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As an evolutionarily conserved DNA-sensing machinery in innate immunity, the cGAS-STING pathway has been reported to play an important role in immune surveillance and tumor suppression. Recent evidence suggests an intriguing tumor- and metastasis-promoting effect of this signaling pathway, either in a cancer cell-autonomous or a cancer cell-nonautonomous, bystander cell-mediated manner. Here, we show a new face of cGAS-STING signaling whose activation in a cancer-cell-autonomous response manner confers drug resistance. Targeted or conventional chemotherapy drug treatment induced cancer cell cytosolic DNA accumulation and triggered subsequent cGAS-STING signaling activation in cancer cell lines and the human cell-derived xenograft tumors. This activation promoted an acquisition and maintenance of drug resistance which was prevented and overcome in vitro and in vivo by blockade of STING signaling. This finding highlights a new face of cGAS-STING signaling and an ability of cancer cells to hijack the evolutionarily conserved inflammatory signaling to counteract drug stress and warrants a caution in combining STING agonist with targeted or conventional chemotherapy drug treatment, a strategy prevailing in current clinical trials.Statement of significancecGAS-STING signaling has long been recognized as playing a key role in triggering antitumor immunity. We reveal a new face of cGAS-STING signaling and an ability of cancer cells autonomously to hijack the evolutionarily conserved inflammatory signaling to counteract drug stress.

Optimal operation of a compressor station is important since it accounts for 25 % to 50 % of a company’s total operating budget. In short-term management of a compressor station, handling demand uncertainty is important yet challenging. Previous studies either require precise information about the distribution of uncertain parameters or greatly simplify the compressor model. We build a two-stage robust optimization framework of power cost minimization in a natural gas compressor station with non-identical compressors. In the first stage, decision variables are the ON/OFF state of each compressor and discharge pressure. The worst-case cost of the second stage is incorporated in the first stage. First-stage decision variables feasibility is discussed and proper feasibility cuts are also proposed for the first stage. We employ a piece-wise approximation and propose accelerate methods. Our numerical results highlight two advantages of robust approach when managing uncertainty in practical settings: (1) the feasibility of first-stage decision can be increased by up to 45 % , and (2) the worst-case cost can be reduced by up to 25 % compared with stochastic programming models. Furthermore, our numerical experiments show that the designed accelerate algorithm has time improvements of 1518.9% on average (3785.9% at maximum).

Acquired resistance represents a bottleneck to molecularly targeted therapies such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in lung cancer. A deeper understanding of resistance mechanisms can provide insights into this phenomenon and help to develop additional therapeutic strategies to overcome or delay resistance. Here, we identified a pharmacologically targetable metabolic mechanism that drives resistance to EGFR TKIs in lung cancer cell lines and patient-derived xenograft mice. We demonstrated that aldo-keto reductase family 1 member B1 (AKR1B1) interacts with and activates signal transducer and activator of transcription 3 (STAT3) to up-regulate the cystine transporter solute carrier family 7 member 11 (SLC7A11). This leads to enhanced cystine uptake and flux to glutathione de novo synthesis, reactive oxygen species (ROS) scavenging, protection from cell death, and EGFR TKI drug resistance in lung cancer cell lines and xenograft mouse models. Suppression of AKR1B1 with selective inhibitors, including the clinically approved antidiabetic drug epalrestat, restored the sensitivity of resistant cell lines to EGFR TKIs and delayed resistance in lung cancer patient-derived xenograft mice. Our findings suggest a metabolic mechanism for resistance to a molecularly targeted therapy and provide a potential therapeutic target for overcoming resistance to EGFR TKIs, including the third-generation inhibitor osimertinib.

Background: Acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) such as erlotinib is a major challenge to achieve an overall clinical benefit of the targeted therapy. Recently, aldehyde dehydrogenase 1 (ALDH1) induction has been found to render lung adenocarcinomas resistant to EGFR-TKIs, and targeting ALDH1A1 becomes a novel strategy to overcome resistance. However, the molecular mechanism underlying such effect remains poorly understood. Methods: Comprehensive assays were performed in a panel of lung adenocarcinoma cell lines and xenografts that acquired resistance to erlotinib. Cancer phenotype was evaluated by cell viability, apoptosis, migration, and epithelial-mesenchymal transition analysis in vitro, tumorsphere formation analysis ex vivo, and tumor growth and dissemination analysis in vivo. Reactive oxygen species (ROS) and reactive carbonyl species (RCS) were detected based on fluorescent oxidation indicator and liquid chromatography coupled to mass spectrometry, respectively. Protein target was suppressed by RNA interference and pharmacological inhibition or ecto-overexpressed by lentivirus-based cloning. Gene promoter activity was measured by dual-luciferase reporting assay. Results: Knockdown or pharmacological inhibition of ALDH1A1 overcame erlotinib resistance in vitro and in vivo. ALDH1A1 overexpression was sufficient to induce erlotinib resistance. Metabolomic analysis demonstrated lower ROS-RCS levels in ALDH1A1-addicted, erlotinib-resistant cells; in line with this, key enzymes for metabolizing ROS and RCS, SOD2 and GPX4, respectively, were upregulated in these cells. Knockdown of SOD2 or GPX4 re-sensitized the resistant cells to erlotinib and the effect was abrogated by ROS-RCS scavenging and mimicked by ROS-RCS induction. The ALDH1A1 overexpressed cells, though resisted erlotinib, were more sensitive to SOD2 or GPX4 knockdown. The ALDH1A1 effect on erlotinib resistance was abrogated by ROS-RCS induction and mimicked by ROS-RCS scavenging. Detection of GPX4 and SOD2 expression and analysis of promoter activities of GPX4 and SOD2 under the condition of suppression or overexpression of ALDH1A1 demonstrated that the RCS-ROS-metabolic pathway was controlled by the ALDH1A1-GPX4-SOD2 axis. The ROS-RCS metabolic dependence mechanism in ALDH1A1-induced resistance was confirmed in vivo. Analysis of public databases showed that in patients undergoing chemotherapy, those with high co-expression of ALDH1A1, GPX4, and SOD2 had a lower probability of survival. Conclusions: ALDH1A1 confers erlotinib resistance by facilitating the ROS-RCS metabolic pathway. ALDH1A1-induced upregulation of SOD2 and GPX4, as well as ALDH1A1 itself, mitigated erlotinib-induced oxidative and carbonyl stress, and imparted the TKI resistance. The elucidation of previously unrecognized metabolic mechanism underlying erlotinib resistance provides new insight into the biology of molecular targeted therapies and help to design improved pharmacological strategies to overcome the drug resistance.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved satisfactory clinical effects in the therapy of non-small cell lung cancer (NSCLC), but acquired resistance limits their clinical application. NRF2 has been shown to enhance the resistance to apoptosis induced by radiotherapy and some chemotherapy. In this study, we investigated the role of NRF2 in resistance to EGFR-TKIs. We showed that NRF2 protein levels were markedly increased in a panel of EGFR-TKI-resistant NSCLC cell lines due to slow degradation of NRF2 protein. NRF2 knockdown overcame the resistance to EGFR-TKIs in HCC827ER and HCC827GR cells. Furthermore, we demonstrated that NRF2 imparted EGFR-TKIs resistance in HCC827 cells via upregulation of GPX4 and SOD2, and suppression of GPX4 and SOD2 reversed resistance to EGFR-TKIs. Thus, we conclude that targeting NRF2-GPX4/SOD2 pathway is a potential strategy for overcoming resistance to EGFR-TKIs.

Various undercoolings 14-232 K of bulk K4169 superalloys were obtained by the method of molten glass fluxing combined with superheating cycling and the mechanical properties of undercooled K4169 with as-solidified state were tested. Microstructures and phases composition in undercooled bulk K4169 superalloy were identified by transmission electron microscope (TEM), scanning electron microscope (SEM) and optical microscopy (OM). The morphology of dendrites, grain size and intergranular phase all change with the increased undercooling. Meanwhile, the relationship between microstructure of undercooled K4169 superalloy and tensile properties was investigated. The experimental results show that the uniform distribution of Laves phase and the decrease of grain size and intergranular phase content are favorable for the improvement of mechanical properties. The maximum tensile strength and elongation obtained at undercooling of 232 K are 932.2 MPa and 6.5 %, respectively.

Changes in cellular metabolism accompany tumor therapeutic resistance. Metabolite concentrations specifically reflect the cellular state. Glutathione (GSH) metabolism maintains the redox homeostasis while also confers therapeutic resistance to cancer cells. However, analytical methods for studying GSH metabolism rely on high-resolution-based untargeted metabolomics. Since the aim of untargeted metabolomics studies is covering as much metabolites as possible, these methods lack sensitivity for simultaneous analysis of intracellular GSH-related metabolites with different polarities and structures. In this study, based on cultured lung cancer cells, we described a rapid, robust and sensitive ultra-performance liquid chromatography-triple quadrupole tandem mass spectrographic method (UPLC-QQQ-MS/MS) to simultaneously quantify a repertoire of GSH-related metabolites, including GSH, GSSG, glycine, cysteine, glutamine, glutamate, cystine, γ-glutamyl-cysteine and cysteinyl-glycine. This method avoided the use of derivatization and/or ion-pairing reagents and was validated according to United States Food and Drug Administration (US FDA) criteria. The lower limit of quantification was determined to be 0.5-100 ng/mL with lower limits of detection at 0.14-10.07 ng/mL. The intra- and inter-day precision values for all the analytes were15% CV, and the accuracy ranged from 85.4% to 114% at three levels of quality control. This method combined simple preparation with rapid analytical procedure (8 min), allowed for high-throughput analysis of GSH metabolism in basic and therapeutic treatment conditions within cultured cells. Our data showed a significant alteration of GSH metabolism in two independent resistant cells compared to sensitive cells. This method monitored the impact of molecularly targeted drugs on GSH metabolism within lung cancer cells and therefore helped identifying potential metabolic vulnerability for the therapeutic resistance in lung cancer.

A novel ubiquitin-like antitumour protein (RBUP) was isolated from fruiting bodies of the edible mushroom Ramaria botrytis. The protein was isolated with a purification protocol involving ion exchange chromatography on DEAE-Sepharose fast flow and gel filtration on Sephadex G-75. SDS-PAGE, Native-PAGE and ultracentrifugation analysis disclosed that RBUP was a monomeric protein with a molecular weight of 18.5 kDa. ESI–MS/MS demonstrated that it shared 69% amino acid sequence similarity with Coprinellus congregates ubiquitin (gi|136667). The protein exhibiting strong anticancer activity towards A549 cells. Analysis by employing AO/EB staining and Annexin V-FITC/PI detection indicated that the cytotoxic effect of RBUP was mediated through induction of apoptosis. Furthermore, RBUP displayed hemagglutinating and deoxyribonuclease activities. A temperature of 40 °C and pH of 7.0 were required for optimal DNase activity. Therefore, it was estimated that RBUP exerted its antitumour effect by inducing apoptosis, and its hemagglutinating and DNase activities were also thought to participate in this effect. These results demonstrated that RBUP was a multifunctional protein with potential medicinal applications.

The coil is the important part of a motor. The traditional monitoring system of the coil can only act when a fault was found. A new fault diagnosis system in motor coil is discussed in the paper. We had built coil fault knowledge base by using data fusion. We had predicted and diagnosed the causes of coil fault quickly by inference rules.

A novel polysaccharide fraction (G1) was obtained from the fungus Fomitiporia punctata (P. Karst.) Murrill. G1 exhibited a molecular weight of approximately 151 kDa. The FT-IR results suggested that the monosaccharide components of G1 possessed furanoid rings and there were β-glycosidic bonds between the sugar units. The 1H NMR results showed that G1 was composed of arabinose, fructose, galactose and glucose in the molar ratio of 1.6:3.8:19.7:19.7, as determined by gas chromatography-mass spectrometry (GC–MS) and high performance liquid chromatography (HPLC). G1 produced significant antioxidant effects as evidenced by its potency in inhibiting erythrocyte hemolysis, and in scavenging hydroxyl radicals and superoxide radicals. The highest rates of inhibition achieved were 73.58%, 36.55% and 50.98% respectively. In addition, G1 brought about 19.6% inhibition of HIV-1 protease activity at the concentration of 50 μg/mL. G1 displayed inhibitory activity toward HIV-1 integrase in the concentration range of 100–1000 μg/mL. The present study indicates that G1 from Fomitiporia punctate (P. Karst.) Murrill is a novel natural antioxidant.

Facing the urgent needs of China's high-quality engineering and technical personnel, the Ministry of Education proposed the training program of outstanding Engineers. The Engineering Training Center, as the practice base, must play an important role in promoting “outstanding plan”. Under the guidance of the cultivation of outstanding engineering, this article mainly explores and practices the following aspects: the position of reform of the practice teaching, reconstruction of the curriculum system and course content, innovation of engineering training teaching model, enhancing the depth of cooperation with the enterprise, efforts to promote the research study.

Based on the working flow of an automated machine assembly line, a fuzzy expert system (FES) for fault diagnosis of the assembly line is developed, which contains user interface, knowledge base, inference engine and history database. The FES adopts fuzzy forward chaining rule-based reference strategy and can predict the severity ponderance of faults according to certainty factor. In addition, fuzzy logic and linguistic terms are also introduced.

We research the super two-stage rapid drill of shaft well boring machine, taking the mathematical model of the drill in the stress field of shaft bottom as theoretical basis. Taking linear elastic and nonlinear features of element material into consideration, we establish element model in the stress field of shaft bottom and material model of stratum rock. Furthermore, we use the finite element method to numerically simulate the fragment intake effect of the super drills with diameter of 400mm and 800mm respectively. The result can be applied in the field of mine exploiting and tunnel advancement.

The definition, status and development of frictionless air cylinder are presented. As design guidance, leakage model of long piston cylinder during starting action stage is built. It shows influences of clearance, length of piston and other parameters on seal ability. Leakage model of another piston with two rows of small pores is introduced and studied. In those structures the number and diameter of holes as well as clearance of piston-cylinder are key factors of leakage. Based on above models and principles, a new type of air bearing piston with pores, pressure distribution groove and seal gaps is proposed and a single-acting frictionless cylinder is designed. Its pneumatic experiments have been done in a set of test system. Test results show this cylinder’s friction is near 0 and it behaves reliable performance under stable pneumatic resource.

OBJECTIVE Mesenchymal hamartoma of the liver (MHL) is a rare disease that makes up about 5%–8% of primitive hepatic tumors in children. The etiology of MHL has been the subject of considerable discussion. The possibility of malignant transformation of MHL is inclusive. To enhance the recognition of MHL in children, we have review the procedures in diagnosis and treatment and present 4 of our own cases. METHODS The clinical characteristics of MHL in 4 children including history, physical examination, lab examination, imaging data and pathology were analyzed and discussed and related to reports from the literature. RESULTS All the cases were diagnosed with B-ultrasonography and CT preoperatively, and were confirmed intra-operatively and histologically. Satisfactory results were reached postoperatively. CONCLUSION MHL is an uncommon benign lesion in children. The main presentation is abdominal painless mass. Diagnosis is aided with B-ultrasonography and CT preoperatively. Complete tumor removal is the best choice for MHL treatment resulting in a good outcome.

Gastrointestinal duplications are rare congenital abnormalities known to occur at any level of the alimentary tract from the mouth to the anus. The cause of intestinal duplication has not been established. Several theories have been put forward to explain different types of duplications. Some of these duplications are large sized and giant, and only 4 cases have been reported.A 4-year-old girl was referred to our hospital with a history of abdominal pain, abdominal distension, and diarrhea mixed with black blood for 20 days. Technetium-99m scintigraphy identified heterotopic gastric mucosa at the middle and lower abdominal region. Enteric duplication was suspected.Operatively, duplication was found to be located at the ileum with abnormal hypertrophy in shape, 50 cm of the ileum was resected, and an ileoileal end-to-end anastomosis was made. Stomach-like mucosa and some ring structures were identified instead of the normal intestinal mucosa when opening this ileal duplication. Microscopically, most of mucosa showed gastric corpusfundic glands.This is an unusual case of enteric duplication. Ultrasonography, computed tomography and technetium-99m scintigraphy are helpful in the diagnosis of duplication.

Eosinophilic granuloma is characterized by single or multiple skeletal lesions occurring predominantly in children, adolescents, and young adults, it accounts for 70% of Langerhans cell histiocytosis. The common sites are the skull, mandible, ribs, spines, and long bones particularly the femur and the humerus. Thoracic rib involvement is rarely seen. It was often regarded as malignant soft tissue tumor. We report an unusual case of eosinophilic granuloma in a female child presented with a solitary lesion at the thoracic rib.

Castleman disease is a rare benign lymph node hyperplasia usually presenting as an asymptomatic mediastinal mass in children. It can present at any extrathoracic site where there is lymphoid tissue. The sites include retroperitoneum, mesentery, axilla, and pelvis. Mesenteric Castleman disease is very rare in children.

The present study investigated the effects of acutely administered dihydroetorphine on mitogen-stimulated lymphocyte proliferation and lymphokine production in mice. These immune functions were significantly suppressed by dihydroetorphine at 24 microg/kg and 128 microg/kg in a dose-dependent fashion. This study further examined the involvement of micro-opioid receptors and alpha-adrenoceptors in the immunomodulatory effects of dihydroetorphine. The micro-opioid receptor antagonist, naloxone (4 mg/kg), and alpha-adrenoceptor antagonist, phentolamine (10 mg/kg), but not the beta-adrenoceptor antagonist, propranolol (10 mg/kg), effectively blocked dihydroetorphine-induced suppression of splenic lymphocyte proliferation and lymphokine production. These results demonstrate that dihydroetorphine has significant immunosuppressive effects in mice and the mechanisms of these effects may lie in its interactions with opioid receptors and adrenergic pathways.

Background The aim of this study was to evaluate the results of ultrasound (US)-guided hydrostatic reduction (UGSED) of intussusceptions in pediatric patients by saline enema. Methods Five thousand two hundred eighteen pediatric patients with intussusceptions treated by UGSED from October 1985 to October 2002 were reviewed retrospectively. Results The success rate of reduction in 5218 patients was 95.5%. Two hundred thirty-seven patients (4.5%) underwent surgery. Colonic perforation occurred in 9 patients (0.17%). Two infants suffered from milk aspiration because of vomiting during the hydrostatic enema reduction. There was no mortality. Conclusions UGSED of intussusceptions avoids radiation exposure. It is reliable and safe. It has high success rate and minimal complications. It is a perfect method for the nonoperative treatment of pediatric intussusception and can be widely used as routine therapy.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue malignant neoplasm that affects young people. It can occur in any region of the body and at any stage of development. But ASPS on the abdominal wall is rarely reported. However, a few cases were reported in children under the age of 10 years. In this study we report a case of ASPS that occurred on the abdominal wall of a 2-year-old patient.

In this paper, three dimensional temperature field in an entire automobile claw-pole generator is studied. Based on computational fluid dynamics (CFD) principles of limited volume, the mathematical model equations including the three-dimensional turbulence flows and heat transfer describing the entire generator heat and rotor high-speed rotation are solved. The finite element method is used and the entire generator model is meshed using bend surface tetrahedral grid. Finally, the simulated results of the three-dimensional temperature distribution in the generator are presented at rated load. The paper is helpful to guide the automotive generator design.

Thoracoabdominal foregut duplication is a rare congenital abnormality. The authors report a case of thoracoabdominal foregut duplication cyst in a 13-year-old male patient. The pathologic report revealed that a thoracic mass with a pseudostratified, ciliated, columnar epithelial lining (respiratory tract epithelium), an abdominal mass with gastric mucosa (alimentary tract epithelium), and the cyst originated from the foregut.

A 4-year-old girl was admitted with a history of abdominal pain for 10 days. Abdominal US showed a large solid mass with homogeneously increased echogenicity. Contrastenhanced CT showed a large, well-defined multilocular mass of largely fat density with enhancing septa occupying most of the abdominal cavity (Fig. 1). Microscopically, the tumor was made up of lobules of mature and immature fat cells and typical lipoblasts with large, atypical and vacuolated nuclei, confirming the diagnosis of a mesenteric lipoblastoma (Fig. 2). Lipoblastoma arising in the mesentery is extremely rare. Although preoperative imaging might be useful to assess the extent of disease and aid in planning surgical resection, it is of little help in differentiating lipomatous tumors [1, 2].

Objectives Wilms tumor (WT) is one of the most common solid tumors in children. It also is the most frequent tumor found in the kidneys. In 5% of cases, it affects both kidneys simultaneously. Extrarenal WTs are extremely rare. The diagnosis of extrarenal WT is almost always made after surgical intervention. The tumor can be located in the retroperitoneum, uterus, cervix, testes, skin, and even the thorax. Methods We report on a 3-year-old girl with an extrarenal WT located in the presacral region. Results The exact mechanism whereby a WT occurs in extrarenal tissues is unknown. The presence of ectopic metanephric blastema cells or the WT gene causing transformation of extrarenal primitive mesonephric or pronephric remnants into WT have both been considered in the embryogenesis. Although imaging examinations are helpful in the definition of retroperitoneal tumors, no characteristic findings are available to diagnose an extrarenal WT before surgery. Conclusions As a rule, the diagnosis of extrarenal WT is made after surgery. Surgical excision is the treatment of choice and the same general therapeutic rules should be followed as when the kidney has been affected. The use of Stage III guidelines for chemotherapy and radiotherapy are appropriate for these patients.

Brain-derived neurotrophic factor (BDNF) and its specific tryrosin kinase receptor-B (TrkB) are highly correlated to the chemoresistance of neuroblastoma (NB) cells and poor prognosis. This study observed the changes of the sensibility of NB cells to chemotherapy drug cisplatin (CDDP) before and after blockage of TrkB-BDNF signal pathway by specific tyrosin kinase inhibitor K252a.Human NB cell line SH-SY5Y (SY5Y) was routinely cultured. Expression of TrkB was induced with nM all trans-retinoid acid (ATRA). Then BDNF, CDDP or K252a were added to the cultured SY5Y cells. Cell livability was assessed by methyl thiazolyl tetrazolium (MTT) assay. TrkB autophosphorylation was determined by Western blot analysis. Cell apoptosis rate was detected by flow cytometry (FCM). The conformation of apoptosis cells was observed by transmission electron microscopy (TEM).The livability and apoptosis rate in SY5Y cells treated with ATRA, BDNF and CDDP were not different from the blank control group. However, after K252a together with ATRA, BDNF and CDDP treatment, the sensibility of SY5Y cells to chemotherapy drug CDDP increased, the livability decreased and the apoptosis rate increased in SY5Y cells when compared with the blank control group (P0.01). K252a treatment resulted in blockage of TrkB autophosphorylation.The blockage of TrkB-BDNF signal pathway by K252a use can increase sensibility of NB cells to chemotherapy and thus decrease the livability of NB cells.

Primary non-Hodgkin's lymphomas of the gastrointestinal tract are rare in children, and few of these lymphomas are located in the sigmoid colon. The preoperative diagnosis rate is low. Complete resection is indicated if it can be done safely. Combination chemotherapy after resection is indicated.

To estimate the clinical and pathological features of pancreatic solid cystic papillary tumor (SCPT) in children.From 2000 to 2005, 8 cases with SCPT of the pancreas were analyzed retrospectively. All cases but one were females. Average age was 12.8 years. By case review, we discussed the clinical and pathological features of SCPT in children.The chief complains were abdominal pain and palpable mass. There were 3 cases in the head, 1 case in the body, and 4 cases in the tail of pancreas. The procedures employed included local resection (1 case), distal pancreatectomy (5 cases), pancreaticoduodenectomy (1 case), and biopsy (1 case). Histological examination showed solid with cystic areas and papillary protrusions in the 8 cases; as for immunohistochemical examinations, the positive rate was 100% for alpha-antitrypsin (AACT), 87.5% for vinmentin, and 62.5% for neuron-specific enolase (NSE). The patients were followed up for 2 months to 4 years but one was lost by follow-up and all were alive postoperatively. SCPT in 2 cases relapsed.Occurring predominantly in young females, SCPT is usually curable by surgical resection with a favorable prognosis.

To detect the PAX3/PAX7-FKHR fusion transcripts to identify genetic alteration in embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS) tissues.One-step reverse transcription- polymerase chain reaction (RT-PCR) were used to detect the expression of the PAX3/PAX7-FKHR fusion transcrips in 16 cases of rhabdomyosarcoma (7 cases of ARMS, 9 cases of ERMS) and 16 specimens were compared to the surrounding normal tissue. Comparative genomic hybridization (CGH) was employed to detect the genomic imbalance (DNA loss or amplification) in 16 RMS cases.PAX3-FKHR fusion transcripts were positive in 3/7 and PAX 7-FKHR fusion transcripts were positive in 2/7 of ARMS patients, respectively, and were all negative in ERMS and Control tumors. There were different chromosome variations for each RMS, chromosome amplification was frequently seen in 1p36 (69%), 5q32 (56%), 8q21 (63%), 13q14 (69%), 19q (63%), 20q (56%). Chromosome loss was frequently seen in 3p21-pter (56%), 9p23-pter (50%), 10q (69%), 16/16q24 (56%).One-step RT-PCR assay for detection specific fusion gene provides a useful tool for confirmation of the diagnosis of RMS in diagnostically difficult cases and in retrospective studies. Chimeric gene transcript resulting from specific chromosomal translocations is a reliable index for the molecular diagnosis of RMS.

To investigate the diagnosis and therapy of mediastinal enterogenous cysts in children.Clinical data of 17 cases with mediastinal enterogenous cysts within 19 years in our hospital were retrospectively analyzed.One case was intramural esophageal cyst and 16 cases were enteric cysts, two among which were complicated with abdominal enteric duplications. Most cases presented with symptoms of respiratory distress. Twelve cases were complicated with vertebral anomalies. Ultrasound of 12 cases and magnetic resonance imaging of 4 cases were helpful in confirming the cystic nature of these lesions. Eight cases had technetium-99m pertechnetate scintigraphy of posterior mediastinum.Most patients present with symptoms of respiratory distress, complicated with vertebral anomalies. Ultrasonography and magnetic resonance imaging may be helpful in confirming the cystic nature of these lesions. Technetium-99m pertechnetate scintigraphy is the most effective method for differentiation of the disease from other mediastinal cysts.

Neuroblastoma (NB) is a pediatric solid tumor derived from neural crest precursor cells. It is resistant to current therapeutic protocols, including high dose chemotherapy. The mechanisms of chemoresistance are very complex. The recent studies have shown that the levels of tyrosine kinase receptor B (TrkB) and brain-derived neurotrophic factor (BDNF) are high in NB tumors with poor prognosis. The aim of this research was to explore the effects of TrkB and BDNF levels on the chemotherapeutic sensitivity in neuroblastoma by using the NB cell line SH-SY5Y in vitro.The expression of TrkB protein was detected with Western-blot after the treatment with different concentrations of all trans-retinoic acid (ATRA). Cell survival rate was analyzed using MTT. Apoptosis was detected using flow cytometry (FCM) and a transmission electron microscope (TEM).(1) The expression of TrkB protein was undetectable in SY5Y. It was positive, however, after the treatment with ATRA (1, 10, 100 nmol/L) for five days. The level of TrkB protein was increased with adding of ATRA at different concentrations. (2) The difference of the survival and apoptotic rate between the BDNF (10 ng/ml) + ATRA (10 nmol/L) + cisplatin (CP, 5 microg/ml) group (survival rate 46.51% +/- 13.44%, apoptosis rate 11.79% +/- 1.53%) and the CP alone group (survival rate 38.51% +/- 9.66%, apoptosis rate 14.95% +/- 2.06%) was not statistically significant (P0.05). The survival rate of the BDNF (50 ng/ml and 100 ng/ml) + ATRA (10 nmol/L) + CP (5 microg/ml) group (66.85% +/- 18.39%, 94.30% +/- 10.71%) was greatly higher than CP alone group (P0.05, P0.01), whereas the apoptotic rate (9.36% +/- 1.03%, 5.20% +/- 1.99%) was significantly lower than that of the CP alone group (P0.01, P0.01). The survival rates of BDNF (100 ng/ml) + ATRA (10 nmol/L) + CP (5 microg/ml) group were higher than those of BDNF (50 ng/ml) + ATRA (10 nmol/L) + CP (5 microg/ml) group (P0.01), whereas the apoptotic rates were lower than those of BDNF (50 ng/ml) + ATRA (10 nmol/L) + CP (5 microg/ml) group (P0.05). There were no significant difference between the ATRA (1 nmol/L) + BDNF (50 ng/ml) + CP group (survival rate 45.33% +/- 11.83%, apoptosis rate 12.48% +/- 2.48%) and the CP alone group in the survival and apoptotic rates (P0.05). The survival rates of the ATRA (10 nmol/L, 100 nmol/L) + BDNF (50 ng/ml) + CP (61.62% +/- 18.53%, 105.02% +/- 5.55%) group were greatly higher than those of the CP alone group (P0.05, P0.01), whereas the apoptotic rate (9.36% +/- 1.03%, 5.05% +/- 1.88%) was significantly lower than that of the CDDP alone group (P0.05, P0.01). The survival rates of the ATRA (100 nmol/L) + BDNF (50 ng/ml) + CP group were higher than those of the ATRA (10 nmol/L) + BDNF (50 ng/ml) + CP group (P0.01), whereas the apoptotic rates were lower than the ATRA (10 nmol/L) + BDNF (50 ng/ml) + CP group (P0.01). (3) Some of the cells showed apoptotic changes in the CP alone group, whereas the intranuclear chromoplasma was well-distributed, the nuclear membrane was clear, and mitochondria, ribosome and solvent were present in the ATRA (10 nmol/L) + BDNF (50 ng/ml) + CP group.The sensitivity of SY5Y to CP was affected by TrkB and BDNF. The higher the level of TrkB and BDNF was, the lower the sensitivity of SY5Y to CP.

Solid cystic papillary tumor (SCPT) of the pancreas in children is rare with limited references of its clinical features and treatment. Therefore, to estimate the clinicopathologic features of SCPT of the pancreas in children is necessary.Clinical data of 8 children with pathologically confirmed SCPT of the pancreas, treated from 2000 to 2005 with surgery, were analyzed retrospectively. The clinicopathologic features were analyzed with literature review.All patients were girls but one, with the average age of 12.8 years. The chief complaints were burbulence, abdominal pain, and palpable mass. The tumors were mainly located in the head or tail of the pancreas. Of the 8 patients, 1 received local resection, 5 received distal pancreatectomy, 1 received pancreatico-duodenectomy, and 1 received only biopsy. Seven patients were followed-up for 2 months to 4 years and were still alive; 2 patients suffered recurrence. All cases showed solid with cystic areas and papillary protrusions. Immunohistochemically, the positive rates were 100% for alpha-antitrypsin, 87.5% for vinmentin, and 62.5% for neuron-specific enolase.SCPT of the pancreas occurs predominantly in young girls, and its pathogenesis is still unknown. Surgical resection is usually curative, and the prognosis is good.

Primary non-Hodgkin's lymphomas of the gastrointestinal tract are rare in children, and few of these lymphomas are located in the sigmoid colon. The preoperative diagnosis rate is low. Complete resection is indicated if it can be done safely. Combination chemotherapy after resection is indicated.

The immunomodulatory effects of dihydroetorphine were systematically investigated in subchronically treated mice. In a dose-dependent fashion, dihydroetorphine (total doses at 444.5, 889 and 1778 μg/kg) lowered the increase of body weight, decreased the weight of the spleen and thymus, weakened the delayed-type hypersensitivity, reduced the generation of antibody-forming cells, inhibited splenic lymphocyte proliferation induced by concanavalin A and lipopolysaccharide, suppressed the production of interleukin-2 in the supernatant of splenocytes induced by concanavalin A, and depleted the ratio of CD4 + and CD8 + subpopulations. Moreover, the physical dependence on dihydroetorphine was also evaluated to confirm that the immunosuppression was concomitant with the addiction to the drug. These results demonstrate that subchronic treatment with dihydroetorphine dose dependently suppresses both humoral and cell-mediated immune function, and that the immunosuppressive effects of dihydroetorphine are much more potent than those of morphine.