Adolescent ; Female ; Humans ; Leukemia ; etiology ; Leukemia, Promyelocytic, Acute ; complications ; Male ; Young Adult

Objective To study the treatment effect on H22 tumor-bearing mice using ultrasound (US) combined with hematoporphyrin-loaded PLGA ultrasound contrast agents (HP-PLGA). Methods Hematoporphyrin-loaded PLGA ultrasound contrast agents were prepared using the technique of double emulsion, and the properties of the contrast agents were detected. Then 30 H22 tumor-bearing mice were averagely divided into 5 groups for different treatment. The growth curve of H22 tumor was depicted within 15 days after treatment. The inhibition rate of tumor quality on the 15th day and the index about apoptosis and proliferation on tumor of each group were measured, respectively. Results Self-made hematoporphyrin-loaded PLGA ultrasound contrast agents had mean size of 602.3 nm with encapsulation efficiency of 63.50% and drug loading of 2.15%. After treatment, tumors of the E group (US+HP-PLGA) grew most slowly compared with other groups. The inhibition rate of tumor quality and the apoptotic index in E group were significantly higher than those in other four groups (P＜0.05), while the proliferation index in E group was significantly lower than that in other groups (P＜0.05). Conclusion Ultrasound combined with hematoporphyrin-loaded PLGA ultrasound contrast agents could inhibit growth and promote the apoptosis of H22 tumor in mice, providing a novel strategy for sonodynamic therapy on the tumor.

BACKGROUND: Studies have showed that Chengzai pill is of distinct significance in the treatment of steroid-induced osteonecrosis of femoral head through increasing bone mineral density, bone weight, bone strength and rigidity, it also reverses the low levels of estrogen. OBJECTIVE: To explore the effect of Chengzai pill on the genes of cell adhesion molecules on bone cells of steroid-induced ostaonecrotic rats, and to understand the role to resume normal blood transport in femoral head of steroid-induced osteonecrosis. DESIGN, TIME AND SETTING: Grouping controlled observation was performed in the Pharmacological Laboratory of Wangjing Hospital of China Academy of Chinese Medical Sciences and laboratory of CapitalBio Corporation between March and August in 2006. MATERIALS: Six male SD rats of 6 months old and weighing (280:1:20) g were used in this study. Chengzai pill was consisted of 22 Chinese medicines, such as Chinese Angelica, Eucommia Bark, Milkvetch Root, Barbary Wolfberry Fruit, Degelatined Deer-hom, Desertliving Cistanche, Eupolyphaga seu Steleophaga, Leech, Danshen Root and Himalayan Teasel Root, which were offered by Beijing Boran Pharmaceutical Co., Ltd. METHODS: The lipopolysaccharide and methylprednisolone were applied to prepare a rat model of steroid-induced osteonecrosis of femoral head. Six rats were divided into model group and Chengzai pill group at random with 3 rats in each group. The rats in the Chengzai pill group were administrated with methylprednisolone for the first time and then 1.5 g/kg Chengzai pill solution, once a day, totally for 6 weeks. The total RNA was extracted from femoral head in all rata 6 weeks later and then gene expression profiling was analyzed. MAIN OUTCOME MEASURES: Gene action pathway of cell adhesion molecules in gene expression profile. RESULTS: Compared with model rats, there were totally 8 downregulated genes of cell adhesion molecules which changed by a minimum of 1.5 folds in cell adhesion molecules pathway of Chengzai pill group, three rats were present with 633 genes (506 down-regulated and 127 up-regulated), 883 genes (640 down-regulated and 243 up-regulated) and 593 genes (408 down-regulated and 185 up-regulated), respectively. MAS software classification analysis showed 79 action pathways were involved in 297 genes.CONCLUSION: Following Chengzai pill administration, those downregulated genes recover the cognitive functions of macrophage and target cell in rats, also renew the normal survival condition of epithelial cells including vascular endothelial cells. Cell adhesion molecules action pathway returns to normal levels. This is the key to resume normal blood transport in femoral head of steroid-induced osteonecrosis.

Objective To evaluate the effect of penehyclidine hydrochloride on Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway in the myocardium of pediatric patients undergoing radical correction of tetralogy of Fallot with cardiopulmonary bypass (CPB).Methods One hundred pediatric patients of both sexes,aged 5 months-3 yr,with body mass index of 13.9-16.0 kg/m2,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ (New York Heart Association classification Ⅱ or Ⅲ),with the left ventricular ejection fraction＞50％,scheduled for elective radical correction of tetralogy of Fallot with CPB,were divided into 2 groups (n =50 each) using a random number table:penehyclidine hydrochloride group (group P) and control group (group C).Penehyclidine hydrochloride was intravenously injected at a dose of O.04 mg/kg immediately after successful internal jugular vein puncture in group P,and the equal volume of normal saline was given instead at the same time in group C.Before anesthesia induction,at 10 min after induction,after re warming to 36 ℃,at 1 h after termination of CPB,at the end of surgery and at 24 h after surgery,venous blood samples were collected to detect the concentrations of tumor necrosis factor-alpha,interleukin-6 (IL-6),IL-8 and cardiac troponin T in plasma (by enzyme-linked immunosorbent assay).Myocardial specimens were obtained from the right auricular appendage after opening of pericardium and at 1 h after aortic unclamping for microscopic examination and for determination of activated NF-κB and TLR4 protein and mRNA expression (by Western blot and real-time polymerase chain reaction,respectively).Results Compared to group C,the concentrations of plasma tumor necrosis factor-alpha,IL-6,IL-8 and cardiac tropnin T were significantly decreased after re-warming to 36 ℃C,at 1 h after termination of CPB,at the end of surgery and at 24 h after surgery,the expression of activated NF-κB and TLR4 protein and mRNA was down-regulated at 1 h after aortic unclamping (P＜0.05),and the pathological changes of myocardium were significantly attenuated in group P.Conclusion The mechanism by which penehyclidine hydrochloride reduces inflammatory responses is related to inhibition of the activation of NF-κB/TLR4 signaling pathway in the myocardium of pediatric patients undergoing radical correction of tetralogy of Fallot with CPB.

Objective To evaluate the effect of ulinastatin pretreatment on endoplasmic reticulum stress during myocardial injury in the patients undergoing mitral valve replacement (MVR) with cardiopulmonary bypass (CPB).Methods One hundred patients of both sexes,aged 35-64 yr,weighing 40-80 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ (New York Heart Association Ⅱ or Ⅲ),scheduled for elective MVR with CPB,were divided into ulinastatin pretreatment group (UP group,n=50) and normal saline control group (NS group,n =50) using a random number table.Ulinastatin 0.5× 104 U/kg was intravenously infused over 1 h before skin incision,and administration was repeated every 4 h until the end of operation in group UP,while the equal volume of normal saline was given instead in group NS.Immediately after opening the right atrium (T0),at 30 min after aortic clamping (T1) and while suturing the right atrium (T2),blood samples were collected from the radial artery for measurement of the concentrations of plasma creatine kinase-MB and cardiac troponin T by enzyme-linked immunosorbent assay.Right auricle specimens were obtained after blood sampling at each time point for determination of the expression of glucose-regulated protein 78,CCAAT/enhancer-binding protein homologous protein and c-Jun N-terminal kinase protein and mRNA (by real-time polymerase chain reaction and Western blot,respectively) and apoptosis in cardiomyocytes (by TUNEL).The apoptosis rate was calculated.Results Compared with group NS,the plasma concentrations of creatine kinase-MB and cardiac troponin T at T1 and T2 and apoptosis rate at T2 were significantly decreased,and the expression of glucose-regulated protein 78,CCAAT/enhancer-binding protein homologous protein and c-Jun N-terminal kinase protein and mRNA was down-regulated at T1 and T2 in group UP (P＜0.05).Conclusion The mechanism by which ulinastatin pretreatment inhibits apoptosis in cardiomyocytes and attenuates myocardial injury is related to decrease in endoplasmic reticulum stress in the patients undergoing MVR with CPB.

Objective To determine the efficacy of liver cancer resection combined with splenectomy for patients with hepatocellular carcinoma with hypersplenism.Methods Among 35 patients with hepatocellular cancer and hypersplenism treated from March 2004 to January 2006 at our hospital,12 patients accepted simultaneous liver cancer resection and splenectomy (the splenectomy group)and 23 only accepted liver cancer resection (the non-splenectomy group).The liver function,platelets and white blood cells were analyzed retrospectively.Results All the operations were successfully carried out.Within 1 week after operation,the white blood cell count increased from (3.2 ± 1.7) × 109/L to (8.5±-5.3) × 109/L,the platelet count increased from (52.6±23.7) × 109/L to (245.3±94.6) ×109/L(P＜0.01) in the group of patients with combined splenectomy,while little change occurred in the non-splenectomy group.The liver function in the splenectomy group recovered to the preoperational value within 1 week.Two years after operation,7 (58.3％) patients were still surviving in the splenectomy group and the mean tumor-free survival was (16.4 ± 4.3) months compared with (14.3 ±5.2) months in 10 (43.5％) patients in the non-splenectomy group,(P＜0.005).Conclusion Liver cancer resection combined with splenectomy was efficacious to hepatocellular cancer with hypersplenism.

OBJECTIVE To investigate the transgenerational effects of a hypothala mic-pituitary-ad-renal (HPA)axis -associated neuroendocrine metabolic progra mming alteration fro m F1 to adult second generation (F2)with prenatal ethanol ingestion.METHODS Pregnant Wistar rats were ad ministered with ethanol (4 mg·kg -1·d -1 )fro m gestational day 1 1 until delivery.F1 rats were fed a high-fat diet fro m postnatal week 4 (PW4)and were cross-mated in PW 16 -20.F2 rats were fed a standard diet fro m PW4 and rectal te mperature was measured in PW20,oral glucose tolerance test (OGTT)was con-ducted in PW21 ,blood sa mples and hypothala mus were collected in PW24 to investigate seru m lipids and HPA axis activity.RESULTS Co mparing to the F2 control group ,rectal te mperature in F2 ethanol group were higher (P<0.01 ),sugar tolerance in F2 male group was i mpaired (P<0.05),seru m corti-costerone and hypothala mus arginine vasopressin (AVP) mRNA were increased (P <0.05);seru m insulin were decreased (P<0.05)and male rats showed i mpaired glucose tolerance (P<0.05);seru m high-density lipoproteincholesterol (HDL-C)decrease (P <0.05)and total cholesterol (TCH)/HDL-C and low density lipoproteincholesterol (LDL-C)/HDL-C ratios were markedly increased (P <0.05,P <0.01 ).CONCLUSION Prenatal ethanol exposure induced metabolic syndro me has transgenerational effects,which may originate fro m the intrauterine progra mming of altered HPA axis-associated neuroen-docrine metabolis m.

A pot experiment was conducted to study effect of drought stress on leaf physiological characteristics and growth of one year old Stellaria dichotoma seedlings. The result showed that plant height and shoot dry weight significantly decreased with decrease in soil water content; however, root length and root dry weight increased at light drought stress and decreased at severe drought stress. The result also showed that with the decrease of soil water content, proline content in S. dichotoma leaves decreased then increase, while solube protein content decreased. Activities of SOD and POD in S. dichotoma leaves significantly decreased as soil water content decreased, while activity of CAT significantly decreased at severe drought stress. Membrane permeability in S. dichotoma leaves increased, while MDA content decreased then increased as soil water decreased. These results suggest that S. dichotoma had osmotic stress resistance ability and reactive oxygen scavenging capacity at light drought stress, which caused S. dichotoma growth was no inhibited at a certain extent drought stress.
Droughts ; Plant Leaves ; enzymology ; growth & development ; metabolism ; Plant Proteins ; metabolism ; Plant Roots ; enzymology ; growth & development ; metabolism ; Proline ; metabolism ; Seedlings ; enzymology ; growth & development ; metabolism ; Stellaria ; enzymology ; growth & development ; metabolism ; Water ; metabolism

Objective To explore the effects of under-expression of large tumor suppressor 1 (LATS1) on activation of Hippo signaling pathway and differentiation, proliferation, migration of bone marrow mesenchymal stem cells (mMSCs) of micein vitro.Methods mMSCs of C57BL/6 mice were divided into normal control (MSC) group, empty vector control (MSC-GFP) group, LATS1-over-expressing (MSC-LATS1) group, empty vector without LATS1 shRNA control (MSC-shControl) group and LATS1-under-expressing (MSC-shLATS1) group. Lentiviral vectors with activated,inactivated LATS1 (the key molecule of Hippo signaling pathway) modifications and empty vectors were constructed and were used to infect mMSCsin vitro. The transduction efficiencies mediated by the lentiviral vectors were evaluated by fluorescence microscopy and flow cytometry. The mRNA expression of LATS1 was quantified by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expressions of LATS1, YAP (p-YAP), 14-3-3 were quantified by Western Blot to evaluate the activation of Hippo signaling pathway. Osteogenic and adipogenic differentiation of mMSCs were evaluated through measurement of Runx2, OSX and C/EBPα, PPAR-γ mRNA by qRT-PCR, as well as Alizarin Red S and Oil red O staining. Proliferation of mMSCs was evaluated using methy thiazdyl tetrazolium (MTT) assay. The scratch test and Transwell chamber test were used to analyze the horizontal and vertical migration ability of mMSCs.Results The transduction efficiencies mediated by the lentiviral vectors were 94.74%-96.10%. Compared with MSC-GFP group, the activation of Hippo signaling pathway was promoted in MSC-LATS1 group [LATS1 mRNA (2-ΔΔCT): 4.37±0.21 vs. 1.20±0.04, LATS1 protein (gray value): 2.21±0.06 vs. 1.09±0.10, p-YAP/YAP protein (gray value): 1.51±0.13 vs. 0.98±0.05, 14-3-3 protein (gray value): 1.92±0.18 vs. 1.10±0.09, allP < 0.05], osteogenic and adipogenic differentiation of mMSCs were decreased in MSC-LATS1 group [mineralization (A value):0.13±0.02 vs. 0.40±0.03, Runx2 mRNA (2-ΔΔCT): 0.51±0.02 vs. 0.98±0.09, OSX mRNA (2-ΔΔCT): 0.41±0.04 vs. 1.04±0.09, lipid accumulation (A value): 0.10±0.02 vs. 0.25±0.03, C/EBPα mRNA (2-ΔΔCT): 0.33±0.03 vs. 1.11±0.09, PPAR-γ mRNA (2-ΔΔCT): 0.29±0.02 vs. 1.04±0.10, allP < 0.05], the proliferation rate of mMSCs at 4-7 days was decreased in MSC-LATS1 group and so were the horizontal and vertical migration of mMSCs [wound healing rate: (18.65±3.53)% vs. (40.29±1.87)%, migrated cells (cells/MP): 35.99±6.18 vs. 103.67±17.77, bothP <0.05]. Compared with MSC-shControl group, the activation of Hippo signaling pathway was inhibited in MSC-shLATS1 group [LATS1 mRNA (2-ΔΔCT): 0.16±0.01 vs. 0.98±0.03, LATS1 protein (gray value): 0.38±0.03 vs. 1.04±0.07, p-YAP/YAP protein (gray value): 0.58±0.04 vs. 1.05±0.06, 14-3-3 protein (gray value): 0.14±0.02 vs. 1.02±0.09, allP < 0.05], osteogenic and adipogenic differentiation of mMSCs were increased in MSC-shLATS1 group [mineralization (A value): 0.93±0.13 vs. 0.44±0.05, Runx2 mRNA (2-ΔΔCT): 1.44±0.12 vs. 0.95±0.04, OSX mRNA (2-ΔΔCT):1.67±0.06 vs. 1.10±0.11, lipid accumulation (A value): 0.47±0.06 vs. 0.28±0.04, C/EBPα mRNA (2-ΔΔCT):3.98±0.61 vs. 0.99±0.10, PPAR-γ mRNA (2-ΔΔCT): 3.05±0.36 vs. 0.98±0.14, allP < 0.05], the proliferation rate of mMSCs at 3-7 days was increased in MSC-shLATS1 group and so were the horizontal and vertical migration of mMSCs [wound healing rate: (80.18±6.98)% vs. (46.18±1.01)%, migrated cells (cells/MP): 212.69±41.21 vs. 115.87±35.15, bothP < 0.05].Conclusions Under-expression of LATS1 promotes the differentiation, proliferation, migration of mMSCs by inhibition of Hippo signaling pathwayin vitro.

Objective:To investigate the characteristics of gonads, the incidence of gonadal tumors and the detection results of SRY gene and Y chromosome microdeletions in 45, X/46, XY chimeras. Methods:The medical records of 45, X/46, XY karyotype or its variant in Jiangxi Children′s Hospital from January 2013 to December 2019 were analyzed retrospectively and analyze the gonadal phenotype and oleculardetection of 45, X/46, YX karyotype.Results:Among the 30 patients with 45, X/46, XY karyotype or its variant, the age of treatment was under 18 years old, with 11 males and 19 females.Fourteen of the patients had undergone prophylactic gonadectomy.Six male cases of unilateral testis and contralateral striated gonads were detected.Pathological section suggested that the gonadal tissue contained testis and ovary in 3 cases, adrenal gland tissue with translocation in 2 cases, and bilateral striated gonad in 8 cases, and both sexes were female.Pathological section indicated that the gonad tissue contained both epididymis and ovary tissue in 1 case, and gonadoblastoma in 1 case.There were 1 case of ovarian dysplasia with granulomatous hyperplasia and 1 case with proliferative nevus cells (mixed nevus). No follicle was found in all patients with B-ultrasound and pathological sections.Among the 11 male children, 5 cases were positive by SRY gene detection.Seven cases by Y chromosome microdeletion detection displayed that 3 cases had partial Y chromosome deletion and 4 cases had no deletion; 10 cases among 19 cases of social gender female patients were detected by SRY gene detection and 9 cases were positive and 1 case was negative; 7 cases were detected by Y chromosome microdeletion and the results are 2 cases with Y chromosome partial deletion, 4 cases with Y chromosome no deletion and 1 case with Y chromosome whole deletion. Conclusions:Most patients with 45, X/46, XY chimera have abnormal gonadal tissue, which has the risk of gonadal tumor, especially among female patients.Most patients had positive SRY gene and had no or partial deletion of Y chromosome.In view of the increased risk of gonadal tumors in these patients, early prophylactic gonadectomy is recommended.