OBJECTIVEThe prognosis for neuroblastoma in advanced stage is still poor, even under conventional chemotherapy. This study aimed to investigate if very high dose chemotherapy in conjunction with autologous peripheral blood stem cell transplantation and 13-cis-retinoic acid could get excellent results in children with high risk neuroblastoma.

METHODSSix children, aged from 4 to 8 years, with stage IV neuroblastoma were included in the study. The duration of the illness before admission was 1 to 12 months. Primary sites of the diseases were in the abdominal cavity (n = 5) and thoracic cavity (n = 1). All of patients had bone marrow metastasis, and one had multiple bone metastasis and orbital metastasis. All of the patients received very high dose chemotherapy, surgery, local radiation (20-30 Gy), and autologous peripheral blood stem cell transplantation as well as 13-cis retinoic acid. Induction chemotherapy included vincristine 0.67 mg/(m2 x 24 h, x 3), cyclophosphamide 2.1 g/(m2 x 24 h, x 2) and doxorubicin 25 mg/(m2 x 24 h, x 3) for 4 courses. Drugs were given as 24 hour-continuous intravenous infusion. Etopside 200 mg/(m2 x 24 h, x 3) and cisplatin 50 mg/(m2 x 24 h, x 3) were given for 2 courses. Conditioning regimen included carboplatin 400 mg/(m2.d) for 4 days, etoposide 300 mg/(m2.d) for 4 days and melphalan 70 mg/(m2.d) for 3 days. 13-cis retinoic acid 160 mg/(m2.d) started on +59 days for 6 courses, each course including 14 days therapy and 14 days rest.

RESULTSSix patients got a complete response before stem cell transplantation. Their bone marrow metastasis disappeared and so did bone and orbital metastasis. However, marrow suppression due to very high dose chemotherapy occurred in all of the patients, which lasted for 3-4 weeks for peripheral leukocyte recovery. Fever occurred after they finished 1/3 course of chemotherapy. Infection, however, was cured with the use of Fortum and Imipenem, ect. Autologous peripheral blood stem cell transplantation was initiated and successful in all cases. Follow-up studies revealed that all the patients were in CR status 4-18 months after transplant, and the cardiac and liver and renal functions were normal. Meanwhile, bone marrow was recovered or in the process of recovery.

CONCLUSIONThe new strategies focused on very high dose chemotherapy, autologous peripheral blood stem cell transplantation and biological therapy might be a good option for patients with advance neuroblastoma.

Abdominal Neoplasms ; therapy ; Bone Marrow Cells ; metabolism ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Isotretinoin ; therapeutic use ; Male ; Neuroblastoma ; therapy ; Peripheral Blood Stem Cell Transplantation ; Treatment Outcome

OBJECTIVEHuman leukocyte antigen (HLA) haploidentical bone marrow is a potential source of donor to children for its availability. The drawback is deleterious graft versus host disease (GVHD) reaction post transplantation because of the incompatibility of HLA antigen expression between donors and recipients, in which donor T lymphocyte is stimulated to proliferate and differentiate. The methoxy polyethylene glycol (mPEG) is a kind of amphoteric compound without immunogenicity, which was used to modify various proteins covalently and to prepare the versatile blood type. If mPEG modification blocks the activation of T cells in grafts, GVHD reaction probably would become less serious and transplantation might become successful. The aim of this study was to verify the improvement of haploidentical bone marrow transplantation (BMT) in a murine model by using mPEG of certain concentration to modify the grafts.

METHODSMale BALB/c mice were chosen as the donor, and female CB(6)F(1) mice as the recipient. There were three groups of mPEG modification, non-modification and irradiation control, and 20 mice in each group. The modified and non-modified mixture of bone marrow and spleen cells (as T lymphocytes) were transplanted to haploidentical lethally irradiated CB(6)F(1) mice via the tail vein. After the transplant, the hematopoietic recovery, survival rate, acute graft versus host disease (aGVHD) and chromosomal karyotype were analyzed and compared with controls.

RESULTSSeventy-five percent (15/20) of mice survived in the group of mPEG modification, while only 40% (8/20) survived in the group without the modification (chi(2) = 5.01, P = 0.025). And 100% mice died in the group of the irradiation control within 2 weeks. The hematopoietic recovery in the group of mPEG modification was show n to be faster than that in the group without modification (P < 0.05). Histopathological examination of the skin, liver and intestine showed typical signs of aGVHD, but the GVHD grading in the group of modification was less severe. The recipient mice in both groups of transplantation surviving for more than 75 days showed complete donor-type implantation by the chimerism examination.

CONCLUSIONThe modification of grafts by mPEG could alleviate aGVHD and improve the survival rate of mice after the haploidentical bone marrow transplantation.

Animals ; Bone Marrow ; drug effects ; immunology ; Bone Marrow Transplantation ; immunology ; Disease Models, Animal ; Graft Survival ; immunology ; Graft vs Host Disease ; immunology ; prevention & control ; HLA Antigens ; immunology ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Male ; Mice ; Mice, Inbred BALB C ; Polyethylene Glycols ; pharmacology ; therapeutic use ; T-Lymphocytes ; drug effects ; immunology

BACKGROUNDAdvances in minimally invasive surgical techniques and neonatal intensive care for neonates have allowed for repair of the neonatal esophageal atresia with tracheoesophageal fistula (EA/TEF) to be approached endoscopically. However, thoracoscopic surgery in children is still performed in only a few centers throughout the world. The aim of this study was to compare the neonatal tolerance to the thoracoscopic repair (TR) and the open repair (OR) and also to discuss anesthetic management in thoracoscopic procedure.

METHODSWe performed a prospective study enrolling newborns diagnosed with EA with distal TEF (type C) receiving the repair surgery between June 2009 and January 2012 in our institution. Data collected included the newborns' gestational age and weight at the time of the operation, operative time, parameters of intraoperative mechanical ventilation, oxygenation, end-tidal carbon dioxide (ETCO2), and analysis of blood gases. Time to extubation and length of stay were also recorded.

RESULTSIntravenous induction with muscle paralysis followed by pressure-control ventilation and tracheal intubation regardless of the position of the fistula can be performed uneventfully in EA/TEF newborns with no additional airway anomalies and large, pericarinal fistulas in our experiences. The thoracoscopic approach appeared to take longer than the open approach. During the procedure of repair, hypercarbia and acidosis developed immediately 1 hour after pneumothorax in both groups. CO2 insufflation did have additional influence on the respiratory function of the newborns in the TR group; values of PaCO2 and ETCO2 were higher in the TR group but the difference did not reach statistical significance. By the end of the procedure, values of PaCO2 and ETCO2 returned to the baseline levels while pH did not, but all parameters made no difference in the two groups. Besides, time to extubation was shorter in the TR group.

CONCLUSIONSThoracoscopic repair of EA/TEF is comparable to the open repair, and is believed to be safe and tolerable in selected patients. A wider range of neonates may be acceptable for thoracoscopic EA/TEF repair with increasing surgical experience.

Esophageal Atresia ; surgery ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Male ; Prospective Studies ; Thoracoscopy ; methods ; Tracheoesophageal Fistula ; surgery

Objective To assess the contribution of contrast-enhanced spectral mammography (CESM) in detecting breast carcinoma of dense breasts. Methods To retrospectively analyze the imaging and clinical data of 52 female patients with breast carcinoma which were confirmed by pathology in Tai'an Central Hospital of Shandong Province from April 2017 to April 2018.All cases classified as dense or uneven dense breasts by DM examination underwent Ultrasound (US), digital mammography (DM), CESM, dynamic contrast enhanced MRI (DCE-MRI).The breast imaging report and data system (BI-RADS) and breast density classification were both evaluated using the 5th edition of BI-RADS. The efficacy of US, DM, DM+CESM, DCE-MRI in detecting breast carcinoma (BI-RADS 5) was evaluated by χ2 test. Results Histopathology confirmed that 87 lesions were malignant and 35 lesions were benign. The sensitivity of US, DM, DM +CESM, DCE-MRI were 66.67％(58/87), 64.37％(56/87), 100.00％(87/87), 100.00％(87/87) and the specificity were 94.28％(33/35), 74.28％(26/35), 85.71％(30/35), 51.43％(18/35), respectively. There was statistically significant difference in specificity (χ2=9.545, P=0.002) and BI-RADS 5 category, detection 39.08％(34/87), 22.99％(20/87), respectively (χ2=5.263, P=0.022) between the DM + CESM group and DCE-MRI group. Conclusion In dense breasts, CESM has a high application value in breast carcinoma diagnosis.

OBJECTIVETo compare the difference of vasomotor functions in aortas segments from Wistar rats between 1-hour and 6-hours after exposure of water-soluble components of fine particulate matter (PM2.5).

METHODSAll 30 Wistar rats were assigned to five groups (n=6 for each group) at random: the blank control group, control group for 1-hour and 6-hours, exposure group for 1-hour and 6-hours. The rats were sacrificed 1-hour or 6-hours later and aorta ring segments were mounted on wire myographs.

RESULTS(1) There was no significant difference in vasomotor functions among three control groups (P>0.05). (2) 1-hour or 6-hours after exposure there was a decrease of contraction elicited by 60 mmol/L KCl in contrast to the control group (P<0.05), whereas no significant change between the exposure group for 1-hour and 6-hours (P>0.05). (3) On the level of 10(-5) or 10(-7) mol/L, 1-hour after exposure there was a decrease in endothelium-dependent acetylcholine (ACh) elicited relaxation precontracted by 10(-6) mol/L NE compared with the control group (P<0.01 or P<0.05), on the level from 10(-5) to 10(-7) mol/L there was a decrease compared with the exposure group for 6-hours (P<0.05), whereas no difference between the exposure group for 6-hours and the control group (P>0.05). On the level from 10(-5) to 10(-9) mol/L, 1-hour after exposure there was a decrease in endothelium-independent sodium nitroprusside (SNP) elicited relaxation precontracted by 10(-6) mol/L NE as compared with the control group (P<0.01 or P<0.05) and a decrease on the level of 10(-6) or 10(-9) mol/L compared with the exposure group for 6-hours (P<0.05), 6-hours after exposure a decrease was caused as compared with the control group on the level from 10(-5) to 10(-7) mol/L (P<0.01 or P<0.05).

CONCLUSIONSInhibition of contraction and impairment of relaxation in aortas should be caused 1-hour after exposure to water-soluble components of PM2.5 in the air, which is weaken 6-hours after exposure.

Acetylcholine ; blood ; Air Pollutants ; toxicity ; Animals ; Aorta, Thoracic ; Male ; Particulate Matter ; toxicity ; Rats ; Rats, Wistar ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects

BACKGROUNDGlioma stem cell (GSC) hypothesis posits that a subpopulation of cells within gliomas have true clonogenic and tumorigenic potential. Significantly, a more controversial correlate to GSC is that cells in different culture conditions might display distinct stem cell properties. Considering these possibilities, we applied an approach comparing stem cell characteristics of C6 glioma cells under different culture conditions.

METHODSC6 cells were cultured under three different growth conditions, i.e., adherent growth in conventional 10% serum medium, non-adherent spheres growth in serum-free medium, as well as adherent growth on laminin-coated flask in serum-free medium. Growth characteristics were detected contrastively through neurosphere formation assay and cell cycle analysis. Markers were determined by immunofluorescence, relative-quantitative reverse transcription (RT)-PCR, Western blotting and flow cytometry. Side population cells were analyzed via flow cytometry. Tumor models were detected by magnetic resonance imaging and hematoxylin & eosin staining. Data analyses were performed with SPSS software (17.0).

RESULTSC6 cells (C6-Adh, C6-SC-Sph and C6-SC-Adh) showed distinctive growth patterns and proliferation capacity. Compared to suspending C6-SC-Sph, adherent C6-Adh and C6-SC-Adh displayed higher growth ratio. C6-SC-Sph and C6-SC-Adh showed enhanced capability of neurosphere formation and self-renewal. High side population ratio was detected in C6-SC-Sph and C6-SC-Adh. CD133 was not detected in all three kinds of cells. Conversely, Nestin and β-III-tubulin were demonstrated positive, nonetheless with no statistical significance (P > 0.05). Interestingly, lower expression of glial fibrillary acidic protein was demonstrated in C6-SC-Sph and C6-SC-Adh. C6-Adh, C6-SC-Sph and C6-SC-Adh were all displayed in situ oncogenicity, while statistical difference of survival time was not confirmed.

CONCLUSIONSC6 glioma cell line is endowed with some GSC phenotypes that can be moderately enriched in vitro when transferred into stem cell culture condition. The resultant tumor-spheres may be not a prerequisite or sound source of GSCs and adherent culture in stem cell medium is not a growth condition in favor of GSCs expanding in vivo.

Animals ; Culture Media ; Glioma ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplastic Stem Cells ; physiology ; Phenotype ; Tumor Cells, Cultured

Objective To study the use of preoperative indocyanine green retention test at 15 minutes (ICG R15) in the prediction of liver functional reserve in patients with hilar cholangiocarcinoma (HCCA).Methods The clinical data of 62 patients with HCCA treated in our department from March 2016 to March 2018 was reviewed.The relationship between preoperative ICG R15 and postoperative hepatic insufficiency was analyzed.The relationship between preoperative ICG R15 and Child-Pugh scoring was also studied.Univariate analysis was used to evaluate the risk factors of postoperative liver dysfunction.Logistic regression was used to assess the independent risk factors of postoperative liver dysfunction.The regression equation between independent risk factors and postoperative liver dysfunction was established.Results Among the 62 patients,ICG R15 was less than 10.0％ in 26 patients,between 10.0％ and 19.0％ in 17 patients,between 20.0％ and 29.0％ in 9 patients,between 30.0％ and 39.0％ in 5 patients,and over 40.0％ in 5 patients.There were 29 patients with a Child-Pugh A grading and 33 patients with a Child-Pugh B grading in the preoperative evaluation of liver function.The Wilcoxon W rank sum test was used to compare the preoperative ICG R15 in patients with Child-Pugh grading A and B separately.The ICG R15 in Child-Pugh grading A patients was significantly lower than those in Child-Pugh B grading patients (P ＜0.05).There were no significant differences in age,gender,history of previous liver diseases,duration of operation,and intraoperative blood loss (P ＞ 0.05) between the normal liver function group and the liver dysfunction group.However,there was a significant difference in the preoperative ICG R15 and preoperative bilirubin levels (P ＜ 0.05) between the two groups.The preoperative ICG R15 and preoperative bilirubin levels were significant risk factors of postoperative hepatic insufficiency.Regression analysis suggested that preoperative ICG R15 level was an independent risk factor of postoperative hepatic insufficiency (P ＜ 0.05).A regression equation:logit(P) =0.185 × preoperative ICG R15-3.152 could be constructed.Conclusions ICG R15 is an ideal clinical indicator for evaluation of preoperative liver functional reserve in patients with HCCA.It predicted the recovery of postoperative liver function.

The industry of Chinese medicinal materials is going through another high-level development stage with some important files issued by Chinese government in the past months, such as "the protection and development plans of Chinese medicinal materials (2015-2020)" and "the strategic development plans of Chinese medicine (2016-2030)". In addition, the effect of "TU Youyou" will not only improve the industry development, but also indicates the increasing international competition intensely. Therefore, one of the core problems of the sustainable-development industry is the training of senior talents under the "New Situation" with opportunity and intense competition. As one of the forefront courses of Chinese Pharmacology, Molecular Pharmacognosy (MP) is a new interdisciplinary science, which integrates the pharmacognosy and molecular biology, and combines many discipline theories and technological systems. MP not only inherits the traditional concepts,but also makes up for the shortages of pharmacognosy, and improves the development of pharmacognosy. Thus, these are importance of MP for cultivation of senior talents, and also the difficult teaching points of MP with no unified teaching mode. We will, in this paper, discuss the possible teaching modes through several aspects for talent cultivation and meeting the needs of social and industry development, such as teaching state of MP, the education of undergraduate and graduate students, social identity, and self renewal of curriculum theories and practice.

This study was to investigate the protective effect of paeoniflorin (PF) on hydrogen peroxide-induced injury. Firstly, "SMILES" of PF was searched in Pubchem and further was used for reverse molecular docking in Swiss Target Prediction database to obtain potential targets. Injury-related molecules were obtained from GeenCards database, and the predicted targets of PF for injury treatment were selected by Wayne diagram. For mechanism analysis, the protein-protein interactions were constructed by String, and the KEGG analysis was conducted in Webgestalt. Then, cell viability and cytotoxicity assay were established by CCK8 assay. Also, the experimental cells were allocated to control, model (200 μmol·L