[Pollution Characteristics and Sources of Wintertime Atmospheric Brown Carbon at a Background Site of the Yangtze River Delta Region in China].

To investigate the pollution characteristics and sources of atmospheric brown carbon (BrC) in Chongming Island, a background site of the Yangtze River Delta (YRD) region in China, PM2.5 samples collected from December 2018 to January 2019 were analyzed to determine their chemical compositions and optical properties. The results showed that the light absorption coefficient (Abs365,M) of BrC extracted by methanol at 365 nm was (5.39±3.33) M-1·m-1, which was 1.3 times of the water extracted BrC. Both increased significantly with the increase of pH values, suggesting that less acidic conditions can enhance the light absorption ability of BrC. In winter, both Abs365 and MAE365 (mass absorption efficiency) were higher in the nighttime than in the daytime. A strong linear correlation observed between Abs365 and levoglucosan (R2=0.72) indicated that many light absorbing substances in Chongming Island were derived from biomass burning emissions. During the campaign, nitro-aromatic compounds (NACs) and PAHs accounted for (1.5±1.1) ng·m-3 and (8.3±4.7) ng·m-3, respectively, contributing to 0.1% and 0.067% of the absorption of the total BrC at 365 nm, respectively. Positive matrix factorization (PMF) analysis further showed that biomass and fossil fuel combustions were the main sources of BrC in Chongming Island in winter, accounting for 56% of the total BrC, followed by secondary formation, accounting for 24% of the total BrC, with road dust contributing only 6%.

[Pollution Characteristics and Source Apportionment of n-Alkanes and PAHs in Summertime PM2.5 at Background Site of Yangtze River Delta].

To investigate the pollution characteristics and sources of organic aerosols at a background site of the Yangtze River Delta, day- and night- PM2.5 samples were collected from May 30th to August 15th, 2018 in Chongming Island, China and measured for their normal alkanes (n-alkanes) and polycyclic aromatic hydrocarbons (PAHs) content employing a GC-MS technique. Concentrations of PM2.5, n-alkanes, and PAHs during the entire sampling period were (33±21) µg·m-3, (26±44) ng·m-3, and (0.76±1.0) ng·m-3, respectively. During the entire campaign, 35% of the collected PM2.5 samples were of a particle loading larger than the first grade of the China National Air Quality Standard (35 µg·m-3), suggesting that further mitigation with respect to air pollution in Chongming Island remains imperative. In the period with a PM2.5 concentration higher than 35 µg·m-3, which was classified as the pollution period, concentrations of n-alkanes and PAHs were one order of magnitude higher than those in the period with PM2.5 less than 15 µg·m-3, which was classified as the clean period. During the entire campaign, OC was higher in the daytime than in the nighttime, mainly due to the daytime photooxidation that enhanced the formation of secondary organic aerosols. During the pollution period, concentrations of EC and other pollutants were higher in the nighttime than in daytime, mainly due to the transport of the inland pollutants by the nighttime land breeze. Such a diurnal difference was not observed for the pollutants in clean periods, mainly due to the relatively clean breeze from East China Sea that diluted the air pollution. Diagnostic ratios showed that 67% of n-alkanes in PM2.5 was derived from fossil fuel combustion. PMF analysis further showed that during the pollution period, vehicle exhausts and industrial emissions were the largest sources of PAHs, both accounting for 51% of the total in PM2.5. In contrast, during the clean periods ship emissions were the largest source, contributing about 45% of the total PAHs, exceeding the sum (38%) of vehicle and industrial emissions.

CAG regimen for refractory or relapsed adult T-cell acute lymphoblastic leukemia: A retrospective, multicenter, cohort study.

Adult patients with relapsed or refractory T-cell acute lymphoblastic leukemia (R/R-T-ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G-CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R-T-ALL patients. Here, we report the multicenter results of 41 patients who received the CAG regimen as salvage therapy. After one cycle of the CAG regimen, complete remission and partial remission were achieved in 33 (80.5%) and two (4.9%) patients, respectively. Failure to respond was observed in six patients (14.6%). Early T-cell precursor (ETP) (n = 26) and non-ETP (n = 15) patients had a similar CR rate (80.8% vs 80.0%, P = .95). Among 41 patients, allo-HSCT was successfully performed in 27 (66%) patients (22 in CR and 5 in non-CR). With a median follow-up time of 12 months, the estimated 2-year overall survival and event-free survival were 68.8% (95% CI, 47.3%-83.0%) and 56.5% (95% CI, 37.1%-71.9%), respectively. The CAG regimen was well-tolerated, and no early death occurred. Our multicenter results show that the CAG regimen is highly effective and safe, representing a novel choice for adult patients with R/R-T-ALL and providing a better bridge to transplantation.

Community-acquired versus hospital-acquired acute kidney injury in patients with acute exacerbation of COPD requiring hospitalization in China.

Purpose: Previous studies have described the incidence, risk factors, and outcomes for patients with acute exacerbations of COPD (AECOPD) developing acute kidney injury (AKI). However, little is known about the differences between community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) in patients with AECOPD. Thus, in this study, we compared prevalence, risk factors, and outcomes for these patients with CA-AKI and HA-AKI. Patients and methods: This study was conducted from January 2014 to January 2017, and data from adult inpatients with AECOPD were analyzed retrospectively. A total of 1,768 patients were included, 280 patients were identified with CA-AKI and 97 patients were with HA-AKI. Results: Prevalence of CA-AKI was 15.8% and that of HA-AKI was 5.5%, giving an overall AKI prevalence of 21.3%. Patients with CA-AKI had a higher prevalence of chronic kidney disease (CKD) and lower prevalence of chronic cor pulmonale than patients with HA-AKI. Risk factors for developing HA-AKI and CA-AKI were similar, such as being elderly, requirement for mechanical ventilation, and a history of coronary artery disease and CKD. Patients with HA-AKI were more likely to have stage 3 AKI and worse short-term outcomes. In comparison with patients with CA-AKI, those with HA-AKI were more likely to require non-invasive mechanical ventilation (31.3% versus 16.8%; P = 0.003) and had a longer duration of mechanical ventilation (11 days versus 8 days; P = 0.020), longer hospitalization (14 days versus 12 days; P = 0.038), and higher inpatient mortality (32.0% versus 13.2%; P < 0.001). Patients with HA-AKI had worse (multivariate-adjusted) inpatient survival than those with CA-AKI (hazard ratio, 1.7 [95% confidence interval, 1.03-2.81; P = 0.038] for the HA-AKI group). Conclusion: AKI was common in patients with AECOPD requiring hospitalization. CA-AKI was more common than HA-AKI but otherwise demonstrated similar demographics and risk factors. Nevertheless, patients with HA-AKI had worse short-term outcomes.

Assembly of an early-matured japonica (Geng) rice genome, Suijing18, based on PacBio and Illumina sequencing.

The early-matured japonica (Geng) rice variety, Suijing18 (SJ18), carries multiple elite traits including durable blast resistance, good grain quality, and high yield. Using PacBio SMRT technology, we produced over 25 Gb of long-read sequencing raw data from SJ18 with a coverage of 62×. Using Illumina paired-end whole-genome shotgun sequencing technology, we generated 59 Gb of short-read sequencing data from SJ18 (23.6 Gb from a 200 bp library with a coverage of 59× and 35.4 Gb from an 800 bp library with a coverage of 88×). With these data, we assembled a single SJ18 genome and then generated a set of annotation data. These data sets can be used to test new programs for variation deep mining, and will provide new insights into the genome structure, function, and evolution of SJ18, and will provide essential support for biological research in general.

Research progress of TREM2 in Alzheimer disease / 中国药理学与毒理学杂志

Alzheimer disease (AD) is a common neurodegenerative disease in the elderly, but nowadays the pathogenesis of AD is unclear. Myeloid cell 2 trigger receptor (TREM2) is one of the most famous and most common rare mutations in neurodegenerative disease research, and its functional site mutation can significantly increase the incidence of AD. In this paper, we summary the structure, localization, and function and related signaling pathways of TREM2, review the latest epide?miological findings of TREM2 associated with the pathogenesis of AD, and speculate on the possible role of TREM2 in the progression of this disease, as well as the expression of TREM2 and the role of soluble TREM2 in AD brain are further elucidated. Based on the potential protective effect of TREM2 in the pathogenesis of AD, Therefore, targeting TREM2 may provide new opportunities and a reference for AD treatment. As the TREM2 variant appears to be widely involved in neurodegenerative diseases, there is an urgent need to further study the function of TREM2 in the brain and to find its ligands involved in TREM2-mediated signaling transduction and its specific role in AD pathogenesis.

[Prognostic significance of EBMT score system for hematological malignancies with allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To evaluate the impact of EBMT score system in patients with hematological malignancies received allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 144 consecutive patients were analyzed retrospectively. According to the EBMT score system, including age, disease status before transplantation, interval between diagnoses to transplantation, donor/recipient sex match and donor type, patients were divided into 3 risk groups: low risk (score 0-1), intermediate risk (score 2-3) and high risk (score 4-7). RESULTS: The median follow-up duration were 413 (10-1827) days for all patients and 837 (166-1827) days for alive patients. The estimated 4-year overall survival (OS), transplant-related mortality (TRM) and relapse rate (RR) were (57.5±4.6)%, (21.6±3.7)% and (42.7±6.1)%, respectively. The 4-year OS, TRM and RR were (72.2±9.0)%, (8.1±4.5)% and (27.3±8.7)% in the low-risk group, significantly superior to both intermediate-risk group [(57.7±6.0)%, (23.1±5.1)% and (44.9±8.3)%] and high-risk group [(36.9±10.2)%, (33.5±9.2)% and (51.5±11.8)%] (P<0.01, 0.02 and 0.009 for OS, TRM and RR respectively). CONCLUSION: The EBMT score system provides prognostic significance for OS, TRM and RR in patients with hematological malignancies received allo-HSCT.

Targeting poly (ADP-ribose) polymerase partially contributes to bufalin-induced cell death in multiple myeloma cells.

Despite recent pharmaceutical advancements in therapeutic drugs, multiple myeloma (MM) remains an incurable disease. Recently, ploy(ADP-ribose) polymerase 1 (PARP1) has been shown as a potentially promising target for MM therapy. A previous report suggested bufalin, a component of traditional Chinese medicine ("Chan Su"), might target PARP1. However, this hypothesis has not been verified. We here showed that bufalin could inhibit PARP1 activity in vitro and reduce DNA-damage-induced poly(ADP-ribosyl)ation in MM cells. Molecular docking analysis revealed that the active site of bufalin interaction is within the catalytic domain of PAPR1. Thus, PARP1 is a putative target of bufalin. Furthermore, we showed, for the first time that the proliferation of MM cell lines (NCI-H929, U266, RPMI8226 and MM.1S) and primary CD138(+) MM cells could be inhibited by bufalin, mainly via apoptosis and G2-M phase cell cycle arrest. MM cell apoptosis was confirmed by apoptotic cell morphology, Annexin-V positive cells, and the caspase3 activation. We further evaluated the role of PARP1 in bufalin-induced apoptosis, discovering that PARP1 overexpression partially suppressed bufalin-induced cell death. Moreover, bufalin can act as chemosensitizer to enhance the cell growth-inhibitory effects of topotecan, camptothecin, etoposide and vorinostat in MM cells. Collectively, our data suggest that bufalin is a novel PARP1 inhibitor and a potentially promising therapeutic agent against MM alone or in combination with other drugs.

[Allogeneic peripheral blood stem cell transplantation from sibling donors for 10 patients with multiple myeloma].

OBJECTIVE: To evaluate the efficacy of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from sibling donors for treatment of multiple myeloma (MM). METHODS: Ten patients with MM received allo-PBSCT with conditioning consisting of fludarabine plus melphalan and cyclophosphamide mostly.CsA plus mycophenolate mofetil (MMF) and short-term MTX were applied to prevent graft versus host disease (GVHD) in 8 patients, FK506 plus short-term MTX in other 2 patients. RESULTS: All patients engrafted successfully, the median time for ANC > 0.5 × 10(9)/L was 16 (12 - 24) days, and for BPC > 20 × 10(9)/L 23 (16 - 102) days. Five patients developed acute GVHD, and only one III-IV aGVHD. Of 9 patients, 7 developed chronic GVHD. The transplant-related mortality (TRM) at 100 days was 10% (1/10), mainly from heart and renal failure and severe infection. The 1-year expected overall survival (OS), 1-year disease-free survival (DFS) and relapse rate were 67.5%, 55.56% and 11.11% respectively. Up to now, 6 patients were still alive, of them 1 patient have survived over 99 months after allo-PBSCT. CONCLUSION: Young MM patients having HLA-identical sibling donors well tolerated allo-PBSCT based on fludarabine to prolong their OS by reducing TRM, though further work is warranted.

[Treatment options and prognosis in newly diagnosed multiple myeloma patients].

OBJECTIVE: To explore the effect of treatment option on the response and outcomes in multiple myeloma (MM) patients suitable for autologous hematopoietic stem cell transplantation (auto-HSCT). METHODS: A total of 71 newly-diagnosed MM patients less than 65 years admitted to RuiJin Hospital from June 2005 to December 2009 were analyzed retrospectively. Among them, 21 received auto-HSCT (HSCT group) with standard conditioning of melphalan 200 mg/m(2), 30 received conventional chemotherapy (conventional group) and 20 received Bortezomib-based therapy (Bortezomib group). The responses and outcomes of different treatments were analyzed. RESULTS: The median follow-up duration for all patients was 18 (1 - 58) months with estimated 3-year overall survival (3-yr OS) of (79.8 ± 6.3)% and progression-free survival (3-yr PFS) of (54.8 ± 9.0)%. Thirty-four patients achieved complete remission (CR) or very good partial remission (VGPR) on induction therapy, which were 80% for the Bortezomib group, 33.3% for the conventional group and 38.3% for the HSCT group. After auto-HSCT the CR + VGPR rate was increased to 76.1% for the HSCT group. Overall, the 3-yr PFS was (26.3 ± 13.8)% (median 21 months), (40.5 ± 20.1)% (median 25 months) and (93.8 ± 6.1)%(median not reached, P = 0.025) for conventional, Bortezomib and HSCT groups respectively. Univariate analysis demonstrated that CR/VGPR after induction (P = 0.020), best response of CR/VGPR (P < 0.01), autoHSCT (P = 0.002) and maintenance therapy after CR/VGPR (P = 0.0005) were associated with improved PFS and that CR/VGPR after induction (P = 0.009), best response with CR/VGPR (P < 0.01), maintenance therapy for any patients (P = 0.035) and maintenance therapy for patients with CR/VGPR (P = 0.031) were associated with OS. In multivariate analysis, only auto-HSCT (P = 0.039) and best response of CR/VGPR (P = 0.009) were independent prognostic factors for PFS and the best response of CR/VGPR was the only independent prognostic factor for OS (P = 0.005). The estimated 3-yr OS was (62.4 ± 13.7)%, (94.1 ± 5.7)% and (87.9 ± 8.3)% respectively for 3 groups. CONCLUSIONS: For newly-diagnosed MM younger than 65 are suitable for auto-HSCT, the best response of CR/VGPR was associated with OS and PFS. Auto-HSCT is also important prognostic factor for PFS. Induction therapy with Bortezomib can achieve rapid CR/VGPR while auto-HSCT as a crucial consolidation therapy and maintenance therapy maybe also important for improvement of long-term outcome.

Intravenous busulfan-cyclophosphamide as a preparative regimen before allogeneic hematopoietic stem cell transplantation for adult patients with acute lymphoblastic leukemia.

The use of i.v. busulfan (BU) instead of the oral formulation can improve outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) by reducing toxicity and transplantation-related mortality (TRM). There are limited reports of i.v. BU used to treat patients with acute lymphoblastic leukemia (ALL). The present study was performed to evaluate the efficacy and toxicity of i.v. BU/cyclophosphamide (CY) conditioning in adult ALL. We retrospectively analyzed 42 consecutive patients who underwent allo-HSCT with BU/CY conditioning between January 2007 and October 2010 with an HLA-matched donor (sibling, n = 18; unrelated, n = 24). Thirty-three patients were in first complete remission (CR1), 2 were in second complete remission (CR2), and 7 were in a more advanced stage. Median patient age was 28 years (range, 17∼55 years). The median follow-up was 15 months (range, 1∼48 months). Overall, 13 patients died, for a 30-month overall survival of 56.5% ± 10.6% (65.7% ± 12.5% for patients in CR1 vs 25.4% ± 15.5% for those in CR2 or beyond; P < .001). Eleven patients experienced relapse between 2 and 26 months after allo-HSCT, with a 30-month relapse rate (RR) of 40% ± 10.9% (32.0% ± 12.7% for patients in CR1 vs 71.4% ± 17.1% for those in CR2 or beyond; P = .001). The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 39.2% ± 8.8%, and that of grade III-IV acute GVHD was 7.4% ± 4.1%. The incidence of chronic GVHD was 63.9% ± 11.7%, and that of extensive chronic GVHD was 19.3% ± 7.9%. Only 2 cases of clinically diagnosed veno-occlusive disease (VOD) were documented (4.7%), and 1 of these patients died of severe VOD. Other BU/CY conditioning-associated toxicities were diffuse alveolar hemorrhage in 1 patient and hemorrhagic cystitis in 8 patients. Four patients died due to TRM, for a 30-month TRM of 9.7% ± 4.6%. This study demonstrates that i.v. BU/CY can be considered a feasible conditioning regimen for adult ALL, with low incidences of VOD and TRM.

[The impact of autologous stem cell transplantation on the prognosis in multiple myeloma].

OBJECTIVE: To evaluate the efficacy of autologous stem cell transplantation (ASCT) in the treatment of multiple myeloma (MM) and its impact on the prognosis of MM. METHODS: Retrospective analysis was performed in 28 patients with MM (group A) treated with ASCT in our hospital from October 1998 to February 2007, compared with those not received ASCT in the same time period including 23 patients with near complete response (nCR) or better (group B) and 25 patients with partial response (PR) (group C). The duration of response (DOR), time to progression (TTP) and overall survival (OS) were compared by Kaplan-Meier method in the 3 groups. RESULTS: Eight patients without nCR or better (7 in PR and 1 in MR) after ASCT achieved CR (2 cases) and nCR (5 cases). Complete response (CR) rate was 10.7% (3 cases) and 42.9% (12 cases) before and after ASCT respectively in group A. DOR was 33 months for group A, 17 months for group B and 18 months for group C, and TTP was 45, 43 and 28 months respectively. After a median follow-up of 30 months, patients in group A and in group B had a trenel of longer OS than in group C although there was no statistically significant difference. CONCLUSIONS: ASCT can further enhance the response, prolong the DOR and TTP and probably OS, and therefore improve the quality of life in MM. MM patients not achieved good response by non-ASCT therapy may benefit from ASCT.

[Detection of serum free light chain and its clinical significance in nonsecretory multiple myeloma].

OBJECTIVE: To explore the clinical significance of serum free light chain (sFLC) levels in nonsecretory multiple myeloma (NSMM). METHODS: Nine NSMM patients were hospitalized in our department from Feb 2002 to Sep 2006 and no M-components was found in their serum and urine by immunofixation electrophoresis (IFE). sFLC was assayed by immuno-nephelometry. The clonality of sFLC was estimated by serum kappa:lambda sFLC ratio. Meanwhile, serum immunoglobulin, total kappa and lambda light chain level were also determined in these patients. RESULTS: Increased serum concentrations of either kappa or lambda sFLC (and abnormal kappa/lambda ratios) were detected in 6 of 9 patients with NSMM although their serum immunoglobulin levels were not elevated and total kappa:lambda light chain ratios (1.32 - 2.20) were in the reference range. All the 9 patients had clonal IgH gene rearrangements. CONCLUSION: Quantification of sFLC by immuno-nephelometry is more sensitive than that of serum total light chain measurement and is helpful in estimating the clonality of the light chain in patients with NSMM.

[Bortezomib-based combination therapy for relapsed or refractory multiple myeloma].

OBJECTIVES: To investigate the efficacy and toxicity of bortezomib based combination therapy for Chinese patients with relapsed or refractory multiple myeloma (MM), and to determine the combination regimen, dosage and cycles in application of bortezomib for MM therapy. METHODS: Forty-six patients with refractory or relapsed myeloma were treated with bortezomib (1.3 mg/m2) as an intravenous bolus twice weekly for 2 weeks on day 1, 4, 8, and 11 in a 3-4 week cycle, in combination with dexamethasone, dexamethasone plus thalidomide, CD (C-cytoxan, D-dexamethasone), MD (M-mitoxsnteone), DCEP (E-etoposide, P-platinol), and DT-PACE regimens (T-thalidomide, A-adriamycin). Response to bortezomib was evaluated according to the criteria of the International Myeloma Working Group (IMWG) before initiation of each cycle. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Forty-nine matched patients with relapsed and refractory MM who received thalidomide based combination therapy were used as a historical control group. RESULTS: Among 43 of the 46 patients whom could be evaluated, the overall response rate was 72.1% (the control group was 51.0%, P < 0. 05), including complete response in 5 patients (11.6%), very good partial response in 12 patients (27.9%), and partial response in 14 patients (32.6%). The overall response rate after one and two cycles was 30.2% and 58.1% (P < 0.05), respectively. The frequent adverse events were thrombocytopenia (62.8%), fatigue (55.8%), nausea (51.2%) and peripheral neuropathy (30.2%); all of the events could be tolerated. The most common adverse event in the control group was constipation( 69.4%), followed by fatigue (59.2%) and dizziness (46.9%). CONCLUSIONS: Bortezomib based combination therapy is a new effective therapy in relapsed or refractory myeloma patients with a higher response rate and different toxicities as compared with thalidomide based combinations.

[Efficacy of thalidomide combined dexamethasone on newly diagnosed multiple myeloma].

BACKGROUND & OBJECTIVE: Thalidomide is effective in treating refractory and relapsed multiple myeloma (MM). However, the efficacy of thalidomide in induction therapy for newly diagnosed MM remains unknown. This study was to evaluate the efficacy of thalidomide combined dexamethasone (TD induction regimen) on previously untreated MM, and observe the adverse events. METHODS: Thirty-nine patients with newly diagnosed MM received oral administration of thalidomide at a dose of 100-300 mg/day continuously and dexamethasone at a dose of 20-40 mg/day on Days 1-4, 9-12, 17-20 in odd months and on Days 1-4 in even months. TD regimen was repeated every 28 days. Thirty-six MM patients who received VAD regimen (vindesine, adriamycin, and dexamethasone) was regarded as a historical matched controls. The efficacy, survival time and adverse events were compared between the two groups. RESULTS: The overall response rates were 71.8% in TD group and 61.1% in VAD group (P>0.05). The median progression-free survival was 14 months in TD group and 9 months in VAD group (P>0.05). Within a median follow-up of 13 months (range, 1-30 months), median overall survival (OS) was not reached in TD group, and was 29 months in VAD group. The most common adverse events (always not higher than grade 2) were constipation, fatigue, dizziness and somnolence in TD group. More grade 3-4 adverse events, included leucopenia and thrombocytopenia, and higher infection rate were observed in VAD group as compared with those in TD group (P<0.05). CONCLUSIONS: The combination of thalidomide and dexamethasone is an effective induction regimen for newly diagnosed MM. It may be considered as a replacement of VAD regimen.

Prognostic factors and staging systems of multiple myeloma:.

BACKGROUND: Previous studies found a range of prognostic factors but no consensus about the proper staging system for multiple myeloma has been achieved. This study explored the prognostic factors to find a staging system for multiple myeloma most suitable for Chinese patients. METHODS: Between February 1990 to August 2004, 206 patients (138 men and 68 women, mean aged (59 +/- 11) years) who were initially diagnosed as multiple myeloma in Changzheng Hospital (Shanghai, China) and had followup records were enrolled in this study. Potential prognostic factors were evaluated by univariate and multivariate analyses. Four staging systems were applied to compare their suitability for the patients. RESULTS: The median survival time of the patients was 33 months. The 1-, 3- and 5-year survival rates were 80.18%, 48.08% and 33.7% respectively. Factors identified as adversely affecting survival were older age, severe bone lesions, low haemoglobin, low platelet, low serum calcium, low serum albumin, high proportion of plasma cells in marrow, high serum creatinine, high serum beta(2) microglobulin and high C-reactive protein. Among these, only C-reactive protein, beta(2) microglobulin, albumin and age were the independent prognostic factors. There were statistically significant survival differences among the three groups in Durie Salmon staging system and Bataille staging system, but not in British Medical Research Council staging system or International Staging System. CONCLUSIONS: High beta(2) microglobulin, high C-reactive protein, low albumin and old age are independent prognostic factors of multiple myeloma. Bataille staging system appears to be optimal for Chinese multiple myeloma patients.

[Clinical features of multiple myeloma patients with extramedullary disease: a report of 40 cases from a single center].

OBJECTIVE: To analyze the clinical and laboratory features and risk factors of multiple myeloma (MM) with extramedullary disease (EM) and its extraosseous localizations at diagnosis and during the course of MM. METHODS: The clinical features, survival rate and prognostic factors were retrospectively analyzed in 40 patients having EM from a total of 418 MM patients hospitalized in Changzheng Hospital from 1993 to 2006. RESULTS: Among the 40 patients, the first three localizations of EM involved soft tissue, pleura or peritoneum and central nervous system (CNS). Median duration of follow-up was 30 months. The median overall survival (OS) was 28 months. Twenty-five patients (6%) were found to have EM at diagnosis (group A), and their median OS was 16 months and 15 patients (3.6%) developed EM during the course of the disease (group B), and their expected median OS was 72 months. There was a significant difference between group A and B (P = 0.0045) for OS. Compared with those in group A, patients in group B had a higher percentage of plasmacytes (P = 0.022) and plasmablasts (P = 0.029) in bone marrow, and less advanced stage for international staging system (ISS) (P = 0.027). Log-rank univariate analysis showed that higher CRP level, higher serum LDH, Stage II and III for ISS, Hb < 110 g/L at diagnosis were poor prognostic factors. However, multivariate analysis with COX model showed none of them were statistically significant. CONCLUSION: EM tumors are not a rare manifestation of MM. Soft tissue in the commonest area involved. Higher serum CRP and LDH level, more advanced stage for ISS, anemia and having EM are poor prognostic factors of MM.

[Prognostic analysis and assessment on the clinical staging systems of multiple myeloma--a report of 206 cases].

BACKGROUND & OBJECTIVE: Multiple myeloma (MM) is a heterogeneous disease of plasma cell tumor with poor prognosis. This study was to explore the prognostic factors of MM in China, and find the most suitable clinical staging systems. METHODS: Univariate and multivariate analyses were carried out on 18 clinical and laboratory indexes from 206 MM patients. These MM patients were classified according to 4 staging systems to compare their survival status. RESULTS: Of the 206 patients, 138 were men and 68 were women, with median age of 59 years (ranged 27-90 years) and median survival time of 33 months. The 2-and 5-year survival rates were 64.7% and 33.7%. Univariate analysis identified 10 prognostic factors: age, the amount of bone marrow plasma cells, hemoglobin, platelet count, adjusted serum calcium, albumin, creatinine, beta2 microglobulin, C-reactive protein, and skeletal disease stage. Multivariate analysis showed that C-reactive protein, beta2 microglobulin, albumin, age were independent prognostic factors. Significant differences of survival period existed among the 3 groups classified according to Durie Salmon staging system and Bataille staging system as well as between group I and group II of International staging system. However, no significant difference was found among the 3 groups classified according to British Medical Research Council staging system and between group II and group III of International staging system. CONCLUSIONS: High level of C-reactive protein, high level of beta2 microglobulin, low level of albumin and old age are correlated to poor prognosis. Durie Salmon staging system and Bataille staging system are suitable for Chinese MM patients.

[Bortezomib in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma].

OBJECTIVE: To investigate the efficacy and toxicity of bortezomib in combination with dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma(MM). METHODS: Sixteen patients(9 males, 7 females, mean age 57. 5 yrs) with refractory or relapsed MM were treated with bortezomib (1. 3 mg/m(2) ) by intravenous bolus twice a week for 2 weeks, or 3. 5 mg once a week in a 21-day cycle, followed by an intravenous injection of dexamethasone 30 - 40 mg. The patients had received one to four courses at least. Response to bortezomib was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation (EBMT) before initiation of each bortezomib chemotherapy course. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3. 0. RESULTS: The median follow-up duration from the beginning of bortezomib treatment was 6 months. Clinical response was observed in 14 patients (87.5%), including near complete response in 6, partial response in 5, minimal response in 3 and no response in 2. The most common adverse events were gastrointestinal symptoms (nausea and vomiting in 12, constipation in 3, severe diarrhea in 3 patients), thrombocytopenia (8 patients) and fatigue(3 patients). The adverse events were subsided on routine supportive care. CONCLUSIONS: Bortezomib in combination with dexamethasone is an effective therapy with a high response rate and manageable toxicities for patients with relapsed or refractory myeloma.

[The effect of cyclin D2 shRNA on the proliferation and apoptosis of LP-1 cell].

OBJECTIVE: To construct cyclin D2 (CCND2) short hairpin RNA ( shRNA) plasmid for repressing the expression of CCND2 in human myeloma cell line LP-1,and to detect its effect on the proliferation and apoptosis of LP-1 cell. METHODS: A CCND2 shRNA model was constructed and cloned into plasmid pGensil-2, then the plasmid was transfected into LP-1 cell in vitro. The CCND2 expression cell proliferation, cell cycle and cell apoptosis of the transfected LP-1 cells were studied by RT-PCR, trypanosome staining, flow cytometry and annexin V assay. RESULTS: The transfection efficiency of LP-1 cell was 34. 2%. In the transfected LP-1 cell CCND2 mRNA expression was reduced significantly, the cell growth was inhibited significantly and the cell cycle was partly arrested in G, phase. The apoptosis rate of the transfected LP-1 cell after 72 h was (25.7+/-4.8)%. CONCLUSION: The inhibition of CCND2 in LP-1 cells could inhibit the cell growth and induce cell apoptosis. CCND2 maybe a new therapeutic target.