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Objective: To analyze the incidence of cytokine release syndrome (CRS) and its impact on the prognosis of patients with relapsed and refractory multiple myeloma (RRMM) following treatment with chimeric antigen receptor T-cell (CAR-T) therapy. Methods: A retrospective collection was conducted of the clinical data of 91 patients with RRMM who underwent CAR-T therapy at the Affiliated Hospital of Xuzhou Medical University from January 2020 to October 2022. Before CAR-T cell infusion, the patient underwent pretreatment with the fludarabine plus cyclophosphamide (FC) regimen. On day 0 (d0), the patient received a dose of 1×10 6 cells/kg of CAR-T. The occurrence of CRS was recorded post-treatment and graded accordingly, with grades 1 to 2 indicating mild CRS and grade≥3 indicating severe CRS. The follow-up cut-off date was February 14, 2023, with a median follow-up time [ M ( Q 1, Q 3 )] of 14.1 (3.1, 37.7) months. Kaplan-Meier survival curve analysis assessed the progression-free survival (PFS) and overall survival (OS) of Grade 1 and Grade 2 CRS patients. Furthermore, univariate logistic regression analysis was conducted to identify factors associated with the development of severe CRS. Results: In a cohort of 91 patients diagnosed with RRMM, there were 51 male and 40 female individuals, with a median age [ M ( Q 1, Q 3 )] of 57 (31, 73) years. All 91 cases (100%) experienced CRS, with 82 cases (90%) classified as mild (grades 1-2) CRS and 9 cases (10%) classified as severe (grades 3-5) CRS. In a study involving 9 patients with severe CRS, 8 cases resulted in mortality. The Kaplan-Meier survival curve analysis revealed that among grade 1 CRS patients, neither the median PFS nor the median OS was achieved. For grade 2 CRS patients, the median PFS was 12 months (95% CI : 4-not achieved), and the median OS was 21 months (95% CI : 4-not achieved). The progression-free survival and overall survival rates of grade 2 CRS patients were both lower than those of grade 1 CRS patients (both P <0.05). Single-factor logistic regression analysis revealed that a high tumor burden ( OR =1.025, 95% CI : 1.002-1.049, P =0.031), a prolonged duration of CRS onset ( OR =0.809, 95% CI : 0.646-0.971, P =0.037) and persistence ( OR =1.758, 95% CI : 1.349-2.481, P =0.001) were identified as significant factors associated with severe CRS in patients with RRMM. Conclusions: Patients with RRMM who undergoes CAR-T therapy have a high incidence of CRS, with a higher mortality rate among those experiencing severe CRS. Furthermore, patients with grade 2 CRS exhibit lower rates of progression-free survival and overall survival compared to those with grade 1 CRS. Factors associated with the development of severe CRS in RRMM patients include high tumor burden and prolonged duration and onset of CRS.

Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts., Methods: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management., Findings: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD., Conclusions: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD., Funding: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007)., Competing Interests: Declaration of interests M.-H.Z. has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk and consulting fees from Boehringer Ingelheim and serves as a consultant for Eieling Technology. L.A.B. has received speaker fees from Novo Nordisk and is on the Steering Committee of ACTION Teens, a multicountry study of adolescent obesity sponsored by Novo Nordisk. All fees received are directed to L.A.B.’s hospital research cost center. M.K. is a consultant for Mirum and Medison Pharma. A.M. has received honoraria from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Janssen. N.B.H.N. has received honoraria for lectures and the role of advisory board member (Adolescents with Obesity) from Novo Nordisk. C.M. is chairman of the board and shareholder of DeFaire Medical AB, scientific advisor and shareholder of Oriflame Wellness AB, scientific advisor of Itrim AB, scientific advisor of and speaker for Novo Nordisk, scientific advisor of Rhythm, and speaker for Astra Zeneca, Semper, and Redeye. C.D.B. has received an independent research grant from Echosens. C.G. has acted as speaker for Merck, Gilead, Abbvie, and Novo Nordisk; has served as an advisory board member for Merck, Novo Nordisk, and Gilead; and has received unrestricted research funding from Theratechnologies Inc. M.T.A.-L. has obtained a grant from Novo Nordisk and has acted in an advisory capacity for MSD and Novo Nordisk and as speaker for Novo Nordisk, Gilead, and Abbie. J.M.P. has received consulting fees from Boehringer Ingelheim, MSD, and Novo Nordisk; speaking fees from Gilead, Intercept, and Novo Nordisk; travel expenses from Gilead, Rubió, Pfizer, Astellas, MSD, CUBICIN, and Novo Nordisk; educational and research support from Madrigal, Gilead, Pfizer, Astellas, Accelerate, Novartis, Abbvie, ViiV, and MSD; and funds from European Commission/EFPIA IMI2 853966-2, IMI2 777377, H2020 847989, and ISCIII PI19/01898. J.-G.F. has received honoraria for lectures from Sanofi, Echosens, Abbott, Novartis, AstraZeneca, Hisky Medical Technologies, and Novo Nordisk; consulting fees from Allergan, Echosens, Novartis, and Terns; and research grants from Sanofi. S.S.S. serves on Mirum and Alberio advisory boards., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy. Methods: A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n =47) and non-transplantation group (NTG; n =121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ 2 test, Kaplan-Meier method and independent sample t -test. Results: Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG ( χ 2 =5.71, P =0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG ( χ 2 =4.32, P =0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P <0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t =-2.15, P =0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P >0.05). Conclusion: Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.

Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS ( P =0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels ( OR =19.668, 95% CI 18.959-20.173, P =0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.

Objective: To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI)., Methods: The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed., Results: The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M 2 ). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections., Conclusion: Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.

Background: The effects of inappropriate dietary calcium intake in early life on later obesity have not been fully elucidated., Aim: To raise the mechanism of maternal calcium intake on the multi-differentiation potential of mesenchymal stem cells among their male offspring., Methods: Four-week-old female C57BL/6N mice were fed by deficient, low, normal and excessive calcium reproductive diets throughout pregnancy and lactation. Bone MSCs (BMSCs) were obtained from 7-day-old male offspring to measure the adipogenic differentiation potential by the Wnt/β-catenin signaling pathway. The other weaning male pups were fed a high-fat diet for 16 wk, along with normal-fat diet as the control. Then the serum was collected for the measurement of biochemical indicators. Meanwhile, the adipose tissues were excised to analyze the adipocyte sizes and inflammatory infiltration. And the target gene expressions on the adipogenic differentiation and Wnt/β-catenin signaling pathway in the adipose tissues and BMSCs were determined by real-time reverse transcription polymerase chain reaction., Results: Compared with the control group, maternal deficient, low and excessive calcium intake during pregnancy and lactation aggravated dietary-induced obesity, with larger adipocytes, more serious inflammatory infiltration and higher serum metabolism indicators by interfering with higher expressions of adipogenic differentiation ( PPARγ, C/EBPα, Fabp4, LPL, Adiponectin, Resistin and/or Leptin ) among their male offspring ( P < 0.05). And there were significantly different expression of similar specific genes in the BMSCs to successfully polarize adipogenic differentiation and suppress osteogenic differentiation in vivo and in vitro , respectively ( P < 0.05). Meanwhile, it was accompanied by more significant disorders on the expressions of Wnt/β-catenin signaling pathway both in BMSCs and adulthood adipose tissues among the offspring from maternal inappropriate dietary calcium intake groups., Conclusion: Early-life abnormal dietary calcium intake might program the adipogenic differentiation potential of BMSCs from male offspring, with significant expressions on the Wnt/β-catenin signaling pathway to aggravate high-fat-diet-induced obesity in adulthood., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

To provide experimental basis and theoretical guidance for further research on the molecular mechanism of notoginsenoside R&#95;1(NGR&#95;1) in the treatment of depression, the present study analyzed the potential mechanism of NGR&#95;1 in the treatment of depression through network pharmacology and verified it by molecular docking and animal experiments. PharmMapper, SwissTargetPrediction, and GeneCards were used to predict the related targets of both NGR&#95;1 and depression to obtain the potential targets of NGR&#95;1 in the treatment of depression. The database for annotation, visualization and integrated discovery(DAVID) was used for GO functional annotation and KEGG pathway enrichment analysis to screen the possible mechanisms of NGR&#95;1 exerting antidepressant effect. Cytoscape 3.9.0 was adopted to construct a protein-protein interaction(PPI) network, and the topological analysis was performed to obtain the core targets. The binding activity of NGR&#95;1 to core targets was tested by molecular docking. The depression model was prepared by injecting lipopolysaccharide(LPS) into the lateral ventricle in mice, and intervened with NGR&#95;1. The antidepressant effect of NGR&#95;1 was detected by behavioral tests and RT-qPCR. The results showed that by network pharmacology, 56 common targets of NGR&#95;1 and depression were predicted, and GO enrichment analysis determined 13 related biological processes, mainly involving G protein-coupled receptor signaling pathway, positive regulation of transcription from RNA polymerase Ⅱ promoter, cytokine-mediated signaling pathway, gene expression, apoptosis, cell proliferation, and signal transduction. In addition, KEGG pathway enrichment analysis identified ten potential pathways, including neuroactive ligand-receptor interaction signaling pathway, lipid and atherosclerosis signaling pathway, cAMP signaling pathway, PI3 K-AKT signaling pathway, and lipid and atherosclerosis signaling pathway. PPI analysis revealed that the core targets included CASP3, VEGFA, IGF1, STAT3, MAPK1, PPARG, MTOR, MAPK14, NR3 C1 and AR, and molecular docking demonstrated that NGR&#95;1 had desirable binding activity to these target proteins. In animal experiments, the results showed that NGR&#95;1 improved the disease behavior of depressed mice, significantly inhibited the neuroinflammatory response(reducing the mRNA expression of Iba-1, TNF-α, IL-1β, and IL-6), and regulated the mRNA expression of lipid and atherosclerosis signaling pathway-related targets(CASP3, STAT3, MAPK1 and MAPK14). This indicated that the antidepressant mechanism of NGR&#95;1 may be related to the regulation of lipid and atherosclerosis signaling pathway. In conclusion, network pharmacology was used to reveal the core targets and pathways of NGR&#95;1, and some of them were verified in animal experiments, which provided the basis for in-depth exploration on the mechanism of NGR&#95;1 in the treatment of depression.

Objective: To investigate the efficacy and safety of humanized CD19-specific chimeric antigen receptor T cells (hCART19s) in treating children and young adults with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) and to analyze relevant factors affecting its curative effect and prognosis. Methods: We conducted a single-center clinical trial involving 31 children and young adult patients with R/R B-ALL who were treated with humanized CD19-specific CAR-T cells (hCART19s) from May 2016 to September 2021. Results: Results showed that 27 (87.1%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi) one month after CAR-T cell infusion. During treatment, 20 (64.5%) patients developed grade 1-2 cytokine release syndrome (CRS) , and 4 (12.9%) developed grade 3 CRS. Additionally, two patients had grade 1 neurological events. During the follow-up with a median time of 19.3 months, the median event-free survival (EFS) was 15.7 months (95% CI 8.7-22.5) , and the median overall survival (OS) was 32.2 months (95% CI 10.6-53.9) . EFS and OS rates were higher in patients who have undergone hemopoietic stem cell transplantation (HSCT) than in those without [EFS: (75.0 ± 12.5) % vs (21.1 ± 9.4) %, P =0.012; OS: (75.0 ± 12.5) % vs (24.6 ± 10.2) %, P =0.035]. The EFS and OS rates were significantly lower in patients with >3 treatment lines than in those with <3 treatment lines [EFS: 0 vs (49.5±10.4) %, P <0.001; OS: 0 vs (52.0±10.8) %, P <0.001]. To the cutoff date, 12 patients presented with CD19(+) relapse, and 1 had CD19(-) relapse. Conclusion: hCART19s are effective in treating pediatric and young adult R/R ALL patients, with a low incidence of severe adverse events and reversible symptoms. Following HSCT, the number of treatment lines can affect the long-term efficacy and prognosis of pediatric and young adult R/R ALL patients.

Objective: This study was carried out to explore clinical treatment and prognosis of patients with AA with different economic status. Methods: We retrospectively analyzed the clinical outcome of 301 patients with AA in our center from April 2008 to November 2017., Results: Treatments included anti-thymocyte globulin (ATG) or anti-lymphocyte globulin (ALG) combined with cyclosporineA (CsA) (9%), allogeneic hematopoietic stem cell transplantation (allo-HSCT) (7%), CsA combined with androgen or CsA alone (hereinafter referred to as CsA group) (77%), no specific therapy (7%). The 5-year overall survival (OS) was higher in patients with non-severe AA (94.6%) compared with those with severe AA (SAA) (66.6%, P <.001), very severe AA (VSAA) (41.3%, P <.001). The 5-year OS was 76.5% in patients with SAA/VSAA treated with ATG/ALG combined with CsA, 75% in allo-HSCT group(P =.936), 63.6% in CsA group ( P =.557), which was significantly higher than no specific therapy group (21.8%, P =.002). For those who responded to CsA , the duration of CsA (median follow-up time: 27 months, 1-101 months) was positively correlated with progression-free survival (r=0.603, P <.001). Multivariate analysis revealed that 36-65 years of age, SAA/VSAA, and no specific therapy were independent risk factors for inferior survival., Conclusion: The treatment of elderly patients with AA still faces challenges. CsA is benefit to the survival of SAA/VSAA patients. AA patients, who responded to initialy CsA treatment, may benefit from prolonged CsA treatment. In view of the side effects of CsA, the timing of withdrawal is worth further exploration.

Objective: To investigate the relationship between the levels of ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH) and interleukin-6 (IL-6) in peripheral serum and cytokine release syndrome (CRS) in patients with relapse and/or refractory multiple myeloma (R/R MM) after receiving chimeric antigen receptor T cells (CAR-T) immunotherapy., Methods: Twenty-eight patients with R/R MM were treated with 1×10 6 /kg humanized CD19 CAR-T and mouse B cell maturation antigen CAR-T cells after pretreatment chemotherapy based on fludarabine and cyclophosphamide. The concentrations of ferritin, CRP, LDH, and IL-6 in peripheral blood were measured regularly within 30 days after infusion, and the correlation between severity of CRS and above indexes was analyzed., Results: Among the 28 patients, 27 cases (96.4%) developed CRS, 24 cases (85.7%) in 1-2 grade CRS and 3 cases (10.7%) in 3-5 grade. The severity grade of CRS of 27 patients was positively correlated with the peak values of ferritin, CRP, LDH, and IL-6 in peripheral blood (r 1 =0.511, r 2 =0.375, r 3 =0.480, r 4 =0.632). The median peak values of ferritin, CRP, LDH and IL-6 in peripheral serum of patients with grade 3-5 CRS were significantly higher than those in patients with grade 0-2 CRS., Conclusion: After receiving CAR-T cellular immunotherapy, the incidence of CRS in patients with R/R MM is higher, but most of them are in grade 1 or 2. The severity of CRS is positively correlated with the levels of ferritin, CRP, LDH and IL-6 in peripheral blood.

Objective: To explore the influence of prognostic nutritional index (PNI) and controlling nutritional status (CONUT) on the prognosis of patients with multiple myeloma. Methods: Data of 157 patients with multiple myeloma (MM) at the affiliated hospital of Xuzhou medical university from January 2014 to December 2018 were retrospectively evaluated. The operating characteristic (ROC) curve analysis was adopted as the optimal cut-off point. PNI and CONUT were grouped based on the cut-off points of 44.45 and 3.5, respectively, and the differences between age, gender, serum calcium, β(2)-microglobulin, serum creatinine, lactate dehydrogenase, and hemoglobin were analyzed. The prognostic factors were analyzed via univariate and Cox multivariate regression analyses. Results: The level of PNI and CONUT is the influencing factor of OS time. The univariate analysis revealed that age, LDH, plasma cell ratio, β(2)-microglobulin, ISS stage, PNI, and CONUT were the risk factors for the prognosis of patients with MM. The multivariate analysis revealed that age ( HR =1.636, 95% CI 1.014-2.640) , plasma cell ratio ( HR =1.953, 95% CI 1.232-3.096) , and PNI ( HR =0.513, 95% CI 0.287-0.917) were the independent prognostic risk factors of patients with MM. Conclusion: Low PNI in patients with MM indicates a poor prognosis, which is an independent prognosis risk factor.

Objective: To study the level and clinical value of Th17 cell subset in the peripheral blood of the patients with aplastic anemia (AA)., Methods: Eighty-five patients with aplastic anemia in our hospital from May 2017 to February 2018 were selected. Among them, 51 patients with poor curative effect were enrolled in group A. and the 34 patients with good curative effect were enrolled in group B, the 35 healthy persons were selected as controls. The levels of serum IL-17, IL-6, IL-4 and IFN-β were analyzed by ELISA; the levels of peripheral blood Th17 cell subset were analyzed by flow cytometry; the expression levels of RORγt and STAT3 mRNA in lymphocytes were analyzed by RT-PCR; the expression levels of RORγt and STAT3 protein in lymphocytes were analyzed by Western blot., Results: There was no significant difference in sex, age, WBC count and complications between group A and group B (P＞0.05). Non-severe aplastic anemia (NSAA) in group B accounted for 23 cases, and the NSAA ratio (23/34) was significantly higher than that in group A (20/51) (P＜0.05). The Hb level (86.25±7.9 g/L) and Plt count (54.7 ± 6.3×10 9 /L) in group B were significantly higher than those in group A (P＜0.05). ELISA showed that the levels of IL-17 and IL-6 in group A were significantly higher than those in control group (P＜0.05); the levels of IL-17 and IL-6 in group B were significantly lower than those in group A (P＜0.05); the levels of IL-4 and IFN-β in group A were significantly lower than those in control group (P＜0.05); the levels of IL-4 and IFN-βin group B were significantly higher than those in group A (P＜0.05). Flow cytometry showed that the proportion of Th17 cells in peripheral blood of group A was higher than that of group B (P＜0.05). RT-PCR showed that the levels of RORγt and STAT3 mRNA in group A were significantly higher than those in control group (P＜0.05), and the mRNA levels of RORγt and STAT3 in group B were significantly lower than those in group A (P＜0.05). Western blot showed that the protein levels of RORγt and STAT3 in group A were significantly higher than those in control group (P＜0.05), and the protein levels of RORγt and STAT3 in group B were significantly lower than those in group A (P＜0.05)., Conclusion: The Th17 cells in peripheral blood of AA patients increase, and the inflammatory reaction in the patients are enhanced. It may be related with the rise of RORγt and STAT3 gene expression, which provides a research direction for clinical treatment of AA.

Objective: To study the safety and effectiveness of humanized CD19-targeted CAR-T cells (hCART19s) for treatment of patients with refractory/relapsed (R/R) B-ALL., Methods: The analyzed patients were 15 children and adults with relapsed/refractory B-ALL who not received treatment with murine CD19 CAR-T cells. The patients received a single dose (1×10 6 /kg) of autologous hCART19 infusion after lymphodepletion chemotherapy based on cyclophosphamide and fludarabine., Results: Among the 15 patients, 13/14 (92.9%) evaluable patients achieved complete remission (CR) or CR with incomplete recovery of blood cells (CRi) on day 30 after hCART19s infusion. At day 180 after the infusion, the overall survival rate was 73.3%, and the leukemia-free survival rate was 69.2%. The cumulative incidence of relapse was 24.5% and non-relapse mortality rate was 7.7%. During treatment,12/15 patients (80%) developed cytokine release syndrome (CRS) of grade 1-2, and 3 patients (20.0%) developed CRS of grade 3-5. Only one patient (6.7%) suffered from the reversible neurotoxicity., Conclusion: hCART19s can effectively treat refractory/relapsed (R/R) adult and children with B-ALL, and the incidence of treatment-related CRS and neurotoxicity is low.

Objective: To establish the reference intervals of the hematological parameters in normal adult people of Xuzhou erea., Methods: The red blood cells (RBC), platelets, white blood cells (WBC) and related parameters were detected by hematoanalyzers in 82514 healthy people including 41257 males and 41257 females in the Medical Center of the Affiliated Hospital of Xuzhou Medical University., Results: The range of RBC count: (4.33-5.51) ×10 12 /L in male and（3.82-4.85）×10 12 /L in female, the range of Hb level: (132-172) g/L in male and（107-145）g/L in female, the range of HCT: 40 %-50 % in male and 34 %-44 % in female, the range of platelet count: (113-268) ×10 9 /L in male and (126-289) ×10 9 /L in female, the range of WBC count: (4.00-9.40) ×10 9 /L in male and （3.54-9.30）×10 9 /L in female, the range of NEUT count: (1.91-5.76) ×10 9 /L in male and（1.67-5.30）×10 9 /L in female, the range of MONO count: (0.18-0.58) ×10 9 /L in male and（0.16-0.52）×10 9 /L in female, the range of LYM is（1.3-3.4）×10 9 /L in male and（1.2-3.1）×10 9 /L in female, etc.Conclusion: There is significant difference in the blood cell parameters between Xuzhou and other areas. Among them, the lower limit of Hb reference interval for adult women in Xuzhou area is obviously lower, and the upper and lower limits of adult Plt reference interval are significantly lower than other areas in China and abroad. The upper and lower limits of the WBC reference interval are close to the domestic areas, but lower than that in some foreign regions. Through this survey, the reference intervals of different hematologic parameters of healthy people in Xuzhou area primarily has been established, Some of the indexes, such as RBC, Hb, HCT, and Plt have significant sex differences. The reference intervals for them have been estublisted respectively.

Objective: To analyze the risk factors and prognosis of hepatic chronic GVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: The clinical data of 147 patients undergoing allo-HSCT from January 2013 to December 2016 were analyzed, the correlation between recipient age and sex, disease state, matched degree of HLA, donor sex, stem cell sources, ATG in GVHD prophylaxis, liver dysfunction during conditioning period, pre-transplant HBsAg, prior aGVHD and hepatic cGVHD were studied, and the correlation between hepatic cGVHD and prognosis were analysed., Results: Thirty-two patients had hepatic cGVHD, cumulative incidence of 26.4%. In univariate analysis, pre-transplant HBsAg + and liver dysfunction during conditioning period were not significantly related with hepatic cGVHD (P>0.05). In multivariate analysis, prior acute GVHD (HR=2.087, P=0.045) was the independent risk factor for hepatic cGVHD, ATG (HR=0.231, P=0.000) was significantly related with a lower incidence of hepatic cGVHD. In univariate analysis, patients with hepatic cGVHD had a lower 2 years relapse rate (P=0.038)., Conclusion: Prior acute GVHD is the independent risk factor for hepatic cGVHD, the ATG can significantly reduce the incidence of hepatic cGVHD. Hepatic cGVHD has been found to relate with a lower 2 years relapse rate.

Objective: To construct humanized anti-CD19 chimeric antigen receptor T cells and investigate its ability to kill leukemia cells in vitro and in vivo. Methods: Humanized anti-human CD19 antibody with a high affinity was obtained based on mouse anti-human CD19 antibody (FMC63). Humanized CD19 CAR-T cells (hCART19) were constructed through transfection of lentivirus carrying a CAR sequence of humanized anti-CD19 scFv into human peripheral CD3(+) T cells. The ability of hCART19 to kill leukemia cells and secrete cytokines was detected by LDH release assay and ELISA. The in vivo tumor-killing effect of hCART19 was evaluated in a leukemia mouse model. Results: Several different humanized CD19 single-chain antibodies which were constructed by IMGT database were expressed in the eukaryotic expression vector and purified followed by acquiring humanized CD19 antibody (Clone H3L2) with similar binding ability to FMC63. Humanized CD19 CAR lentivirus vector was constructed and transfected into T cells to obtain hCART19 cells. The LDH release experiment confirmed that the killing rate of target cells was increased gradually along with the increased E/T ratio. When the ratio of E/T was 10∶1, the killing rate of target cells by hCART19 reached a maximum. When Raji cells were used as target cells, the hCART19 cells group had a significantly higher kill rate [(87.56±1.99)%] than the untransduced T cells group [(19.31±1.16)%] and the control virus transduced T cells group [(21.35±1.19)%]( P <0.001). ELISA analysis showed that the secretion of IL-2 [ (10.56±0.88) pg/ml] and IFN-γ [ (199.02±12.66) pg/ml] in the hCART19 cells group were significantly higher than those in the untransduced T cells group [IL-2: (3.55±0.26) pg/ml; IFN-γ: (37.63±0.85) pg/ml] and the control virus transduced T cells group [IL-2: (2.92±0.32) pg/ml; IFN-γ: (52.07±3.33) pg/ml]( P <0.001). The above experiments also showed similar results when CHO-K1-CD19 cells were used as target cells. Moreover, in a human leukemia xenograft animal model, the results showed that mice in the untransduced T cells group and the control virus transduced T cells group all died within 20 to 30 days, and the hCART19 cell group survived >40 days, which was more than the survival time of the other two groups of mice. The difference was statistically significant ( χ (2)=11.73, P =0.008). Conclusion: Humanized CD19 CAR-T cells with anti-leukemic activity have been successfully constructed, which will lay a foundation for clinical studies in the future.

Objective: To investigate the effects of calcium supplementation during the pregnancy and early infancy stage on body mass index (BMI) and gut microbiota in the infants. Methods: A total of 1 752 healthy pregnant women and their infants (breast feeding) in two maternal and child health care hospitals of Beijing were chosen as the subjects in this study from May to October 2016. Questionnaires were used to obtain the general information and supplementation of calcium and vitamin D in mothers and their infants. The body length and weight of infants at birth and 6 months were recorded to calculate the BMI. The random number table method was used to randomly select 40 infants from each group for gut microbiota analysis (If less than 40 infants were all included in this study, 23 infants in the pregnancy and early infancy would be all treated with calcium supplements. There were 6 infants who was not added calcium during the pregnancy but added in the early infancy). Then it was compared that the effects of calcium supplementation during the pregnancy and early infancy on the BMI and gut microbiota composition of infants were determined at birth and 6 months. Results: Compared to the group with no calcium supplementation during the pregnancy ((12.76±1.23), (17.68±0.76)kg/m(2)), the BMI of infants at birth and 6 months in the group with calcium supplementation during the pregnancy ((13.51±0.47), (17.91±0.23)kg/m(2)) were significantly higher( P< 0.05). In the group with maternal calcium supplementation, the BMI at 6 months ((18.63±0.52)kg/m(2)), BMI increment ((5.71±0.54)kg/m(2)) and the content of lactobacillus (21.04%±3.68%) in the only calcium supplementation subgroup in the early infancy were higher than those in only vitamin D supplementation subgroup ((17.69±0.89) kg/m(2), (4.17±1.01) kg/m(2) and 12.28%±3.86%) ( P< 0.05). In the group without maternal calcium supplementation, the content of lactobacillus (20.15%±4.87%) in the only calcium supplementation subgroup were also higher than those in only vitamin D supplementation subgroup (14.64%±3.71%) ( P< 0.05). Conclusion: Appropriate calcium supplementation during the pregnancy is good for the growth and development of the fetus. Calcium supplementation in the early infancy could increase the BMI of infants, and promote the growth of intestinal lactobacillus.

Objective: To investigate the effects of docosahexenoic acid (DHA) supplementation on infant's growth and BMI during pregnancy. Methods: A total of 1 516 healthy pregnant women delivered their babies in two maternal and child health care hospitals in Beijing and were chosen as the subjects in this cohort study from May to October 2015. Self-developed questionnaires were used to gather general information of the subjects, including age, height, weight, weight gain during pregnancy, delivery mode, DHA supplementation etc ., before giving birth. Information on body length, weight, head circumference and BMI at birth and 6 months postnatal, of the infants were recorded. Breast milk was collected to test the fatty acid profiles by using the gas chromatography (GC) method at one to three months postnatally. Results: The overall rate of DHA supplementation was 47.76% among the pregnant women, in which introduction of DHA from the early and second stage of the pregnancy accounted for 49.31% and 39.64% respectively. When DHA supplementation began from the early pregnant stage, the DHA concentration showed an increase in the milk ( P <0.05), whereas the supplementation began from the second and third stages did not affect the milk DHA concentration ( P >0.05). Higher height and lower BMI were seen in the infants at birth and 6 months in the supplementation group when comparing to the non-supplementary group ( P <0.05), with the greatest effects noticed in the earliest supplementation group. Specifically, the head circumference appeared larger from the early pregnant stage in the DHA supplementary group, than that in the non-supplement group ( P =0.001). The increment of head circumference was larger than that in the other groups when the infants were 6-month old ( P <0.01). Results from the partial regression analysis showed that during pregnancy, there were positive correlations between DHA supplementation and height ( r =0.324, r =0.216), head circumference ( r =0.221, r =0.302) as well as the increment of head circumference ( r =0.276) at birth and 6 months ( P <0.05). Whereas, a negative correlation was shown between DHA and the infants' BMI ( r =-0.310, r =-0.371) ( P <0.05) when supplementation was given during maternal pregnancy. Conclusions: When DHA supplementation program was carried out during maternal pregnancy, it could increase the height and head circumference and inhibit the rapid increase of BMI in the infants BMI. Our findings seemed helpful in promoting brain development and preventing the childhood obesity.

Objective: To evaluate the clinical significance of thrombopoietin (TPO) level in diagnosis of pateints with aplastic anaemia (AA)., Methods: The TPO levels in sera from 54 AA patients and 119 healthy controls were examined. A total of 92 samples were collected from AA patients including 43 samples harvested at diagnosis, 23 samples in the cytopenic period after treatment, and 26 samples of patients in partial (n=10) or complete remission (n=16) following immunosuppressive treatment. Serum TPO levels were assessed by a sandwich-antibody ELISA that utilized a polyclonal rabbit antiserum for both capture and signal., Results: Serum samples from normal donors revealed a mean TPO level of 95.3±54.0 pg/ml, the mean TPO levels in AA sera collected at diagnosis and before onset of treatment were 2728±1074 pg/ml (P<0.001) compared with normal controls; mean platelet count at that time: 27×10 9 /L). Serum TPO levels of AA patients in partial or complete remission after immunosuppressive treatment were significantly lower than TPO levels at diagnosis (P<0.001). However, despite normal platelet counts (mean 167×10 9 /L), TPO levels remained significantly elevated in complete remission (mean TPO 1009±6590 pg/ml (P<0.001) compared with normal controls. There was a significant negative correlation between serum TPO levels and platelet counts in AA patients (coefficient of correlation r=-0.70, P<0.001)., Conclusion: TPO levels are highly elevated in sera of patients with AA. Thrombopoietin did not return to normal levels in remission, indicating normal platelet count in remission of AA needs sustained high level of TPO.

Objective: To explore the effect of Caspase 1 inhibitor Ac-YVAD-CMK on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) and its mechanism., Methods: Experiments were divided randomly into 3 groups: allogeneic hematopoietic stem cell transplantation combined with splenic cell infusion group (TS group, n=12), allogeneic hematopoietic stem cell transplantation combined with splenic cell infusion plus injection of low dose Caspase 1 inhibitor group (TS+low dose of C group, n=16) and plus high dose Caspase1 inhibitor (TS+high dose of C group, n=19). The body weight of mice in each group was dynamically detected, and the clinical manifestation of GVHD and score of aGVHD were determined, and the chimerism rate of mice was detected after transplantation for 14 days. Th1, Th2 and Th17 cells in peripheral blood were examined by flow cytometry. Peripheral proinflammatory cytokines IL-1β, IFN-γ, IL-1α and IL-18 were examined by enzyme-linked immunosorbent assay(ELISA). The tissues sections of GVHD target organs (liver, lung, colon and skin) were stained with HE for histopathologic examination and histopathologic score., Results: Ac-YVAD-CMK could alleviate murine aGVHD and pathological injury, decreare the incidence and severity of aGVHD in recipient mice. The detection of Th cell subsets in peripheral blood by flow cytometry showed that compared with TS group, the Th1 cell ratio in TS+low dose of C and TS+high dose of C groups was significantly reduced (P<0.05), while the Th2 and Th17 cell ratio was significantly enhanced (P<0.05) in TS+low dose of high dose of C groups. The detection of peripheral inflamematory cytokines by ELISA demonstrated that the inflammatory cytokines including IL-1β,IFN-γ,IL-18 and IL-1α were reduced significantly (P<0.05)., Conclusion: Ac-YVAD-CMK can improve aGVHD by inhibiting Caspase 1 and reducing the release of some inflammatory cytokines, thereby alleviated the aGVHD pathological damage.

Introduction: Previously, we demonstrated the importance of T-cell immune response cDNA 7 (TIRC7) in acute immune thrombocytopenia (ITP). As the downstream molecule of TIRC7, cytotoxic T lymphocyte antigen-4 (CTLA-4) has been verified its negative regulation of acute ITP. This study aimed to investigate the exact role of CTLA-4 and its relationship with TIRC7 in acute ITP., Patients and Methods: 37 patients with acute ITP were enrolled and received dexamethasone (40mg/day) for 4 consecutive days. Patients who had platelet counts more than 50×10(9)/L or less were defined as responders or non-responders after treatment. The plasma, protein and mRNA levels of CTLA-4 and TIRC7 were monitored by ELISA, western blot and q-PCR, respectively., Results: After high-dose dexamethasone therapy, CTLA-4 levels were significantly elevated not only in acute ITP patients (P<0.001; P<0.0001) but also in acute ITP responders (P<0.0001; P<0.0001). The levels of CTLA-4 were negatively correlated with the levels of TIRC7 before and after treatment; IFN-γ (Th1), IL-17 (Th17) and IL-22 (Th22) levels were all elevated, which were decreased after treatment not only in patients with acute ITP (P<0.01) but also in acute ITP responders (P<0.01)., Conclusions: CTLA-4 level might reflect treatment efficacy and it might be associated with the pathogenesis of acute ITP., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This study was aimed to explore the influence of recipient age on the occurrence of acute graft-versus-host disease (aGVHD) in mice. 8 - 10 weeks aged C57BL/6 (H-2K(b)) mice were selected as donors, 18 - 20 weeks aged and 8 - 10 weeks aged BALB/c (H-2K(d)) mice were served as recipients. 18 - 20 weeks and 8 - 10 weeks aged mice were all randomly divided into three groups: normal control group (without any treatment); irradiation alone group [administered a total body irradiation (TBI) without bone marrow transplantation] and model group [infused with bone marrow mononuclear cells 5 × 10(6) and splenocytes 5 × 10(5) from donor C57BL/6 (H-2K(b)) mice through caudal vein no more than 4 h after TBI]. The general state and survival rate of all mice were observed everyday. The factors (the chimerism in peripheral blood, T lymphocyte and their subsets, the percentage of Th1 cells) of mice in model groups were measured by flow cytometry on day 5, 10, 15, 20, 25, 30 after TBI, the leukocytes in peripheral blood were also calculated by direct microscopic counting. The histological examinations of liver, intestine and skin were done by hematoxylin and eosin staining on day 5, 15, and 25 after TBI. All above data were compared between model groups. The results indicated that murine model with aGVHD was established in two model groups. Compared with 8 - 10 weeks aged mice, the 18 - 20 weeks aged mice showed higher survival rate and lower clinical scores (P < 0.05); the reconstitution time of leukocyte and chimerism in peripheral blood were delayed (P < 0.05); The ratio of CD8(+)T lymphocytes and Th1 cells in peripheral blood were lower (P < 0.05); the histological changes of liver, intestine and skin were little. It is concluded that 18 - 20 weeks aged recipient mice exhibited a lower incidence of aGVHD than 8 - 10 weeks aged recipient mice.

Objective: To find out the nasendoscopic changes of velopharyngeal configuration and movement after palatoplasty with or without velopharyngeal muscle reconstruction., Methods: The nasendoscopy was taken in forty-one patients with palatoplasty, 22 repaired by velopharyngeal muscle reconstruction and 19 with modified von Langenbeck's procedure (non-reconstructive group)., Results: In patients with velopharyngeal muscle reconstruction, the velopharyngeal ports are smooth and full with a definite reduction in size than patients without velopharyngeal muscle reconstruction. During phonation, the complete and marginal velopharyngeal competence rate in reconstructive group (90.91%) is higher than the group of non-reconstruction (37.31%) The major velopharyngeal closure is circular movement in reconstructive group, otherwise coronal closure in nonconstructive group., Conclusions: Based the observation of nasendoscopy, the velopharyngeal muscle reconstruction in palatoplasty has more definite improvement to velopharyngeal closure than non-reconstructive procedure. Palatoplasty with velopharyngeal muscle reconstruction could reduce the size of velopharyngeal port and make the complete velopharyngeal closure easier.

Objective: To study the cellular phenotype conversion of human mesenchymal stem cells (MSCs) cocultured with human sweat gland cells (SGCs) and the contribution of extracellular signal-regulated kinase (ERK) pathway in the process., Methods: MSC and SGC were isolated, amplified , and identified with two-step immunohistochemistry method. The primary SGCs were heat-shocked at 47 degrees C. Then the supernatants were collected immediately and 24hr later. The 3rd passage of MSCs were divided into control, SGC supernatant (cells were cultured in DMEM/F12 medium containing 30% SGC supernatant), SGC supernatant + EGF (cells were cultured in DMEM/F12 medium containing 30% SGC supernatant and 50 microg/L EGF), and SGC supernatant + PD98059 (cells were cultured in DMEM/F12 medium containing 30% SGC supernatant and 10 micromol/L PD98059) groups. The positive expression of CK7and CEA in MSCs were detected on the 7th post-stimulation day (PSD) by flow cytometry. The expression of ERK and phosphorylated ERK were determined with Western blotting., Results: The positive expression rate of CK7 and CEA was (5.76 +/-0.10)%, (2.01 +/- 0.09)% in SGC supernatant group; (7.31 +/- 0.21)% and (7.27 +/- 0.12)% in SGC supernatant + EGF group; and (1.63 +/- 0.11)%, (1.54 +/- 0.07)% in SGC supernatant + PD98059 group; they were all obviously higher than that in control group (P < 0.01). Moreover, ERK expression was observed in all groups. The expression of pERK in SGC supernatant + EGF group was higher than that in SGC supernatant group, but almost no expression of pERK was found in the SGC supernatant + PD98059 and control groups., Conclusion: Indirect coculture of MSCs with SGCs can induce the phenotype conversion of MSCs through ERK pathway.

Objective: To evaluate a method for the reconstruction of defects of perineum and groin with pedicled anterolateral thigh fasciocutaneous flaps., Methods: From July 2003 to February 2005, 12 pedicled anterolateral thigh fasciocutaneous flap based on the perforators of lateral circumflex femoral artery had been designed and transferred to the defects of perineum and groin., Results: Anterolateral thigh fasciocutaneous island flaps were performed in twelve patients. The size of the transferred flap ranged from 8 cm x 11 cm to 18 cm x 20 cm. Only one patient developed superficial cutaneous necrosis in the posterior aspect of the flap because of fecal contamination and infection. The wounds healed secondarily., Conclusions: Despite variable vascular anatomy and technical difficulties in elevating the anterolateral thigh flap, the anterolateral thigh flap is a good choice for perineum and groin reconstruction.

Objective: To evaluate the aesthetic outcome after application of rectangle periosteous flap to cover corrugator., Methods: On the basis of regular rhytidectomy, a inter-eyebrow periosteous flap is applied to cover the fascia flap of corrugator by means of turnover. This manipulation helps to separate the skin from the muscle and prevent the re-adherence between the skin and muscle., Results: The approach was applied on 15 cases. The follow-up ranged from 6 months to 1 year. The results were satisfactory., Conclusions: The method is effective in elimination of inter-eyebrow crease.

Objective: To analysis various complications of 30 patients of breast augmentation by injected polyacrylamide hydrogel and discuss the treatment through periareolar incision., Methods: All patients were classified according to the different complications. Open suction technique and partial mastectomies via periareolar incisions were performed in all patients, Only one patient had immediately breast reconstruction with prosthesis, five patients received secondarily breast prostheses implantation via a axillary incision., Result: All the symptoms were relieved after remove of polyacrylamide hydrogel., Conclusions: Polyacrylamide hydrogel should be prohibited for injected breast augmentation at present. A double-blinded randomized clinical study, controlled animal experiments and a large sample questionnaire survey for complications are necessary. The periareolar approach is valuable technique and can remove polyacrylamide hydrogel as completely as possible.

Objective: To find a procedure for facial rejuvenation which is simple, safe with lasting aesthetic results based on facial anatomic study., Methods: Anatomy study was performed on 12 sides from 6 head specimens. Observe the range and thickness of fat lateral to the nasolabial grooves. Observed the location of the skin retaining ligaments and reappraised their functions combining with clinical observations., Results: Skin and subcutis and SMAS (including mimic muscles) become slackening with aging, but the loosening degrees are different, especially in the region lateral to the nasolabial groove. So they should be handled respectively. The fat lateral to the nasolabial groove is thick and is mobile with aging . So the subcutaneous detachment need not beyond the anterior border of the masseter. In the past two years, we performed rhytidectomy on 100 patients by limited subcutaneous detachment and SMAS double-plication. Satisfactory results were obtained. There are no serious complications observed., Conclusions: Rhytidectomy by limited subcutaneous detachment and SMAS double-plication is a simple and safe procedure with lasting aesthetic results.

Objective: To explore a new method to reconstruct the defect of the distal foot., Methods: A distally based dorsum pedis island flap pedicled with the first dorsal metatarsal artery was designed and transferred to the defect of the distal foot., Results: Five patients were treated with this flap, which ranged from 2 cm x 4 cm to 6 cm x 7 cm in size. Four flaps survived completely, one flap had marginal necrosis and healed after conservative therapy., Conclusions: The reverse first dorsal metatarsal artery flap, with good blood circulation and easy manipulation, is a good option for the defects of the distal foot.

Objective: To evaluate the effect of palatoplasty with or without velopharyngeal muscular reconstruction on the velopharyngeal closure under the lateral radiography., Methods: The lateral radiographs and cephalometric analysis were taken in sixty-two patients with cleft palate and velopharyngeal insufficiency, 32 repaired with velopharyngeal muscular reconstruction and 30 with modified von Langenbeck's procedure (non-reconstructive group)., Results: In patients with velopharyngeal muscular reconstruction, the velopharyngeal competence, the reductive rate of nasopharynx, the distance reduction in lower part of the mobile nasopharynx during phonation and the distance in middle part of mobile nasopharyngo in rest were superior to that without velopharyngeal muscular reconstruction, and there were variform PPW eminence-soft palate contact in velopharyngeal closure. The patients with complete or good velopharyngeal closure had a definite reduction in nasopharynx, compared to the patients with velopharyngeal insufficiency in the non-reconstructive group., Conclusions: The functional area for velopharyngeal closure after palatoplasty might be located in the middle part of mobile nasopharynx. The velopharyngeal muscular reconstruction in palatoplasty could reduce the size of nasopharynx and improve the coordination movement of velopharyngeal closure.

Objective: To evaluate the effect of exteral use of papaverine cream on enhancement of skin graft., Methods: Five mini-pigs were used for the study. 20 full-thickness wounds were created on the back of each animal. Along the midline of the abdomen, a 40 cm x 2 cm full-thickness skin graft was harvested and the wound sutured.The full-thickness graft was prepared and trimmed to 2 cm x 2 cm of 0.6 mm thickness split-skin grafts, which were transplanted to each wound with tie-over bolsters. The sutures were removed 2 weeks after the operation. Twelve pairs of 100%-survived skin grafts were selected and divided into group A (the left side) and group B (the right side), with each pair locating on the same and opposite position. From the day of suture removal, 2% papaverine cream was used to group A while plain cream was used to group B. The grafts were measured and observed for healing condition at the time of suture removal and the first, second, third, fourth, fifth, and sixth month. The surface area of the graft was measured and the shrinking ratio was calculated. After the animals were killed at the sixth month, samples of the skin grafts were taken and processed with 10% formalin, routine paraffin wax and Hematoxylin-eosin staining. The tissue structure was observed and the results were analyzed statistically., Results: The grafts in two groups did not have significant differences at the time of suture removal. Observations from the first to the sixth month showed that the two groups had significant differences in skin graft contracture and histological changes. HE stains demonstrated that the skin grafts in group A had less fibroblasts, more microvessels and orderly-arranged collagenous fibers., Conclusions: External use of papaverine cream can inhabit the contraction of skin grafts. It is a safe, effective, simple, and reliable method,which has the advantages of easy delivery,cheapness, less injury and infection,and no side effects.

Objective: To investigate the expression of the estrogen receptors(ER) in breast hypertrophy and micromastia., Methods: The quantity of ER within breast tissue in 13 patients with mammary hypertrophy strictly elected was determined using DCC single dot test. The results were compared with that measured in 13 patients with micromastia., Results: The average of the quantity of the ER was respectively (5.33 +/- 5.70) fmol/mg and (1.17 +/- 0.86) fmol/mg in mammary hypertrophy ground and in the micromastia group. There was obvious significant between the two groups in a statistics basis (P < 0.05) ., Conclusions: The breast hypertrophy is related to the excessive expression of ER within breast tissue,while the micromastia and breast hypotrophy are related to the lower level or the expression inhibition of ER.

Objective: This experiment is to test the survival enhance effect of leptin in grainy fat transplantation., Methods: The 0.6 g grainy fat was obtained from the Wistar mouse subcutaneous tissue in the abdomen. It was then mixed with 0.9% NS and 20 ng/ml leptin and transplanted in the head subcutaneously. The transplanted tissue was taken out after 10, 20 and 40 days. After being weighed, the tissue was dyed with HE staining and VEGF staining. The data was analyzed with SPSS software., Results: The fibrous membrane around the tissue in leptin group was thin and there was less fat cell necrosis, compared with the control group. The remained-weight rate was 108.3%, 83.3% and 66.3% in 10, 20 and 40 days after the surgery. The differences were statistic significant between the leptin groups and the control (P < 0.05). The examinations of the HE and VEGF stain showed that there was the rich vascularization in leptin treated tissue., Conclusion: Leptin could enhance the survival of the transplanted grainy fat due to its angiogenesis effect.

Objective: To study the polypropylene mesh acted for the moulding and support., Methods: Four mini-pigs were used in this experimental research. A polypropylene mesh was implanted under the skin on one side of each pig. An expander was thereafter placed in the deep layer to imitate the action of gravity to the skin and mesh. The specimens were collected in two different times for the biomechanics and histology examinations., Results: The biomechanical data were shown lower and the histological properties were found changeable in the expanded skin without the mesh support, compared with the normal skin. However, the changes did not occur in the expanded skin with the mesh support. Furthermore, the tensile strength and elastic modulus of the polypropylene mesh were significant less than the human skin., Conclusion: The Polypropylene mesh could prevent the extended skin effectively and has moulding and support effects.

Objective: To study the applications of bone grafts from the cranium or mandible in the repair of posttraumatic deformities of the nose., Methods: From 1997 to 2002, a total of 44 patients, who presented with secondary nose deformity as well as facial fractures, were reconstructed by autogeneous outer table grafts of the calvarial or mandibular bone after facial skeleton reposition. In this series, 32 cases used the calvarial bone, 12 cases used the mandible bone, which was harvested through a coronal incision and an oral approach respectively., Results: The surgical incisions healed primarily in all patients with minimal scar. The facial appearance was greatly improved. No implant infection, extrusion and shift were observed in the postoperative follow-up of 6 months to 2 years. There was not obvious bone resorption, nor donor site morbidity., Conclusion: Autogeneous calvarial and mandibular bone was an ideal material of bone graft in reconstruction of severe posttraumatic deformities of the nose. Compared with other autogeneous and alloplastic materials, the outer table of the calvarial and mandibular bone produced less morbidity of the donor site, invisible scar, no rejection and less resorption.

Objective: To evaluate a technique for decreasing the tension of the nasal floor during the procedures of repairing complete clef lip., Methods: With the designation of an inferior turbinate mucosal flap combined with an oral mucosal flap in the splitting side, the tension was effectively decreased and the nasal floor was closed easily. Eighteen patients was selected for the treatment with this technique since 2000. The follow-ups were 10 to 24 months., Results: All of the patients showed wound healing well with the significant improvement in the donor site., Conclusion: The above mentioned technique may effectively decrease the tension and be used to close the nasal floor safely. It could also reduce the incidence of the complications.

Objective: The purpose of this study was to search for a perfect treatment for the complications after polyacrylamide hydrogel injection for augmentation mammaplasty., Methods: 48 patients who accepted polyacrylamide hydrogel injection for augmentation mammaplasty were included in this study. Operations were performed for the complications of polyacrylamide hydrogel injection. The clinical data were analyzed and the experience in the treatment of the complications was summarized., Results: All patients were satisfied with the result of the operation. The B-ultrasonic examination showed that no visible polyacrylamide hydrogel remained in the cavity., Conclusion: The best therapy for the complications of polyacrylamide hydrogel injection was removing of the polyacrylamide hydrogel and the pathologic tissue and irrigation of the cavity.

Objective: To investigate the behaviors of the children suffered from the secondary deformity after the repair of the cleft lip., Methods: With the application of the PCPI, eighty patients with the secondary deformity after the repair of the cleft lip were selected in this study and 134 normal children was used for the control., Results: In the age between 6 and 11 years, there were no significant difference of the behaviors between the children suffered from secondary deformity of cleft lip and the normal children,but in the age from 12 to 16, the children with the deformity showed more behavior problems with the social withdraw and the poor social relationships, compared with the normal children., Conclusion: The children with the secondary deformity after cleft lip repair in adolescence could have the tendency to suffer from the behavior problems, especially showing the social withdraw and the poor social relationships.

Objective: To improve the survival of mesenchymal stem cells (MSCs) for prefabrication of an osteo-musculo-cutaneous flap., Methods: In a mouse model, the compound of MSCs and p(3HB-co-3HH) were embeded in the latissimus dorsi muscle as an experimental group and the muscle pocket of the buttock as the control. The examinations of the HE staining, hybridization in situ of osteonectin mRNA and Von kossa staining were used to evaluate the results., Results: The expression of osteonectin mRNA and the Von kossa staining showed that the latissimus dorsi muscle group was superior to the control in 2 weeks and 4 weeks after the surgery in vivo., Conclusion: The results indicate that the above-mentioned technique may be a good alternative for the prefabrication of the osteo-musculo-cutaneous flap.

Objective: To evaluate the collagen changes of allografting an acellular dermal matrix (allo-ADM)., Methods: The allo-ADM was grafted underneath the skin of SD rats. The content of collagen and the proportion of type I to III collagen was examined with a biochemical assay., Result: The content of collagen and the proportion of type I to III collagen in the allo-ADM group showed no significant changes., Conclusion: The allo-ADM could keep long time in the body and it may be an ideal material for soft tissue filling.

Before performing plastic and aesthetic surgery around the buccal area, the authors reviewed the anatomical structures of the buccal fat pad in 11 head specimens (i.e., 22 sides of the face). The enveloping, fixed tissues and the source of the nutritional vessels to the buccal fat pad and its relationship with surrounding structures were observed in detail, with the dissection procedure described step by step. The dissection showed that the buccal fat pad can be divided into three lobes-anterior, intermediate, and posterior-according to the structure of the lobar envelopes, the formation of the ligaments, and the source of the nutritional vessels. The buccal, pterygoid, pterygopalatine, and temporal extensions (superficial and profound) are derived from the posterior lobe. The buccal fat pad is fixed by six ligaments to the maxilla, posterior zygoma, and inner and outer rim of the infraorbital fissure, temporalis tendon, or buccinator membrane. Several nutritional vessels exist in each lobe and in the subcapsular vascular plexus forms. The buccal fat pads function to fill the deep tissue spaces, to act as gliding pads when masticatory and mimetic muscles contract, and to cushion important structures from the extrusion of muscle contraction or outer force impulsion. The volume of the buccal fat pad may change throughout a person's life. Based on the findings of the dissections, the authors provide several clinical applications for the buccal fat pad, such as the mechanism of deepening the nasolabial fold and possible rhytidectomy to suspend the anterior lobe upward and backward. They suggest that relaxation, poor development of the ligaments, or rupture of the buccal fat pad capsules can make the buccal extension drop or prolapse to the mouth or subcutaneous layer. As such, the authors refined their methods and heightened their focus when using the buccal fat pad to perform a random or pedicled buccal fat pad fat flap or to correct a buccal skin protrusion or hollow.

From May 1979 to April 1987, 528 cases of cleft palate were repaired with different techniques. Complications occurred in 91 cases. The techniques of operation and prevention of complication were discussed.