Objective:To investigate the clinical characteristics, treatment and prognosis of newly-treated patients with primary central nervous system lymphoma (PCNSL).Methods:Clinical data of 117 newly-treated PCNSL patients who were admitted to the First Hospital of Jilin University, the Fifth Medical Center of Chinese PLA General Hospital, Harbin Medical University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College from August 2009 to February 2018 were retrospectively analyzed. The patients' age, sex, Eastern Cooperative Oncology Group (ECOG) physical status (PS) score, pathological type, involvement of deep brain tissue, number of lesions, cerebrospinal fluid protein concentration, International Extranodal Lymphoma Study Group (IELSG) score, Memorial Sloan Kettering Cancer Center (MSKCC) score, treatment strategy, and response after the first-line therapy were analyzed using univariate and multivariate Cox proportional hazards models to identify the independent influencing factors for progression-free survival (PFS) and overall survival (OS) of PCNSL patients. Kaplan-Meier method was used for survival analysis.Results:In 117 newly-treated PCNSL patients, 59 cases (50.4%) presented with increased intracranial pressure or focal neurological symptoms at diagnosis; there were 65 cases (55.6%) with single lesions and 52 cases (44.4%) with multiple lesions; 1 patient (0.9%) had lymphoma of T-cell origin, and 116 cases (99.1%) had diffuse large B-cell lymphoma (DLBCL). Among 95 evaluable patients, 41 patients (43.2%) achieved complete remission (CR), 20 patients (21.1%) achieved partial remission (PR), 16 patients (16.8%) achieved stable disease (SD), and 18 patients (18.9%) had progressive disease (PD). In 117 patients with median follow-up of 66.0 months (95% CI 57.9-74.1 months), the median PFS and OS were 17.4 months (95% CI 11.5-23.3 months) and 45.6 months (95% CI 20.1-71.1 months), respectively. The 2-, 3- and 5-year PFS rates were 41.2%, 28.6% and 19.3%, and OS rates were 63.7%, 52.4% and 46.3%, respectively. Univariate Cox regression analysis showed that baseline high-risk MSKCC score group was an adverse prognostic factor for PFS ( P = 0.037), and the first-line chemotherapy with ≥4 cycles of high-dose methotrexate (HDMTX), HDMTX in combination with rituximab, ≥4 cycles of rituximab in combination with HDMTX, and achieving CR or ≥PR after the first-line treatment reduced the risk of disease progression and prolonged the PFS time (all P <0.01); age >60 years old, ECOG-PS score of 2-4 points, elevated cerebrospinal fluid protein concentration, high-risk IELSG score, and high-risk MSKCC score were adverse prognostic factors for OS, and ≥4 cycles of HDMTX and achieving CR or ≥PR after the first-line treatment were favorable factors for OS. Multivariate Cox regression analysis verified that rituximab in combination with HDMTX (yes vs. no: HR = 0.349, 95% CI 0.133-0.912, P = 0.032) and achieving ≥PR after the first-line chemotherapy (yes vs. no: HR = 0.028, 95% CI 0.004-0.195, P < 0.001) were independent favorable factors for PFS; age >60 years old (>60 years old vs. ≤60 years old: HR = 10.878, 95% CI 1.807-65.488, P = 0.009) was independent unfavorable factor for OS, while ≥4 cycles of HDMTX treatment (≥4 cycles vs. <4 cycles: HR = 0.225, 95% CI 0.053-0.947, P = 0.042) was independent favorable factor for OS. Conclusions:The older the PCNSL patients at initial treatment, the worse the prognosis. Intensive and continuous treatment for achieving deeper remission may be the key for improving the outcome of PCNSL patients.

Antiporters/genetics* ; Carcinoma, Papillary/pathology* ; Humans ; Neoplasm Metastasis/genetics* ; Sulfate Transporters/genetics* ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/pathology*

Objective:To investigate the efficiency and pharmacoeconomics of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for mobilization of peripheral blood stem cells (PBSCM) in patients with multiple myeloma (MM).Methods:The data of 91 patients with newly treated MM who were hospitalized in the First Hospital of Jilin University and Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 2015 to October 2017 were retrospectively analyzed. According to the patient's wishes, a high-dose chemotherapy combined with subcutaneous injection of PEG-rhG-CSF or recombinant human granulocyte colony-stimulating factor (rhG-CSF) was used for stem cell mobilization in 42 and 49 patients, respectively. The number of mononuclear cells (MNC) and CD34 + cells collected after mobilization, the maximum absolute neutrophil count (mANC), the cost of mobilization, and the engraftment time of white blood cells and platelets after transplantation were compared between the two groups. Results:The median number of MNC collected after mobilization in the PEG-rhG-CSF group and rhG-CSF group were 5.86×10 8/kg [(1.08-24.54)×10 8/kg] and 6.61×10 8/kg [(0.83-33.80)×10 8/kg], and the difference was not statistically significant ( U = 883.00, P = 0.245); while the median number of CD34 + cells collected after mobilization in the PEG-rhG-CSF group was higher than that in the rhG-CSF group [5.56×10 6/kg (0.94-19.90)×10 6/kg and 4.82×10 6/kg (1.12-14.61)×10 6/kg], and the difference was statistically significant ( U = 732.00, P = 0.038). The median number of mANC during mobilization in the PEG-rhG-CSF group was lower than that in the rhG-CSF group [20.50×10 9/L (7.26-61.30)×10 9/L and 32.08×10 9/L (6.92-69.99)×10 9/L], and the difference was statistically significant ( U = 490.00, P = 0.001). After autologous stem cell transplantation (ASCT), the time-to-recovery of white blood cell count (WBC) to 1.0×10 9/L in the PEG-rhG-CSF group was shorter than that in the rhG-CSF group [(11.59±1.98) d vs. (12.93±2.83) d], and the difference was statistically significant ( t = -2.395, P = 0.019), and the time-to-recovery of platelet count (Plt) to 20.0×10 9/L in the PEG-rhG-CSF group was also shorter than that in the rhG-CSF group [(12.86±2.62) d vs. (14.80±5.47) d], but the difference was not statistically significant ( t = -1.749, P = 0.085). The total mobilization cost of the PEG-rhG-CSF group was not statistically different from that of the rhG-CSF group [(21 405.47±7 365.98) yuan vs. (22 976.83±10 264.34) yuan, t = -0.721, P = 0.474]. Conclusions:PEG-rhG-CSF combined with high-dose chemotherapy is an effective option for PBSCM in MM patients, and its mobilization cost is equivalent to rhG-CSF. Therefore, PEG-rhG-CSF may be a better choice for PBSCM in MM patients.

Iodine transporters of basement membrane of thyroid follicular epithelial cells can participate and exchange the iodine ions across intracellular and extracellular. Among all of the iodine rich organs, iodine ions which only exist in colloidal of thyroid follicular epithelial cells can be functioned as the raw materials, which after oxidation, iodization and coupling, to synthesize thyroid hormone (TH) and to exert its biological functions. Therefore, the iodine transported function of iodide transporters plays a pivotal role for TH biosynthesis. Furthermore, functional studies show that the abnormal expression or dysfunction of iodide transporters might serves as tumor promoters or inhibitors via regulated the mTOR signal pathway, the MAPKs signal pathway, and the NF-κB signal pathway, together contributed to the regulation of cell proliferation, invasion, metastasis and apoptosis, in which plays the role of non iodide transported function. Therefore, the non iodine transported function of iodide transporters may plays the crucial role of tumor occurrence and progression of carcinoma. Based on this information, present study was devoted to systematic summarize the iodine transported function and non iodine transported function (may affects occurrence and progression of carcinoma) of the classical iodide transporters [sodium iodide symporter (NIS) and pendrin] and novel iodine transporters[ (cystic fibrosis transmembrane conductance regulator (CFTR) , sodium multivitamin transporter (SMVT) , and anoctamin 1 (ANO1) ], respectively, in order to provide a theoretical basis and literature review reference for underlying the mechanism of iodine transporters and its regulated signal pathways for the occurrence and progression of carcinomas.

Iodine transporters of basement membrane of thyroid follicular epithelial cells can participate and exchange the iodine ions across intracellular and extracellular. Among all of the iodine rich organs, iodine ions which only exist in colloidal of thyroid follicular epithelial cells can be functioned as the raw materials, which after oxidation, iodization and coupling, to synthesize thyroid hormone (TH) and to exert its biological functions. Therefore, the iodine transported function of iodide transporters plays a pivotal role for TH biosynthesis. Furthermore, functional studies show that the abnormal expression or dysfunction of iodide transporters might serves as tumor promoters or inhibitors via regulated the mTOR signal pathway, the MAPKs signal pathway, and the NF-κB signal pathway, together contributed to the regulation of cell proliferation, invasion, metastasis and apoptosis, in which plays the role of non iodide transported function. Therefore, the non iodine transported function of iodide transporters may plays the crucial role of tumor occurrence and progression of carcinoma. Based on this information, present study was devoted to systematic summarize the iodine transported function and non iodine transported function (may affects occurrence and progression of carcinoma) of the classical iodide transporters [sodium iodide symporter (NIS) and pendrin] and novel iodine transporters[ (cystic fibrosis transmembrane conductance regulator (CFTR) , sodium multivitamin transporter (SMVT) , and anoctamin 1 (ANO1) ], respectively, in order to provide a theoretical basis and literature review reference for underlying the mechanism of iodine transporters and its regulated signal pathways for the occurrence and progression of carcinomas.

Objective: To analyze the frequency and composition of risk-related cytogenetic abnormalities (CAs) in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The frequency and composition of risk-related CAs from a cohort of 1 015 Chinese patients with NDMM were determined by interphase fluorescence in situ hybridization (iFISH) , individually or in combination. Results: Of the cohort of 1 015 Chinese patients with NDMM, the frequencies of IgH arrangement, del (13q) /13q14, 1q gain and del (17p) were 54.0%, 46.4%, 46.1% (35.8% and 12. 7% for 3 or more than 3 copies) and 9.9%, respectively. Among 454 patients who had the baseline information for all risk-related CAs [except t (14;20) , which was not covered by the FISH panels performed routinely at all five centers], the frequencies of t (4;14) , t (11;14) or t (14;20) were 14.1%, 11.2% and 4.8%, respectively; of them, 44.3% patients carried 2 or more CAs (28.0%, 13.4% and 2.9% for 2, 3 or ≥4 CAs) ; 83.3%, 95.0% or 68.6% patients with 1q gain, del (17p) or IgH rearrangement had 1 or more additional CA (s) , with del (13q) /13q14 as the most frequently accompanied CA; 57.7% patients carried at least 1 HRCA; the incidences of double-hit (DH) MM (DHMM) (=2 HRCAs) and triple-hit (TH) (THMM) (≥3 HRCAs) were 14.3% and 2.9%, respectively. Conclusions Our results provided an up-to-date profile of CAs in Chinese NDMM patients, which revealed that approximately 58% patients might carry at least 1 HRCA, and 17% could experience so-called DHMM or THMM who presumably had the worst outcome.

Objective: To explore the preventive effect and possible molecular mechanism of dietary supplementation of N-carbamylglutamate (NCG) in the implantation of carbon disulfide (CS₂) into embryo implantation disorders. Methods: embryo implantation disorder model was established by single intraperitoneal exposure to CS₂ on the 3rd, 4th, and 5th days after pregnancy. Endometrial tissues were collected for 24h after exposure to CS₂ for western-blot and immunohistochemical staining. Results: The number of embryo implantation was increased in NCG+CS₂ group, compared with CS₂ alone group. Day 4 of pregnancy when CS₂-exposed after 24 h, the expression of pAKT protein in NCG+CS₂ group was significantly increased (P<0.05), the expression level of pAMPK protein in NCG+CS₂ group was significantly decreased, compared with CS₂ alone group, respectively. Immunohistochemical results showed that pAKT, pAMPK, AKT and AMPK proteins were expressed in luminal epithelial cells, glandular epithelial cells and stromal cells of endometrium; Day 4 of pregnancy when CS₂-exposed after 24 h, deep staining of ATK and pAKT protein in NCG+CS₂ group, the AMPK and pAMPK protein staining became lighter. Conclusion Dietary supplementation of NCG can interfere with the embryo loss induced by CS₂ by altering the total amount of AKT/AMPK molecules.

Objective: To study the effect of CS2 on dendritic cells (DCs) in the uterus and the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor(fms-like tyrosine kinase-1, Flt-1), and to explore the toxic mechanism of CS2-induced embryo implantation dysfunction. Methods: The Kunming mice were randomly divided into control group,gestational day 4(GD4) exposure group and GD5 exposure group. The endpoints of each group(GD5, GD6, GD7) was set up according to their respective exposure time points. The mice in the exposure group were given intraperitoneal injection of CS2 at an injection dose of 631.4 mg/kg and the control group was given olive oil. The effect of CS2 on DCs in the uterus of pregnant mice was observed by flow cytometry. The levels of VEGF and Flt-1 were measured by Real-time quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Results: In the GD4 and GD5 exposure groups, the number of DCs in the uterus of pregnant mice decreased at all endpoints and the GD5 endpoint in the GD4 exposure group decreased by 21%(P=0.039), when compared with the control group. In the GD4 exposure group, the levels of VEGF mRNA and protein in the uterus of the pregnant mice were 79% and 30% lower than those in the control group, respectively (P=0.03、P=0.017); the levels of Flt-1 mRNA and protein at the endpoints of GD6 and GD7 in the uterus decreased by 54%, 36%, 60% and 56%, respectively, when compared with the control group(P=0.017、P=0.012、P=0.004、P=0.007). In the GD5 exposure group, the levels of VEGF mRNA and protein in the uterus of pregnant mice at the endpoint of GD7 decreased by 62% and 36%, when compared with the control group (P=0.005、P=0.035); the levels of Flt-1 mRNA and protein in the uterus at the endpoint of GD7 decreased by 60% and 44%, respectively, when compared with the control group (P=0.004、P=0.009). Conclusion CS2 reduced the number of DCs in the uterus of pregnant mice, and affected the non-immune function of DCs, which affected uterine angiogenesis, this may be one of the mechanisms of CS2-induced embryo implantation dysfunction.

Objective To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM).Methods It was a prospective,multi-center,observational study.A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015.Relevant information was recorded,such as baseline clinical data,cytogenetic abnormalities,treatment regimens,and duration of treatment,safety,and survival.Results (1)There were 126 relapsed and refractory MM (RRMM) patients,25 newly diagnosed patients and 19 maintenance patients.The evaluable RRMM patients accounted for 120 cases,among which 74 cases(61.7％) reached the partial response (PR) or above,and a very good partial response (VGPR) in 16 patients (13.3％),a complete response (CR) in 14 cases (11.7％),a strictly complete response (sCR) in 4 cases (3.3％).Thus,a VGPR or above in 34 patients accounted for 28.3％.(2)The median follow-up was 13 months,the median time to progression 12 months.The median survival after receiving lenalidomide was 19 months,and the median overall survival (OS) was 62 months.(3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype,international staging system (ISS) Ⅰ-Ⅱ,t(4;14) negative (detected by fluorescence in situ hybridization),non-bortezomib resistance and response to previous regimens.As to OS,nonbortezomib resistance,response to previous regimens and non-primary refractoriness were positive factors.Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival (PFS),non-bortezomib resistance and non-primary refractoriness for OS.(4) Grade 3 or 4 adverse events that occurred in more than 10％ of all enrolled patients were neutropenia (12.7％),leukocytosis (11.5％) and thrombocytopenia (12.7％).Owing to intolerance of toxic side effects,7 cases withdrew lenalidomide.Conclusions No matter what combination,regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7％,a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable.In addition,the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS,non-bortezomib resistance and non-primary refractoriness for OS.Clinical trail registration Clinicaltrials.gov,NCT01947309

OBJECTIVE: To observe the early adverse effect index caused by short-term-repeated exposure to cadmium chloride via oral perfusion in male rats. METHODS: Forty specific pathogen free healthy male SD rats were randomly divided into four groups: control group,low-,middle-and high-dose groups. The rats of low-,middle-and high-dose groups were treated with cadmium chloride 1. 11,3. 51 and 11. 06 mg/kg body weight,respectively,and the control group rats was treated with the same volume of ultra pure water,by gavage once a day for four weeks. During the experimental duration,the body weights of the rats were taken and activity status of the rats was observed. After the experiment,the rats were executed,and some indicators of main organ coefficients,blood routine,serum biochemical indexes,urine related effect indexes and bone mineral density were measured. RESULTS: During the experimental duration,rats of high-dose group showed the symptoms such as decreased activity,increase repose,move slowly and skin duller. Comparing with control group at the same time points,the body masses of the high-dose group of the 1-4 weeks were lower(P < 0. 05).After the experiment,comparing with control group,the weights of kidney and spleen of the high-dose group decreased significantly(P < 0. 05) and the liver coefficient increased significantly(P < 0. 05). The cadmium levels in blood,urine,liver,kidney and thighbone of the middle-and high-dose groups were higher than those of the control group(P < 0. 05).The red blood cell counts of the low-and middle-dose groups increased significantly(P < 0. 05). The level of hemoglobin of middle-and high-dose groups decreased(P < 0. 05),and the activity of alanine aminotransferase in high-dose groups increased significantly(P < 0. 05). Comparing with control group,the levels of urine α_1-microglobulin and urine β_2-microglobulin in urine of the middle-dose group were decreased(P < 0. 05) and the level of urine urea nitrogen increased(P < 0. 05),but there were no significantly changes of the above three indexes in the high-dose group(P >0. 05). There were no significant difference of the levels of N-acetyl-beta-D glucosaminidase in urine between control and treatment groups(P > 0. 05). Simultaneously,in high-dose group,the weight of thighbone,the bone calcium content and bone mineral density reduced significantly than those of the control group(P < 0. 05). CONCLUSION: Skeletal effects can be used as an early toxic effect sensitive index of short-term-repeated experiments exposure to cadmium chloride via oral perfusion in male rats.