Résumé
OBJECTIVE:To study the effects of rhei radix and astragali radix on renal protection and intestinal barrier function in rats with chronic renal failure(CRF),and analyze its pharmacological mechanism from the theory of"gut-renal axis"in TCM. METHODS:Rat models of CRF were established by 5/6 nephrectomy. Rats were randomly divided into sham operations group (group J,n=6),model group(group M,n=8),and administration groups(n=9),which included benazepril group(group Y, positive control,2 mg/kg),rhei radix high-dose,medium-dose,low-dose groups(group DH,DM,DL,calculated by crude drug as 3,1.5,0.75 g/kg),and astragali radix high-dose,medium-dose,low-dose groups (group HH,HM,HL,calculated by crude drug as 6,3,1.5 g/kg). After 1 week of modeling,rats in each administration group were intragastrically administrated,once a day,for 5 weeks. Rats in group J,M were intragastrically administrated equal volume distilled water. After 12 h of administration, the 24 h urine protein(Upr),serum levels of creatinine(SCr),urea nitrogen(BUN),uric acid(UA)and plasma endotoxin level were detected,and kidney index was calculated. Changes in renal tissue,villi of small intestinal mucosal tissue and crypt depth were observed by microscope. RESULTS:Compared with group J,24 h urine volume and 24 h water drinking volume of rats in group M were increased,24 h Upr,serum levels of SCr,BUN,UA,plasma endotoxin level,and kidney index were increased, with statistical significances(P<0.05 or P<0.01). Most glomerular volume were increased and rigid in group M,showing intersti-tial infiltration in large number of inflammatory cells;villus length,villus width,mucosal thickness and villus length/crypt depth ra-tio of intestinal mucosa were decreased (P<0.05 or P<0.01),and crypt depth was increased (P<0.01). Compared with group M,24 h urine volume in group DM,DL,HM,HL was decreased;24 h water drinking volume in group HM was decreased;24 h Upr,serum levels of SCr,BUN levels,and kidney index of rats in each administration group were decreased. Except for group HH,serum UA levels in other administration groups was decreased;and except for group HH,HM,HL,plasma endotoxin level in other administration groups was decreased,with statistical significances(P<0.05 or P<0.01). The pathological morphologies of renal tissue,intestinal mucosal tissue and intestinal villi in each administration group were improved to varying degrees. CONCLU-SIONS:Both rhei radix and astragali radix can effectively reduce the metabolic toxin levels of rats,improve filtration function of glomerular and enhance the exclusion of metabolic trash,which may be restoring the intestinal function to achieve the goal of treat-ing CRF. And both show optimal effect in medium dose.
Résumé
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
Résumé
Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder.There have been many advances in the diagnosis,prognosis and management of multiple myeloma at the 21th European Hematology Association Annual Meeting,especially SMM being discussed as a topic.These include a revised disease definition,new prognostic factors and new treatment options.
Résumé
Objective To investigate the value of 1q21 amplification in newly diagnosed myeloma patients.Methods Fifty-two cases of newly diagnosed multiple myeloma from June 2008 to June 2010 were enrolled.Fluorescence in situ hybridization (FISH) was used to detect the 1q21 amplification,and the clinical characteristics and treatment response were analyzed.Results 1q21 amplification was discovered in 30 of 52 patients (57.7 ％),Clinical characteristics such as gender,malignant pleural effusion,extramedullary plasmacytoma,bone destruction,β2 microglobulin,ALB,hemoglobin,blood calcium,plasma cell proportion,clinical stage seemed to have no correlation with 1q21 amplification.The 52 patients all received bortezomibbased regimens.The response rates were not significant difference between patients with and without 1q21 amplification,the OS was also not significant difference [26 months (6-30 months) vs 30 months (12-85 months),P =0.409],but the patients with presence of 1q21 gain resulted in significantly shorter PFS [8 months (1-30 months) vs 20 months (3--48 months),P=0.019].Multivariate analysis showed 1q21 with more than two additional genetic abnormalities was an independent prognostic predictor (P =0.031).Conclusion 1q21 amplification is one of the adverse prognostic predictors,the response rate is not significant difference between patients with and without 1q21 amplification in bortezomib-based group,but the 1q21 amplification could result in significantly shortened PFS.
Résumé
Objective To investigate the efficacy and toxicity of bortezomib in combination with ifosfamide, methylprednisolone, thalidomide (V-CMPT) for the treatment of multiple myeloma (MM). Methods Twenty-four patients with newly diagnosed or relapsed/refractory MM were treated with V-CMPT. This regimen was repeated every three weeks as one cycle, and each case received two cycles. We adopted the examination of bone marrow and M protein and other hematological markers to evaluate the condition of disease and the therapeutic response. Results Of the nine patients with newly diagnosed MM, three achieved a complete remission (CR), five of a partial response (PR), and 1 of a minor response (MR). Of the patients with relapsed/refractory MM, two achieved a CR, two had a near CR (nCR), three had a PR, six had a MR, and two were no chang (NC). There was no obvious difference in the two groups (P = 0.511, P = 1.000). The overall response rate (ORR) was 91.7 %, and the CR/nCR rate was 29.2 %. After two cycles, the levels of hemoglobin, the serum albumin and the serum β2-microglobulin were obviously improved. The main adverse events were transient, including gastrointestinal reaction, thrombocytopenia, neuropathy, which could be controlled during the interval of chemotherapy or by symptomatic treatment and had no influence on the chemotherapy.Conclusion V-CMPT regiman was effective against the newly diagnosed and relapsed/refractory MM and could improve the related hematological markers with high response rate and tolerable toxicities.
Résumé
Objective The aim of this phase Ⅱ study was to determine the efficacy and safety of combined bortezomib and thalidomide (VT) regime as initial treatment for newly diagnosed multiple myeloma (MM) in China. Methods Thirty-four patients were enrolled in this study and received VT regime up to 21-day cycles. Bortezomib (1.3 mg/m2) was administered intravenously on days 1, 4, 8, and 11, while oral thalidomide ( 100 mg/day) was given from days 1 to 21. The primary end point was clinical response.The secondary end point was safety. Results Among the 34 patients, 20 were male, 14 were female, with a median age of 59 years, and 15 in international stage system (ISS) Ⅲ ,18 in ISS Ⅱ , 1 in ISS Ⅰ . Among them, 28 completed 2 cycles' treatment and achieved an overall response rate (ORR) of 92.9%; 26 were able to complete the planned 8 cycles of therapy. After 8 cycles, the ORR was 100% ( complete response 30. 8%, near-complete response 23.1%, partial response 42. 3%, minimal response 3.8% ). After followed up with a median time of 12 months, the estimated rate without progress of disease was 62%, and the estimated continous remission rate of 12 months was 62%. The median survival time was not achieved. The most common adverse events were mild to moderate ( grades 1, 2). The main toxicities were hematologic (53. 3% ), gastrointestinal ( 40. 0% ), peripheral neuropathy ( 38.0% ), fatigue ( 36. 6% ) and fever (32. 0% ). Conclusions VT regime provides a very high ORR and complete response rate in the treatment of newly diagnosed MM patients. No patients experienced deep venous thrombosis. In conclusion,bortezomib in combination with thalidomide is a very effective regimen for newly diagnosed MM patients and the toxicities are manageable.
Résumé
Objective To investigate the clinical characteristics, prognosis and treatment of pleural effusion of multiple myeloma. Methods From Jun 2005 to March 2010, of 162 patients with multiple myeloma treated in our department were complicated with pleural effusion, whose the proportion male to female was 8:7 and the median age was 56.8 (37-68) years. The diagnosis of malignant pleural effusion was dependent on physical examination, chest X ray, pleural aspiration and pleural fluid cytology. According to internatinal system stages and Durie-Salmon stages, the patients were staged. Results The results of pleural fluid cytology showed that the myeloma cells were positive in 13 patients and was negative in the other 2 patients. All patients received the chemotherapy regimen including bortezomib, large dose of glucocorticoids and cisplatin, cyclophosphamide, etoposide or prednisone (DECP). Although pleural effusion was controlled in some degrees, but were quickly relapsed. Eleven patients died, 2 of steady disease and 2 follow-up. Conclusion Multiple myeloma with myelomatous pleural effusion was very poor in the prognosis. Myelomatous pleural effusion was taken as a late manifestation in multiple myeloma or prediction of the aggressive behavior of the disease.
Résumé
Objective To evaluate the clinical features of POEMS syndrome. Methods The clinical materials of 4 patients with POEMS syndrome were analysed retrospectively. Results All 4 patients presented polyneuropathy, abnormal globulinemia and endocrinopathy. All were treated with corticoid, cyclophosphamide and thalidomide. Some patients were treated with human immunoglobulin. Conclusion POEMS syndrome was a rare disease with involvement of multiorgan which result in difficult diagnosis. So for suspected cases, a necessary examination to avoid misdiagnosis should be given.
Résumé
Objective To obserue that bortezomib lead to hepatic impairment and even hepatic insufficiency. Methods Four multiple myeloma patients with hepatic impairment in velcade therapy were analyzed. All of 4 patients ranged from 46 to 60-year-old were relapsed and refractory, including 3 cases of male and 1 of female; 2 of K light chain type, 1 of non secretion type and 1 of IgGλλ biclonal type; 3 in stage ⅢB and 1 in stage ⅢA. Results Four patients had normal hepatic function before bortezomib therapy, but all appeared hepatic impairment during therapy. ALT and aspartate aminotransferase were increased by 2-80 and 1.5-70 times compared with before the chemotherapy, respectively, and bilirubin and alkaline phosphatase in 2 patients and glutamyltranspeptidase in 1 patient were increased. Hepatic function restored normally after patients were given liver securing drug and discontinued bortezomib therapy. Conclusion It isn't rare that bortezomib causing hepatic impairment in the patients with multiple myeloma.
Résumé
Objective To investigate the clinical features of multiple myeloma (MM) complicated by extramedullary plasmacytomas(EM). Methods Twenty five patients were enrolled into the study. The proportion male to famale was 15:10 and the median age 55. 2 years. The distribution of different isotypes was IgA ten, IgG nine and light chain λ five. The sites of complicating plasmacytoma included muscle, bone, skin, rectum, and testicles. The most common site was muscle. Results Patients with complicated extramedullary plasmacytomas at the time of diagnosis received traditional treatment, including vincristiuum, adriamycin, dexamethasonum, mephalan, presnisone, thalidomide and bortezomib. Rates of overall response (ORR) were 80%. Plasmacytomas occurring after the diagnosis of MM received cisplatin, etoposide, cyclophosphamide, presnisone, or bortezomib ORR were 66. 7% ,50. 0%. Conclusion These results lend support to the efficacy of bortezomib in the treatment of plasmacytoma. MM cases with unconventional disease recurrence are likely to be seen due to sub-clinical seeding of turnout cells suggestive of the presence of an EM clone of plasma cells with a high degree of chemoresistance. Available data in the literature concerning the optimal therapy for patients with EM relapse were reviewed.
Résumé
Objective To explore the clinical characteristics of Waldenstrom macroglobulinemia (WM) and enhance the level of diagnosis and treatment. Method The data of 15 patients with WM in our 68.5(60-79) years, male/female =2.75/1. Main clinical manifestations were fatigue, loss of weight, splenomegaly and lymphadenopathy. All the patients accepted the treatment of alkylating agents, purine nucleoside analogs, bortezomib or thalidomide respectively. The follow-up period for the patients was 4 months to 10 years and the median follow-up time was 82 months. Conclusion WM may often be seen in old male patients with varied clinical manifestations. The primary treatment is chemotherapy, but the disease is incurable. Bortezomib and thalidomide may improve the therapeutic effect.
Résumé
BACKGROUND: Osteosarcoma is the most common type of bone tumor and generally occurs between the age of 10 to 25; moreover, in clinical practice osteosarcoma is found to occur more often in minority nationalities in Xinjiang Autonomous Region. Do its incidence and prognosis vary between nationalities at gene levelOBJECTIVE: To observe the different expressions of p53, bcl-2 and proliferative cell nucleus antigen (PCNA) gene during the development of osteosarcoma between various Xinjiang nationalities.DESIGN: Non-randomized comparative experiment taking clinical pathological specimens as subjects.SETTING: Immunohistochemical Laboratory, the Pathological Center of Xinjiang Medical University.PARTICIPANTS: Totally 52 pieces of specimen were obtained from excised osteosarcoma tissues in the Pathological Department, the First Affiliated Hospital of Xinjiang Medical University, and the Pathological Department, the First Affiliated Hospital of Shihezi University, between January 1,1984 and December 31, 2001. The 52 cases of osteosarcoma included 29cases derived from male patients and 23 from female patients; among them there were 12 cases of Kazak minority, 17 cases of Uygur minority and 23cases of Han nationality. Other 32 specimens were obtained from 32 patients with tumor-like lesions (such as osteofibrous dysplasia or fibrous dysplasia), including 7 cases of Kazak minority, 11 cases of Uygur minority,and 14 cases of Han nationality. The informed consent was obtained from the patients.METHODS: This experiment was carried out at the Immunohistochemical Laboratory, the Pathological Center of Xinjiang Medical University. LSAB method was used to detect p53, bcl-2 and PCNA expression in the two groups. The first antibody was re placed by PBS as blank control, and the available positive expression was taken as positive control. P53 protein and PCNA were observed to express in cell nucleus, appearing obvious redbrown granules with positive expression, whereas Bcl-2 protein was expressed in cytoplasm.lationship between the expression of Bcl-2, p53 and PCNA in osteosarcoma.of different nationalities: The expression of p53, bcl-2 and PCNA in Kazak minority, Uygur minority and Han nationality was not remarkable p53, bcl-2 and PCNA in osteosarcoma and bone tumor-like lesions: The expression of P53, Bcl-2 protein and PCNA in osteosarcoma was remarkably higher than that in tumor-like lesions (42.31% vs. 3.13 %, 59.62%sion of bcl-2, p53 and PCNA in osteosarcoma: There was a close correlation between bcl-2 and p53, as well as between bcl-2 and PCNA in osteosarcoma tissues (X2 =5.818 2, 4.900 0, P＜0.05).CONCLUSION: The results indicate that there was no statistical difference between various nationalities in the expression of p53, bcl-2 and PCNA, as well as osteosarcoma differentiation. Suggesting that these genes may share the common regulation during the development of osteosarcoma,which is less associated with their nationality-related hereditary background.