1.Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study.
Wei SHEN ; Zhi ZHENG ; Xin-Zhu LIN ; Fan WU ; Qian-Xin TIAN ; Qi-Liang CUI ; Yuan YUAN ; Ling REN ; Jian MAO ; Bi-Zhen SHI ; Yu-Mei WANG ; Ling LIU ; Jing-Hui ZHANG ; Yan-Mei CHANG ; Xiao-Mei TONG ; Yan ZHU ; Rong ZHANG ; Xiu-Zhen YE ; Jing-Jing ZOU ; Huai-Yu LI ; Bao-Yin ZHAO ; Yin-Ping QIU ; Shu-Hua LIU ; Li MA ; Ying XU ; Rui CHENG ; Wen-Li ZHOU ; Hui WU ; Zhi-Yong LIU ; Dong-Mei CHEN ; Jin-Zhi GAO ; Jing LIU ; Ling CHEN ; Cong LI ; Chun-Yan YANG ; Ping XU ; Ya-Yu ZHANG ; Si-Le HU ; Hua MEI ; Zu-Ming YANG ; Zong-Tai FENG ; San-Nan WANG ; Er-Yan MENG ; Li-Hong SHANG ; Fa-Lin XU ; Shao-Ping OU ; Rong JU
Chinese Journal of Contemporary Pediatrics 2022;24(2):132-140
		                        		
		                        			OBJECTIVES:
		                        			To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China.
		                        		
		                        			METHODS:
		                        			A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined.
		                        		
		                        			RESULTS:
		                        			The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05).
		                        		
		                        			CONCLUSIONS
		                        			It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
		                        		
		                        		
		                        		
		                        			Female
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		                        			Fetal Growth Retardation
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		                        			Gestational Age
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		                        			Hospitalization
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		                        			Humans
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		                        			Incidence
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		                        			Infant
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		                        			Infant, Newborn
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		                        			Infant, Premature
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		                        			Infant, Very Low Birth Weight
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		                        			Prospective Studies
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		                        			Risk Factors
		                        			
		                        		
		                        	
2.Comparison of efficacy between laparoscopic and open proximal gastrectomy with double-tract reconstruction for Siewert type Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction.
Fei MA ; Liang Qun PENG ; Chang Peng LIU ; Yong Lei ZHANG ; Lei WANG ; Bin ZHANG ; Qi MA ; She Qing JI ; Jun Hui CHAI ; Xian Ce TANG ; Er Jiang ZHAO ; Ya Wei HUA
Chinese Journal of Gastrointestinal Surgery 2021;24(5):420-425
		                        		
		                        			
		                        			Objective: To compare the efficacy between laparoscopic and open proximal gastrectomy with double-tract reconstruction for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) 18 to 80 years old; (2) Siewert II and III AEG was confirmed by preoperative gastroscopy and biopsy, which could not be resected by endoscopy; patients undergoing radical proximal gastrectomy with double-tract reconstruction; (3) contrast-enhanced abdominal CT staging was cT1-2N0M0; (4) Eastern Cooperative Oncology Group (ECOG) physical status score <2 points, American Association of Anesthesiologists (ASA) grade 1 to 2; (5) patients agreed to perform proximal gastrectomy and signed an informed consent. Those who had undergone neoadjuvant radiochemotherapy, suffered from serious mental diseases and had incomplete data were excluded. According to the above criteria, clinical data of 84 consecutive patients with Siewert II and III AEG undergoing surgery at General Surgery Department of The Affiliated Tumor Hospital of Zhengzhou University from October 2010 to December 2018 were collected and analyzed. Of 84 patients, 61 underwent open proximal gastrectomy with double-tract reconstruction (OPG group), while 23 underwent laparoscopic proximal gastrectomy with double-tract reconstruction (LPG group). The perioperative complications and postoperative reflux esophagitis of two groups were compared. A P-value of <0.05 was considered to be statistically significant. Results: Among 84 cases, 74 were male and 10 were female. There were 43 cases of Siewert type II and 41 cases of Siewert type III. There were no significant differences in age, gender, body mass index, comorbidities, Siewert type, and tumor staging between the two groups (all P>0.05). As compared to the OPG group, the LPG group had longer operation duration [(223±21) minutes vs. (161±14) minutes, t=15.352, P<0.001], less intraoperative blood loss [195 (150, 215) ml vs. 208 (192, 230) ml, Z=2.143, P=0.032], and shorter time to flatus [(2.8±0.7) days vs. (3.3±0.9) days, t=2.477, P=0.015]. There were no significant differences in the number of harvested lymph nodes, time to the first meal and postoperative hospital stay between the two groups (all P>0.05). Postoperative complications developed in 2 cases (8.7%, 1 case each for anastomotic leakage and intestinal obstruction) in the LPG group and 5 cases (8.2%, 1 case each for anastomotic leakage, anastomotic bleeding, and anastomotic stenosis, 2 cases of incision infection) in the OPG group (χ(2)=5.603, P=0.231). The median follow-up was 41.2 (12.8-110.5) months. One patient (1.6%,1/61) had obvious reflux symptoms in the OPG group, compared with none in the LPG group (χ(2)=0.644, P=0.422). Esophagitis occurred in 1 case (4.8%, 1/21) in LPG group, compared with 4 patients (7.1%, 4/56) in the OPG group, without significant difference between the two groups (χ(2)=0.505, P=0.477). Conclusion: Laparoscopic proximal gastrectomy with double-tract reconstruction is safe and feasible without increasing the risk of postoperative complication and reflux esophagitis.
		                        		
		                        		
		                        		
		                        			Adenocarcinoma/surgery*
		                        			;
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Esophagogastric Junction/surgery*
		                        			;
		                        		
		                        			Female
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		                        			Gastrectomy
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Laparoscopy
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Retrospective Studies
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		                        			Stomach Neoplasms/surgery*
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		                        			Treatment Outcome
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		                        			Young Adult
		                        			
		                        		
		                        	
3.3D digital image microscope system-assisted vasovasostomy and vasoepididymostomy in rats.
Peng LI ; Na-Chuan LIU ; Er-Lei ZHI ; Chen-Cheng YAO ; Zhi-Liang ZHAO ; Zhi-Yong YU ; Qi-Meng LI ; Yu-Hua HUANG ; Jie-Chang JU ; Wen-Bin HUANG ; Husanjan ROZI ; Zhi-Yong JI ; San-Wei GUO ; Ru-Hui TIAN ; Zheng LI
Asian Journal of Andrology 2021;23(4):396-399
		                        		
		                        			
		                        			Optimal vision and ergonomics are essential factors contributing to the achievement of good results during microsurgery. The three-dimensional (3D) digital image microscope system with a better 3D depth of field can release strain on the surgeon's neck and back, which can improve outcomes in microsurgery. We report a randomized prospective study of vasoepididymostomy and vasovasostomy using a 3D digital image microscope system (3D-DIM) in rats. A total of 16 adult male rats were randomly divided into two groups of 8 each: the standard operating microscope (SOM) group and the 3D-DIM group. The outcomes measured included the operative time, real-time postoperative mechanical patency, and anastomosis leakage. Furthermore, a user-friendly microscope score was designed to evaluate the ergonomic design and equipment characteristics of the microscope. There were no differences in operative time between the two groups. The real-time postoperative mechanical patency rates were 100.0% for both groups. The percentage of vasoepididymostomy anastomosis leakage was 16.7% in the SOM group and 25.0% in the 3D-DIM group; however, no vasovasostomy anastomosis leakage was found in either group. In terms of the ergonomic design, the 3D-DIM group obtained better scores based on the surgeon's feelings; in terms of the equipment characteristics, the 3D-DIM group had lower scores for clarity and higher scores for flexibility and adaptivity. Based on our randomized prospective study in a rat model, we believe that the 3D-DIM can improve surgeon comfort without compromising outcomes in male infertility reconstructive microsurgery, so the 3D-DIM might be widely used in the future.
		                        		
		                        		
		                        		
		                        	
4.Outcomes of 138 myelodysplastic syndrome patients with HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation.
Qian Qian WANG ; Zi Xian LIU ; Xiao Li ZHAO ; Gui Xin ZHANG ; Jian Feng YAO ; Xiao Hui ZHENG ; Li Ning ZHANG ; Yu Yan SHEN ; Xing Li ZHAO ; Yi HE ; Yong HUANG ; Rong Li ZHANG ; Jia Lin WEI ; Qiao Ling MA ; Ai Ming PANG ; Dong Lin YANG ; Wei Hua ZHAI ; Er Lie JIANG ; Si Zhou FENG ; Ming Zhe HAN
Chinese Journal of Hematology 2020;41(2):132-137
		                        		
		                        			
		                        			Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ(2)=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ(2)=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ(2)=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ(2)=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions: HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.
		                        		
		                        		
		                        		
		                        			Graft vs Host Disease
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		                        			Hematopoietic Stem Cell Transplantation
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		                        			Humans
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		                        			Leukemia, Myeloid, Acute
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		                        			Myelodysplastic Syndromes
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		                        			Retrospective Studies
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		                        			Siblings
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		                        			Transplantation Conditioning
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		                        			Transplantation, Homologous
		                        			
		                        		
		                        	
5.Pathological characteristics and survival analysis of 355 patients with gastroenteropancreatic neuroendocrine neoplasms
Yong LI ; Yongfei WANG ; Bibo TAN ; Limian ER ; Qun ZHAO ; Liqiao FAN ; Zhidong ZHANG ; Yu LIU
Chinese Journal of Oncology 2020;42(5):426-431
		                        		
		                        			
		                        			Objective:Biological behavior, pathological characteristics and prognostic factors of 355 cases with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) were analyzed in this retrospective study.Methods:In our study, 355 patients pathologically diagnosed as GEP-NENs were identified from April 2006 to November 2017 in the Fourth Hospital of Hebei Medical University. The biological behavior, pathological characteristics and prognosis were analyzed retrospectively.Results:There were 355 patients (228 males and 127 females) with a mean age of 58.3±10.7 years. GEP-NENs were detected most frequently in the stomach (48.2%), followed by the pancreas (16.1%), colorectum (14.1%), esophagus (7.6%), duodenum/jejunum(5.6%), liver (4.2%), appendix (2.3%) and gallbladder/bile duct (2.0%). The main clinical manifestations of non-functional GEP-NENs were abdominal pain (88/350, 25.14%), ventosity (77/350, 22.00%) and dysphagia (68/350, 19.43%), which were generally lacking specificity at the first diagnosis. 295 patients were treated surgically, including 45 cases of endoscopic resection and 250 cases of laparoscopic operation. Concerning to pathological grading, there were 22.5% (80/355) patients in grade 1 (G1), 12.7% (45/355) in grade 2 (G2), and 58.9% (209/355) in grade 3 (G3). The median follow-up time was 34 months. Furthermore, the 1-, 3- and 5-year overall survival calculated by Kaplan-Meier method were 80.1%, 59.8%, and 57.5%, respectively. Univariate analysis revealed that tumor site, treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis, tumor size, preoperative leukomonocyte level and preoperative plasma albumin were associated with overall survival (all P<0.05). Multivariate analysis showed that treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis and tumor size were independent prognostic factors for GEP-NENs (all P<0.05). Conclusions:The clinicopathological characteristics of GEP-NENs should be mastered by clinicians, and the standard treatment measures were also needed to be formulated based on the prognostic factors in order to improve the prognosis of patients.
		                        		
		                        		
		                        		
		                        	
6.Pathological characteristics and survival analysis of 355 patients with gastroenteropancreatic neuroendocrine neoplasms
Yong LI ; Yongfei WANG ; Bibo TAN ; Limian ER ; Qun ZHAO ; Liqiao FAN ; Zhidong ZHANG ; Yu LIU
Chinese Journal of Oncology 2020;42(5):426-431
		                        		
		                        			
		                        			Objective:Biological behavior, pathological characteristics and prognostic factors of 355 cases with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) were analyzed in this retrospective study.Methods:In our study, 355 patients pathologically diagnosed as GEP-NENs were identified from April 2006 to November 2017 in the Fourth Hospital of Hebei Medical University. The biological behavior, pathological characteristics and prognosis were analyzed retrospectively.Results:There were 355 patients (228 males and 127 females) with a mean age of 58.3±10.7 years. GEP-NENs were detected most frequently in the stomach (48.2%), followed by the pancreas (16.1%), colorectum (14.1%), esophagus (7.6%), duodenum/jejunum(5.6%), liver (4.2%), appendix (2.3%) and gallbladder/bile duct (2.0%). The main clinical manifestations of non-functional GEP-NENs were abdominal pain (88/350, 25.14%), ventosity (77/350, 22.00%) and dysphagia (68/350, 19.43%), which were generally lacking specificity at the first diagnosis. 295 patients were treated surgically, including 45 cases of endoscopic resection and 250 cases of laparoscopic operation. Concerning to pathological grading, there were 22.5% (80/355) patients in grade 1 (G1), 12.7% (45/355) in grade 2 (G2), and 58.9% (209/355) in grade 3 (G3). The median follow-up time was 34 months. Furthermore, the 1-, 3- and 5-year overall survival calculated by Kaplan-Meier method were 80.1%, 59.8%, and 57.5%, respectively. Univariate analysis revealed that tumor site, treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis, tumor size, preoperative leukomonocyte level and preoperative plasma albumin were associated with overall survival (all P<0.05). Multivariate analysis showed that treatment, operation type, depth of tumor invasion, TNM staging, pathological grading, vascular embolus, lymph node metastasis and tumor size were independent prognostic factors for GEP-NENs (all P<0.05). Conclusions:The clinicopathological characteristics of GEP-NENs should be mastered by clinicians, and the standard treatment measures were also needed to be formulated based on the prognostic factors in order to improve the prognosis of patients.
		                        		
		                        		
		                        		
		                        	
7.Recent research advances of 1-deoxynojirimycin and its derivatives.
Ting-Ting TONG ; Er-Hu ZHAO ; Hai-Long GAO ; Yong-Hui XU ; Yong-Ju ZHAO ; Gang FU ; Hong-Juan CUI
China Journal of Chinese Materia Medica 2018;43(10):1990-1997
		                        		
		                        			
		                        			The 1-DNJ named 1-deoxynojirimycinis (2R,3R,4R,5S)-2-(hydroxymethyl) piperidine-3,4,5-triol, which is the nature active components existingin mulberryresources including leaves, stems, roots and silkworm larva, silkworm chrysalis, etc.The 1-deoxynojirimycin is a polyhydroxylated piperidine alkaloid, which was first found in Streptomyces as an antibiotic. Then the Japanese researchers isolated it from the mulberry root. 1-DNJ can inhibit postprandial hyperglycemia by suppressing intestinal alpha glucosidase. Therefore, 1-DNJ is often used to treat treating diabetes and complicating disease and to prevent obesity and weight-related disorders. With the development of the researches, 1-deoxynojirimycin and its derivtiv was discovered to possess anti-hyperglycemic, anti-virus, anti-tumor functions and so on. Therefore,based on our current studythe existing knowledge on source, technique preparation process, pharmacokinetics, bioactivties,and in silico target fishing of 1-DNJ were summarized, so that the researchers may use it to explore future perspective of research on 1-DNJ.
		                        		
		                        		
		                        		
		                        	
8.Clinical and laboratory characteristics of chronic active Epstein-Barr virus infection in children.
Jun-Qing MAO ; Shi-Long YANG ; Hua SONG ; Fen-Ying ZHAO ; Xiao-Jun XU ; Min-Er GU ; Yong-Min TANG
Chinese Journal of Contemporary Pediatrics 2014;16(11):1081-1085
OBJECTIVETo study the clinical and laboratory characteristics of chronic active Epstein-Barr virus (EBV) infection (CAEBV) in children and to provide a basis for the diagnosis and treatment of CAEBV.
METHODSThe clinical data of 13 children with CAEBV, as well as 15 cases of acute EBV infection (AEBV) as controls, were analyzed, including clinical manifestations, EBV antibodies, EBV DNA, and peripheral blood lymphocyte subsets.
RESULTSBoth groups of patients had infectious mononucleosis-like symptoms such as fever, hepatomegaly, splenomegaly, and lymphadenectasis, but CAEBV patients had a longer course of disease and continuous and recurrent symptoms. Compared with the AEBV group, the CAEBV group had a significantly higher EBV DNA load in peripheral blood (P<0.05), a significantly higher VCA-IgG titer (P<0.05), and significantly lower numbers of white blood cells, lymphocytes, B cells, total T cells, CD4+ T cells, and CD8+ T cells in peripheral blood (P<0.05). Among 13 CAEBV patients followed up, 8 cases died, 2 cases showed an improvement, 2 cases had a recurrence, and 1 case was lost to follow-up after being transferred to another hospital. All the AEBV patients were cured and had no recurrence during the one-year follow-up.
CONCLUSIONSThe clinical manifestations of CAEBV vary in children. It is difficult to distinguish CAEBV from AEBV early. More attention should be paid to CAEBV because of its severe complications, poor prognosis, and high mortality. Measurement of EBV DNA load, VCA-IgG titer, and lymphocyte subsets in peripheral blood may be helpful in the diagnosis and differential diagnosis of CAEBV.
Adolescent ; Child ; Child, Preschool ; Chronic Disease ; Epstein-Barr Virus Infections ; diagnosis ; immunology ; virology ; Female ; Humans ; Infant ; Lymphocyte Subsets ; immunology ; Male
9.Expression and clinical significance of Notch1 on the membrane of bone marrow CD38(+)CD138(+) plasma cells in the patients with multiple myeloma.
Yi-ran ZHAO ; Rong FU ; Jing GUAN ; Shan GAO ; Hui LIU ; Er-bao RUAN ; Wen QU ; Yong LIANG ; Guo-jin WANG ; Xiao-ming WANG ; Hong LIU ; Yu-hong WU ; Jia SONG ; Hua-quan WANG ; Li-min XING ; Jun WANG ; Li-juan LI ; Zong-hong SHAO
Chinese Journal of Hematology 2012;33(4):274-277
OBJECTIVETo investigate the expression of Notch1 on the membrane of bone marrow CD38(+)CD138(+) plasma cells in the patients with multiple myeloma (MM), and explore the importance of Notch signaling pathway in the formation and progression of MM.
METHODSThirty three MM patients and 15 healthy controls were enrolled in this study. The expression of Notch1 on the membrane of bone marrow CD38(+)CD138(+) and CD38(+)CD138(-) plasma cells were analyzed by flow cytometry. The clinical data of MM patients were also analyzed.
RESULTSThe ratio of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients was (60.21 ± 25.06)% which was significantly higher than those of CD38(+)CD138(-) plasma cells of MM patients (39.84 ± 18.94)% (P = 0.000) and controls (38.34 ± 19.39)% (P = 0.004). There was no statistical difference between the two latter groups (P > 0.05). The expression of Notch1 on CD38(+)CD138(+)plasma cells from 24 newly diagnosed MM patients was correlated to the level of malignant plasma cells in there bone marrow (r = 0.914, P = 0.000), serum level of lactate dehydrogenase (LDH) (r = 0.754, P = 0.007), and β(2)-MG(r = 0.716, P = 0.013). The ratio of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients who had renal dysfunction was correlated to their abnormal serum creatinine levels. The expression of Notch1 on CD38(+)CD138(+) plasma cells from 17 MM patients who received VD (bortezamib and dexamethasone) chemotherapy was correlated to the ratio of plasma cell reduction after the first VD chemotherapy (r = 0.842, P = 0.000).
CONCLUSIONThe expression of Notch1 on the membrane of CD38(+)CD138(+) plasma cells of MM patients was significantly higher than those of CD38(+)CD138(-) plasma cells of MM patients and controls. Notch1 overexpressed plasma cells were sensitive to the early VD therapy, and correlated to the progression and long term outcome of MM.
ADP-ribosyl Cyclase 1 ; immunology ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; metabolism ; Case-Control Studies ; Cell Count ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; immunology ; metabolism ; Plasma Cells ; immunology ; metabolism ; Prognosis ; Receptor, Notch1 ; metabolism ; Syndecan-1 ; immunology
10.Diagnostic significance of Th1/Th2 cytokine pattern in childhood hemophagocytic lymphohistiocytosis.
Xiao-jun XU ; Yong-min TANG ; Ning ZHAO ; Hua SONG ; Shi-long YANG ; Shu-wen SHI ; Wei-qun XU ; Bin-hua PAN ; Ling-yan ZHANG ; Jun-qing MAO ; He-ping SHEN ; Min-er GU ; Jing XIA
Chinese Journal of Pediatrics 2011;49(9):685-689
OBJECTIVETo illustrate the diagnostic value of Th1/Th2 cytokine pattern in childhood hemophagocytic lymphohistiocytosis (HLH) and its diagnostic accuracy.
METHODThe BD(TM) CBA Human Th1/Th2 Cytokine Kit II was used to measure the serum Th1 and Th2 cytokines, including Interferon-gamma (IFN-γ), tumor necrosis factor (TNF), interleukin (IL)-10, IL-6, IL-4 and IL-2 in 50 patients with de novo HLH admitted to our hospital from Oct. 2005 to Aug. 2009. The above cytokine levels were also determined in 250 healthy volunteers and 235 patients with sepsis as controls.
RESULTThe primary features of these patients were prolonged high-grade fever (50/50), hepatomegaly (44/50), splenomegaly (38/50), hemocytopenia (47/50), hyperferritinemia (49/50), coagulopathy (44/50), hemophagocytosis in bone marrow (42/50), liver dysfunction (42/50) and hypertriglyceridemia (42/50). The IFN-γ, TNF, IL-10, IL-6, IL-4 and IL-2 levels for healthy children were (4.6 ± 1.8) ng/L, (4.0 ± 1.2) ng/L, (6.5 ± 1.3) ng/L, (6.0 ± 1.5) ng/L, (2.9 ± 0.8) ng/L and (2.6 ± 0.7) ng/L, while the median levels of them in acute phase of HLH children were 1138.5 (49.2 - 5000.0) ng/L, 3.4 (1.0 - 25.1) ng/L, 740.5 (26.5 - 5000.0) ng/L, 66.1 (3.9 - 4472.6) ng/L, 3.9 (1.0-32.8) ng/L and 4.0 (1.0 - 51.1) ng/L, respectively. The cytokine levels decreased to 9.1 (1.9 - 180.1) ng/L, 2.9 (1.0 - 11.0) ng/L, 11.4 (2.9 - 184.2) ng/L, 6.5 (1.0 - 44.8) ng/L, 2.7 (1.0 - 6.5) ng/L and 4.1 (1.0 - 12.0) ng/L respectively after remission. The IFN-γ, IL-10 and IL-6 levels in acute phase were significantly higher than those after remission and those of the healthy control (P all < 0.001). IL-4, IL-2 and TNF slightly elevated or at normal range in acute phase of HLH. The patients with sepsis showed a different cytokine pattern, with an extremely high level of IL-6 (median: 251.3 ng/L, range: 8.4- > 5000.0 ng/L) and moderately elevated level of IL-10 (median: 46.5 ng/L, range: 3.1 - 5000.0 ng/L), whereas IFN-γ was only slightly elevated (median: 9.2 ng/L, range: 1.3 - 498.8 ng/L). When the criteria for HLH set as the following: IFN-γ > 100 ng/L, IL-10 > 60 ng/L and the concentration of IFN-γ higher than that of IL-6, the specificity reached as high as 98.7% and the sensitivity was 88.0% for the diagnosis of HLH among patients with HLH and sepsis. Meanwhile, the positive predictive value (PPV) and negative predictive value (NPV) could reach 93.6% and 97.5%, respectively.
CONCLUSIONThe significant increase of IFN-γ and IL-10 with slightly increased level of IL-6 is a sensitive and specific cytokine pattern for childhood HLH, which is helpful for its diagnosis and differential diagnosis.
Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Cytokines ; blood ; Female ; Humans ; Infant ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukin-6 ; blood ; Lymphohistiocytosis, Hemophagocytic ; blood ; diagnosis ; Male ; Sensitivity and Specificity ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism ; Tumor Necrosis Factor-alpha ; blood
            
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