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Objective: To analyze the genotypes and clinical phenotypes of patients with epilepsy associated with IQSEC2 gene variants. Methods: The genotypes, seizure types, electroencephalogram, neuroimage of 6 patients with IQSEC2 gene variants in the Department of Pediatrics, Peking University First Hospital from July 2019 to October 2021 were analyzed. Results: There were 5 males and 1 female. Six variants were de novo, including 2 frameshift variants (c.3801_3808dup/p.Q1270Rfs*130, c.1459_1460delAT/p.M487Vfs*2), 2 nonsense variants (c.3163C>T/p.R1055*, c.1417G>T/p.E473*), 1 in-frame deletion (c.2295_2297del/p.N765del) and 1 missense variant (c.2293A>G/p.N765D). Age at seizure onset ranged from 3 months to 2 years and 5 months. Multiple seizure types were observed, including epileptic spasms in 5 patients, focal seizures in 5 patients, tonic seizures in 3 patients, myoclonic seizures in 3 patients, atypical absence seizures in 2 patients and atonic seizures in 2 patients. All 6 patients showed global developmental delay before seizure onset. There were other clinical manifestations, including autistic features in 3 patients, microcephaly in 3 patients, dystonia in 2 patients and binocular esotropia in 1 patient. The electroencephalogram showed slow background activity and hypsarrhythmia in all 6 patients. Brain magnetic resonance imaging showed abnormal in 5 patients and normal in 1 patient. Five patients were diagnosed with infantile spasms. Among them, 4 patients had late-onset infantile spasms. One patient was unclassified developmental epileptic encephalopathy. The age of last follow-up ranged from 3 years and 2 months to 7 years and 2 months. All 6 patients still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset of patients with IQSEC2 gene variants usually begins after 1 year of age. The common seizure types include epileptic spasms and focal seizures. Patients usually have a global developmental delay before seizure onset. IQSEC2 variants could be related to developmental and epileptic encephalopathy, and most patients are diagnosed with late onset infantile spasms. Epilepsy associated with IQSEC2 gene variants is usually refractory.

Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.

Objective: To analyze the cystic fibrosis transmembrane conductance regulator (CFTR) gene variations and phenotypes in 7 Chinese children. Methods: In this retrospective study, the data of 7 children with CFTR gene variations admitted to Children's Hospital of Chongqing Medical University from December 2013 to October 2020 were extracted. The general information, clinical manifestations, gene variations, diagnosis and treatment were summarized. Results: Among the 7 children, 2 were males and 5 were females, aged 5.2(0.5-11.3) years. Main clinical manifestations included malnutrition (5 cases), recurrent respiratory infection (4 cases), bronchiectasis (3 cases), steatorrhea (3 cases), vomiting in infancy (2 cases), liver cirrhosis (2 cases), meconium ileus (1 case), metabolic alkalosis and hypochloremia (1 case). A total of 15 variations were found by whole exon sequencing and Sanger sequencing, among which 3 were newly discovered, and 7 were missense mutations. Four children were diagnosed as CF, and the other 3 were diagnosed as CFTR related disease (CFTR-RD). Compared with CF patients, the pancreatic insufficiency and typical CF lung disease were relatively mild in CFTR-RD patients. After treatment, 6 children were clinically improved, while the rest one withdrew treatment due to critical pulmonary infection and disturbance of water-electrolyte metabolism. Conclusions: The loci and phenotypes of CFTR gene variants vary hugely and the pathogenicity of some variations are not clear. Whole exon sequencing can facilitate the identification of CF-and CFTR-RD-causing variaions. For the cases not compatible with CF, CFTR-RD should be considered and evaluated by timely gene detection, so as to carry out appropriate long term management.

With the improvement of diagnosis and treatment, tumor has become a chronic disease, and an increasing number of older patients will live with tumors. This change has led to an increase in demand for intensive care unit (ICU) and a challenge to the traditional ICU treatment concept. The option of ICU consists of two parts. The first is the option for admission. Since classic predictors of mortality are no longer relevant, we suggest broadening the criteria for ICU admission. Patients during the first course of cancer therapies should be treated with a full-code status similar to that of other patients without malignancy. Patients whose clinical response to therapy was not available or undetermined should be allowed an ICU trial that consists of unlimited invasive support, including anti-cancer therapies such as ambulatory chemotherapy. Do everything that can be done to save the patients who might benefit from ICU treatment. The second is the option of therapeutic end point. An interdisciplinary meeting, including an ethics consultation, should be held after 3-6 days'ICU trial to make end-of-life decisions with relatives of patients if the SOFA score shows clinical deterioration with no available therapeutic options. The treatment goals should shift from curative or supportive therapies to end-of-life care. we could integrate hospice and palliative care with intensive care more effectively and efficiently. That would be the future of oncological ICUs.

Objective: To investigate the therapeutic mechanism of baicalin on rat brain glioma., Methods: Deep brain glioma models were established by injection of glioma cell line C6 cells into the brain of Wistar rats. The rats at 7 days after modeling were randomly divided into tumor control group (0.9% NaCl solution 30 mg×kg(-1)×d(-1) gavage)and experimental groups. The experimental rats was divided into 3 groups: low dose group (50 mg×kg(-1)×d(-1)), middle dose group (100 mg×kg(-1)×d(-1)) and high dose group (200 mg×kg(-1)×d(-1)), given the baicalin by gavage. Pathological and electron microscopic changes were observed. The expressions of p53 and Bcl-2 were determined by immunohistochemistry, and the changes of MRI, the average survival time and body weight of the rats in each group after treatments were analyzed., Results: Compared with the control group, the tumor diameter and volume of high dose group rats before sacrifice were significantly reduced (P < 0.01), and the survival time was significantly prolonged (P < 0.01). Immunohistochemistry revealed strong positive expression rate of mutant p53 (84.47 ± 3.74)% and moderately positive rate (47.28 ± 2.38)% in the control group, significantly higher than that in the negative group (12.91 ± 1.07)% (P < 0.01). The positive rate of mutant p53 of the high dose group was (46.42 ± 2.19)%, significantly lower than that of the control group (84.47 ± 3.74)% (P < 0.01). The expression rate of Bcl-2 in the control group was strongly positive (86.51 ± 4.17)% and moderate positive (48.19 ± 2.11)%, significantly higher than that of the negative group (10.36 ± 1.43)% (P < 0.01). Electron microscopy revealed that baicalin caused damages of the cell nuclei and organelles in the gliomas., Conclusions: Baicalin has significant inhibitory effect on glioma in vivo, and its mechanism may be related to cell apoptosis induced by down-regulated expression of mutant p53, but not related with Bcl-2 expression.

Objective: Along with the elevation of survival rate of very low birth weight infants (VLBWI), the enteral feeding of VLBWI has become one of the most important factors, which influence the length of stay, short and long-term prognosis. This study aimed to explore safe and effective clinical protocols of VLBWI enteral feeding., Method: According to different correlative degree of related factors to VLBWI enteral feeding, different scoring system was formulated for the enteral feeding and monitoring proposal of VLBWI. The safety and efficacy of the score system was evaluated., Result: Forty-eight VLBWIs in group A was not treated with any score system, gestational age (30.0 ± 2.1) weeks, birth weight (1173 ± 170) g; while 48 VLBWIs in group B were guided with the scoring system, gestational age (30.3 ± 1.7) weeks, birth weight (1133 ± 238) g, there was no significant difference between two groups. The incidence of newborn respiratory distress syndrome of group B was significantly higher than that of group A (P = 0.016). The time of umbilical catheterization of group B was longer than that of group A. There was no significant difference in the incidence of other complications between two groups. The beginning milk volume, milk volume on the third, seventh, fourteenth, twenty-first, twenty-eight day of group B were significantly higher than that of group A [5.6 vs. 3.5 ml/(kg·d), P = 0.008, 12.3 vs. 5.7 ml/(kg·d), P = 0.000, 29.1 vs 8.9 ml/(kg·d), P = 0.000, 62.5 vs. 44.6 ml/(kg·d), P = 0.020, 98.1 vs. 71.5 ml/(kg·d), P = 0.005, 128.0 vs. 102.4 ml/(kg·d), P = 0.011]. The time achieving full enteral feeding of group B was shorter than that of group A (26.7 vs 32.9d, P = 0.007). The incidence of necrotizing enterocolitis in group B was lower than that of group A(0/48 vs. 4/48, P = 0.041). There was no significant difference of the total amino acid dosage between two groups. The total dosage of fatty emulsion was less, and the duration of parenteral nutrition was shorter in group B than in group A (50.3 vs. 73.9 g/kg, P = 0.000, 31.5 vs. 37.8 d, P = 0.016). There was no significant difference in length of stay between two groups. VLBWI of group B began to gain weight earlier [5.0 (4.3, 6.0) vs. 5.0 (5.0, 7.0) d, P = 0.028], regained birth weight earlier (9.2 vs. 11.6 d, P = 0.001), and got more weight in the second week (178 vs. 138 g, P = 0.020)., Conclusion: VLBWI guided with the scoring system achieved full enteral feeding faster, and shortened the duration of parenteral nutrition without increasing the incidence of necrotizing enterocolitis.

Objective: To investigate the changes of drug sensitivity of spindle poison-induced polyploid tumor cells to chemotherapeutic agents and its possible mechanism., Methods: Nocodazole in a dose of 100 ng/ml was used to induce polyploidization in a breast cancer cell line MDA-MB-231 cells. The polyploid cells (T-MDA-MB-231) were sorted by flow cytometry. The morphological changes and proliferation of T-MDA-MB-231 cells were compared with that of MDA-MB-231 cells. The cell growth inhibition was assessed by MTT assay. The cells were treated with paclitaxel, docetaxel, vincristine, epirubicin, 5-Fu, VP16 and oxaliplatin, respectively. Those cells were labeled with annexin V-FITC/PI and analyzed by flow cytometry. Bcl-2 was knocked down in T-MDA-MB-231 cells using SiRNA and their growth inhibition was evaluated by MTT assay to evaluate the reversing effect of Bcl-2-silencing on drug resistance., Results: The polyploid T-MDA-MB-231 cells grew in vitro continuously and maintained constant DNA content. They had a larger cell size, and grew more slowly than MDA-MB-231 cells. The IC(50(s)) of T-MDA-MB-231 cells were significantly higher than that of the MDA-MB-231 cells: paclitaxel: (6.37 ± 0.07) vs. (2.05 ± 0.83) µmol/L; docetaxel: (32.98 ± 1.48) vs. (11.95 ± 0.98) µmol/L; vincristine: (35.28 ± 1.66) vs. (14.58 ± 0.94) µmol/L; oxaliplatin: (19.07 ± 0.45) vs. (9.75 ± 1.05) µmol/L; 5-Fu: (85.49 ± 3.21) vs. (31.35 ± 1.51) µmol/L; and epirubicin: (0.53 ± 0.06) vs. (0.15 ± 0.01) µmol/L, (all P < 0.05). The IC(50(s)) of VP16 in T-MDA-MB-231 cells was (2.85 ± 0.50)µmol/L, significantly lower than the (12.20 ± 1.55) µmol/L in MDA-MB-231 cells (P < 0.05), and that of T-MDA-MB-231 cells after Bcl-2-knocked down by siRNA was (19.59 ± 0.48) µmol/L, significantly higher than the (12.20 ± 1.55) µmol/L in the MDA-MB-231 cells (P < 0.05). The IC(50(s)) of docetaxel of T-MDA-MB-231 cells after Bcl-2-knocked down by siRNA was (21.52 ± 0.68) µmol/L, significantly decreased and lower than that before Bcl-2 silencing (32.98 ± 1.48) µmol/L., Conclusions: Our results indicate that polyploid tumor cells induced by spindle poison Nocodazole are more resistant to most of chemotherapeutic drugs. Downregulation of Bcl-2 increases the sensitivity of polyploid cells to docetaxel. The high expression of Bcl-2 may be one of the drug resistance mechanisms of polyploid tumor cells. The polyploid tumor cells are relatively sensitive to VP16, suggesting that VP16 might be an effective candidate drug for treatment of chemoresistant polyploid tumors.

Objective: To summarize the clinical characteristics and prognosis of newborn aristolochic acid nephropathy induced by akebia., Method: Retrospective analysis of clinical manifestations, therapy and prognosis was made upon data of 3 newborn infants with renal function lesion induced by akebia., Result: Three infants who were fed with Chinese herbal medicines containing akebia trifoliate suffered from acute renal failure, renal glomerular and tubular injury, with symptoms of vomiting, diarrhea, and oliguria. Laboratory tests manifested hyperpotassemia, hyponatremia, elevation of serum creatinine and urea nitrogen, and metabolic acidosis. Renal glomerular lesion was mild, presented with proteinuria and increased serum β(2) microglobin. Renal dysfunction was manifested with alkaline urine, glucosuria, positiveness of urine glucose, ketone and aminoaciduria, and increased urine β(2) microglobin excretion. After symptomatic treatment for 3 to 4 weeks, the renal function of these infants recovered. Proteinuria, aminoaciduria and glucosuria turned negative within 5 to 8 months, 3 months to 1 year, and 9 months to 3 years, respectively. Urine pH decreased to 7.0 after 5.0 - 5.5 years. All cases took citric acid mixtures for 5.5 to 6 years. A 12-years follow-up demonstrated that serum creatinine of 3 cases were within normal range during the first 11 years of life, however recent follow-up showed increased serum creatinine of case 1 and case 2, except for serum creatinine of case 3 remained normal. The estimated glomerular filtration rate (eGFR) of all the 3 cases decreased. Among which, eGFR of case 1 and case 2 were lower than 90 [ml/(min·1.73 m(2))], and decreased 1.1 [ml/(min·1.73 m(2))] and 0.6 [ml/(min·1.73 m(2))] per year during recent six years, respectively. No obvious decrease of eGFR was observed in case 3. Blood gas analysis and urine routine were normal, yet blood and urine β(2) microglobin excretion were still high. Urinary N-acetyl-β-D-glucosaminidase increased again after having returned to normal., Conclusion: Newborn aristolochic acid nephropathy induced by akebia might induce acute renal failure and renal tubules injury. Renal function could recover after symptomatic treatment in short-term. Nevertheless, glomerular filtration rate presents a slow descending tendency and renal tubules lesion lasted for many years, which requires a long-term follow-up.

Objective: To explore the effect of aggressive nutritional support in early life on growth of preterm infants during hospitalization., Method: Two retrospective cohorts of preterm infants were compared; 81 infants of group A (born between January 1, 2005 and June 30, 2006) and 79 infants of group B (June 1, 2009 and November 30, 2010) with gestational age above 28 weeks and birth weight between 1000 g and 2000 g, transfered to NICU of PUMCH within 12 hours after birth, hospitalized for > or = 2 weeks, who were free of major congenital anomalies and survived to discharge were recruited. The comparison of enteral and parenteral nutrition, growth rate, biochemical indices during hospitalization between these both groups were made., Result: Compared to group A, group B was given greater volume of amino acid infusion on the 3(rd) and 7(th) day of life [2.00 (2.00, 2.50) g/kg vs 1.50 (1.50, 2.00) g/kg, 3.00 (2.00, 3.00) g/kg vs 2.00 (1.80, 2.60) g/kg, all P < 0.001], and Consumed more milk and total energy intake on the 3rd day of life [9.41(2.66, 18.74) ml/kg vs 14.47 (4.23, 30.77) ml/kg, P < 0.05, (64.87 ± 16.04) kcal/kg vs (55.62 ± 17.68) kcal/kg, P = 0.001]. Total energy intakes after a week of life were similar between the two groups. More infants received human milk fortifier in group B (62.8% vs 14.3%, P = 0.001). After stratification according to weight, both very low birth weight infants and infants with birth weight between 1500 g and 2000 g in group B grew more rapidly (P < 0.001). The percentage of growth retardation was increased after hospitalization in group A (65.4% vs 40.7%, P < 0.05), there were no statistically significant differences in group B. The mean Z scores at birth were comparable. The mean Z scores by discharge were higher in group B (-1.24 vs -1.54, P < 0.05). Serum albumin, prealbumin and urea values were similar in both groups at birth, but higher in group B after two weeks of life (P < 0.001). Before discharge, Serum albumin, prealbumin, and urea values in group B was higher (P < 0.001)., Conclusion: Improvements in nutritional practices in early life of preterm infants effectively enhanced the growth and improved the nutritional status of preterm infants during hospitalization.

Objective: To review the clinical data of enteral feeding of extremely low birth weight infants (ELBWI), and analyze the influencing factors., Method: From Jan. 2000 to Jan. 2010, data of 31 ELBWI from Peking Union Medical College Hospital were retrospectively collected. ELBWI were assigned to different groups according to the time achieving full enteral feeding, comparison was done between two groups for enteral feeding., Result: Twenty-four infants were analyzed, their mean gestational age was (29.0 ± 1.8) weeks (26.14 - 34.43 weeks), birth weight (882 ± 67) g (730 - 970 g), there were 11 infants in group A, whose time for achieving full enteral feeding was (27 ± 6)days, there were 13 infants in group B, whose time achieving full enteral feeding was (46 ± 10)days. The ratio of asphyxia (18.2% vs. 61.5%, P = 0.047), duration of umbilical vein catheterization longer than 10 days (18.2% vs. 61.5%, P = 0.047), and duration of mechanical ventilation longer than 14 days (27.3% vs. 76.9%, P = 0.038) in group A was higher than in group B. The milk volume on the 21st and 28th day in group A was much more than that in group B [(88.9 ± 35.4) ml vs. (37.4 ± 34.9) ml, P = 0.002; (121.1 ± 37.4) ml vs. (53.2 ± 33.1) ml, P = 0.000]. There were no significant differences between the two groups in gestational age, birth weight, patent ductus arterious, erythrocytosis, dysglycemia, sepsis, the time to begin enteral feeding, the beginning milk volume, the adding milk volume in the 1st, 2nd week, and the milk volume on the 3rd, 7th, 14th day., Conclusion: Asphyxia, duration of umbilical vein catheterization, and duration of mechanical ventilation are likely to influence the enteral feeding of ELBWI, ELBWI with successful enteral feeding could show good tolerance in the 3rd week. But individual program should be made for enteral feeding of ELBWI, because enteral feeding could be influenced by multiple factors.

Objective: To explore the relationship between WT1-induced T-cell subsets and graft-versus-host disease (GVHD) after nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST)., Methods: Peripheral blood mononucleated cells (PBMCs) from 19 patients who expressed WT1 and developed GVHD after NST were simulated by WT1126-134 peptide in vitro, and proportions of WT1-induced-T-cell subsets (Tc1, Tc2, Th1, Th2 cells) before and after transplant were detected by intracellular cytokine staining (ICCS) assay. WT1-specific CD8(+) CTLs of 14 patients with HLA-A*0201 were detected by HLA-A*0201/WT1 pentamer., Results: (1) 17 of 19 patients developed GVHD, among whom proportions of Tc1 and Th1 cells, achieved peak value in 16 patients at occurrence of GVHD (P = 0.039); (2) The peak proportions of Tc1 and Th1 cells in patients with aGVHD above grade II were higher than those with grade I, but being no statistical difference (P = 0.900 and P = 0.140, respectively); (3) The peak proportion of Th1 cells (P = 0.004), but not Tc1 cells (P = 0.060) in patients with extensive cGVHD was significantly higher than that in patients with limited one; (4) Proportions of Tc1, Th1 and WT1(+)CD8(+)CTL in patients without GVHD were similar to those in patients with Grade I aGVHD, but lower than those in aGVHD above grade II., Conclusion: GVHD promotes the generation of WT1-induced GVL effect, and the intensity of the latter maybe correlated with the intensity of GVHD, especially cGVHD. Th1 cells play a more important role in the enhancement of WT1-induced GVL effect in extensive cGVHD patient than in limited cGVHD patients.

Objectives: To understand the value of measuring neonatal cerebral regional oxygen saturation (rSO2) using near infrared spectroscopy (NIRS) in assessing cerebral oxygenation, to establish the normal range of neonatal cerebral rSO2 and to collect data of the changes of cerebral rSO2 under certain disease status., Methods: Nine large hospitals participated in the multicenter randomized clinical trial from Jan 2007 to Apr 2008. Using the NIRS human tissue oximeter (TSAH-100) independently developed in China, the cerebral rSO2 of 223 normal full-term and 95 otherwise healthy preterm neonates without any special disease, was detected at 1, 2 and 3 days after birth, respectively. The cerebral rSO2 of 102 neonates with diseases which may affect the cerebral oxygenation, was also detected during the severe phases. The pulse oxygen saturation (SpO2) measured at the finger tip, and also the arterial oxygen saturation (SaO2) measured by blood gas analysis, which could indicate the oxygen supply of the whole body, were obtained simultaneously. The correlations among cerebral rSO2, pulse SpO2 and arterial SaO2 were analyzed., Results: (1) The cerebral rSO2 of the normal full-term neonates was (62+/-2)%. Cerebral hypoxia was defined as rSO2 lower than 58%. The cerebral rSO2 of the normal full-terms was steady at 1, 2 and 3 days after birth respectively, without any significant differences among them (F=0.610, P>0.05). The cerebral rSO2 of the neonates with diseases was (55+/-7)%, which was significantly lower than that of the normal full-term neonates (t=15.492, P<0.05). (2) The cerebral rSO2 was positively correlated with the SpO2 (r=0.74, P<0.01) and the SaO2 (r=0.71, P<0.01). (3) Under some special diseases, the changes of cerebral rSO2 was asynchronous with those of the SpO2: (1) For 18 cases under severe cerebral damages or under relatively low hemoglobin concentration, the cerebral rSO2 was significantly low (50%-58%), but the SpO2 was still normal (above 90%). (2) During the recovery of some critically ill neonates, the increase of cerebral rSO2 was lagged as compared with that of pulse SpO2. Especially, during the severe phases of 6 cases with multi-organ failure, the SpO2 and the cerebral rSO2 were both significantly low (55%-80% for SpO2, and 44%-50% for cerebral rSO2); when the diseases were alleviated, although the SpO2 recovered to above 85%, the cerebral rSO2 was still significantly low (around 50%). (3) In 3 cases, during the severe phases of serious hypoxic-ischemic encephalopathy (HIE), the cerebral rSO2 significantly increased to 70%-72%, which was significantly higher than the normal value (62%)., Conclusions: The range of cerebral rSO2 of the normal full-term neonates was (62+/-2)%. Cerebral oxygenation can be externally indicated by the rSO2 noninvasively and continuously measured by NIRS, which was positively correlated with traditional pulse SpO2 and arterial SaO2. In some special diseases, the rSO2 measured by NIRS can be helpful for clinical diagnoses and treatments.

Objective: Extrauterine growth restriction in preterm infants secondary to suboptimal nutrition is a major problem in neonatal intensive care units (NICUs). This study was designed to investigate the nutritional support and growth of premature infants who were discharged from 10 tertiary NICUs in different areas in China and evaluate the effects of high risk factors on their growth., Methods: Data of 1000 premature infants (100 infants from each hospital) were retrospectively collected, the data included their gestational age, the growth parameters at birth, complications, enteral and parenteral nutritional support strategies, the growth parameters at discharge and length of hospital stay from Jan. 1, 2005 to Jun. 30, 2006. The growth parameters, including body weight, length and head circumference, were evaluated according to growth curve of newborns in China with their gestational age at birth and corrected gestational age on discharge. Growth retardation was defined as less than the 10th percentile of the expected value. The risk factors which might result in growth retardation of premature infants were assessed with logistic regression. P < 0.05 was considered as significant., Results: Of the 1000 premature infants enrolled in this study, the data of 974 premature infants were finally eligible. The median gestational age of the 974 premature infants was 32.6 (31.0-34.1) weeks and median birth weight was 1732.2 (1447.9-2030.3) g. Three hundred and seventy-eight premature infants were born at < 32 weeks of gestational age and the body weight of 285 premature infants was < 1500 g at birth. The median time for initial enteral feeding was 2.0 (1, 3) days of life, 77.0% of the premature infants were fed with formulas for low birth weight, and 13.6% were fed with human milk mixed with the formulas for low birth weight. For parenteral nutrition, amino acid solutions were administered in 87.3% of premature infants and median time to begin was 2.5 (2, 3) days of life, median duration of administration was 11 (6, 17) days. Lipid emulsions were supplied in 56.9% of premature infants and median time to begin was 3 (2, 5) days of life, median duration of administration was 12 (7, 18) days. During hospital stay, 74.1% of the premature infants achieved recommended diet indexes of 120 kcal/(kg.d) (including both enteral and parenteral intakes) and mean time for achieving was (16.3 +/- 9.4) days of life, 84.1% of the premature infants reached enteral feeding of 100 kcal/(kg x d) and the mean time to achieve was (17.0 +/- 9.4) days of life. The lower the gestational age of premature infants was, the longer the time for achieving these goals was. Mean loss of weight was 7.54% +/- 4.7% of birth weight and the day for regaining to birth weight was (10.92 +/- 5.10) days. The lower the gestational age at birth, the more the loss of weight, and the longer the time for regaining to birth weight. Mean growth velocity after regaining to birth weight during hospital stay was (13.4 +/- 6.0) g/(kg x d). Mean length of hospital stay was (26.4 +/- 12.9) days. Of the 696 singletons, 60.0%, 58.9% and 29.5% of the infants had growth retardation by weight, length and head circumference respectively on discharge, while the morbidity increased by 32.7%, 30.9% and 10.2%, respectively, compared with those at birth., Conclusions: Morbidity of growth retardation was high among premature infants at birth by weight, length and head circumference. Such growth retardation was further worsened before discharge. Birth weight below the 10th percentile of expected value, later introduction of enteral feeding and lower growth velocity during hospital stay were risk factors for postnatal growth retardation of premature infants. More aggressive nutritional support strategy needs to be considered for improving the nutritional status and development of premature infants in China.

Objective: To analyze the expression of midkine (MK) gene in acute leukemia patients, and explore the relationship between the gene and leukemia., Methods: The MK gene expression levels were detected by real-time quantitative RT-PCR (RQ-RT-PCR) in bone marrow (BM) of 181 acute leukemia (AL) patients and 31 normal controls., Results: MK gene was expressed in all AL patients, normal controls and AL patients in complete remission (CR). Compared with that in control group and CR group, MK gene expression was significantly increased in AL patients (P < 0.01 and P < 0.05, respectively). No statistical difference was found between CR group and control group. The expression of MK showed a notable increase in all B-ALL subtypes (including pro-B-ALL, common-B-ALL and pre-B-ALL) as well as in adult and childhood B-ALL patients (P < 0.01). Moreover, the gene expression in B-ALL was also significantly higher than that in TALL, HAL and FAB subtypes of AML (P < 0.01). In addition, M2 patients showed significantly increased in MK expression compared with that in normal controls (P < 0.01) and in other FAB subtypes of AML (P < 0.05). Median MK expression level in M3 patients was also significantly higher than that in normal controls (P < 0.05), but there was no statistical difference between M3 and other AL subtypes excepting for M2 and B-ALL. MK expression in CD34 positive patients was significantly higher than that in CD34 negative ones (P < 0.01) and within M2 patients, MK expression was higher in patients with t (8 ;21) than in those without the translocation (P < 0.05)., Conclusion: MK gene expression is increased with different levels in B-ALL, M2 and M3 patients, which provides novel insights into the leukemogenesis of acute leukemia.

Objective: To study the source of noise in level III NICU in Beijing region, evaluate preliminary intervention measures, and improve the NICU environment by reducing the noise., Method: Noise measurements were performed in level III NICU of three hospitals (A, B and C) in Beijing region by dosimeter (B&K 2231, Denmark), during loud hours and quiet hours. In addition, the loud hours were divided into shift time, nursing time and operating time. "Quiet hours" represents the intervals among shift, nursing and operating time. The noise inside/outside incubator was recorded, measures to reduce the noise, including putting plastic foam in incubator, covering sheet and blanket outside incubator were taken, and an educational program was implemented for the staff to decrease noise in the NICU environment., Results: Among the three hospitals, the average noise of was (62.60 +/- 2.33) dB during the loud time, and (55.80 +/- 2.61) dB during the quiet time, with a difference of 7 dB (P < 0.05). There was a significant decrease of 2.7 - 3.3 dB during shift time with the averages of A hospital (62.3 +/- 1.5) dB, B hospital (65.10 +/- 2.44) dB and C hospital (61.80 +/- 1.91) dB (F = 9.57, P < 0.05 and P < 0.01), separately. There was a significant decrease of 3 dB during nursing time with the averages of A hospital (62.0 +/- 2.4) dB, B hospital (64.90 +/- 1.06) dB (P < 0.01), respectively, and 2.5 - 3.0 dB during treatment time with the averages of A hospital (60.7 +/- 2.2) dB, B hospital (63.30 +/- 1.19) dB (P < 0.05), separately. After educating the staff in hospital A, there was a significant decrease of 4.7 dB from (61.70 +/- 2.12) dB to (56.90 +/- 2.49) dB in the loud time (P < 0.01), no significant difference during quiet time from (55.0 +/- 1.7) dB to (53.90 +/- 0.88) dB (P > 0.05). There was a significant decrease of 10 dB (P < 0.01) between the averages of inside of incubator (58.60 +/- 3.43) dB and outside of incubator (67.10 +/- 1.87) dB; After installing foam material inside incubator with the average of (56.20 +/- 1.83) dB, there was a significant decrease of 2.8 dB (P < 0.01); covering sheet (in front and back) with the averages of (57.00 +/- 1.47) dB and (55.3 +/- 1.3) dB, respectively, and single or double blanket outside incubator (in the front and the back) noise value (54.50 +/- 1.33) dB, (54.10 +/- 1.15) dB and (54.70 +/- 0.63) dB and (54.10 +/- 1.14) dB, separately, there was a decrease of 1 - 4 dB (P < 0.05 and P < 0.01)., Conclusion: The noise in level III NICU in Beijing region is much higher than that allowed by regulations in Europe and the USA. Staff behavior and the acoustical characteristics of the facility determine the level of noise; herein to staff behavior is the main cause. The level of noise can be lowered considerably by simply making the staff aware of the problem. At the same time, covering incubator and installing plastic foam material also significantly decreased the noise, the methods are simple, feasible and should be applied constantly.

Objective: To investigate pig7 expression level in acute leukemia (AL) and its clinical significance and explore the possible mechanisms for pig7 silence in terms of methylation control., Methods: Expression levels of pig7 mRNA in bone marrow samples from 138 patients with de novo AL and 21 normal controls and in 6 leukemic cell lines were detected by quantitative real-time reverse transcription PCR (RT-PCR). Differentiation induction effect by all-trans retinoic acid (ATRA) and concomitant change in pig7 expression were also monitored in NB4 cells. Endonuclease analysis was employed to determined the identity of pig7 transcript present in AL samples. Methylation specific PCR (MSP) was used to elucidate if hypermethylation was responsible for pig7 silence in AL., Results: Compared with that in normal control, pig7 expression was markedly decreased (0.62 vs 18.30, median, P < 0.01) in AL patients on progression (at diagnosis, relapse or refractory). No significant difference was observed between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). AL at diagnosis had a higher pig7 level than those with relapsed or refractory disease (1.43 vs 0.16, median, P < 0.05). The complete remission (CR) rate after chemotherapy was found to be significantly correlated with pig7 expression levels (P < 0.05). Differentiated NB4 cells showed an increased level of pig7 expression (from 1.61 +/- 0.72 to 44.75 +/- 3.93, P < 0.01). Only one form of pig7 transcripts i.e., Small integral membrane protein of late endosome (SIMPLE), was detected in AL patients. Hypermethylation of pig7 promoter was identified in K562 and HL-60 cells, in contrast to non-methylation predominant in U937 cells., Conclusion: Aberrant down-regulation of pig7 provides novel insights into leukemogenesis and therapy response prediction in AL.

Objective: Nosocomial infections (NIs) have become a matter of major concern in neonatal intensive care units (NICU). The objectives of this study were to investigate the incidence of nosocomial infections of newborn infants in NICU and to explore the risk factors and strategies of infection control., Methods: The study enrolled 638 hospitalized newborn infants from Apr 2003 to Dec 2004. The clinical data, such as the clinical manifestation, the condition of colonized bacteria, were collected and analyzed by using SPSS software., Result: There were 88 times of nosocomial infections in 74 newborn infants. The overall incidence of nosocomial infections was 11.6%. The mean duration from admission to first episode of NI was 7.98 +/- 4.58 days. The incidence density was 14.9 per 1000 NICU patient-days. Catheter-correlated hematogenous infection rate was 18 per 1000 umbilical or central line-days; the ventilator-associated nosocomial pneumonia rate was 63.3 per 1000 ventilator days. The smaller the gestational age and the lower the birth weight, the higher the incidences of nosocomial infection. The duration of hospitalization was longer in these infected infants than those non-infected infants. Univariate analysis indicated that gestational age < or = 32 W, the parenteral nutrition, birth weight < or = 1500 g and mechanical ventilation, apnea, small for gestational age infant, central venous catheter (P < 0.05) were risk factors for NIs. Multivariate analysis identified 3 independent risk factions: the parenteral nutrition ([OR] = 7.185 [95% CI, 3.399 - 15.188]), birth weight < or = 1500 g ([OR] = 3.310 [95% CI, 1.100 - 9.963]) and mechanical ventilation ([OR] = 2.527 [95% CI, 1.092 - 5.850]). The most common infection was pneumonia (45.4%). The mortality rate of nosocomial infections was 4.1%. Bacterial surveillance was examined by nasopharyngeal and rectal swab culture immediately on hospital admission and then once a week. The incidence rate of NIs was 24.8% in patients whose nasopharyngeal and rectal swab culture indicated bacterial colonization, and 1.9% in patients without bacterial colonization (chi(2) = 79.7, P < 0.001)., Conclusion: It is important to identify the high risk factors for nosocomial infections in newborn infants in NICU. Reducing the duration of the parenteral nutrition and the virulence manipulation as far as possible and getting the message of individual bacterial colonization in NICU may be conducive to decrease of the incidence of nosocomial infections and provide reference for rational clinical drug administration.

Objective: To investigate the therapeutic effect of conditioning regimen containing fludarabine in nonmyeloablative allogeneic peripheral blood stem cells transplantation (NAST) in the treatment of hematological diseases., Methods: Thirty-six patients with acute leukaemia, severe aplastic anaemia, MDS and myelofibrosis received NAST from HLA matched donors' G-CSF mobilized peripheral blood stem cells after nonmyeloabalative conditioning. The conditioning regimen consisted of CTX, Ara-C, CsA, anti-CD(3) antibody or anti-thymocyte globulin and with or without fludarabine. GVHD prophylaxis was performed with cyclosporine combined methotrexate (no MMF group, n = 5) or mycophenolate mofetil (MMF group, n = 31)., Results: All of the treatment was generally well tolerated and all cases achieved engrafted of the donor cells. In fludarabine group, engraftment was observed in 87.5% (14/16) patients with complete donor chimerism, graft failure was 12.5% (2/16) and in no fludarabine group, 80% (16/20) and 20% (4/20), respectively. The incidence of acute GVHD (grade I - IV) was 27.8% (10/36) and chronic GVHD 22.2% (8/36). In fludarabine group, grade I - II aGVHD was 37.5%, in no fludarabine group, 20%. cGVHD was 12.5% in fludarabine group and in no fludarabine group 30%, respectively. Interstitial pneumonia (IP) was observed in 16.7% (6/36) of the patients, being 18.7% (3/16) and 15% (3/20) in fludarabine and no fludarabine group, respectively. Overall survival rate was 80.5% (29/36) with a median follow-up of 13 months., Conclusions: There was no significant difference between fludarabine based (n = 16) and non-fludarabine based conditioning regimen (n = 20) in NAST for the treatment of hematological diseases, regarding for incidence of GVHD, IP, engraftment and survival.

Objective: To explore the significance of nonmyeloablative allogeneic peripheral blood hematopoietic stem cell transplantation in the treatment of hematological diseases., Methods: A nonmyeloablative conditioning regimen consisted of CD(3) monoclonal antibody, cyclosporine A, cyclophosphamide and cytarabine was used for allogeneic stem cell transplantation in 33 patients with hematological diseases. Of them, 11 were acute leukemia (AL) in first complete remission (CR(1)), 4 AL-CR(2) approximately 3, 3 refractory AL, 4 severe aplastic anemia (SAA), 7 chronic myeloid leukemia (CML), 2 myelodysplastic syndrome, 1 each of chronic lymphocytic leukemia (CLL) and myelofibrosis., Results: All 33 patients passed the hematopoietic suppression stage smoothly and achieved engraftment of the donor cells. There were 24 cases of full donor chimerism (13 cases converted from mixed chimerism), 4 mixed chimerism (MC) and 5 developed graft rejection. Of the 33 cases, 7 (21.2%) developed acute GVHD and chronic GVHD, 25 (75.8%) still live and 8 (24.2%) died., Conclusions: Nonmyeloablative allogeneic peripheral blood stem cells transplantation is a safe, less toxic and curative approach for patients with hematological disease.

Objective: The study aimed to investigate the clinical characteristics of enteral feeding in very low birthweight infants (VLBWI), to determine the risk factors associated with feeding intolerance, and to analysis the beneficial factors in order to improve gut motility and maturation., Methods: The study was carried out in 38 VLBWI, birthweight (1,314 +/- 180) g, in the NICU of authors' department. They were divided into feeding tolerance and intolerance groups, and earlier enteral feeding and later groups. Comparison was made between two groups about the associate factors., Results: The incidence of feeding intolerance was 55 per cent. There was a significant difference in two groups about the clinical factors (gestational age, birth weight, the age of the first feeding, time of full enteral feeding and the hospitalized days). The significant risk factors associated with feeding intolerance were the smaller gestational age, umbilical catheterization, theophylline therapy, and delay of the time when the first feed was commenced., Conclusion: If vital signs are stable, trophic feeding in VLBWI should be commenced as soon as possible during the first 6 days of life. Early trophic feeding, slowly increase the feeding volume, carefully fast, and moving bowel were suggested and will improve feeding tolerance and gastrointestinal maturation.