cell colony forming ability was compared by colony forming test. The CD138 expression was detected by flow cytometry. The expression of ABCG2 mRNA was detected by reverse transcription PCR; CCK-8 assay and colony forming test were used to evaluate the effect of bortezomib on the cell proliferation, vitality and colony forming ability of the two populations. The results showed that the myeloma cell lines had a small proportion of SP cells, especially, RPMI 8226 cells accounted for the highest proportion of SP cells (7.10 ± 2.69)%, which have also been confirmed under the fluorescence microscope; the proliferative activity and cell colony forming ability of SP cells were significantly higher than those of MP cells (P < 0.05). The expression levels of CD138 in SP and MP cells were not significantly different (P > 0.05). RT-PCR results showed that SP cells expressed the drug-resistance gene ABCG2, but MP cells hardly express these genes. The inhibition rate of bortezomib on SP cells was significantly lower than that on MP cells (P < 0.05), however, the difference was not significant (P > 0.05) at bortezomib 40 nmol/L. Bortezomib could reduce colony formation in the both two cell populations, but more severe reduction appeared in the MP cells. It is concluded that the myeloma cell line contain a small amount of SP cells with the cancer stem cell characteristics.

[Genetic analysis of a family with super-male syndrome].

OBJECTIVE: To identify the genetic cause for a family featuring language retardation using combined cytogenetic and molecular genetic methods. METHODS: Following conventional G-banded karyotype analysis, the additional Y chromosome was identified by fluorescence in situ hybridization (FISH) and multiplex ligation dependent probe amplification (MLPA). Whole genome array comparative genomic hybridization (aCGH) was also carried out to detect minor structural chromosomal abnormalities. RESULTS: The proband's karyotype was determined as 47,XY,+?, and the unknown aberrant chromosome was identified as Yqh+ with FISH, MLPA and aCGH. No other chromosomal abnormality was found in the pedigree. CONCLUSION: Cytogenetic methods combined with FISH, MLPA, and aCGH can efficiently identify the origin of unknown chromosomes and provide accurate clues for clinical diagnosis and treatment.

Kurthia huakuii sp. nov., isolated from biogas slurry, and emended description of the genus Kurthia.

A novel facultatively anaerobic bacterium, designated strain LAM0618(T), was isolated from biogas slurry samples collected from the large-scale anaerobic digester of Modern Farming Corporation in Hebei Province, China. Cells of strain LAM0618(T) were Gram-stain-positive, motile, non-spore-forming and short-rod-shaped. The optimal temperature and pH for growth were 30 °C and 7.0, respectively. The strain did not require NaCl for growth but tolerated up to 70 g NaCl l(-1). The major fatty acids of strain LAM0618(T) were iso-C(15 : 0), anteiso-C(15 : 0), iso-C(14 : 0), C(16 : 0) and C(18 : 0). The predominant menaquinones of strain LAM0618(T) were menaquinone 7 (MK-7) and menaquinone 6 (MK-6). The main polar lipids of strain LAM0618(T) were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and six unknown glycolipids. The genomic DNA G+C content was 41 mol% as determined by the Tm method. Analysis of the 16S rRNA gene sequence revealed that strain LAM0618(T) was a member of the genus Kurthia, and was most closely related to 'Kurthia massiliensis' DSM 24639, Kurthia zopfii DSM 20580(T), Kurthia gibsonii DSM 20636(T) and Kurthia sibirica DSM 4747(T), with 96.9, 95.7, 95.6 and 94.9 % sequence similarity, respectively. Based on its phenotypic and genotypic properties, strain LAM0618(T) is suggested to represent a novel species of the genus Kurthia, for which the name Kurthia huakuii sp. nov. is proposed. The type strain is LAM0618(T) ( = ACCC 06121(T) = JCM 19187(T)).

[Effects of down-regulated TRAF6 gene expression on the proliferation and apoptosis in multiple myeloma cells].

OBJECTIVE: To investigate the down-regulated TRAF6 gene expression and its effects on proliferation and apoptosis in multiple myeloma (MM) cells. METHODS: Detection of TRAF6 expression were conducted by RT-PCR and Western blot in MM cell lines of KM3, U266, RPMI8226 and primary cells from patients. RPMI8226 cell lines were transfected with siRNA of TRAF6. The efficiency of transfection was identified by using of fluorescence microscope, RT-PCR, and Western blot. The levels of proliferation were analyzed by CCK-8 method under the different concentrations of siRNA. Apoptosis rate were detected with Hoechst33258/PI double staining by flow cytometry. Apoptosis related proteins Bcl-2, BAX, and NF-κB signal pathway were observed before and after siRNA transfection by Western blot. RESULTS: The levels of TRAF6 mRNA and protein in MM cell lines, especially in primary myeloma cells, were significantly higher than those in controls. After transfected with 50 nmol/L siRNA in RPMI8226 cells, the relative level of TRAF6 mRNA (0.49±0.24) was significantly lower than that in non-transfected group (1.87±0.23) and idling group (1.74±0.35). The proliferation rate of siRNA transfected cells decreased with dose dependence (P<0.01). The apoptosis rates increased from 11.20% (before transfection) to 51.82% (after transfection), accompanied by down-regulated Bcl-2 protein, NF-κB signal pathway (p-p65 and p52), and up-regulated BAX protein. CONCLUSION: TRAF6 expression was high in myeloma cells. TRAF6 siRNA could inhibit proliferation of myeloma cells and induce apoptosis mediated by NF-κB classical and alternative pathway in myeloma cells.

Isolation and characterization of a novel cinosulfuron degrading Kurthia sp. from a methanogenic microbial consortium.

A novel bacterial strain LAM0713 was isolated from a methanogenic bacterial complexes and identified as Kurthia sp. based on morphological, cultural, physio-biochemical characteristics and analysis of 16S rDNA sequence. Strain LAM0713 was found to be capable of utilizing cinosulfuron as sole nitrogen source for growth over a wide range of temperature (20-40 °C) and pH (5.0-9.0). Response surface methodology was used to optimize the degradation conditions. Strain LAM0713 could efficiently degrade 92.4% of initially supplemented 50 mg·L(1) cinosulfuron under the optimum conditions (pH 6.9, 31.8 °C) within 5 days. Five intermediates formed during cinosulfuron degradation were detected by liquid chromatography mass spectrometry (LC-MS), and a metabolic pathway for cinosulfuron degradation was proposed via cleavage of the sulfonylurea bridge. It is the first report showing that Kurthia sp. strain could degrade sulfonylurea herbicides, suggesting that strain LAM0713 may provide new insight into microbial degradation of herbicides.

Retrospective study of modified SMILE chemotherapy for advanced-stage, relapsed, or refractory extranodal natural killer (NK)/T cell lymphoma, nasal type.

Extranodal natural killer/T cell lymphomas, nasal type (ENKLs), which are a group of non-Hodgkin lymphomas with poor prognoses, are much more common in China than in Western countries. Here, we retrospectively assessed the impact of two treatment regimens on clinical response and survival among 42 ENKL patients. All patients were diagnosed with stage IV, relapsed, or refractory ENKL. Twenty patients received modified SMILE (consisting of L-asparaginase, methotrexate, ifosphamide, etoposide, and dexamethasone) chemotherapy, and 22 control patients received CHOP (consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone) treatment. Higher complete response (CR) and overall response rates (ORR) (CR 45.0 vs. 13%, ORR 70 vs. 36%) were observed among the patients treated with the modified SMILE regimen (Fisher's exact = 0.040, Pearson χ(2) P = 0.030). Similarly, a higher ORR rate was observed among Epstein-Barr virus-positive patients (ORR 50.0 vs. 18.0%, Fisher's exact = 0.049). The treatment group was also significantly associated with longer overall survival (OS) and progression-free survival (PFS) (Log-rank, P = 0.0341, P = 0.0142, respectively), but OS did not seem to be longer. Treatment-related toxicity was monitored in all patients throughout the protocol. There were no significant differences in the incidence of hematological and non-hematological toxicities between the two groups (P < 0.05), with the exception of peripheral neuropathy (treatment = 0 control = 5, Fisher's exact = 0.049).