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Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.
Subject(s)
Humans , Middle Aged , Receptors, Chimeric Antigen/therapeutic use , Retrospective Studies , Immunotherapy, Adoptive/adverse effects , Lymphoma, Large B-Cell, Diffuse/drug therapy , Cell- and Tissue-Based Therapy , Antigens, CD19/adverse effectsABSTRACT
Objective To investigate the relationship between blood uric acid levels and total burden scores(TBS)of carotid plaques in elderly patients with non-dialysis dependent chronic kidney disease(CKD). Methods Seventy-seven elderly patients with non-dialysis dependent CKD were included.All clinical data were collected,and stepwise multiple linear regression was conducted to determine independent factors for TBS of carotid plaques in elderly patients with non-dialysis dependent CKD. Results Compared with the control group,TBS was significantly higher in the smoking group(P= 0.035),hypertension group(P= 0.014)and diabetic group(P= 0.041).In addition,correlation analysis showed that hemoglobin,low-density lipoprotein cholesterol,uric acid,C-react protein and estimated glomerular filtration rate were significantly correlated with TBS(all P<0.05).Furthermore,stepwise multiple linear regression analysis showed that TBS was markedly correlated with low-density lipoprotein cholesterol(P = 0.007,)and uric acid(P = 0.001). Conclusions Uric acid is an independent factor for TBS of carotid plaques in elderly patients with non-dialysis dependent CKD.
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Objective To investigate the effect of depression on morning blood pressure surge ( MBPS) in maintenance hemodialysis( MHD) patients with hypertension. Methods 67 MHD patients with hypertension were included in this study.All clinical data were collected,and ambulatory blood pressure mo-nitor was used to monitor patient''''''''s blood pressure in 24 hours.Self-rating depression scale(SDS) was used to survey 67 MHD patients,and multivariable logistic regression was conducted to determine independent risk factors for morning hypertension in MHD patients with hypertension. Results There were 14 depression pa-tients in non-morning hypertension group ( 35. 0％) , 18 depression patients in morning hypertension group (66.7％),and the difference was significant(χ2=6.479,P=0.011).In addition correlation analysis showed that age(r=0.027,P=0.044),24 h systolic pressure(r=0.284,P=0.020),24 h diastolic pressure(r=0.278,P=0.023),fasting blood-glucose (r=0.293,P=0.039),low-density lipoprotein cholesterol (r=0.345,P=0.016),and the standard score of SDS(r=0. 276,P=0.024)were significantly correlated with MBPS .Furthermore,multivariable logistic regression showed that the standard score of SDS(OR=1.101,95％CI=1.018-1.191,P=0.016) ,24 h diastolic pressure ( OR=1.070,95％CI=1.007-1.136,P=0.028) and fast-ing blood-glucose (OR=2.127,95％CI=1.118-4.049,P=0.022)were independent risk factors for morning hypertension in MHD patients with hypertension ( OR=1. 101, 95％CI:1. 018-1. 191, P=0. 016 ) . Conclu-sion Depression,24 h diastolic pressure and fasting blood-glucose can increase the risk of morning blood pressure surge in patients with MHD hypertension.
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Objective To explore the feasibility of fabricating a self-powered and implantable stimulator . Methods Based on pyroelectric effect and high penetrability of infrared ray , an implantable stimulator was designed and fabricated .The electrical performance of stimulator was measured under infrared ray illumination .We conducted the animal experiments in vitro and in vivo to observe the response of gastrocnemius contraction under stimulation .Results The stimulator could output the electrical signal under the periodical infrared ray illumination .The output voltage and current were proportional to the intensity of infrared ray ,which could reach up to 1 .2 V . A real-time electrical stimulation of frog gastrocnemius was conducted and obvious contraction was observed .The tension values increased with the increase of infrared intensity .We further carried out the in vivo experiment with a frog in order to evaluate the performance of the stimulator after being implanted into the body . The gastrocnemius would also be made to contract even though the infrared intensity decayed when through the skin .Conclusion The proposed pyroelectric stimulator can be self-powered and controlled through near-infrared illumination .This study can provide some guidance for solving the problems of implantable power .
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OBJECTIVE:To observe the efficacy and safety of cyclophosphamide,leflunomide sequentially combined with prednisone in the treatment of membranous nephropathy in stage Ⅱ. METHODS:72 patients with membranous nephropathy in stageⅡwere randomly divided into group A(24 cases),B(24 cases)and C(24 cases). All patients were given angiotensin convert-ing enzyme inhibitor (ACEI) Benazepril hydrochloride tablet,warfarin,dipyridamole,calcium and other conventional treatment. Based on it,group A was orally given 50 mg Compound cyclophosphamide tablet,twice a day,for continuous 3 months+1.0 mg/(kg·d)Prednisone tablet,it was reduced 5 mg every 2 weeks after 2 months,then it reduced 2.5 mg every 2 weeks when 30 mg/day,and then it maintained 4-6 months when 10 mg/day,it lasted for 12 months. Group B was given 50 mg Leflunomide tablet,it changed as 20 mg/day after 2 d,and for continuous 6 months+Prednisone tablet(the same dosage and usage as group A). Group C was given Compound cyclophosphamide tablet(the same dosage and usage as group A)was orally given in 1-3 months,and Leflu-nomide tablet(the same dosage and usage as group B)in 4-9 months Prednisone tablet(the same dosage and usage as group A). Clinical efficacy,24 h urinary protein,albumin,total cholesterol,serum creatinine,alanine aminotransferase before and after 3, 6,9 and 12 months and incidence of adverse reactions in all groups were observed. RESULTS:Before treatment,there were no significant differences in the 24 h urinary protein,albumin,total cholesterol,serum creatinine and alanine aminotransferase among all groups(P>0.05). After treatment,24 h urinary protein,total cholesterol,serum creatinine and alanine aminotransferase in all groups were significantly lower than before,and they gradually decreased by treatment time,24 h urinary protein in group C was lower than group A and B,albumin was significantly higher than before and gradually increased by treatment time,and group C was higher than group A and B,the differences were statistically significant(P0.05). The total effective rate in group C was significantly higher than group A and B,the dif-ference was statistically significant (P0.05). And there was no significant difference in the incidence of adverse reactions among 3 groups (P>0.05). CONCLUSIONS:Based on the conventional treatment,the efficacy of cyclophosphamide,leflunomide sequentially combined with glucocorticoid is superior to cyclophosphamide or leflunomide alone in the treatment of membranous nephropathy in stageⅡ,with similar safety.
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A strain producing eggshell membrane protease (ESM protease) was isolated from the soil and identified as Pseudomonas aeruginosa. The enzyme isolated from the fermentation liquid of this strain and purified by ammonium sulfate precipitation, quadratic anion-exchange chromatography exhibited eggshell membrane degrading activity of 304.5 U/mg. By SDS-PAGE, the protein molecular mass is 32 kD. The N-terminal amino acid sequence of this protease is: Ala, Glu, Ala, Gly, Gly, Val, Ala, Gly, Lys, Glu, Asp, Ala, Ala, Glu, Leu.
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Objective To discuss the diagnostic value of CT in the hip joint dislocation.Methods We analyzed and compared 17 cases of the hip dislocation examined by X-ray and CT.Results X-ray plain film displayed hip joint dislocation in 15 cases,fractures in 10 cases,soft tissue swelling in 9 cases,widened hip joint space in 6 cases and bone fragment in 3 cases after restoration.CT showed hip joint dislocation and fractures in 17 cases,soft tissue swelling in 15 cases,widened hip joint space in 11 cases and bone fragment in 10 cases after restoration.Conclusion For the direction and the degree of hip joint dislocation,acetabulum fracture,bone fragment in articular space and soft tissue swelling,CT has distinct advantage.We find that CT may be one of a routine method in hip joint dislocation,especially after restoration.