OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome

Objective To investigate the effects of DL-3-n-Butylphthalide(NBP)on proliferation and apoptosis of 1-methyl-4-phenyl-pyridinium (MPP +)-induced SH-SY5Y cells, and mechanisms via mixed lineage kinase 3 (MLK3) signaling pathway. Methods The SH-SY5Y cells were divided into control group,MPP+group,NBP group and URMC-099 group,that cultured normally,with 1 mmol/L MPP+for 24 hours,with 10μmol/L NBP for 3 hours and then with MPP+for 24 hours,and with 200 nmol/L MLK3 inhibitor URMC-099 for 3 hours and then with MPP+for 24 hours,respectively.The morphology of SH-SY5Y cells was observed under inverted phase contrast mi-croscope and the survival rate was measured with 3-(4,5-Cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays.The apoptosis was quantified under flow cytometry with Annexin V/PI fluorescence staining,and the nuclear morphology was observed with Hoechst 33342 staining.The expression of phosphorylated protein of MLK3(p-MLK3),c-Jun N-terminal kinase(p-JNK),extra cellular regulated protein ki-nases(p-ERK1/2)were detected with Western blotting.Results Compared with the control group,the survival rate reduced and apoptosis in-creased in MPP+group(P<0.05),with the increase of p-MLK3 and p-JNK and decrease of p-ERK1/2 d(P<0.05).Compared with MPP+group,the survival rate increased and apoptosis reduced in both NBP and URMC-099 groups(P<0.05),with the decrease of p-MLK3 and p-JNK and increase of p-ERK1/2(P<0.05).Conclusion NBP can decrease the apoptosis and promote the proliferation of SH-SY5Y cells in-duced by MPP+,which may be associated with inhibiting MLK3 signaling pathway,and regulating the downstream p-JNK and p-ERK1/2.

BACKGROUNDAcute kidney injury (AKI) has been recognized as a major healthcare problem affecting millions of patients worldwide. However, epidemiologic data concerning AKI in China are still lacking. The objectives of this study were to characterize AKI defined by RIFLE criteria, assess the association with hospital mortality, and evaluate the impact of AKI in the context of other risk factors.

METHODSThis prospective multicenter observational study enrolled 3,063 consecutive patients from 1 July 2009 to 31 August 2009 in 22 ICUs across mainland China. We excluded patients who were admitted for less than 24 hours (n = 1623), younger than 18 years (n = 127), receiving chronic hemodialysis (n = 29), receiving renal transplantation (n = 1) and unknown reasons (n = 28). There were 1255 patients in the final analysis. AKI was diagnosed and classified according to RIFLE criteria.

RESULTSThere were 396 patients (31.6%) who had AKI, with RIFLE maximum class R, I, and F in 126 (10.0%), 91 (7.3%), and 179 (14.3%) patients, respectively. Renal function deteriorated in 206 patients (16.4%). In comparison with non AKI patients, patients in the risk class on ICU admission were more likely to progress to the injury class (odds ratio (OR) 3.564, 95% confidence interval (CI) 1.706 - 7.443, P = 0.001], while patients in the risk class (OR 5.215, 95% CI 2.798-9.719, P < 0.001) and injury class (OR 13.316, 95% CI 7.507-23.622, P < 0.001) had a significantly higher probability of deteriorating into failure class. The adjusted hazard ratios for 90-day mortality were 1.884 for the risk group, 3.401 for the injury group, and 5.306 for the failure group.

CONCLUSIONSThe prevalence of AKI was high among critically ill patients in Chinese ICUs. In comparison with non-AKI patients, patients with RIFLE class R or class I on ICU admission were more susceptibility to progression to class I or class F. The RIFLE criteria were robust and correlated well with clinical deterioration and mortality.

Acute Kidney Injury ; epidemiology ; etiology ; pathology ; Adult ; Aged ; China ; epidemiology ; Female ; Humans ; Intensive Care Units ; statistics & numerical data ; Male ; Middle Aged ; Prospective Studies ; Risk Factors

OBJECTIVETo explore the effect of ricin temperature response gel on breast cancer and its regulatory effect on immune function in rats.

METHODSRicin was purified by chromatography and identified by immunoblotting. The rat subcutaneously transplanted breast cancer model was established. Forty model rats with a tumor diameter of about 3.0 cm were subjected to the study. They were randomized into four groups equally: the model group and three treated groups (blank gel, ricin, ricin-gel) were administered with blank gel, ricin, and ricin temperature response gel via percutaneous intratumor injection, respectively. The tumor was isolated 10 days later for the estimation of tumor inhibition rate (TIR) by weighing, pathologic examination, and detection of tumor apoptosis-associated genes bcl-2 and bax with semiquantitative RT-PCR. Also, peripheral blood was obtained to test T-lymphocyte subsets, the killing function of lymphocytes, and the contents of tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2). The outcomes were compared between groups.

RESULTSThe TIR in the ricin-gel group was 61.8%, with the pathologic examination showing extensive tumor tissue necrosis. Compared with the model group, after ricin temperature response gel treatment, bcl-2 expression was down-regulated, bax expression was up-regulated, CD4+ lymphocytes and CD4+/CD8+ ratio in peripheral blood were increased, the killing function of lymphocytes was enhanced, and the contents of TNF-α and IL-2 were elevated (P < 0.05 or P < 0.01).

CONCLUSIONIntratumor injection of ricin temperature-responsive gel showed significant antitumor effect on breast cancer and could enhance the immune function in the tumor-bearing rat.

Animals ; Antineoplastic Agents ; administration & dosage ; Apoptosis ; drug effects ; CD4-CD8 Ratio ; Disease Models, Animal ; Female ; Gels ; therapeutic use ; Immunohistochemistry ; Immunomodulation ; drug effects ; Injections, Intralesional ; Interleukin-2 ; immunology ; metabolism ; Mammary Neoplasms, Experimental ; drug therapy ; immunology ; pathology ; Random Allocation ; Rats ; Rats, Wistar ; Ricin ; administration & dosage ; Sensitivity and Specificity ; Temperature ; Tumor Necrosis Factor-alpha ; immunology ; metabolism

Objective To investigate the role of dual oxidase-1 (DUOX-1) inducing airway hyperresponsiveness in human bronchial epithelium.Methods The human bronchial epithelial cells were divided into several groups:control group,tumor necrosis factor-α (TNF-α) group,methyl-β-cyclodextrin (M-β-CD) + TNF-α group,desipramine (DES) + TNF-α group,diphenylene iodonium (DPI) + TNF-α group and apocynin (APO) + TNF-α group.Fractionation was performed by sucrose gradient centrifugation and the protein DUOX-1 was measured by western blotting.The lipid raft clusters and its colocalization with DUOX-1 were confocal analysed.The intracellular reactive oxygen species (ROS) accumulation was measured by fluorescence of reactive oxygen probe of intracellular measurement.Sigmastat 3.02 software was used to analyze the data.Results (1) Detection of ROS,control group:1.00± 0.00 ; TNF-α group:1.95± 0.16 ; M-β-CD + TNF-α group:0.91 ± 0.16 ; DES + TNF-α group:1.49± 0.20 ; DPI + TNF-α group:1.03 ± 0.16 ; APO + TNF-α group:1.47 ± 0.26.The difference was statistically significant (F =3.83,P ＜0.05).(2) Extracts in rafts to lipid rafts region represents the ratio of total protein,protein content DUOX-1each group,control group:0.21 ± 0.02; TNF-α group:0.49 ± 0.04; M-β-CD + TNF-α group:0.08 ±0.02 ; DES + TNF-α group:0.09 ± 0.03 ; the difference was statistically significant (F =3.96,P ＜ 0.05).(3) DUOX-1 protein fluorescence values,control group:1.72 ± 0.21; TNF-α group:8.11 ± 1.23; M-β-CD + TNF-α group:1.51 ± 0.32; DES + TNF-α group:1.43 ± 0.11 ; the difference was statistically significant (F =4.87,P ＜ 0.05).(4) DUOX-1 gene detection,control group:1.00 ± 0.00 ScrRNA +TNF-α group:1.75 ± 0.04; DUOX-1siRNA + TNF-αgroup:1.15 ± 0.02; the difference was statistically significant (F =4.19,P ＜ 0.05).Conclusion TNF-α can induce DUOX-1 expression increasing in lipid raft,then the DUOX-1 can be activated to increase reactive oxygen species level; acidic sphingomyelinase inhibitor desipramine can inhibit this process,the results disclose that the process will depend on the ceramide of lipid raft.

OBJECTIVETo investigate the effect of granulocyte colony stimulating factor (G-CSF) on myeloid-derived suppressor cells (MDSCs) in the bone marrow and peripheral blood, and explore the relationship between MDSC and graft-versus-host disease (GVHD).

METHODSBone marrow, peripheral blood and peripheral blood stem cells were obtained from 12 healthy hemopoietic stem cell donors before and on day 5 after G-CSF mobilization. Flow cytometry was employed to examine the number of MDSC, and the relationship between MDSC number and the incidence of GVHD was analyzed.

RESULTSIn normal physiological conditions, MDSC could be detected in the peripheral blood and bone marrow with a cell percentages of (1.35±0.35)% and (2.44±1.11)%, respectively, showing a significantly higher cell percentage in the bone marrow (P=0.015). On the 5th day after G-CSF mobilization, the percentage of MDSCs increased to (4.01±1.82)% in the peripheral blood and to (4.38±2.19)% in the bone marrow, showing no significant difference between them (P=0.083). The mobilization caused a significant increase in the number of MDSCs in the peripheral blood (P=0.047) but not in the bone marrow (P=0.761). The number of MDSCs in the collected samples showed a significant inverse correlation to the incidence of GVHD (P=0.048).

CONCLUSIONSMDSCs are present in the peripheral blood and bone marrow of healthy donors, with a greater number in the bone marrow. G-CSF can mobilize the MDSCs from the bone marrow to the peripheral blood to increase number of MDSCs in the peripheral blood, which may contribute to a lowered incidence of GVHD in hematopoietic stem cell transplantation (HSCT).

Adolescent ; Adult ; Bone Marrow Cells ; cytology ; Female ; Graft vs Host Disease ; prevention & control ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Hematopoietic Stem Cell Mobilization ; methods ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; T-Lymphocytes ; cytology ; drug effects ; metabolism ; Young Adult

OBJECTIVETo detect the expression of membrane-bound HLA-G (mHLA-G) and serum HLA-G (sHLA-G) in acute leukemia patients and investigate the correlation between HLA-G expression and the occurrence and development of acute leukemia.

METHODSEnzyme-linked immunosorbent assay and flow cytometry were used to detect the expression levels of sHLA-G and mHLA-G in 40 newly diagnosed leukemia cases, 10 refractory and relapsed leukemia cases, and 30 leukemia cases receiving chemotherapy. Ten normal individuals served as the normal control group.

RESULTSThe mean serum level of sHLA-G in normal individuals was 5.87±2.07 ng/ml, as compared to 10.05±6.58 ng/ml in newly diagnosed leukemia patients and 12.32±5.85 ng/ml in refractory and relapsed cases. The mean level of mHLA-G in normal individuals, newly diagnosed cases, and refractory and relapsed cases were (0.29±0.20)%, (0.60±0.44)%, and (0.77±0.41)%, respectively. The mean levels of sHLA-G and mHLA-G were significantly higher in the newly diagnosed cases than that in the normal controls (P<0.05), and significantly higher in patients before chemotherapy than in those with complete remission after chemotherapy (P<0.05).

CONCLUSIONHLA-G expression levels might influence the treatment outcomes and can serve as a prognostic factor for acute leukemia.

Acute Disease ; Adolescent ; Adult ; Aged ; Case-Control Studies ; Female ; HLA-G Antigens ; blood ; metabolism ; Humans ; Leukemia ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis ; Young Adult

OBJECTIVETo investigate the expression of T cell receptor (TCR) Vgamma genes in patients with graft-versus-host disease (GVHD) after allogenic hematopoietic stem cell transplantation (allo-HSCT).

METHODSThe expression levels of the TCR Vgamma I-III genes in peripheral blood mononuclear cells (PBMNCs) from 18 patients with GVHD following allo-HSCT were determined using real-time fluorescence quantitative PCR, with 12 healthy individuals serving as the normal controls.

RESULTSThe expression level of TCR Vgamma II gene in the PBMNCs from patients with GVHD was significant lower than that in the normal controls. The expression patterns of TCR Vgamma I-III subfamilies also underwent alterations in patients with GVHD, and the expression level of TCR Vgamma II gene was significantly lower than that of TCR Vgamma I gene or TCR Vgamma III gene.

CONCLUSIONThe low expression of TCR Vgamma II subfamily might be related to the pathogenesis of GVHD in patients receiving allo-HSCT.

Adult ; Case-Control Studies ; Female ; Graft vs Host Disease ; genetics ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; Receptors, Antigen, T-Cell, gamma-delta ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Young Adult

OBJECTIVETo evaluate the impact of luteinizing hormone-releasing hormone (LHRH) on the protection of thymic function after allogenic hematopoietic stem cell transplantation (allo-HSCT).

METHODSMurine model of MHC mismatched allogeneic HSCT (C57BL/6-->BALB/c) was established. The severity of acute graft-versus-host-disease (GVHD) was assessed according to a clinical scoring system. The intra-cellular levels of IFN gamma, TNFalpha and IL-1 beta in thymocyte were analyzed by protein array and thymic function by quantification of signal-joint TCR rearrangement excision circles (sjTRECs).

RESULTSAll recipients in group A (allogeneic mice), B (allogeneic LHRH castrated-mice) and C (syngenic mice) achieved hematopoietic reconstitution. White blood cell (WBC) over 1.0 x 10(9)/L in groups A, B and C were on day (11.2 +/- 1.4), day (9.8 +/- 0.6) and day (9.7 +/- 0.7), respectively (P = 0.003, 0.002). The onset of acute GVHD in group B was (14.1 +/- 0.7) d and in group A was (11.4 +/- 1.2) d (P = 0.000). All mice in groups A and B developed acute GVHD. No mice occurred aGVHD in group C. The average scores of acute GVHD in groups A and B were (9.1 +/- 0.7) and (5.1 +/- 1.0), respectively (P = 0.000). The levels of IFN gamma, TNFalpha and IL-1 beta in control group were (2.3 +/- 2.5) ng/ml, (1.7 +/- 1.1) pg/ml and (1.8 +/- 1.2) pg/ml, respectively. The IFN gamma levels in groups A, B and C were (10.5 +/- 2.1) ng/ml, (6.7 +/- 2.1) ng/ml and (5.2 +/- 3.3) ng/ml, TNFalpha levels were (7.0 +/- 2.6) pg/ml, (4.3 +/- 0.8) pg/ml and (3.0 +/- 1.8) pg/ml, and IL-1 beta levels were (24.9 +/- 9.0) pg/ml, (17.4 +/- 3.9) pg/ml and (10.8 +/- 3.1) pg/ml, respectively. There were significant differences in the levels of cytokines between group A and the control group (P = 0.000, 0.000, 0.000). The levels of cytokines in group B were significantly higher than those in control group (P = 0.000, 0.003, 0.000). The levels of IFN gamma and IL-beta in group C were significantly higher than those of in control group (P = 0.015, 0.013), and so did in group A than in group B (P = 0.002, 0.002, 0.004), and in group A than in group C (P = 0.000, 0.000, 0.000). The analysis of linear regression showed that the average levels of IFN gamma and TNFalpha paralleled with aGVHD scores (r(2) = 0.359, P = 0.045; r(2) = 0.228, P = 0.019). The average sjTRECs copies/1000 PBMNCs were (39.4 +/- 44.7) in the control group and (12.3 +/- 13.0), (58.0 +/- 71.8) and (19.6 +/- 14.6) in groups A, B and C, respectively. There was no significant difference in the multiple comparisons of peripheral blood levels of sjTRECs among these four groups (P = 0.468).

CONCLUSIONIFN gamma, TNFalpha and IL-1 beta might be involved in the damage to the thymus by acute GVHD. Sex steroid inhibitor can not only reduce the severity of thymic damage after allo-HSCT, but also reduce the severity of aGVHD and the mechanism might be associated with the reduction of intra-cellular levels of IFN gamma in thymocyte.

Animals ; Castration ; methods ; Female ; Gonadotropin-Releasing Hormone ; therapeutic use ; Graft vs Host Disease ; pathology ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Interferon-gamma ; metabolism ; Interleukin-1beta ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Thymus Gland ; immunology ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism