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Objective To investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine growth retardation (IUGR) rats by giving the IUGR new born rats different protein level diet. Methods IUGR rat model was built by starvation of pregnant female rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4 groups: normal control group (C group); IUGR control group(S group), IUGR low-protein diet group (SL group), and IUGR high-protein diet group (SH group). Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT), and disaccharidase at the 4th week. Results (1) The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA were significantly higher than those of normal control group and IUGR control group. The intestinal weight and length, and the activities of lactase and saccharase, of the SH group also reached the normal control group level. (2) The SL group kept on small size, the serum IGF-1, IGFBP3, and most of intestinal histological indexes were all significantly lower than other groups. (3) IGF-1, IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight and length. Conclusions The serum IGF1 was a sensitive index to the catch-up growth. The early nutritional intervention of high-protein diet after birth is helpful for the catch-up growth of IUGR through promoting the intestinal development and the absorption of nutrition. [ABSTRACT FROM AUTHOR]

Background: Pediatric acute myeloid leukemia (AML) has poor prognosis and high rate of relapse and mortality, and exploration of new treatment options is still critically needed., Objectives: To summarize the outcome of our new treatment strategies for pediatric AML, which is characterized by dual induction and acute lymphoblastic leukemia (ALL) elements consolidation., Design: Retrospective, single-arm study., Methods: From July 2012 to December 2019, an intensive chemotherapy protocol was used for newly diagnosed children with AML, which contains dual induction, three courses of consolidations based on high-dose cytarabine, and two courses of consolidations composed of high-dose methotrexate, vincristine, asparaginase, and mercaptopurine (ALL-like elements). Blasts were monitored by bone marrow smears at intervals, and two lumbar punctures were performed during chemotherapy. We retrospectively analyzed the efficacy and safety of this study. The last follow-up was on 26 May 2023., Results: A total of 70 pediatric AMLs were included. The median age at diagnosis was 6.7 (0.5-16.0) years. The median initial WBC count was 23.74 × 10 9 /L, 11 of whom ⩾100 × 10 9 /L. After dual induction, there were 62 cases of complete remission (CR), 5 cases of partial remission, and 3 cases of nonremission. The CR rate was 88.57%. The median follow-up time was 5.8 (0.2-9.4) years, the 5-year overall survival was 78.2% ± 5%, the event-free survival (EFS) was 71.2% ± 5.6%, and the cumulative recurrence rate was 27.75%. The 5-year EFS of patients with initial WBC < 100 × 10 9 /L ( n  = 59) and ⩾100 × 10 9 /L ( n  = 11) were 76.4% ± 5.7% and 45.5% ± 15% ( p  = 0.013), respectively. A total of 650 hospital infections occurred. The main causes of infection were respiratory tract infection (26.92%), septicemia (18.46%), stomatitis (11.85%), and skin and soft-tissue infection (10.46%)., Conclusion: This intensive treatment protocol with dual induction and ALL-like elements is effective and safe for childhood AML. Initial WBC ⩾ 100 × 10 9 /L was the only independent risk factor in this cohort., Trial Registration: It is a retrospective study, and no registration on ClinicalTrials.gov., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Objective: Recent studies have suggested that there is a close relation between microRNA and acute leukemia (AL). The aim of this study was to investigate and better understand the classification and diagnosis of AL as well as pathogenesis and prognosis of this disease., Methods: A total of 93 children with AL and and 12 cases of idiopathic thrombocytopenic purpura (as control group) were enrolled in this study. Microarray chip analysis of their bone marrow samples was conducted to evaluate the microRNA profiles. Quantitative real-time PCR was performed for validating the abnormal expression of microRNA., Results: The microRNA expression profiles were different between acute granulocytic leukemia and acute lymphoblastic leukemia and also between the three subtypes (M1, M2 and M3) of acute granulocytic leukemia according to FAB classification based on leukemic cell differentiation. These three subtypes of leukemia could be identified by unsupervised hierarchical cluster analysis of microRNA expression and had specific up-regulation of miR-335, miR-126 and miR-125b, respectively. However, in the M2 and M3 subtypes with positive AML1-ETO and PML-RARα, respectively, which have a better prognosis, the expressions of miR-126 and miR-125b were significantly higher than those with negative AML1-ETO and PML-RARα. Further more, miR-335 and miR-146 were up-regulated in acute granulocytic leukemia observed in this study, which are different from those reported for adult patients., Conclusions: microRNA cascade may serve as new biomarkers for the classification and diagnosis of pediatric AL. It is also suggested that there might be different pathogenesis and prognosis between AL types related to specific expression and regulation of microRNA.

Objective: To observe the ultracytochemical localization of H(+)-adenosine triphosphatase (H(+)-ATPase) in the cell organelles., Methods: The localization of H(+)-ATPase in the cell organelles was observed in the hepatocytes and renal cells of Wistar rats using routine ultracytochemical methods., Results: H(+)-ATPase activities were observed on the lysosomal membrane and nuclear envelope of the hepatocytes and proximal tubule epithelial cells of the nephron in Wistar rats., Conclusion: This finding supports the hypothesis that H(+)-ATPase (V-ATPase) is present on the plasma membrane and in the endomembrane system.

Objective: To explore the role of protein kinase D3 (PKD3) in the regulation of matrix metalloproteinases 7 (MMP-7) expression in prostate cancer cells., Methods: PC-3 cells were either stimulated with 100 nmol/L PMA to activate PKD3 kinase activity, or transiently transfected with PKD3 siRNA, and the relative expression level of MMP-7 mRNA were analyzed by real-time PCR using 2(-delta delta Ct) method. MMP-7 mRNA levels were also analyzed and quantified in HEK293 cells with over-expression of wild-type PKD3, PKD3 knockdown (using PKD3 siRNA), or over-expression of wild-type PKD3 followed by PKD3 knockdown., Results: MMP-7 mRNA expression in PC3 cells was significantly decreased after PMA-induced PKD3 kinase activation. In contrast, PKD3 knockdown by siRNA transfection markedly increased MMP-7 mRNA level (P<0.01). MMP-7 mRNA level in HEK293 cells was significantly decreased by PKD3 over-expression, whereas obviously increased by PKD3 knockdown. Down-regulation of MMP-7 mRNA level in HEK293 induced by PKD3 over-expression was rescued by PKD3 knockdown., Conclusion: PKD3 may contribute to the malignant progression of prostate cancer cells through negative regulation of MMP-7 expression.

Objective: To investigate the role of PKD3 in prostate-specific antigen (PSA) expression regulation in androgen-dependent prostate cancer cells and explore the mechanism., Methods: LNCaP cells containing low level of PKD3 were transfected with pEGFP-C2 or pEGFP-PKD3 plasmid followed by dihydrotestosterone (DHT) treatment, and PSA mRNA level was analyzed by RT-QPCR using 2(-delta delta Ct) method. Wild-type or kinase-dead PKD3 plasmids, human androgen receptor plasmid pSVAR0, pMMTV-luc of AR luciferase reporter and renilla luciferase reporter pRL-SV40 were cotransfected into HEK293 cells, and after treatment with DHT for 24 h, the cells were harvested and AR transcriptional activity were determined by dual-luciferase reporter assay. The subcellular localization of endogenous PKD3 and AR and their colocalization induced by DHT were observed by confocal microscopy., Results: PSA mRNA level triggered by DHT was significantly increased by overexpression of pEGFP-PKD3 in LNCaP cells compared with that in pEGFP-C2 control cells (P<0.001). AR transcription in response to DHT treatment was also significantly up-regulated by wild type PKD3 expression (P<0.001), but partially down-regulated by kinase-dead PKD3 mutant (P<0.01). Endogenous PKD3 and AR in LNCaP cells not only translocated from the cytoplasm to the nucleus, but also colocalized with each other after DHT stimulation., Conclusion: Elevated AR transcriptional activity and enhanced expression of PSA induced by PKD3 in response to DHT treatment suggest that PKD3 contributes to the proliferation and malignant growth of androgen-dependent prostate cancer cells.

Objective: To explore the feasibility of surgical design for mandibular retrusion using three-dimensional software., Methods: Three-dimensional reconstruction was performed by Mimics software based on the preoperative CT data. The model of the maxillofacial region was imported into Rapidform software for measuring the associated parameters and Geomagic software for simulation of osteotomy. The reliability of the virtual operation was validated during the surgery., Results: The model of mandibular retrusion was reconstructed and successfully used to simulate the surgery. The simulation result was applied in subsequent actual surgery and good surgical outcomes were achieved., Conclusion: The three-dimensional software can be used to simulate the surgery for mandibular retrusion and improve the predictability and accuracy of the surgery.

Aim: To investigate the intestine and body development of intrauterine growth retardation (IUGR) rats under early different protein diet and to analyze the correlation between leptin and intestine and body development., Methods: An IUGR rat model was established by food restriction of pregnant female rats. Fifty-six neonatal IUGR rats and 24 neonatal normal rats were randomly divided into normal control group (C group), IUGR model group (SC group), low protein diet IUGR group (SL group), and high protein diet IUGR group (SH group). Eight rats were killed per group at wk 0, 4, and 12. Serum leptin, body weight (BW), body length (BL), intestinal weight (IW), intestinal length (IL), and intestinal disaccharidase (including lactase, maltase, and saccharase) were detected., Results: BW (4.50+/-0.41 g), BL (5.96+/-0.40 cm), IW (0.05+/-0.01 g), and IL (15.9+/-2.8 cm) in neonatal IUGR rats were much lower than those in C group (6.01+/-0.55 g, 6.26+/-0.44 cm, 0.10+/-0.02 g, 21.8+/-2.7 cm, P<0.05), while intestinal lactase and maltase activities were higher than those in C group. SH group showed the fastest catch up growth and their BW, BL, IW, and IL reached the C group level at wk 4. SC group showed relatively slower catch up growth than SH group, and their BW, BL, IW did not reach the C group level at wk 4. SL group did not show intestine and body catch up growth. Intestinal maltase (344+/-33 micromol/(min.g)) and saccharase activities (138+/-32 micromol/(min.g)) in SL group were both markedly lower than those in C group (751+/-102, 258+/-27 micromol/(min.g), P<0.05). There were no significant differences in lactase activities at wk 4 and disaccharidase activities at wk 12 among all groups (P>0.05). The leptin level in SL group (0.58+/-0.12 ng/mL) was the highest in all groups, and much lower in SH group (0.21+/-0.03 ng/mL) than that in any other IUGR groups at wk 4 (P<0.05). Leptin was negatively related to BW (r = -0.556, P = 0.001), IW (r = -0.692, P = 0.001) and IL (r = -0.738, P = 0.000) at wk 4, while no correlation was found at wk 12., Conclusion: High protein diet is a reasonable early nutritional mode to IUGR rats in promoting intestine and body catch up growth.

Objective: To observe the selective killing effect of adenovirus (Ad)-mediated double suicide gene driven by kinase domain-containing receptor(KDR) promoter on human colorectal cancer LoVo cells and human umbilical vein endothelial ECV304 cells., Methods: The plasmid pAdEasy-KDR-CDglyTK was transfected into 293 packaging cells for amplification of the infectious Ad and used to infect the KDR-producing cells (ECV304 and LoVo) and the KDR-nonproducing cells (LS174T) respectively. The three cells were treated with the prodrugs 5-flurocytosine (5-FC) and ganciclovir (GCV) at different concentrations after infection. The killing effects of the fusion gene system on the cells were evaluated. The distribution of cell cycle was detected by flow cytometry., Results: The infection rates of the recombinant Ad were similar among the 3 cells, gradually increasing with the increment of multiplicity of infection (MOI) and reaching 100% with the MOI of 200. The LoVo cells and ECV304 cells infected with Ad-KDR-CDglyTK were highly sensitive to both of the prodrugs (P>0.1), whereas the infected LS174T cells failed to exhibit similar sensitivity (P<0.001). The killing effect of CD/TK fusion gene on the target cells was much stronger than that of either suicide gene (P<0.001). The cell cycle of LoVo cells was arrested at G1 phase., Conclusion: The CD/TK fusion gene system driven by KDR promoter can selectively kill KDR-expressing human colorectal cancer LoVo cells and endothelial cells.

Objective: To investigate the association between the expression of turnor necrosis factor alpha (TNF-alpha) mRNA in fat tissue of intrauterine growth retarded (IUGR) rats and insulin resistance, and the long-term effects of early different nutritional diet., Methods: The IUGR rat model was established by food restriction of pregnant rats. A total of 32 newborn IUGR rats were randomly divided into 4 groups: IUGR model (S/N) group, IUGR high caloric diet (A) group, IUGR high caloric and high protein diet (B) group, IUGR high protein diet (C) group. Only the mother rats were given those different diets individually, and all IUGR newborn pups were lactated for 3 weeks. From the beginning of the 4(th) week, all IUGR pups were weaned and fed with normal diet till the end of the experiment. Eight normal birth weight newborn rats were used as the control group fed with the normal diet. Weight, perirenal fat weight, fasting glucose and insulin concentration and quantified TNF-alpha mRNA expression in adipose cell were measured at the 48(th) week. The insulin sensitive index (ISI) and the relation index between TNF-alpha mRNA and fat weight, fat weight/body weight (fw/bw) ratio and ISI were calculated., Results: ISI of IUGR model group, IUGR A and B groups was lower than normal control group, while perirenal fat weight, fw/bw and the expression of TNF-alpha mRNA in adipose cells were all significantly higher (P < 0.05 or 0.01). There were no significant differences in these indexes between IUGR C group and normal control groups (P > 0.05). A positive correlation was found between TNF-alpha mRNA and fat weight and fw/bw (r(1) = 0.755, r(2) = 0.782, P = 0.000). Significant inverse associations between ISI and TNF-alpha mRNA (r = -0.556, P = 0.000) and fw/bw (r = -0.513, P = 0.02) were also found., Conclusion: The occurrence of insulin resistance in IUGR rats is possibly associated with central obesity and accumulation of the abdominal fat and adipose cell over-expression of TNF-alpha. The adipose TNF-alpha may be an important pathogenic factor of insulin resistance of IUGR. High protein diet is a reasonable nutritional intervention. Because it promotes the skeleton muscle catch-up growth but not fat catch-up growth, it can avoid the occurrence of central obesity and insulin resistance in IUGR rats.

Objective: About 20 - 50% individuals with intrauterine growth retardation (IUGR) could not achieve catch-up growth and remain small in size till adulthood. There are few reports on the relation between intestinal development and body catch-up growth of IUGR. Studies showed that early "nutritional programming" would results in long-term effects on the body growth and organic function, and gastrointestinal development is closely related to the body development as well. The authors aimed to study the effect of early nutritional interventions on serum IGF1, IGFBP3, intestinal development and catch-up growth of pups with IUGR by using diets with different protein and caloric levels during the first four weeks of life., Methods: An IUGR rat model was established by maternal nutrition restriction during pregnancy. Thirty-two IUGR female pups were divided randomly into 4 groups (8 pups in each group) and eight normal female pups as control. The groups and interventions were (1) Normal control group (C group); (2) IUGR control group (S group), (3) IUGR low-protein diet group (SL group); (4) IUGR high-protein diet group (SH group); (5) IUGR high-caloric group (SA group). The serum IGF1, IGFBP3, body weight, body length, and intestinal weight, length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT) were measured at the 4(th) week of life., Results: (1) At the 4(th) week, the serum IGF1 (724.0 +/- 153.5 ng/ml), IGFBP3 (9.69 +/- 3.13 ng/ml), and VH (416.9 +/- 46.3 microm), VSA (115.9 +/- 24.0 x 10(3) microm(2)), MT (583.9 +/- 68.5 microm) in the SH group were significantly higher than those of normal control group (539.4 +/- 198.4 ng/ml, 4.77 +/- 2.98 ng/ml and 322.1 +/- 25.8 microm, 85.8 +/- 17.8 x 10(3) microm(2), 480.0 +/- 61.5 microm) and IUGR control group (P < 0.05). The intestinal weight (1.91 +/- 0.16 g) and length (80.67 +/- 9.47 cm) in the SH group was not significantly different from the normal control group (2.24 +/- 0.22 g and 74.77 +/- 9.06 cm, P > 0.05). The SH group showed the fastest catch-up growth. Their body weights (40.14 +/- 11.03 g) at the 3(rd) week and body lengths (23.61 +/- 0.49 cm) at the 4(th) week of life reached the normal ranges of the control group (44.65 +/- 5.36 g and 23.10 +/- 1.42 cm, P > 0.05). (2) The serum IGF1 (346.7 +/- 85.3 ng/ml), IGFBP3 (1.4 +/- 0.21 ng/ml), body weight (21.41 +/- 3.54 g) and body length (15.96 +/- 1.29 cm) and the most of intestinal indexes in the SL group were markedly lower than other groups at the 4(th) week of life (P < 0.05)., Conclusion: The serum IGF1 was a sensitive marker to reflect the catch-up growth and nutritional status, and IGF1 was positively correlated with the intestinal development and body growth. When given different nutritional interventions during the first four weeks of life, high protein diet is more helpful for the IUGR catch-up growth by promoting the intestinal development and the absorption of nutrition.

Objective: To investigate the effects of pregnancy malnutrition on the occurrence of insulin resistance (IR) in rat offspring during adult stage and to find out the relationship between TNF-alpha and IR; and to find out a reasonable early nutritional intervention measure for the prevention of IR, through giving different diets to offspring., Methods: An IUGR model was built by maternal nutrition restriction. 80 newborn IUGR female pups were randomly divided into 4 groups, the mother rats were given the following diet respectively for 3 weeks after delivery, pups were fed by mother milk: (1) The IUGR (intrauterine growth retardation) rat model was used and the animals were divided into: IUGR control group (group S/N) fed with normal diet, (2) IUGR high-caloric diet group (group A), (3) IUGR high-protein and high-caloric diet group (group B) and (4) IUGR high-protein isocaloric diet group (group C). Each group had 20 pups and another 20 normal female pups were fed with normal diet as the normal control group (group C/N). All pups were weaned at the 4th week of age and fed with normal diet till the end of the experiment. At the 12th week (adulthood) and 48th week (senility) of life, body weight and length, the fasting blood glucose, insulin concentration, TNF-alpha of adipose tissue and body weight were measured. Body mass index (BMI), ISI (insulin sensitive index), IRI (insulin resistant index) and HBCI (beta cell insulin excretion index) and their correlation to TNF-alpha were calculated., Results: At 12th week and 48th week of life, the insulin sensitivity of IUGR model group was significantly lower than group C/N, although there was no significant difference of body weight between these two groups. TNF-alpha was negatively correlated with ISI, positively correlated with IRI and no relation to HBCI. Group A and B was fatter and developed more severe IR. There were no significant differences in ISI, IRI, HBCI and TNF-alpha between group C and group C/N., Conclusions: IUGR offspring of pregnancy malnutrition mother rats showed IR at the age of 12th week. TNF-alpha was closely related to the occurrence of IR in IUGR pups. IUGR pups fed with high caloric diet or high protein and caloric diet at the early postnatal period amplified the metabolic abnormality. The high protein isocaloric diet is effective early nutritional intervention measure for the prevention of occurrence of IR at adulthood.

Objective: To determine whether epidermal growth factor receptor (EGFR) expression contributes to tumor growth of poorly differentiated human nasopharyngeal carcinoma CNE-2 cell lines., Methods: An expression vector containing a N-terminal fragment (1.35 kb) of human EGFR in the antisense orientation was transfected into CNE-2 cell lines via lipofectamine. The established clones resistant to G418 were isolated and characterized, and the tumor-inhibiting effect of antisense EGFR expression was evaluated in terms of tumor growth and metastasis at different time after subcutaneous inoculation into nude mice., Results: Down-regulated EGFR expression in the cells with antisense vector transfection was demonstrated by ligand binding assay. The growth rate and the ability to grow in soft agarose of these antisense transfectants were also reduced. After inoculation into nude mice, EGFR antisense transfectants showed a longer latency period, slower tumor growth and lower metastatic rates to the lymph nodes and lung in comparison with the parental cells., Conclusions: These results suggest that these EGFR antisense cDNA-transfected CNE-2 cells are of value to further delineate the role of EGFR in the development and progression of nasopharyngeal carcinoma.

Phospholipase C-gamma1 (PLC-gamma1) activation has been reported to enhance cell survival during the cellular response to oxidative stress. We studied the role of protein kinase C (PKC) pathways in mediating PLC-gamma1 survival signalling in oxidative stress by using mouse embryonic fibroblasts genetically deficient in PLC-gamma1 (Plcg1(-/-)) and its wild type (Plcg1(+/+)). PLC-gamma1 was activated by H(2)O(2) treatment in a dose- and time-dependent manner. Activation of PKC was also markedly increased in both cell lines treated with H(2)O(2) (1-5 mM), but with low doses (50-200 microM), PKC activation was considerably decreased in Plcg1(-/-) cells. After treatment with H(2)O(2), PKC-dependent phosphorylation of Bcl-2 and cell viability of Plcg1(-/-) cells decreased dramatically and caspase-3-like activity increased significantly compared with that of the wild-type cells. Furthermore, pretreatment of Plcg1(+/+) cells with PKC-specific inhibitor decreased levels of PKC-dependent Bcl-2 phosphorylation, enhanced caspase-3 activity and their sensitivity to H(2)O(2). On the contrary, treatment of Plcg1(-/-) cells with PKC-specific activator increased the Bcl-2 phosphorylation, decreased caspase-3 activity and improved their survival. These results suggest that PLC-gamma1 mediates survival signalling in oxidative-stress response by PKC-dependent phosphorylation of Bcl-2 and inhibition of caspase-3.