[Mechanism and Clinical Significance of NAMPT in Multiple Myeloma].

OBJECTIVE: To investigate the mechanism and clinical value of nicotinamide phosphoribosyltransferase (NAMPT) in multiple myeloma (MM). METHODS: RT-qPCR and Western blot were used to detect the expression of NAMPT in MM cells and normal bone marrow mononuclear cells. The biological function of NAMPT was analyzed by cell proliferation and apoptosis assay, small interfering RNA silencing, overexpression assay and chromatin immunoprecipitation assay. RESULTS: The mRNA and protein expression levels of NAMPT in MM cell lines (MM1R, MM1S, U266 and RPMI-8226) were significantly higher than those in normal bone marrow mononuclear cells (P < 0.001), and were most obvious in U266 cells. Compared with Si-NC group, the proliferation of U266 cells in Si-NAMPT group was significantly inhibited at 24, 48 and 72 h after transfection (P =0.006, P < 0.001, P =0.001), and the apoptosis rate of U266 cells was significantly increased at 48 h after transfection (P < 0.001). Compared with Flag-NC group, U266 cell proliferation in Flag-NAMPT group was significantly increased (P =0.003, P =0.002, P < 0.001), while the apoptosis rate decreased significantly at 48 h after transfection. The expression of NAMPT in U266 cells was regulated by XBP1 at transcriptional level. The proliferation rate of U266 cells with XBP1 or NAMPT stable knockout or MKC3946 pretreated with bortezomib was significantly decreased, the levels of BCL-2 mRNA and protein were also significantly decreased, while the levels of BAX mRNA and protein were significantly increased, moreover, the cleavage degree of caspase-3 significantly decreased, while caspase-3/7 activity increased dramatically (P < 0.05). CONCLUSIONS: The high expression of NAMPT in MM cell line can promote MM cell proliferation and inhibit apoptosis. NAMPT is regulated by IRE1α-XBP1 signaling pathway in U266 cells. Stable knockdown of NAMPT or blocking of IRE1α-XBP1 pathway can significantly increase the sensitivity of U266 cells to bortezomib.

[Expression and Clinical Significance of NAMPT in Bone Marrow of Patients with Multiple Myeloma].

OBJECTIVE: To study the expression level of nicotinamide phosphoribosyltransferase (NAMPT) in multiple myeloma (MM), its relationship with clinical indicators, prognosis and potential role. METHODS: Immunohistochemical staining was used to detect the expression of NAMPT in bone marrow biopsies of patients with newly diagnosed multiple myeloma (NDMM) and patients with iron deficiency anemia (IDA) hospitalized during the same period. According to the median expression level of NAMPT, NDMM patients were divided into high expression group and low expression group. The correlation between NAMPT expression level and clinical baseline data was analyzed, and survival analysis was performed to evaluate the relationship between NAMPT expression level and prognosis. The GSE24080 and GSE19784 datasets were used to analyze the effect of NAMPT on the prognosis. Gene set enrichment analysis (GSEA) explored the possible mechanism of NAMPT involved in MM cell function. RESULTS: The mean staining intensity of NAMPT in bone marrow tissue of 31 NDMM patients was 0.007±0.002, and that of 10 IDA patients was 0.002±0.002 (P < 0.05). The median expression level of NAMPT was 0.0041 in NDMM patients, and the mean staining intensity of high expression group and low expression group was 0.007±0.005 and 0.002±0.001, respectively (P < 0.001). There were certain differences in lactate dehydrogenase (LDH), C-reactive protein (CRP) and ISS staging between high expression group and low expression group (P < 0.001), while no significant differences in other indicators. The overall response rate (ORR) of high expression group was significantly lower than that of low expression group (P < 0.001). The median survival time of patients in high expression group was significantly shorter than that in low expression group (P =0.024). The results of bioinformatics analysis showed that the event-free survival (EFS) rate and overall survival (OS) rate of low NAMPT group were both higher than high NAMPT group (P =0.037, P =0.009), and NAMPT was an independent prognostic factor for EFS and OS (P =0.006, P =0.020). GSEA suggested that NAMPT might affect MM cell function through mTORC1 signaling pathway. CONCLUSIONS: The expression level of NAMPT in bone marrow of NDMM patients is significantly higher than that of IDA patients, and the high expression of NAMPT may be correlated with late ISS stage, and high level of LDH and CRP. Patients with high expression of NAMPT have worse response to bortezomib and survival time may be shorter. NAMPT may be involved in the occurrence and development of MM through mTORC1 signaling pathway.

[Research Progress on Mechanism of Bortezomib Resistance in Multiple Myeloma].

Multiple myeloma (MM) is a common plasma cell malignancy, accounting for the second largest hematological malignancy. Proteasome inhibitors represented by bortezomib (BTZ) have been the main treatment for patients with newly diagnosed and relapsed or refractory myeloma in nearly two decades. Although BTZ has improved the prognosis of MM patients, MM remains incurable in most patients, mainly because MM cells become resistant to BTZ. This review is to better understand the mechanism of MM resistance to BTZ and explore possible new therapeutic strategies.

[Clinical Characteristics and Survival Analysis of Patients with Plasma Cell Leukemia].

OBJECTIVE: To investigate the clinical characteristics, therapeutic response and prognosis of patients with plasma cell leukemia (PCL) and improve the understanding of this disease. METHODS: The clinical manifestations, laboratory tests and treatment response of 27 patients with plasma cell leukemia treated in The Second Hospital of Shanxi Medical University from December 2010 to August 2019 were analyzed retrospectively, and their clinical characteristics were summarized. Kaplan-Meier method was used for survival analysis. RESULTS: There were 18 cases of primary plasma cell leukemia (pPCL) and 9 cases of secondary plasma cell leukemia (sPCL). The male to female ratio was 1.7∶1. The median age was 62 years old. The first manifestations were bone pain, fatigue, fever, splenomegaly and bleeding, and a large number of plasma cell infiltration was observed in the morphological examination of peripheral blood and bone marrow cells. 13 cases were detected by immunotyping and all of them expressed CD38/CD138. 8 cases underwent karyotype analysis, and 3 cases were normal, clonal abnormalities occurred in 5 cases. FISH detection was performed in 12 cases, of which 8 cases were abnormal. In 17 cases of bortezomib based chemotherapy, the ovevall response rate was 52.9%, which was higher than that in the non-bortezomib group, but there was no significant difference between the two groups (P =0.242). The overall median survival time of 27 patients was 6.4 months, the median progression-free survival time was 3.5 months, and the median survival time of patients with pPCL and sPCL was 8.2 months and 2.4 months, respectively, the difference between the two groups was statistically significant (P =0.031). CONCLUSION: PCL is highly invasive and has diverse clinical manifestations, and is not sensitive to traditional chemotherapy. The median survival time of patients with pPCL is relatively longer than that of patients with sPCL. The chemotherapy regimen based on bortezomib improves the treatment effectiveness and prolongs the survival time of PCL patients.

[Expression of NAMPT in Patients with Multiple Myeloma and Its Correlation with Clinical Manifestation].

OBJECTIVE: To analyze the expression level of nicotinamide phosphoribosyltransferase (NAMPT ) in bone marrow of multiple myeloma (MM) patients and its correlation with clinicopathological features, clinical efficacy and prognosis. METHODS: RT-qPCR and Western blot were used to detect the expression of NAMPT mRNA and protein in bone marrow mononuclear cells from 85 newly diagnosed MM patients (including 17 relapsed MM patients) and 15 healthy donors, and explore the correlation of the expression of NAMPT gene with clinicopathological features and efficacy. Kaplan-Meier method was used to analyze the effects of NAMPT on progression-free survival (PFS) and overall survival (OS), and univariate and multivariate survival analysis were performed. RESULTS: The median expression level of NAMPT mRNA in bone marrow of newly diagnosed and relapsed MM patients was significantly higher than that of healthy donors (P <0.001). The expression of NAMPT mRNA in relapsed MM patients was significantly higher than that in newly diagnosed MM patients (P <0.001), which was consistent with the expression of NAMPT protein. ISS staging, lactate dehydrogenase and C-reactive protein levels, p53 deletion and the proportion of myeloma cells were increased in high NAMPT expression group compared with low NAMPT expression group (P <0.001). Compared with complete remission group, NAMPT mRNA expression was significantly up-regulated in partial remission group, progression group and relapsed group (P <0.001). The median OS and PFS of patients in high NAMPT expression group was 27.3 and 14.9 months, respectively, which was significantly shorter than 39.1 and 27 months in low NAMPT expression group (P =0.048, P <0.001). Both univariate and multivariate analysis showed that NAMPT expression was correlated with PFS and OS. CONCLUSION: The expression level of NAMPT in newly diagnosed and relapsed MM patients is significantly higher than that in normal controls, and its up-regulation is related to the adverse clinical characteristics, efficacy and prognosis of MM patients. NAMPT is an independent prognostic risk factor of MM.

[Hematological Neoplasms Secondary to Malignant Solid Tumors with Radiotherapy and Chemotherapy: a Clinical and Prognostic Analysis].

OBJECTIVE: To explore the clinical characteristics, treatment and prognosis of therapy-related hematological neoplasms patients secondary to malignant solid tumors. METHODS: The clinical features, treatment and prognosis of 36 hematological neoplasms patients secondary to malignant solid tumors with radiotherapy and chemotherapy in the Second Hospital of Shanxi Medical University were retrospectively analyzed. RESULTS: The 36 patients with therapy-related hematological neoplasms had a median age of 60 (47-81) years, 14 were male and 22 were female. Among them, 22 cases were acute myeloid leukemia, 5 cases were acute lymphoblastic leukemia, 4 cases were multiple myeloma, 3 cases were myelodysplastic syndrome, and 2 cases were non-hodgkin's lymphoma. The median latency of malignant tumor to hematological neoplasm was 42.5 (12-120) months. The median survival time of therapy-related hematological neoplasms was 10.5 (1-83) months, and the 3-year overall survival (OS) rate was 24.3%. The therapy-related acute myeloid leukemia patients had a very poor prognosis, with a median survival of 7 (1-83) months and a 3-year OS rate of 21.4%. CONCLUSION: The prognosis of therapy-related hematological neoplasms secondary to malignant solid tumors with radiotherapy and chemotherapy is poor, and individualized treatment should be implemented according to the clinical situation of patients.

[Clinical Characteristics and Survival Analysis of Patients with Chronic Myelomonocytic Leukemia].

OBJECTIVE: To investigate the clinical characteristics, prognostic factors and efficacy of hypomethylating agent (HMA) in patients with chronic myelomonocytic leukemia (CMML). METHODS: The clinical data of 37 newly diagnosed patients with CMML was analyzed retrospectively, and their clinical characteristics and the efficacy of HMA were summarized. Kaplan-Meier and Log-rank test were used for univariate survival analysis, and Cox proportional hazards regression model was used for multivariate analysis. RESULTS: The median age at diagnosis was 67 years old. Their common manifestations included fatigue, bleeding, abnormal blood routine and fever. Most patients had splenomegaly. According to FAB classification, there were 6 cases of myelodysplastic CMML and 31 cases of myeloproliferative CMML, while according to WHO classification, 8 patients belonged to CMML-0, 9 patients to CMML-1 and 20 patients to CMML-2. At the time of diagnosis, the median white blood cell count was 32.84×109/L, median hemoglobin (Hb) was 101 g/L, median platelet count was 65×109/L, median absolute monocyte count was 9.53×109//L, median absolute neutrophil count (ANC) was 11.29×109//L and median lactate dehydrogenase (LDH) was 374 U/L. Cytogenetic abnormalities were found in 4 cases among the 31 patients who underwent karyotype analysis or fluorescence in situ hybridization detection. There were 12 patients who had analyzable results and gene mutations were identified in 11 cases, including ASXL1, NRAS, TET2, SRSF2 and RUNX1. Among the 6 patients who were treated with HMA and could be evaluated for efficacy, 2 patients achieved complete remission, 1 patient achieved partial remission and 2 patients achieved clinical benefit. Compared with the non-HMA treatment group, overall survival (OS) time was not significantly prolonged in the HMA treatment group. Univariate analysis showed that Hb<100 g/L, ANC≥12×109/L, LDH≥250 U/L and peripheral blood (PB) blasts ≥5% were significantly associated with poor OS, while WHO classification CMML-2, Hb<100 g/L, ANC≥12×109/L, LDH≥250 U/L and PB blasts≥5% were significantly associated with poor leukemia-free survival (LFS) (P<0.05). Multivariate analysis showed that ANC≥12×109/L and PB blasts≥5% were significantly associated with poor OS and LFS (P<0.05). CONCLUSION: CMML has high heterogeneity in clinical characteristics, genetic changes, prognosis and treatment response. HMA can not significantly improve the survival of CMML patients. ANC≥12×109/L and PB blasts≥5% are independent prognostic factors of OS and LFS in patients with CMML.

Mendelian randomization study highlights hypothyroidism as a causal determinant of alopecia areata.

Background: Although observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear. Objectives: This study aimed to investigate the genetic variants associated with hypothyroidism and their potential impact on the risk of developing alopecia areata. Methods: genome-wide association study summary statistics for hypothyroidism (30,155 cases and 379,986 controls) and alopecia areata (289 cases and 211,139 controls) were obtained from the IEU OpenGwas project. The inverse variance-weighted method was used as the primary analysis method to evaluate the causality between hypothyroidism and alopecia areata, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. Furthermore, the function of causal SNPs was evaluated by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction networks. Result: Utilizing two-sample Mendelian randomization analysis, we found that the single-nucleotide polymorphisms (SNPs) of hypothyroidism (OR = 1.40, 95% CI: 1.12-1.75, p = 3.03×10-3) significantly increased the risk of alopecia areata ( 289 cases and 211,139 controls ). KEGG pathway analysis showed that the candidate genes were mainly enriched in virion-herpesvirus, Th1 and Th2 cell differentiation, Th17 cell differentiation, T-cell receptor signaling pathway, PD-L1/PD-1 checkpoint pathway in cancer and Toll-like receptor signaling pathway. Protein-protein interaction networks results showed that CTLA4, STAT4, IL2RA, TYK2, IRF7, SH2B3, BACH2, TLR3, NOD2, and FLT3. Conclusion: This study provided compelling genetic evidence supporting a causative association between hypothyroidism and alopecia areata, which could potentially inform the development of more efficacious treatment strategies for patients afflicted by alopecia areata.

Perithyroidal hemorrhage caused by hydrodissection during radiofrequency ablation for benign thyroid nodules: Two case reports.

BACKGROUND: Hydrodissection is a widely used technique during radiofrequency ablation (RFA) for benign thyroid nodules. Although it could effectively avoid thermal injury to the surrounding critical structures and achieve complete treatment, routine operation of the remaining needle could cause perithyroidal hemorrhage. In this report, we present 2 cases of perithyroidal hemorrhage during RFA caused by a hydrodissection needle, which have not been reported before. CASE SUMMARY: A 21-year-old female and a 45-year-old male were admitted for RFA for benign thyroid nodules. Considering that their nodules were adjacent to the recurrent laryngeal nerve, the needle used for hydrodissection was placed and remained between the dorsal capsule of the lateral lobe and the recurrent laryngeal nerve. During the procedure, active bleeding near the needle appeared on ultrasonography (US). Although moderate pressure was quickly applied to the neck for several minutes, contrast-enhanced US (CEUS) still showed an active hemorrhage. A radiofrequency electrode was placed at the bleeding point under the guidance of CEUS to stop the bleeding, and the procedure was finally confirmed to be successful by CEUS, without other complications. CONCLUSION: Hydrodissection during RFA of benign thyroid nodules was associated with a risk of perithyroidal hemorrhage. The timely recognition of this acute hemorrhage could help in the timely control of the bleeding, and CEUS-guided ablation of the bleeding point could be useful.

[The Relationship between Hematopoietic Scoring System Composed of HB，PLT and MCV and Prognosis and Curative Effect of Multiple Myeloma Patients].

OBJECTIVE: To investigate the prognostic value of hemopoietic scoring system composed of hemoglobin (HB), platelet count (PLT) and mean corpuscular volume (MCV) in MM patients and its correlation with curative effect. METHODS: The clinical data of 172 newly diagnosed MM patients treated by bortezomib as the first-line regimen in our hospital from May 2014 to December 2019 were collected, three variables (HB≤100 g/L, PLT≤150×109/L, MCV≥96 fl) were introduced, each variable was distributed 1 score, the patients were divided into four groups (0, 1, 2 and 3 points in group 1, 2, 3 and 4, respectively), and the clinical characteristics and prognosis of the patients in the four groups were analyzed. The initial efficacy evaluation after 3-4 courses of treatment was carried out, and the curative effect of the patients in the different hematopoiesis score groups were compared. RESULTS: The median OS time of the patients in group 1, 2, 3 and 4 was 27.0, 22.5, 20.7 and 18.1 months, while the median PFS time were 23.0, 19.0, 18.0 and 14.0 months, respectively. The OS and PFS of the patients in low score group were significantly better than those in high score group (P=0.045, P=0.048). There was no significant difference in the curative effect of the patients treated by bortezomib after 3-4 courses (P>0.05). CONCLUSION: Hematopoiesis score can preliminarily predict the overall survival of newly diagnosed MM patients, but there is no significant difference between different scoring groups in the initial curative effect.

[Clinical Characteristics and Prognosis of Multiple Myeloma Patients with Myelofibrosis].

OBJECTIVE: To investigate the clinical characteristics and prognosis of multiple myeloma patients with myelofibrosis. METHODS: The clinical data of 263 patients with multiple myeloma (including 92 patients with myelofibrosis) treated in the department of hematology of our hospital from January 1, 2016 to June 31, 2020 were collected and retrospectively analyzed, the patients were divided into combined group and uncombined group. The MM stage, MM type, genetic characteristics and therapeutic effect of the patients in combined group and uncombined group were observed, and the relationship between the curative effect and the degree of myelofibrosis change of the patients in combined group was analyzed. RESULTS: There was no statistically difference in the MM staging and classification between multiple myeloma patients with or without myelofibrosis (P>0.05). The positive rate of FISH results of the patients in combined group was significantly higher than those in uncombined group, and was significantly correlated to 1q21 amplification, D13S319 deletion, and IgH breakage (P<0.05). After treatment, the effective rate of the patients in uncombined group was significantly higher than those in combined group, and the degree of fibrosis in the effective patients in combined group was significantly reduced. CONCLUSION: The survival rate of the patients with multiple myeloma complicated with myelofibrosis is shorter than that of the patients without myelofibrosis, and the overall prognosis is poor.

[Evaluation of the Efficacy and Safety of Chemotherapy in Elderly Patients with Multiple Myeloma under Different Frailty Scores].

OBJECTIVE: To compare the efficacy and safety of different chemotherapy regimens in elderly multiple myeloma (MM) patients with different Frailty scores. METHODS: The clinical data of elderly patients with MM were retrospectively analyzed, including age, treatment regimen, efficacy, adverse reactions, and the Frailty score included in the activity of daily living score, the instrumental activity of daily living scale and the Charlson comorbidity index. The patients were divided into fit group, mediate fit group and frail group according to the scoring standard. The treatment efficiency and adverse reaction rates of elderly MM with different physical conditions treated by different chemotherapy regimens were analyzed. RESULTS: Among the 70 patients, the effective rates of the patients in fit group, the mediate fit group, and the frail group were 79.5%, 81%, and 40%, and the effective rates of the fit patients in double and triple groups were 54.5% and 89.3%, 70% and 90.9% for mediate fit patients, 42.9% and 33.3% for frail patients, the triple regimen in fit patients showed obvious advantages, and the difference showed statistically significant (P<0.05), while the efficacy for mediate patients and frail patients showed no significant difference. During the induction of bortezomib, the incidence of adverse reactions for the patients in the triple group (78.6%) was higher than 67.9% in the double group, and the difference showed no statistically significant (P>0.05).There was no significant difference in the 1-year overall survival rate of the patients and with molecular genetic abnormalities among each groups. CONCLUSION: The therapeutic effect is related to the patient's physical condition. For patients with healthy physique, the triple regimen should be used first. For patients with weak physical constitution, the chemotherapy regimen with low drug toxicity should be selected for safety.

[Advances of Sirolimus in the Treatment of Patients with Autoimmune Cytopenia---Review].

Autoimmune cytopenia is a general term for all hemocytopenia diseases caused by humoral or cellular immunity abnormalities, and its common immune mechanism determines the importance of immunosuppressive therapy. Sirolimus, as an immunosuppressant against of mTOR, induces immune tolerance by adjusting Treg cells, which has application prospect in the treatment of refractory autoimmune cytopenia. This article reviews the mechanism, application, and possible adverse reactions of sirolimus in the treatment of idiopathic autoimmune cytopenia.

[Early Diagnosis of One Multiple Myeloma Patient with Cold Agglutinin Syndrome as the Initial Presentation].

OBJECTIVE: To analyze one case of multiple myeloma (MM) initially presenting cold agglutinin syndrome (CAS), so as to improve clinical understanding and screening of this disease. METHODS: The clinical data, laboratory examination, bone marrow result, diagnosis and treatment of the patient were analyzed and summarized to provide ideas and clinical experience for the early diagnosis and treatment of CAS secondary to MM. RESULTS: The clinical manifestations of asthenia, hemolysis, jaundice and scattered livedo reticularis were caused by CAS secondary to MM, which was different from the general Raynaud's phenomenon. IgMκ type MM was definitely diagnosed according to the morphological features of bone marrow cells and immunofixation electrophoresis. After 3 courses of chemotherapy with BAD regimen and enhanced thermal support, anemia was corrected, M protein was decreased and the cold agglutinin phenomenon was significantly reduced. The evaluation of efficacy reached very good partial response. CONCLUSION: There are very few MM patients with CAS as the initial presentation, so it is easy to misdiagnose. Early diagnosis and individual therapy are particularly important, which requires clinicians to observe and gain experience further.

Leonurine-Repressed miR-18a-5p/SOCS5/JAK2/STAT3 Axis Activity Disrupts CML malignancy.

Leonurine, an active natural alkaloid compound isolated from Herba leonuri, has been reported to exhibit promising anticancer activity in solid tumors. The aim of this study was to explore whether leonurine is able to inhibit chronic myeloid leukemia (CML) malignancy. Here, we found that leonurine dose dependently inhibited the proliferation, migration, colony formation and promoted apoptosis of CML cells. Furthermore, leonurine markedly reduced CML xenograft growth in vivo. Mechanically, leonurine upregulated SOCS5 expression, thus leading JAK2/STAT3 signaling suppression. Silencing of SOCS5 by its siRNA abrogated the effect of leonurine on CML cells, demonstrating that SOCS5 mediates the anti-leukemia effect of leonurine. Notably, we observed that miR-18a-5p was remarkably increased in CML cells. Treating CML cells with leonurine significantly decreased miR-18a-5p expression. Moreover, we found miR-18a-5p repressed SOCS5 by directly targeting its 3'-UTR. miR-18a-5p downregulation induced by leonurine reduced the biological activity of CML cells by relieving miR-18a-5p repression of SOCS5 expression. Taken together, leonurine exerts significant anti-leukemia efficacy in CML by regulating miR-18a-5p/SOCS5/JAK2/STAT3 axis.

[Responses of soil nitrogen to the transition from desert grassland to shrubland in eastern Ningxia, China]. / å®å¤ä¸œéƒ¨è’æ¼ è‰åŽŸ-çŒä¸›åœ°è½¬å˜è¿‡ç¨‹åœŸå£¤æ°®ç´ å“åº”.

In this study, desert grassland, grassland edge, shrubland edge, shrubland were selec-ted as four transition sites in a nearly 30 years typical desert grassland-shrubland mosaic formed by anthropogenic shrub introduction. Soil properties and soil microbial characteristics under vegetation patches and bare interspace in each site were investigated to examine the responses of soil nitrogen to the desert grassland-shrubland state transition. It was shown that the aboveground biomass increased with transition from desert grassland to shrubland. Annual herbs increased largely with the introduction of shrubs. Soil moisture, microbial biomass and total nitrogen and carbon decreased with the transition. The abundance of microogranisms was lower in grassland edge and shrubland edge, and then increased in shrubland, which was slightly higher than that of desert grassland. With respect to nitrogen, nitrate content reached the highest level of 28.45 mg N·kg-1 and ammonium reached the lowest level of 4.81 mg N·kg-1 in shrubland, which were significantly increased by 52.3% and decreased by 10.4% compared with desert grassland. In addition, soil moisture and microbial biomass nitrogen was positively correlated across all sites. The relationship between mine-ralized nitrogen and soil moisture was non-linear, as they were positively correlated in desert grassland and grassland edge, but negatively correlated in shrubland edge and shrubland. During the 30-year transition from desert grassland to shrubland, our results showed that soil total nitrogen and microbial biomass nitrogen were significantly decreased, but mineralized nitrogen, especially for nitrate, significantly increased over time, indicating that soil nitrification was inhibited in desert grassland but accelerated in shrubland.

[Clinical Characteristics and Survival Analysis of Patients with IgD Multiple Myeloma].

OBJECTIVE: To explore the clinical features, prognosis and survival of patients with IgD multiple myeloma (MM). METHODS: The clinical data of 20 patients with IgD MM was analyzed retrospectively. The prognostic factors and survival analysis was carried out. We summarized their clinical characteristics. The survival analysis was carried out by Kaplan-Meier method, and the prognostic factor were analyzed by using log-rank test for single factor analysis of observation index. Variables of P<0.15 in single factor analysis were enrolled in multifactor cox regression analysis. RESULTS: IgD MM patients accounted for 4.3% of all MM patients in the same period, among which 80% were male, the median age of patients was 57.5(35-77) years old, 90% of the patients belongs to λ light chain type. At the time of diagnosis, 18 patients (90%) were in DS-Ⅲ stages, while 10 patients were in ISS-Ⅲ stage. The first clinical manifestations were fatigue, bone pain, kidney function impairment, anemia (Hb<100 g/L) in 14 cases (70%), 12 cases (60%) with osteolytic bone destruction≥3, combined with renal impairment in 8 cases (40%), and elevated blood calcium in 11 cases (51.4%). In only 5 patients the ratio of albumin to globntin was inverted, hypoalbuminemia accounted for 40%, and globulin increase accounted for only 15%. FISH results showed that the positive rate of 1q21 amplification (50%) was the highest, and it was easy to occur at the same time as other cytogenetic abnormalities. Extramedullary infiltration occurred in 4 cases (20%). The analysis of prognostic factors showed that only the increase of lactate dehydrogenase (LDH) level was an independent poor prognostic factor for IgD MM patients. Extramedullary infiltration and various cytogenetic abnormalities were found in 2 IgD MM patients with primary drug resistance, suggesting that extramedullary infiltration and various cytogenetic abnormalities may be prognostic factors, but the difference was not statistically significant, Which maybe related to the small sample size. All 20 patients were treated with bortezomib-containing regimen, of which 19 patients were evaluated, 17 patients (89.4%) showed effective, including CR+VGPR (52.6%), PR (31.5%), MR (5.3%), 2 patients primary drug resistance. The median PFS and OS was 9.5 and 10.5 months, respectively. CONCLUSION: IgD MM is a rare and invasive disease. Increased LDH is an independent prognostic factor. Bortizomib-containing regimen can improve the prognosis of IgD MM patients.

[Clinical Analysis of 46 Cases of Multiple Myeloma with Extramedullary Disease].

OBJECTIVE: To investigate the effect of clinical baseline data on prognosis in patients with multiple myeloma (MM) complicated by extramedullary disease (EMD). METHODS: The clinical data of 46 MM patients with EMD were retrospectively analyzed. The clinical data and survival prognosis of MM patients in primary EMD group and recurrent EMD group were analyzed. The classified baseline data were expressed by the number of cases (percentage), the χ2 test was used to compare the two classification data groups. The OS and PFS curves were drawn by multiplication positive limit method (Kaplan-Meier). Log-rank test was used for the univariate analysis of prognosis, and COX proportional risk regression model was used for the multiple factors of prognosis. RESULTS: ß 2 microglobulin≥2.7 g/L, lactic dehydrogenase≥250 U/L, serum calcium≥2.75 mmol/L, plasma cells in bone marrow≥60% were the poor prognostic factors for PFS. Serum calcium≥2.75 mmol/L and the plasma cells in bone marrow≥60% were the poor prognostic factors for OS. Multivariate regression analysis enroling the statistically significant factors in univariate analysis baseline date in factors in showed that plasma cell level≥60% in bone marrow was independent poor prognostic factors for PFS, and serum calcium≥2.75 mmol/L was an independent poor prognostic factor for OS. The IgG type is the most common type of MM complicated by EMD. The remission depth of primary EMD group≥VGPR was lower than that of recurrent EMD group, and there was significant difference between the two groups (P<0.05), and the median OS time of patients with primary EMD group was shorter than that of patients with recurrent EMD group, the difference was statistically significant (P<0.05). The 3-year survival rates of primary EMD group and recurrent EMD group were 10.0% and 34%, respectively, there was no significant difference between the two groups (P>0.05). The 5-year survival rate was 0 and 20%, respectively, there was significant difference between the two groups (P<0.05). CONCLUSION: The remission depth of primary EMD group≥VGPR is lower than that of recurrent EMD group，and the OS time of patients in primary EMD group is shorter than that in recurrent EMD group. Bortezomib-based chemotherapy could not improve the prognosis of patients with primary EMD and recurrent EMD, and the prognosis of patients with primary EMD is even worse.

[Clinical Characteristic, Prognosis and Treatment Outcome of Elderly Multiple Myeloma Patients with Impaired Renal Function].

OBJECTIVE: To explore the risk factors, prognosis and curative effect of elderly patients with MM renal damage. METHODS: 118 patients with primary elderly MM treated in our hospital from January 2011 to December 2018, were enrolled analyzed retrospectively. The clinical characteristics and prognosis of renal function impairment group (RI group) and normal renal function group (non-RI group) were compared. The difference of renal efficacy and survival benefit between the patients treated with bortezomib, thalidomide (combination group) and chemotherapy regimen containing only one of them (single drug group) in RI group was compared. RESULTS: Univariate analysis showed that DS stage, pulmonary infection, uric acid, ß 2 microglobulin and leukocyte in RI group were higher than those in non-RI group, but hemoglobin was lower than that in non-RI group (P<0.05). Multivariate logistic regression analysis showed that ß 2 microglobulin was the independent risk factor for renal damage in elderly patients with MM. Kaplan-Meier method showed that the OS and PFS in RI group were significantly lower than those in non-RI group (P<0.05). The renal efficacy in the combined treatment group was significantly better than that of the single drug group (P<0.05), and it could bring benefit to the PFS of the elderly patients with MM renal damage (P<0.05). CONCLUSION: The prognosis of elderly MM patients with impaired renal function is poor. The prognosis of these patients can be improved by selecting chemotherapy regimen containing bortezomib and thalidomide at the same time, and monitoring, controlling all kinds of risk factors actively.