[New agents-based induction chemotherapy followed by autologous stem cell transplantation and maintenance treatment strategy for multiple myeloma: a single center retrospective study of 300 cases].

Objective: To examine the survival and influential factors of an integrated approach of novel agents, autologous hematopoietic stem cell (auto-HSCT) , and maintenance therapy in patients with multiple myeloma (MM) patients from a single center over the past 15 years. Methods: In our center, 300 MM patients who received an integrated strategy of new agents, auto-HSCT, and maintenance therapy over 15 years were retrospectively and prospectively analyzed. Results: The complete remission rates (CR) and ≥very good partial remission rates (VGPR) following induction therapy, transplantation, and maintenance therapy were respectively 35.3% and 55.2% , 72.4% and 80.0% , 89.2% , and 93.4% . When compared to patients receiving double-drug induction, the ≥VGPR and ORR of patients receiving triple-drug induction were improved. No difference existed in CR, ≥VGPR, and ORR between the PAD (bortezomib + liposome doxorubicin+ dexamethasone) and RAD (lenalidomide + liposome doxorubicin + dexamethasone) regimens, but the benefits speed differed. The negative rate of flow minimal residual disease following induction, transplantation, and maintenance was 18.8% (54 cases) , 41.4% (109 cases) , and 58.7% (142 cases) , respectively. The median time to progress (TTP) was 78.7 months and the median overall survival (OS) was 109 months. The median TTP for RISS-Ⅰ-Ⅲ patients were 111.8 months, 77.4 months, and 30.6 months, and the median OS was 118.8 months, 91.4 months, and 48.5 months, respectively. At various points during treatment, the TTP and OS of patients obtaining CR and MRD negative were longer than those of patients who did not obtain CR and MRD negative. TTP was noticeably shorter in high-risk cytogenetic patients compared to standard-risk patients even when CR was acquired during induction. There was no difference in TTP between patients with high-risk cytogenetics and those with standard-risk cytogenetics if MRD negative was acquired during induction. According to a multivariate analysis, the R-ISS stage was a poor predictor of TTP and OS at various treatment intervals. Therapeutic effectiveness was a newly independent prognostic factor following treatment. Conclusion: A median survival of almost 10 years is possible for MM patients who receive an integrated strategy of induction regimens followed by auto-HSCT and maintenance therapy, which significantly improves prognosis. However, this approach did not significantly benefit high-risk cytogenetic MM patients.

Protective effect of estrogen receptors (ERα/ß) against the intervertebral disc degeneration involves activating CCN5 via the promoter.

OBJECTIVE: Due to the decrease of estrogen and estrogen receptor (ER) in postmenopausal women, they have a higher risk of intervertebral disc degeneration (IDD) than men. This study aims to explore how ERα and ERb interact with CCN5 and protect IDD. PATIENTS AND METHODS: We used Chromatin immunoprecipitation (ChIP) and Luciferase reporter assay to determine whether the ERα/b protein binds to CCN5 promoter and activates its expression. We used TNF-α to induce nucleus pulposus (NP) cell degeneration to simulate the IDD process. The change of the expression of ERα/ß and CCN5 was measured in the degenerated NP cells. To understand the function of ERα/ß in the NP cells degeneration, we upregulated the ERα/b gene expression by vector transfection or 17b-estradiol (E2) stimulation. Besides, we also used the CCN5 gene-silenced NP cells by siRNA transfection as a comparison to determine the role of CCN5. We tested the cell proliferation and principal components of the extracellular matrix (ECM) to value the degree of NP cell degeneration. RESULTS: ERα and ERß protein can bind to the same promoter regions of CCN5 and activate its expression, respectively. TNF-α degraded NP cells with a reduction of cell proliferation, collagen II, ACAN, ERα, ERß, and CCN5 expression, and increased collagen I/III, and MMP-13 expression. Upregulated ERα or ERß resulted in the maintains of CCN5 and alleviated the NP cell degeneration. Besides, 17ß-E2 supplement increased the ERα, ERß, and CCN5 expression, as well as stable NP cells phenotype. However, it was partly abolished by the silencing of CCN5. CONCLUSIONS: Upregulation of ERα and ERß protects the NP cell degeneration during IDD through the activation of CCN5 by binding to its promoter.

[Bortezomib-based induction chemotherapy followed by autologous hematopoietic stem cell transplantation and maintenance in 200 patients with multiple myeloma: long-term follow-up results from single center].

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.

Quit Intentions and Attempts among Smokers in Sub-urban Nepal: Findings from the Dhulikhel Heart Study.

Background The most effective way for smokers to avoid or minimize the harmful effects is to quit smoking. Smoking cessation has been attributed to multiple factors operating at physiological, psychological, environmental and social level. There is common consensus that smoking cessation programs should be tailored for specific populations. However, there has been lack of data regarding factors that influence smoking cessation in Nepal, which has hindered the development of effective smoking-cessation interventions. Objective To assess the prevalence of quit attempts, successful quitting and the factors associated with them in a randomly selected, population-based adult participants in sub-urban Nepal. Method This cross-sectional study utilized data from the first wave of the baseline survey of the Dhulikhel Heart Study (DHS). A total of 2225 households of Dhulikhel city were enumerated and a third of the households (n=735) were randomly selected. Questions on tobacco use were ascertained using the questions based on the WHO STEPS survey questionnaire and questions on past quit attempts. Result Out of 1073 participants, 248 (23.1%) were current smokers and 99 (9.2%) were former smokers. Only 58% of the current smokers mentioned that they had attempted to quit smoking. When asked if they were interested in quitting if helped, almost 90.5% mentioned they were willing. Brahmins were less likely to have quit smoking (former smoker) compared to Newars (OR: 0.41, 95% CI: 0.18-0.90). We also observed that those who had high alcohol consumption were less likely to have quit smoking (OR: 0.36, 95% CI: 0.17-0.76). We didn't find any meaningful significant association between socio-demographic factors or other CVD risk factors and the quit attempts. Conclusion As the country braces to address the burden of non-communicable diseases in Nepal, it is crucial to incorporate tobacco cessation programs in the national health system to meet the global target of bringing tobacco consumption to less than 5% by 2040. We recommend future studies to get a broader understanding of quit effort and factors associated with thereby supporting the development of evidence-based strategies to address tobacco cessation.

Prevalence and Correlates of Tobacco Use in a Suburban community of Nepal: Findings from the Dhulikhel Heart Study.

Background Smoking and oral tobacco use are important risk factors for cancer and other chronic diseases. The distribution of tobacco consumption in Nepal varies across the population subgroups. There is little information on the correlates of tobacco use among suburban population in Nepal. Objective To estimate the prevalence of smoking and oral tobacco use; and determine the socio-demographic and other CVD risk factors associated with them in a suburban population of Dhulikhel, Nepal. Method This cross sectional study utilized data from the first wave of the baseline survey of the Dhulikhel Heart Study (DHS). A total of 2225 households of Dhulikhel city were enumerated and a third of the households (n=735) were randomly selected. Questions on tobacco use were ascertained from 1073 adults age 18 years and older using the questions based on the WHO STEPS survey questionnaire. Result More than a third (36%) of the men were current smokers and 12% reported regular use of oral tobacco. About 14% of the women were current smokers and only 0.5% reported to use oral tobacco regularly.In the multivariate analysis, sex, ethnicity, education, alcohol consumption and body mass index were significantly associated with tobacco use. Males were 2.6 times as likely as females to smoke (95%: 1.53-4.59; p<0.001). Brahmin/Chhetri were 2.8 times more likely to smoke compared to Newars (95% Ci: 1.53-5.18; p=0.001). Education reduced the odds of smoking; compared to those with no formal education, those with up to high school and those with a high school degree or higher were 0.50 (95% CI: 0.27-0.92; p=0.02 ) and 0.38 (95% CI: 0.16-0.91; p=0.03) percent less likely to smoke, respectively. Moderate drinkers were 8 times more likely (95% CI: .54 - 18.40; p<0.001) and high drinkers were 13 times (95% CI: 6.63 - 24.26; p<0.001) compared to non-drinkers. Regarding oral tobacco use males were 15 times as likely as females to use oral tobacco (95% CI: 4.1-58.8; p<0.001). Compared to Newars, Brahmin/Chhetri were 2.7 times as likely to use oral tobacco (95% CI: 1.08 - 6.66; p=0.03). Conclusion Although Nepal has made some progress in passing progressive laws for tobacco control, and national surveys have shown slight reduction on tobacco use, this is far from satisfactory to meet the global target of bringing tobacco consumption to less than 5% by 2040. We recommend future studies to focus on socio-cultural, gender and behavioral aspects of tobacco use in addition to the epidemiological aspects.

Baseline concentrations and spatial distribution of trace metals in surface soils of Guangdong province, China.

A total of 260 surface soil samples were collected to investigate the spatial distribution of trace metals in Guangdong province, one of the fast developing regions in China. The results show that the upper baseline concentrations of Cu, Pb, Zn, Cd, Ni, Cr, and Hg were 28.7, 57.6, 77.8, 0.13, 23.5, 87.0, and 0.15 mg kg(-1), respectively. Regional parent materials and pedogenesis are the primary factors influencing the concentrations of trace metals, and various anthropogenic activities are the second most important factors. The spatial distribution of trace metals is correlated to the geological characters with high concentrations of trace metals always located in regional fault areas, basins, and the Pearl River Delta alluvial plain and to the low concentrations associated with the other areas in Guangdong province.

Spatial distributions and potential risk analysis of total soil selenium in Guangdong Province, China.

A total of 260 soil profiles were examined to investigate the spatial distribution of total soil selenium (Se) in Guangdong province, China. In the investigated area, the soil Se concentrations follow an approximately lognormal distribution. The soil Se geometric mean concentration of 0.23 mg kg(-1) is higher than that of Chinese soils; however, Se concentration varies over the study area. The baseline concentration of 0.13 to 0.41 mg kg(-1) indicates that the soil Se concentration is mostly in the range of deficiency to medium level for surface soils in Guangdong province. In A-, B-, and C-horizon, soil Se spatial distribution is correlated with the nature of the parent material, with high Se concentration mainly located in limestone and sandshale areas and low Se concentration associated with purple shale and granite areas. The spatial distribution pattern of soil Se concentrations suggests that potential Se deficiency may be an issue for human health in this province. Moreover, due to soil degradation and erosion, calculated soil Se exported into surrounding waters could reach approximately 23,000 kg yr(-1) in the study area.

Total fluoride in Guangdong soil profiles, China: spatial distribution and vertical variation.

A total of 260 soil profiles were reported to investigate the fluoride distribution and vertical variation in Guangdong province. The soil fluoride contents followed an approximately lognormal distribution. Although the soil fluoride geometric mean concentration of 407 mg/kg is lower than that of China, its content varied from 87 to 2860 mg/kg. An upper baseline concentration of 688 mg/kg was estimated for surface soils. In A-, B-, and C-horizon soil fluoride spatial distribution presented similar patterns that high fluoride concentration mainly located in limestone, purple shale, and sandshale areas, indicated that soil fluoride spatial distribution was primarily dependent on the regional bedrock properties rather than anthropogenic inputs. From A- to C- horizon soil fluoride geometric mean concentration had an increasing tendency of 407, 448, and 465 mg/kg. This vertical variation was the result of the intensive eluviation under the subtropical hydrothermal condition, and had closely related with soil properties, such as lower organic matters and clay content variations. Moreover, the soil degradation and erosion was also an important pathway of soil fluoride movement, as a result the soil fluoride exported into surface and groundwaters would reach about 4.1x10(4) t year-1 in the study area.

[Studies on tissue culture of Dendrobium chrysotoxum Lindl in vitro].

OBJECTIVE: To set up a system for the culture of Dendrobium chrysotoxum in vitro. METHOD: Tissue culture, fire fly luminescence and phenol-H2SO4 method. RESULT: The embryo could germinate with or without light, the MS, 1/2MS, B5, N6 mediums are suitable to the growth and the differentiation of sprout with light, 0.5 mg.L-1 NAA and 1 mg.L-1 6-BA, and ATP have regular changes, the content of polysaccharide was 2.833% in plant and 7.254% in sprout. CONCLUSION: The light has no effects on the embryo germination, but the phytohormone, nitrogen source and organized elements are important to the growth and differentiation of the sprout which should be transferred to the MS, 1/2MS, B5, N6 mediums in time supplemented with NAA [symbol: see text] 6-BA, ATP may be served as the dynamic indication of nourishment demand in the plant. The content of polysaccharide in the sprout is higher and can be utilized.