Sweet syndrome associated with moderate leukocyte adhesion deficiency type I: a case report and review of the literature.

Sweet syndrome is an acute febrile neutrophilic dermatosis characterized by the infiltration of neutrophils into the skin. It may occur idiopathically or be linked to malignancies, inflammatory or autoimmune diseases. Leukocyte adhesion deficiency type I (LAD-I) is an inborn error immunity wherein leukocytes lack adhesion molecules necessary for migration to infection sites due to mutations in the CD18 gene encoding ß2 integrins. We present a case of a 16-month-old female initially diagnosed and treated for Sweet syndrome based on histopathological findings with recurrent flare episodes. Subsequent workup revealed LAD-I, making this case the first documented association between Sweet syndrome and LAD-I. Moreover, we reviewed the pertinent literatures detailing the concurrence of neutrophilic dermatosis and immunodeficiency disorders. This case underscores the significance of comprehensive evaluation for Sweet syndrome patients who are refractory to conventional treatments.

[Effect of donor and recipient HLA mismatched locus on the prognosis of childhood with leukemia after umbilical cord blood transplantation].

Objective: The aim of the study was to investigate the impact of the sites of high-resolution human leukocyte antigen (HLA) mismatch on the prognosis of children with leukemia undergoing umbilical cord blood transplantation (UCBT). Methods: Clinical data and high-resolution HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 locus gene information were collected in the children who underwent the UCBT for the first time at Children's Hospital of Soochow University between January 2016 and June 2023. In each locus, according to whether the two genes were compatible, they were divided into a compatible group (two genes were perfectly matched) and a non-compatible group (one gene was not matched). In different loci, the differences in occurrence, recurrence, non-recurrence death and survival of acute graft versus host disease (aGVHD) were compared between the two groups. Multivariate Cox regression was employed to analyzed the influencing factors for overall survival rate, and Fine-Gray proportional hazards model was employed to analyze the influencing factors of other outcome events. Results: A total of 100 patients were enrolled (55 males and 45 females), whose age [M (Q1, Q3)] at the time of transplantation was 3.9 (2.0, 6.5) years. There were 55 cases in the HLA-A matched group and 45 cases in the mismatched group. The 5-year non-recurrence mortality (NRM) in the HLA-A matched group was lower than that in the mismatched group (P=0.024). The cumulative incidence of aGVHD within 100 days after transplantation in the HLA-A matched group was lower than that in the mismatched group (P=0.017), and there were no statistically significant differences in other outcome events between the groups (all P>0.05). There were 70 cases in the HLA-B matched group and 30 cases in the mismatched group. The 5-year cumulative recurrence rate in the HLA-B matched group was higher than that in the mismatched group (P=0.027). There were 79 cases in the HLA-C matched group and 21 cases in the mismatched group, and there were no statistically difference in the outcome events between the groups (P>0.05). There were 73 cases in HLA-DRB1 matched group and 27 cases in mismatched group. The 5-year overall survival rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.036), the 5-year cumulative recurrence rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.028), and the 5-year NRM in HLA-DRB1 matched group was lower than that in mismatched group (P=0.008). The cumulative incidence of aGVHD within 100 days after transplantation in the matched group was lower than that in the mismatched group (P=0.010), and and there were no statistically significant difference in other outcome events between the groups (P>0.05). There were 68 cases in HLA-DQB1 matched group and 32 cases in mismatched group. There was no statistical difference in outcome events between the two groups (all P>0.05). The risk of aGVHD in HLA-A mismatched group was higher than that in HLA-A matched group (HR=1.25, 95%CI: 1.12-1.38). The risk of recurrence in HLA-B mismatched group was lower than that in HLA-B matched group (HR=0.77, 95%CI: 0.63-0.91). Mismatched group at HLA-DRB1 compared with matched group at HLA-DRB1, had a higher risk of aGVHD (HR=1.37, 95%CI: 1.26-1.48), a higher risk of non-recurrence death (HR=1.39, 95%CI: 1.28-1.50), and a higher risk of death (HR=1.27, 95%CI: 1.18-1.36). No association was found between HLA-C and HLA-DQB1 locus with the risk of aGVHD, recurrence, non-recurrence death, and survival (all P>0.05). Conclusions: In UCBT, the risk of aGVHD in children with matching HLA-A sites of donor and recipient is lower than that in children with incompatible HLA-A sites. Compared with children with incompatible HLA-DRB1 sites, children with HLA-DRB1 matched sites has a lower risk of acute GVHD, a lower 5-year NRM, and a higher risk of death. The recurrence rate of children with matching HLA-B loci is higher than that of children without matching HLA-B loci.

[Adiponectin improves endometrial receptivity in rats with polycystic ovary syndrome by upregulating the PPARα/HOXA10 pathway].

OBJECTIVE: To explore the role of the PPARα/HOXA10 signaling pathway in mediating the effect of adiponectin (APN) for improving endometrial receptivity in a rat model of polycystic ovary syndrome (PCOS). METHODS: Forty female SD rat models with letrozole-induced PCOS were randomized, with 10 normal rats as the control, into 4 equal groups for treatment with APN alone, APN combined with GW6471 (a specific PPARα inhibitor) or the vehicle for 20 days, or no further treatment (PCOS model group). GW6471 treatment (daily dose of 1 mg/kg) and vehicle treatment were initiated on the 11th day following the start of APN treatment, all administered via intraperitoneal injection. The rats were observed for changes in estrous cycle, body weight, ovarian index and morphology, uterine index and morphology, serum hormone levels and lipid metabolism parameters. Endometrial expressions of PPARα and HOXA10 were detected with immunohistochemistry and Western blotting. The development of endometrial pinopodes was observed under electron microscope, and pregnancies of the rats were recorded. RESULTS: The rat models of PCOS exhibited obvious estrous cycle disorders with significantly prolonged estrous interval, increased body weight and ovarian index, decreased uterine index, disordered serum hormones and lipid metabolism (P < 0.05), and polycystic ovarian changes, and these changes were significantly improved by APN treatment. Endometrial expressions of PPARα and HOXA10 were significantly lowered in PCOS rats and effectively up-regulated after APN treatment, but GW6471 treatment obviously blocked the effect of APN (P < 0.05). APN showed strong protective effect against PCOS-induced impairment of endometrial pinopode development, and this effect was obviously attenuated by GW6471. APN also significantly increased the pregnancy rate and embryo number in PCOS rats, while GW6471 obviously reduced the embryo number and caused developmental retardation of the embryos. CONCLUSION: APN can improve endometrial receptivity in PCOS rats by upregulating the PARα/HOXA10 pathway.

[Analysis of clinical characteristics of children with adenoid hypertrophy and pharyngolaryngeal reflux].

Objectives: To explore the clinical characteristics of children with adenoid hypertrophy (AH) and laryngopharyngeal reflux (LPR) by detecting the expression of pepsin in adenoids as a standard for AH with LPR. Methods: A total of 190 children who were admitted for surgical treatment due to AH were included in the study. The main clinical symptoms of the patients were recorded, and the degree of adenoid hypertrophy was evaluated. Before the surgery, Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were used to evaluate the reflux symptoms. After the surgery, pepsin immunohistochemical staining was performed on the adenoid tissue, and according to the staining results, the patients were divided into study group (pepsin staining positive) and control group (pepsin staining negative). SPSS 19.0 software was used for statistical analysis. Quantitative data conforming to normal distribution between the two groups were tested by two-independent sample t test, and quantitative data with skewed distribution were tested by Mann-Whitney U test. Results: The positive rate of pepsin staining in the 190 AH patients was 78.4% (149/190). The study group had higher levels of preoperative symptoms such as erythema and/or congestion of the pharynx(2.1±0.7 vs. 1.8±0.6,t=2.23), vocal cord edema[1.0(0, 1.0) vs. 1.0(0, 1.0), Z=2.00], diffuse laryngeal edema[0(0, 1.0) vs. 0(0, 0), Z=2.48], posterior commissure hypertrophy[(1.4±0.6 vs. 1.1±0.5), t=2.63], and a higher total score on the RFS scale than the control group(6.2±2.7 vs. 5.0±2.6, t=2.47), with statistical differences (P<0.05). The sensitivity and specificity of RFS score in diagnosing AH with LPR were 24.8% and 80.5%, respectively. When RFS>5 was used as the positive threshold, the sensitivity and specificity of RFS score in diagnosing AH with LPR were 61.1% and 58.5%, respectively. There was a statistical difference in the number of positive cases of RFS score between the study group and the control group(91 vs. 17,χ2=5.04,P=0.032). Conclusions: LPR is common in AH children. Children with AH and LPR have specific performance in electronic laryngoscopy, such as erythema with edema in the pharynx, posterior commissure hypertrophy, and vocal cord edema.

The Effect of Histogram Analysis of DCE-MRI Parameters on Differentiating Renal Tumors.

BACKGROUND: We aimed to assess the role of histogram analysis of DCE-MRI parameters for accurately distinguishing renal clear cell carcinoma from renal hamartoma with minimal fat. METHODS: Patients with renal tumors were enrolled from January 2013 to December 2015, including renal clear cell carcinoma (n = 39) and renal hamartoma (n = 10). Preoperative DCE-MR Imaging was performed, and whole-tumor regions of interest were drawn to obtain the corresponding histogram parameters, including skewness, kurtosis, frequency size, energy, quartile, etc. Histogram parameters differences between renal clear cell car-cinoma and renal hamartoma with minimal fat were compared. The diagnostic value of each significant parameter in predicting malignant tumors was determined. RESULTS: Histogram parameters of the DCE map contributed to differentiating the benign from malignant renal tumor groups. Histogram analysis of DCE maps could effectively present the heterogeneity of renal tumors and aid in differentiating benign and malignant tumors. ROC analysis results indicated that when frequency size = 1,732 was set as the threshold value, favorable diagnostic performance in predicting malignant tumors was achieved (AUC - 0.964; sensitivity - 84.6%; specificity - 100%), followed by skewness, Energy, Entropy, Uniformity, quartile 5, quartile 50, and kurtosis. CONCLUSIONS: Histogram analysis of DCE-MRI shows promise for differentiating benign and malignant renal tumors. Frequency size was the most significant parameter for predicting renal clear cell carcinoma.

[Efficacy of decitabine combined with low dose chemotherapy on children with acute myeloid leukemia].

Objective: To evaluate the efficacy of decitabine combined with low dose chemotherapy (LDC) in the treatment of high-risk, refractory and relapsed pediatric acute myeloid leukemia (AML). Methods: Clinical data of 19 AML children treated with decitabine combined with LDC in the Department of Hematology, Children's Hospital of Soochow University from April 2017 to November 2019 were analyzed retrospectively. The therapeutic response, adverse effects and survival status were analyzed,and the outcomes of patients were followed up. Results: Among 19 AML cases, there were 10 males and 9 females. Five cases were high-risk AML, 7 cases were refractory AML, and 7 cases were relapsed AML. After one course of decitabine+LDC treatment, 15 cases achieved complete remission, 3 cases got partial remission, and only 1 case didn't get remission. All patients received allogeneic hematopoietic stem cell transplantation as consolidation therapy. The follow-up time of all cases was 46 (37, 58) months, 14 children had survived. The cumulative three-year overall survival rate was (79±9) %, events free survival rates was (68±11) %, and recurrence free survival rate was (81±10) %. The most common adverse effects related to the induction treatment were cytopenia (19 cases) and infection (16 cases).There were no treatment-related death during the therapy. Conclusion: Decitabine combined with LDC is a safe and effective option for high-risk, refractory and relapsed AML children, which provides an opportunity for HSCT.

[Challenges and countermeasures in the development of artificial intelligence research in ophthalmology].

The advent of artificial intelligence (AI) technology has led to revolutionary advancements in the diagnosis and treatment of ophthalmic diseases, introducing a novel AI-assisted diagnostic approach for ophthalmology that is rich in imaging diagnostic technologies. However, as clinical applications continue to evolve, AI research in ophthalmology faces challenges such as the lack of standardized datasets and innovative algorithm models, insufficient cross-modal information fusion, and limited clinical interpretability. In response to the growing demand for AI research in ophthalmology, it is essential to establish ophthalmic data standards and sharing platforms, innovate core algorithms, and develop clinical logic interpretable models for the screening, diagnosis, and prediction of eye diseases. Additionally, the deep integration of cutting-edge technologies such as 5G, virtual reality, and surgical robots would advance the development of ophthalmic intelligent medicine into a new phase.

[Association of vitamin D nutritional status with body muscle mass in school-age children adolescents].

Objective: To investigate the association between vitamin D nutritional status and the body muscle mass in children. Methods: Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing were selected through stratified cluster sampling in baseline survey. A follow-up investigation was conducted in 2019. The questionnaire survey and the detection of serum 25-hydroxyvitamin D [25(OH)D] level were conducted. The bioelectrical impedance analysis (BIA) apparatus was used to measure body muscle mass, and muscle mass index (MMI) was calculated. Multivariable linear models were used to analyze the association of vitamin D nutritional status with the baseline and follow-up MMI measures. Results: A total of 10 890 children aged (11.5±3.3) years(boys accounting for 49.6%) were included in the analysis. The average 25(OH)D level was (35.4±12.0) nmol/L, with an adequacy ratio of 11.1%. After multivariate linear regression adjustment for age, sex, body fat mass, smoking status, alcohol use status, dairy supplement, calcium supplement, physical activity, and pubertal development, no statistically significant association between vitamin D nutritional status and baseline MMI level was observed (P>0.05). For the follow-up MMI, the Z-score increased by 0.008 (P=0.058) for per 10 nmol/L increase in 25(OH)D, which were 0.002 (P=0.815) and 0.037 (P=0.031) higher in children with insufficient and adequate vitamin D than those with vitamin D deficiency, respectively (P for trend =0.089). Subgroup analysis showed that in the normal BMI group, for per 10 nmol/L increase in 25 (OH) D, the MMI at baseline survey and MMI Z-score at follow-up of children with adequate vitamin D and increased by 0.019 and 0.014, respectively (both P<0.05). Conclusions: Vitamin D nutritional status was related to muscle mass in children, and children with adequate vitamin D tended to obtain higher MMI. Children and adolescents are encouraged to maintain sufficient vitamin D levels, strengthen nutrition and exercise to promote body health.

[Advances and controversies of statins application in prevention and treatment of hepatocellular carcinoma].

Statins, as lipid-regulating drugs, have been widely used in the treatment for hyperlipidemia and the primary and secondary prevention of cardio-cerebrovascular diseases. Hepatocellular carcinoma (HCC) is a serious burden of liver disease in China with poor prognosis, thus effective adjuvant drug used for HCC treatment has attracted much attention. Statins can suppress tumor growth, decrease the risk of tumorigenesis and postoperative recurrence of HCC, extend the survival time and improve the therapeutic effect of other treatment, therefore might increase the benefit obtained by the HCC patients. Statins also can impact the expression of MAPK/ERK signaling pathway, promote the apoptosis of malignant cells and ameliorate the HCC risk of hepatitis B virus infected patients. Statins not only prevents the HCC, but also has part therapeutic effect on the different stage of HCC. Although it can't replace the operation, radiofrequency ablation, molecular targeted treatment and immunotherapy currently, statins may be a potential adjuvant drug to provide clinical benefit for HCC patients. The advancement of statins application in the prevention and treatment of HCC has attracted more attention recently, however, discussion and controversy also existed about whether it can eventually become an adjuvant therapy for HCC. The purpose of this paper is to summarize and comment on the new development and disputes of statins application in the prevention and treatment of HCC in recent years, to provide help for the future clinical practice.

[Diagnostic value of serum amyloid A, procalcitonin and hypersensitive C-reactive protein for pulmonary tuberculosis complicated by pneumonia].

OBJECTIVE: To assess the value of serum amyloid A (SAA), procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in the diagnosis of pulmonary tuberculosis (PTB) complicated by pneumonia. OBJECTIVE: We collected serum samples from patients with pneumonia, patients with PTB, patients with PTB complicated by pneumonia and patients with PTB complicated by sepsis hospitalized in our hospital between April, 2019 and April, 2020. Serum levels of SAA, PCT and hs-CRP were tested, and receiver- operating characteristic (ROC) curves were used to evaluate their efficacy for predicting PTB with concurrent pneumonia and the possibility of differentiating PTB cases with pneumonia from those with sepsis using these 3 parameters. We also tested serum levels of SAA, PCT and hs-CRP in patients with PTB and those with PTB complicated by pneumonia admitted from May to July in 2020 to verify the accuracy of these 3 parameters combined for predicting the complication of PTB by pneumonia. OBJECTIVE: Compared with the patients with PTB, the patients with pneumonia had significantly higher SAA and hs-CRP levels; serum SAA, PCT and hs-CRP levels were all significantly elevated in patients with PTB complicated by pneumonia (all P < 0.05). The levels of hs-CRP, white blood cell, D-dimer, FIB, APTT and neutrophil ratio were positively correlated with serum SAA level (all P < 0.05). The areas under the ROC curve (AUC) for serum SAA, PCT, and hs-CRP were 0.762, 0.781, and 0.800, respectively, and their combined AUC was 0.849 (all P < 0.001). For predicting PTB complicated by pneumonia, SAA combined with PCT had the same sensitivity (53.85%) and specificity (90.48%) as SAA, PCT and hs-CRP all combined. Serum SAA and PCT levels were similar between PTB patients with pneumonia and those with sepsis. OBJECTIVE: Combined detection of serum SAA and PCT levels can be helpful in the diagnosis of PTB complicated by pneumonia, but neither of them is capable of differentiating the complication of pneumonia from sepsis possibly due to influence by abnormal blood coagulation.

[Application of obesity indicators based on body fat in the screening of persistent dyslipidemia among school-aged children].

Objective: To explore the screening effect of obesity assessed by body fat indicators on persistent dyslipidemia among children. Methods: Data were obtained from the baseline and follow-up survey of 'School-based Cardiovascular and Bone Health Promotion Program.' BMI, fat mass index (FMI), and fat mass percentage (FMP) were used to define obesity. Dyslipidemia, diagnosed both in the baseline and a follow-up survey, was defined as persistent dyslipidemia. The area under the receiver operating characteristic curve (AUC) was used to compare the predictive capabilities of obesity defined by different indicators on persistent dyslipidemia. Results: A total of 10 783 children (boys accounted for 49.6%) were included in the analysis, with the average age as (10.9±3.3) years old. The detection rates of persistent high TC, high LDL-C, low HDL-C, high TG, and high non-HDL-C were 1.3%, 1.2%, 4.3%, 1.3%, and 0.8%, respectively. In boys, the capabilities of FMI- and FMP-defined obesity in the prediction of persistent high LDL-C [FMI: AUC=0.626 (95%CI: 0.558-0.694), P=0.024; FMP: AUC=0.642 (95%CI: 0.574-0.710), P=0.004] and high non-HDL-C [FMI: AUC=0.637 (95%CI: 0.584-0.689), P=0.017; FMP: AUC=0.641 (95%CI: 0.588- 0.693), P=0.018] were significantly higher than BMI-defined obesity. Besides, obese boys defined by FMI had the stronger capability in predicting persistent low HDL-C than that defined by BMI [AUC=0.784 (95%CI: 0.742-0.826) vs. 0.750 (95%CI: 0.726-0.773), P=0.047]. In girls, the capabilities of FMI- and FMP-defined obesity in the prediction of persistent dyslipidemia were not statistically different from BMI. Conclusions: The obesity assessed by body fat performed better in predicting persistent high LDL-C, low HDL-C, and high non-HDL-C than that assessed by BMI among boys, which can be further applied to cardiovascular disease prevention.

[Clinical efficacy and safety of specific immunotherapy for allergic rhinitis with cervical lymph node injection].

Objective: To evaluate the clinical efficacy and safety of intralymphatic immunotherapy with cervical lymph node injection for allergic rhinitis. Method: A retrospective analysis of 81 patients with allergic rhinitis(AR) who had received specific immunotherapy with cervical lymph node injection in 2016 in the first people's Hospital of Foshan was conducted. The neck lymph node immunotherapy under the guidance of color Doppler ultrasound consisted of three sessions, and in each session 50 Tu(Arog) was delivered. The scores of nasal and ocular symptoms, drug score and adverse reactions during treatment were recorded before and after treatment, and the efficacy and safety were observed. Result: Before treatment, the nasal symptoms score of 81 AR cases of mite allergy was 7.00±1.65. After 1,2 and 3 sessions of cervical lymph node immune therapy and 1 year after completion of treatment, the nasal symptom scores were 4.37±1.88, 4.26±1.80, 4.22±1.80, and 4.09±2.10,respectively, which were significantly lower than that before treatment(P<0.01). The quality of life score was 53.68±9.28 before treatment, which decreased to 23.01±13.28 one year after treatment, and the difference was statistically significant(P<0.01). The drug score was 3.27±1.17 before treatment, which decreased to 1.00±1.05 1 years after treatment, and the difference was statistically significant(P<0.01). During treatment and 1-year follow-up, only 8 cases had mild local reactions, and no systemic adverse reactions occurred. Conclusion: Cervical lymph node injection specific immunotherapy can significantly relieve the symptoms of dust mite allergic rhinitis. The treatment is effective and safe, and greatly shortens the duration of immune treatment.

[The association between blood lipids and calcaneus bone mineral density in children and adolescents aged 6-16 years in Beijing].

Objective: To investigate the association between blood lipid and calcaneus bone mineral density (BMD) in children and adolescents aged 6-16 years in Beijing. Methods: Children and adolescents were selected in 30 schools (8 primary schools, 21 middle schools and one 12-year education school) from Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by using a stratified cluster sampling method from November 2017 to January 2018. A total of 14 303 students in grade 1 to 4 of primary school, grade 1 of junior and senior middle school were enrolled after excluding subjects who were not able to participate into this study due to trauma or other uncomfortable physical conditions or with missing key values or with diabetes and kidney diseases. Questionnaire survey, blood lipid and calcaneus BMD were conducted. Multivariate linear regression was applied to quantify the association between calcaneal BMD as a dependent variable and blood lipid level as an independent variable after adjusting for the potential confounding factors. Furthermore, quantile regression was used to analyze the association between blood lipid level and different percentiles (P(25), P(50) and P(75)) of ultrasonic velocity values of bone mineral density, and parallel test was conducted for regression coefficients of different percentiles. Results: A total of 14 303 participants aged (11.4±3.3) years (49.9% boys) were involved in the analysis. The mean age of 14 303 participants was (11.0±3.3) years. 7 142 boys accounted for 49.9%. The mean±SD of calcaneal BMD, total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) were (1 540.9±33.8) m/s, (3.90±0.76), (2.18±0.62), and (1.40±0.32) mmol/L, respectively. The P(5)0 (P(25), P(75)) of triglyceride (TG) was 0.69 (0.49-0.94) mmol/L. After the adjustment of age, height, smoking, drinking, vitamin D and calcium supplementation, dairy intake, physical activity, FMI, and MMI, a significantly inverse association (P<0.05) between TG level and calcaneus BMD was observed in both genders, which the regression coefficients (95%CI) in boys and girls were -0.064 (-0.085, -0.044) and -0.073 (-0.094, -0.053), respectively. Conclusion: The level of BMD was associated with TG in boys and girls. Therefore, it is important to prevent children from hypertriglyceridemia for the bone health promotion.

The therapeutic efficacy of pediatric ALL patients with MLL gene rearrangement treated with CCLG-ALL2008 protocol.

OBJECTIVE: In this study, we retrospectively evaluated the therapeutic efficacy of China Children Leukemia Group-ALL2008 (CCLG-ALL 2008) protocol in pediatric patients with mixed-lineage leukaemia (MLL) gene rearrangement of acute lymphoblastic leukemia (ALL) to identify the prognostic factors. PATIENTS AND METHODS: Six hundred and thirty-four patients with ALL were enrolled in this study between June 2008 and Dec 2014. High-risk group (HR) consisted of 217 cases, of which 28 cases were MLL related positive (first group), 22 cases were BCR/ABL positive (second group), and 167 cases were negative with MLL related or BCR/ABL (third group). The therapeutic efficacy was evaluated at the time points of day 8 (TP1), day 15 (TP2), day 33 (TP3) and 12th week (TP4) with the protocol, respectively. Overall-survival (OS) and relapse-free-survival (RFS) and treatment-related mortality (TRD) were analyzed as well. RESULTS: The first group accounted for 4.4% of all patients. Compared with the second and third group, the first group had more cases younger than 2 years, with initial leukocytes ≥50×109/L, and poor response on TP2. Moreover, patients older than 2 years old had a good 5 years OS (84% ± 9% vs. 37% ± 20%, p<0.05) and RFS (84% ± 9% vs. 29% ± 17%, p<0.05). There were no significant differences in the recurrence rate, TRD, 5 years OS and RFS among three groups. For the first group, compared with good response to prednisone, patients with poor response to prednisone had a poor 5 years RFS (41% ± 17% vs. 81% ± 10%, p<0.05). Multivariate Cox regression analysis identified that RFS and OS were influenced by such factors as age, MLL fusion partners, and prednisone response (p<0.05). CONCLUSIONS: Such factors as younger age than 2 years old, MLL/AF4 fusion gene, poor response to prednisone, or no complete remission (CR) on TP3 were poor prognostic parameters in predicting the outcome in childhood ALL with MLL gene rearrangement treated with CCLG-ALL 2008 protocol.

[The safety of decitabine as bridging pretreatment regimen before hematopoietic stem cell transplantation in pediatric hematological malignancies].

The safety of decitabine as bridging treatment before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with refractory hematological malignancies was evaluated. All 11 cases succeeded in hematopoietic reconstitution. The main adverse reaction was hematological toxicity. Neither did infections occur, nor drug-induced liver damage and renal impairment during decitabine administration. Most cases showed grade Ⅰ-Ⅱgastrointestinal adverse events. One case was diagnosed as severe acute graft versus host disease and died of intracranial hemorrhage on day 61 after allo-HSCT. The other 10 patients survived. Decitabine bridge is a safe regimen before allo-HSCT in children with refractory hematological malignancies.

Suppressed CCL2 expression inhibits the proliferation of leukemia cells via the cell cycle protein Cyclin D1: preliminary in vitro data.

OBJECTIVE: Chemokine (C-C motif) ligand 2 (CCL2) is a member of the CC subfamily, which displays chemotactic activity for monocytes and basophils. This molecule plays a very important role in many solid tumors and shows changes in the bone marrow microenvironment. However, its role in acute myeloid leukaemia (AML) is still unclear. MATERIALS AND METHODS: In this study, we established a HL-60 cell line with CCL2 knockdown to explore its effect on leukemogenesis. Lentivirus with CCL2-knockdown was successfully constructed after screening effective CCL2 short hairpin RNA (shRNA) sequences and was transfected into HL-60 cells, which was further validated at the mRNA and protein levels by real-time polymerase chain reaction (PCR) and Western blotting, respectively. RESULTS: Low expression of CCL2 significantly decreased HL-60 cell growth by increasing the cell arrest at G1 phase by 12% more than controls. We applied RNA sequencing technology to discriminate the gene expression profiles between the cells with CCL2 knockdown and the controls, and Cyclin D1 was selected for further experiments as its expression level was significantly downregulated, which was validated at the mRNA and protein levels. Cyclin D1 knockdown experiments showed that the cell proliferation rate was evidently decelerated, and cell cycle analysis also indicated a similar pattern for CCL2. CONCLUSIONS: Our study revealed that Cyclin D1 is an effector that mediates CCL2's function in cell proliferation by blocking cells at G1 phase.

MicroRNA-544 inhibits inflammatory response and cell apoptosis after cerebral ischemia reperfusion by targeting IRAK4.

OBJECTIVE: Stroke remains the most common malignant cerebrovascular event in the world. The correlation between the expression of miR-544 and the degree of cerebral ischemia reperfusion (CIR) injury has not been well recognized in recent years. This study focuses on the effect of miR-544 on inflammation and apoptosis after CIR. PATIENTS AND METHODS: Plasma expression of miR-544 in ischemic stroke (IS) patients and healthy controls was determined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The effects of miR-544 on cerebral infarction and neurological deficits were verified in vitro by tail vein injection of Ago-miR-544. Western blotting was utilized to examine protein expressions of key proteins involving in inflammation and apoptosis in mouse brain. Western blotting, immunofluorescence staining and luciferase assays were used to demonstrate whether miR-544 influences the expression of interleukin-1 receptor-associated kinase 4 (IRAK4), downstream inflammatory and apoptosis-related proteins. RESULTS: MiR-544 was found decreased in peripheral blood of IS patients compared with healthy controls. MiR-544 has been shown to relieve neurological deficits and reduce the volume of cerebral infarction in mice. Overexpression of miR-544 ameliorated the inflammation and apoptotic responses in brain tissue after ischemia reperfusion by down-regulating the expression of IRAK4, whereas the low expression was opposite in vivo and in vitro. CONCLUSIONS: We found that miR-544 may participate in controlling inflammation and apoptosis after ischemia-reperfusion by targeting IRAK4, providing possible diagnostic indicators and therapeutic targets for IS.

Correlations of neuronal apoptosis with expressions of c-Fos and c-Jun in rats with post-ischemic reconditioning damage.

OBJECTIVE: Transcription factors (c-Fos and c-Jun) have been considered to play roles in the initiation of programmed nerve cell death. However, the roles of c-Fos and c-Jun protein expressions in neuronal apoptosis of rats with post-ischemic reconditioning damage were not clarified. Therefore, the aim of this study was to investigate the correlations of protein expressions of c-Fos and c-Jun with neuronal apoptosis of rats with post-ischemic reconditioning damage. MATERIALS AND METHODS: Rat models of post-ischemic reconditioning were established firstly. Then, apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay, and the gene expression levels of apoptosis-related proteins [cytochrome c (Cyt c), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax)] were detected by reverse transcription-polymerase chain reaction (RT-PCR). Lastly, Western blotting was used to determine the protein expression levels of c-Fos and c-Jun, and the expressions of c-Fos and c-Jun in brain tissues of models were measured by immunohistochemistry. RESULTS: Treatment group had significantly increased malonaldehyde (MDA) level and significantly decreased superoxide dismutase (SOD) activity in rat cortex compared with those in control group (p<0.05). The number of TUNEL positive cells in the right cortex of rats in the treatment group was clearly higher than that in control group. Among them, post-ischemic reperfusion group had reduced level of Bax in the cytoplasm, but increased Bax level in the mitochondrion, and lowered expression level of Bcl-2 in both mitochondrion and cytoplasm in comparison with control group. Dynamic detection results of c-Jun were in synchronization with those of apoptosis proteins, and maximum expression occurred at 24 h after treatment. CONCLUSIONS: c-Jun may play a role in the initiation of apoptotic cell death in these neurons.