1.Efficacy and Safety of Total Oral Regimens Containing Pomalidomide as a Second-line Treatment Strategy in Multiple Myeloma Patients
Jie XIAO ; Xiuju WANG ; Shuangfeng XIE ; Yiqing LI ; Guoyang ZHANG ; Wenjuan YANG ; Hongyun LIU ; Danian NIE
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(6):902-911
		                        		
		                        			
		                        			[Objective]To evaluate the efficacy and safety of total oral regimens containing pomalidomide as a second-line treatment strategy in multiple myeloma.[Methods]A total of 22 patients with multiple myeloma placed on total oral regimens containing pomalidomide as a second-line therapy from March 2020 to December 2023 were retrospectively analyzed to evaluate the treatment response,survival and safety.[Results]The median age of the 22 patients was 71.5 years old. The total oral treatment regimens containing pomalidomide included IPD (7 cases),PCD (11 cases),XPD (2 cases),and PD (2 cases). The median number of treatment cycles was 14. Among the 13 patients with prior lenalidomide exposure,ORR was 53.85%,of which 23.08% was ≥VGPR. In 9 patients without prior lenalidomide exposure,the ORR was 77.78%,and of which 55.56% was ≥VGPR. There was no significant difference in ORR between these two groups (P=0.38). In 12 patients with high genetic risk,the ORR was 50%,and ≥VGPR was 16.67%. The median follow-up time was 10.6 months. Disease progressed in 10 patients and death occurred in 6 patients of them. The median progression free survival (PFS) was not reached (not reached and 10.6 months in non-lenalidomide-exposure patients or lenalidomide-exposure patients,respectively).The high grade treatment-related adverse events (AEs)(≥3 ) were reported in 18.18% patients,including granulocytopenia,thrombocytopenia,and pulmonary infection. There was no treatment-related death.[Conclusion]Total oral regimens containing pomalidomide as a second-line therapy is generally effective and safe for multiple myeloma patients.
		                        		
		                        		
		                        		
		                        	
2.Successful treatment of acute leukemia by secondary transplantation after the first haploidentical hematopoietic stem cell transplantation failure
Kezhi HUANG ; Yiqing LI ; Shaofan XIE ; Jie XIAO ; Wenjuan YANG ; Shuangfeng XIE ; Liping MA ; Danian NIE
Organ Transplantation 2023;14(3):427-
		                        		
		                        			
		                        			Objective To evaluate the feasibility of secondary transplantation for patients with acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation. Methods Two acute leukemia patients underwent the first haploidentical hematopoietic stem cell transplantation from two donors with thalassemia, and the number of collected CD34+ cells was 2.57×106/kg and 1.99×106/kg per donor, respectively. The first haploidentical hematopoietic stem cell transplantation failed. Secondary transplantation was performed from two non-thalassemia donors, and the number of collected CD34+ cells was 4.28×106/kg and 5.75×106/kg per donor, respectively. A reduced-intensity conditioning regimen consisting of fludarabine (Flu), busulfan (Bu) and antithymocyte globulin (ATG) was adopted for the secondary transplantation. Results For two recipients, the time of secondary transplantation of neutrophil and platelet was +12 d and +10 d, +10 d and +10 d, respectively. Up to the final follow-up (+1 062 d and +265 d after secondary transplantation), the primary diseases of both two recipients have been completely relieved without evident post-transplantation complications. Conclusions Secondary transplantation with reduced-intensity conditioning regimen may successfully treat acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation.
		                        		
		                        		
		                        		
		                        	
3.Haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph- high-risk B-cell acute lymphoblastic leukemia
Menglin FAN ; Yu WANG ; Ren LIN ; Tong LIN ; Fen HUANG ; Zhiping FAN ; Yajing XU ; Ting YANG ; Na XU ; Pengcheng SHI ; Danian NIE ; Dongjun LIN ; Zujun JIANG ; Shunqing WANG ; Jing SUN ; Xiaojun HUANG ; Qifa LIU ; Li XUAN
Chinese Medical Journal 2022;135(8):930-939
		                        		
		                        			
		                        			Background::Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods::This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results::A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups (P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups ( P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%; P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%; P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%; P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%; P= 0.041), respectively, in the HID and MSD groups. Conclusion::HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registration::ClinicalTrials.gov: NCT01883180, NCT02673008.
		                        		
		                        		
		                        		
		                        	
4.Microglia-Derived NLRP3 Activation Mediates the Pressor Effect of Prorenin in the Rostral Ventrolateral Medulla of Stress-Induced Hypertensive Rats.
Li HU ; Shutian ZHANG ; Kokwin OOI ; Xuehai WU ; Jiaxiang WU ; Jian CAI ; Yinggang SUN ; Jijiang WANG ; Danian ZHU ; Fuxue CHEN ; Chunmei XIA
Neuroscience Bulletin 2020;36(5):475-492
		                        		
		                        			
		                        			Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.
		                        		
		                        		
		                        		
		                        	
5.Value of near focus narrow-band imaging for differential diagnosis between hyperplastic polyp and sessile serrated adenoma/polyp
Zili XIAO ; Ping XIANG ; Feng LI ; Renxiang HUANG ; Danian JI ; Zhijun BAO
Chinese Journal of Digestive Endoscopy 2019;36(8):568-571
		                        		
		                        			
		                        			Objective To evaluate the value of near focus narrow-band imaging ( NF-NBI ) in differentiating hyperplastic polyp ( HP ) and sessile serrated adenomas/polyp ( SSA/P ) . Methods Data of 65 cases of pathologically confirmed HP or SSA/P with clear NF-NBI images in Huadong Hospital Affiliated to Fudan University from October 2017 to September 2018 were retrospectively analyzed. Three senior doctors observed the images of NF-NBI, including expanded crypt opening ( ECO ) and thick & branched vessel ( TBV) . The results were compared with pathological results in order to analyze differential diagnostic value of ECO and TBV for HP and SSA/P. Results Among 65 lesions, 44 were SSA/P and 21 were HP. The sensitivity, specificity, and accuracy of ECO, TBV, and ECO combined with TBV for differential diagnosis between HP and SSA/P were 80. 3%( 106/132 ) , 85. 7%( 54/63 ) and 82. 1%( 160/195 ); 38. 6%( 51/132) , 82. 5%( 52/63 ) , and 52. 8%( 103/195 ); and 84. 8%( 112/132 ) , 73. 0%( 46/63 ) , and 81. 0%(158/195), respectively. Conclusion ECO under NF-NBI has a high sensitivity for diagnosis of SSA/P . ECO combined with TBV is helpful for differential diagnosis between HP and SSA/P .
		                        		
		                        		
		                        		
		                        	
6.Exploration of PBL and mini-CEX in the clinical probation teaching for medical students of eight-year program in hematology department
Jie XIAO ; Liping MA ; Danian NIE ; Shuangfeng XIE ; Yiqing LI ; Xiuju WANG ; Yudan WU ; Hongyun LIU
Chinese Journal of Medical Education Research 2018;17(8):822-825
		                        		
		                        			
		                        			Objective The study explored the feasibility of PBL teaching approach and mini-CEX scores evaluation method in hematology probation teaching practice. Methods 54 medical students of eight-year program were selected in the study and they were in hematology department of Sun Yat-sen Memorial Hospital for clinical probation. The study compared PBL teaching approach with traditional training method, and used mini-CEX to evaluate the students' clinical competence. Results The performance of PBL teaching group is better than traditional teaching group in the aspect of inquiry skill, clinical diagnosis, therapy plan and humanistic care (P<0.05). There is no significant difference of basic knowledge, physical examination skill and clinical operational skills between these two groups. More than 85%of the students in PBL group are satisfied with the teacher in the aspect of participation, feedback, guidance, correction and assistance. Conclusion Through this teaching practice, the study provides new methods for improving the teaching of pre-internal clinical practice in hematology department.
		                        		
		                        		
		                        		
		                        	
7.Risk factors of pathological discrepancy between biopsy and excisional specimen from gastric low-grade intraepithelial neoplasia and early gastric cancer
Feng LI ; Ping XIANG ; Qi OUYANG ; Fuxing XU ; Renxiang HUANG ; Zili XIAO ; Danian JI ; Yun ZHOU ; Tao SUN
Chinese Journal of Digestive Endoscopy 2018;35(5):336-340
		                        		
		                        			
		                        			Objective To investigate the risk factors of pathological discrepancy between biopsy and excisional specimen from gastric low-grade intraepithelial neoplasia (LGIN) and early gastric cancer (EGC). Methods A retrospective analysis was conducted on the data of 235 patients who underwent endoscopic submucosal dissection or surgical resection and diagnosed as LGIN or EGC ( including high-grade intraepithelial neoplasia) by postoperative pathology. Patients were grouped by whether there was significant pathological discrepancy between biopsy and excisional specimen. Univariate and multivariate analyses were used to analyze the risk factors for significant pathological discrepancy. Results Significant pathological discrepancy occurred in 33 cases (14. 0%). Univariate analysis showed that protruding lesion, non-reddish surface, without erosion or ulcer, diffused pathological type and number of biopsy were related to the pathological discrepancy (all P<0. 05). Multivariate analysis suggested that small number of biopsy blocks (OR=0. 574, 95%CI: 0. 363-0. 908, P=0. 018) was an independent risk factor for significant pathological discrepancy. Conclusion The pathological discrepancy between biopsy and excisional specimen from gastric LGIN and EGC are common. Multiple biopsies can improve the accuracy of biopsy and reduce the occurrence of pathological discrepancy with excisional specimen.
		                        		
		                        		
		                        		
		                        	
8.Risk factors for miss rate of colorectal adenomas during conventional colonoscopy
Danian JI ; Ping XIANG ; Yun ZHOU ; Feng LI ; Zili XIAO ; Renxiang HUANG
Chinese Journal of Digestive Endoscopy 2017;34(7):490-494
		                        		
		                        			
		                        			Objective To determine risk factors for the miss rate of colorectal adenomas during colonoscopy.Methods A total of 981 patients,diagnosed as having at least one polyp in colonoscopy,received a second colonoscopy in 6 months from November 2012 to March 2016.All polyps were removed in the second colonoscopy.Bio-information of patients such as sex,age,surveillance interval and features of polyps such as number,size,shape,location,pathology,withdrawal time,bowel preparation was retrospectively analyzed.Factors associated with the miss rates in these patients were analyzed with Chisquare and was also analyzed with Logistic regression model for multiple factors.Results A total of 981 patients were selected according to the inclusion and exclusion criteria,including 604 males and 377 females.Miss rates of males and females were 38.9% (235/604) and 27.9% (105/377) (P<0.01)respectively.Age ranged from 25 to 87 years with mean age being 61.0±9.7 years.Miss rates of senior patients <65 and ≥65 years were 31.5%(195/619) and 40.1%(145/362) respectively (P<0.01).A total of 1 728 adenomas were found in first colonoscopy.A total of 2 267 adenomas were found in the second colonoscopy.The adenoma miss rate was 23.8% (539/2 267).The miss rate of adenoma whose size ≤ 5 mm was 42.5% (311/732);and that of larger size of 6 to 9 mm was 17.8% (194/1 090);that of even larger size,i.e.,≥10 mm,was 7.6%(34/445)(P<0.01).Miss rates of Is,Isp,Ip,LST and Ⅱ adenomas in shape were 28.4%(489/1 720),9.3%(24/235),6.6% (12/182),9.0%(6/67) 20.5% (8/39) respectively (P>0.05).Location with highest adenoma miss rate were descending colon,ascending colon and transverse colon,27.8%(64/230),25.5%(120/470),25.5% (161/632) respectively.Miss rates of high and low risk adenoma were 44.8% (277/618) and 17.4% (63/363) (P<0.01).The highest adenoma miss rate of all the pathology type was tubular adenoma.The adenoma miss rate was 26.9% (449/1 671) (P<0.01).Miss rates of good and poor bowel preparation were 30.2% (271/897) and 82.1% (69/84) (P<0.01).Miss rates of adequate and inadequate withdrawal time were 24.3% (174/717) and 62.9% (166/264) (P<0.01).Conclusion Male,old-age,diameter ≤ 5 mm,poor bowel preparation and inadequate withdrawal time,high risk adenoma are the risk factors for missed adenoma.But the shape and location of adenoma are not the risk factors.
		                        		
		                        		
		                        		
		                        	
9. Risk-factor analysis of poor graft function after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia
Chenyan SHI ; A MAMAL ; Zenghui LIU ; Xiaoxiong WU ; Linghui XIA ; Danian NIE ; Yongrong LAI ; Fengqi DUAN ; Haowen XIAO ; Zujun JIANG ; Yonghua LI ; Yang XIAO
Chinese Journal of Hematology 2017;38(9):761-766
		                        		
		                        			 Objective:
		                        			To investigate the risk factors of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA) .
		                        		
		                        			Methods:
		                        			Clinical data from 111 SAA patients who received allo-HSCT were analyzed retrospectively. Factors including age, gender, interval to transplantation, the level of serum ferritin before transplantation were analyzed by Cox multivariate regression analysis.
		                        		
		                        			Results:
		                        			Among the 111 patients who underwent allo-HSCT, 16 developed PGF (14.4%) . Multivariate analysis showed donor type (
		                        		
		                        	
10.A bioequivalence evaluation of long-chain triacylglycerol/medium-chain triacylglycerol emulsion in beagle dogs
Mingwei ZHU ; Zhuming JIANG ; Jingsheng LIU ; Dakui LI ; Wei LIU ; Danian TANG ; Dan MEI ; Xiaoxiao LI ; Suodi ZHAI ; Fang FANG ; Junmin WEI ; Jinduo CAO
Chinese Journal of Clinical Nutrition 2017;25(6):329-334
		                        		
		                        			
		                        			Objective Long-chain triacylglycerol (LCT) by three producers,each mixed with the same medium-chain triacylglycerol (MCT),were compared with the brand MCT/LCT in causing focal necrosis of hepatocytes in beagle dogs (a bioequivalence evaluation).Methods 21 beagle dogs (male,0.7-1.5 years old,10-15 kg) were used in this study.According to the sources of the LCT,the animals were divided into Group A (LCT made in China),Group B (LCT made in Japan),Group C (LCT made in Germany),and the control group (the brand 10% MCT/LCT).Central venous port was placed via the lumber vein of the animals under general anesthesia.After 2 weeks of rehabilitation,MCT/LCT was administered through this port for 28 days at 9 g/ (kg · d) [while the routine dose used clinically was 1 g/ (kg · d)].The laboratory indexes and the pathomorphism of the liver and kidney were studied single blindly.Results Laboratory tests,including liver and kidney function,blood coagulation function and lipid metabolism,did not identify differences among emulsions with different sources of LCT.Liver biopsy at day 28 showed no focal necrosis in Group C and the control group;there was minor damage in Group B;and Group A had obvious liver necrosis.and the pathological findings of other organs are similar.No significant difference was observed in biopsies of other organs.Conclusions Emulsions with different sources of LCT varied in their damage to the liver.Generics with LCT of higher quality were equivalent to the brand MCT/LCT in terms of safety.
		                        		
		                        		
		                        		
		                        	
            
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