OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q₁, Q₃) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.
Aged ; Humans ; Aged, 80 and over ; Frailty/epidemiology* ; Sleep Duration ; Prospective Studies ; Sleep/physiology* ; China/epidemiology*

OBJECTIVE: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment. METHODS: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized. RESULTS: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-β-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died. CONCLUSION PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.
Caspofungin/therapeutic use* ; Child ; Child, Preschool ; Dyspnea ; Female ; Humans ; Male ; Pneumonia, Pneumocystis/therapy* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Respiratory Sounds ; Retrospective Studies

OBJECTIVE: To analyze the clinical characteristics and treatment effects of children with acute megakaryoblastic leukemia without down syndrome (non-DS-AMKL). METHODS: The clinical data of 19 children with non-DS-AMKL treated in the Pediatric Hematology Ward in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from May 2008 to April 2018 were analyzed retrospectively. The clinical characteristics, laboratory test and treatment methods of the children were concluded. All patients were followed up to evaluate the effect of treatment. RESULTS: The 19 cases of children included nine male and ten female, the median age of onset was 2 years old. The clinical manifestations showed nonspecific. The median white blood cell of peripheral blood was 15.88×10 CONCLUSION Non-DS-AMKL was rare in children and difficult to be diagnosed. Determination of MICM classification as early as possible was helpful for diagnosis, and genetic testing played an important role for diagnosis and prognosis evaluation. Early hematopoietic stem cell transplantation in patients with CR after chemotherapy might be an effective way to cure AMKL.
Child ; Child, Preschool ; DEAD-box RNA Helicases ; DNA Helicases ; Down Syndrome ; Female ; Humans ; Leukemia, Megakaryoblastic, Acute/genetics* ; Male ; Prognosis ; Retrospective Studies ; Trisomy

OBJECTIVE: To analyze the clinical features and prognosis of 28 children with myelodysplastic syndrome (MDS) and to screen the high risk factors affecting the prognosis so as to provide the new ideas for standard of clinical diagnosis and therapy. METHODS: The clinical data of 28 children with newly diagnosed MDS treated in our hospital from March 1994 to July 2016 were analyzed retrospectively, the features of disease onset and the results of laboratory examination were summarized, all MDS children were followed up, the prognosis and the high risk factors affecting the prognosis were evaluated. RESULTS: In all 28 MDS children, the ratio of male to female was 1.8∶1, the incidence of MDS was observed in boys, while the low incidence of MDS was found in older children. The clinical manifestations were mainly the decrease of three series blood cells in 16 cases (57.14%), other cases presented simple anemia (7.1%), simple thrombocytopenia (7.1%), neutropenia with anemia (14.29%), and anemia with thrombocytopenia (14.28%).The bone marrow image showed mainly hyperplasia (82.14%), and the pathological hematopoiesis, moreover the manifistation of pathological hematopoiesis was different in forma and degree; the bone marrow biopsy showed the typical abnormal localization of immature precursor(ALIP) accepted for 33.33%; the chromosome karyotype detection showed the detected rate of chronosome abnormality was 41.18%. The median follow-up time was 1.75 years. 5 children with MDS received the hematopoietic stem cell transplantation (HSCT), among them 1 dead and 4 maintained CCR; Out of other 23 patients no-received HSCT, 7 cases given up treatment after confirmed diagnosis, 16 cases received the chemotherapy (2 cases given up treatment after CR, 5 cases transformed into AML, 3 cases relapsed, 3 cases maintained CCR), 11 cases dead, 9 cases failed to be followed up. The 5-years OS rate and EFS rate in all patients were predicted as (38.2±11.3)% and (35.3±11.3)%,respectively, among them, the OS and EFS rates of patients received the HSCT allo superior to those of patients did not received HSCT ［(80.0±17.9）% vs.(22.8±11.5）%］ (P<0.05) and ［(80.0±17.9)% vs (17.5±11.1)%］(P<0.05). Analysis showed that in addition to receiving the HSCT(P<0.05), platelet decrease in peripheral blood(P<0.01), the age, sex, existance of micromegakaryocytes in bone marrow and progressive MDS or no influenced not on the prognosis(P>0.05). CONCLUSION The children MDS is rare and easy to be misdiagnosis, moreover displays more high heterogeneity and poor prognosis, thereby the early diagnosis is crucial, in addition, the system of prognosis evaluation is imperative to be perfected. The HSCT may be the effective method for curative treatment of childhood MDS.
Child ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Karyotyping ; Male ; Myelodysplastic Syndromes ; Prognosis ; Retrospective Studies

The sialyl Lewis X (SLex) antigen encoded by the FUT7 gene is the ligand of endotheliam-selectin (E-selectin).The combination of SLex antigen and E-selectin represents an important way for malignant tumor metastasis.In the present study,the effect of the SLeX-binding DNA aptamer on the adhesion and metastasis of hepatocellular carcinoma HepG2 cells in vitro was investigated.Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining were conducted to detect the expression of FUT7 at both transcriptional and translational levels.The SLex expression in HepG2 cells treated with different concentrations of SLeX-binding DNA aptamer was detected by flow cytometry.Besides,the adhesion,migration,and invasion of HepG2 cells were measured by cell adhesion assay,and the Transwell migration and invasion assay.The results showed that the FUT7 expression was up-regulated at both mRNA and protein levels in HepG2 cells.SLeX-binding DNA aptamer could significantly decrease the expression of SLex in HepG2 cells.The cell adhesion assay revealed that the SLeX-binding DNA aptamer could effectively inhibit the interactions between E-selectin and SLex in the HepG2 cells.Additionally,SLeX-binding DNA aptamers at 20 nmol/L were found to have the similar effect to the monoclonal antibody CSLEX-1.The Transwell migration and invasion assay revealed that the number of penetrating cells on the down-side of Transwell membrane was significantly less in cells treated with 5,10,20 nmol/L SLeX-binding DNA aptamer than those in the negative control group (P＜0.01).Our study demonstrated that the SLeX-binding DNA aptamer could significantly inhibit the in vitro adhesion,migration,and invasion of HepG2 cells,suggesting that the SLeX-binding DNA aptamer may be used as a potential molecular targeted drug against metastatic hepatocellular carcinoma.

The Grainyhead-like 3 (GRHL3) is involved in epidermal barrier formation,neural tube closure and wound repair.Previous studies have suggested that GRHL3 has been linked to many different types of cancers.However,to date,its effects on human colorectal cancer (CRC) has not been clarified yet.Our microarray analysis has indicated predominant GRHL3 expression in CRC.The purpose of this study was to investigate the expression and significance of GRHL3 in CRC tumorigenesis using CRC tissues and paired paracancerous tissues,as well as using distinct CRC cell lines (HT29 and DLD1).We observed increased GRHL3 expression at both mRNA and protein levels in CRC tissues and CRC cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.Moreover,silencing GRHL3 with siRNA could suppress CRC cell proliferation,viability and migration in vitro.We also found that knockdown of GRHL3 could promote cell cycle arrest at G0/G1 phase in HT29 cells and DLD1 cells,and induce cell apoptosis in HT29 cells.Together,our study revealed the down-regulation of GRHL3 in vitro could inhibit CRC cell activity and trigger cell cycle arrest at G0/G1 phase and apoptosis.

OBJECTIVETo study the expression of NPAS2 in colorectal cancer (CRC) and analyze its relationship with the clinicopathological parameters and prognosis of the patients.

METHODSReal-time q-PCR was used to detect the expression of NPAS2 mRNA in 40 fresh CRC tissues and paired adjacent tissues; immunohistochemistry was used to detect the expression of NPAS2 protein in 120 paraffin-embedded tumor and adjacent tissues. The relationship between NPAS2 expression level and the 5-year survival rate of 78 CRC patients with follow-up data were analyzed with Kaplan-Meier survival analysis.

RESULTSCompared with the adjacent tissues, fresh CRC tissue expressed significantly lower NPAS2 mRNA levels (P<0.01). Among the paraffin-embedded CRC tissues, 19.2% were positive for NPAS2 expression, as compared to a much higher rate of 62.5% in the adjacent tissues (P<0.05). The expression of NPAS2 was correlated with the tumor size, lymph node metastasis and TNM stages (P<0.05) but not with the patients' gender, age, distant tumor metastasis, differentiation, or invasion. Patients with high NPAS2 expression levels had a significantly higher 5-year survival rate than those with low NPAS2 expressions (P=0.0001).

CONCLUSIONNPAS2 is down-regulated in CRC and closely correlated with the malignant biological behavior of the tumor and 5-year survival of the patients, suggesting its value in predicting the prognosis of the CRC patients.

Basic Helix-Loop-Helix Transcription Factors ; metabolism ; Colorectal Neoplasms ; diagnosis ; metabolism ; Down-Regulation ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Nerve Tissue Proteins ; metabolism ; Prognosis ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Survival Rate

Objective To assess the molecular biological characteristics of occult hepatitis B virus ( HBV ) infected blood donors in Shaoxing.Methods 8692 blood donors were screened using ELISA.The occult HBV infection was determined by DNA analysis among the HBsAg negative subjects.DNA sequencing and mutational analysis were further performed in the HBV DNA positive samples.The overall situation of occult HBV infection was hereby evaluated and the possible underlying mechanisms discussed.Results Among the 8644 HBsAg negative subjects out of 8692 blood donors,8 were HBV DNA positive.The occult HBV infection rate was 0.92‰(8/8692).Among the 8 samples,6 were genotype C (75％) and 2 genotype B (25％).In addition,a specific mutation in "a" epitope was observed in 7OBI virus strains by amino acid analysis.Conclusion There were occult HBV infected among blood donors in Shaoxing,which is probably associated with the gene mutation of HBV virus.

OBJECTIVETo study the prevalence of different types of neural tube defects (NTDs) in Luliang Prefecture, Shanxi province, where the prevalence of NTDs is unusually high and the correlation between NTDs prevalence and patterns.

METHODSA surveillance population-based birth defects was performed in Luliang Prefecture, Shanxi province.

RESULTSThe results of our study showed that the prevalence of NTDs was 2-fold higher in Luliang Prefecture than in other areas of Shanxi province. Unusual patterns of NTDs were found, however, multiple NTDs were relatively common in Luliang Prefecture, accounting for over 13% of all NTDs cases in China.

CONCLUSIONThe prevalence of NTDs is associated with its patterns.

Child, Preschool ; China ; epidemiology ; Humans ; Infant ; Infant, Newborn ; Neural Tube Defects ; classification ; epidemiology ; Risk Factors