Objective:To analyze the treatment outcomes and prognoses of children with head and neck non-parameningeal rhabdomyosarcoma (HNnPM RMS).Methods:A retrospective analysis was performed on the clinical data of children with HNnPM RMS admitted to Beijing Children′s Hospital from September 2012 to September 2022. The clinical features, comprehensive treatment modes and prognoses of the patients were analyzed. The overall survival rate (OS) and event free survival rate (EFS) were calculated using the Kaplan-Meier method, and univariate analysis was performed using the Log-rank test.Results:A total of 70 children were included in this study, 38 males and 32 females, with a median age of 47 months (2-210 months). Pathological subtypes including the embryonal in 27 cases, the alveolar in 36 cases and the spindle cell and sclerosing in 7 cases. Thirty children (83.3%) with alveolar type were positive for FOXO1 gene fusion. All 70 children underwent chemotherapy, including 38 with neoadjuvant chemotherapy and 32 with adjuvant chemotherapy. Sixty of 70 children underwent surgery, of whom, 10 underwent two or more surgeries. There were 63 children underwent radiotherapy, including 54 with intensity-modulated radiation therapy, 4 with particle implantation and 5 with proton therapy. The median follow-up was 45 (5-113) months, the 5-year OS was 73.2%, and the 5-year EFS was 57.7%. Univariate analysis showed lymph node metastasis ( χ2=5.022, P=0.025), distant metastasis ( χ2=8.258, P=0.004), and high Intergroup Rhabdomyosarcoma Study (IRS) group ( χ2=9.859, P=0.029) as risk factors for poor prognosis. Before June 2016, the 5-year OS based on BCH-RMS-2006 scheme was 63.6%, and after 2016, the 5-year OS based on CCCG-RMS-2016 scheme was 79.6%. Conclusion:Multidisciplinary combined standardized treatment can offer good treatment outcome and prognosis for children with HNnPM RMS. Local control is a key to the efficacy of comprehensive treatment.

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

Objective:To investigate whether SKA1 is a key molecule regulating malignant proliferation of liver cancer, and further explore its mechanism to provide molecular theoretical basis for subsequent targeted therapy.Methods:The data of liver cancer from TCGA database were analyzed by bioinformatics technology. The expression of SKA1 in liver cancer was analyzed. At the same time, we also analyzed the relationship between the expression of SKA1 and the prognosis of patients with liver cancer. The hepatoma cell line overexpressing SKA1 was constructed by liposome-mediated cell transfection technique, and the effect of SKA1 on the proliferation of hepatoma cells was further tested by CCK-8 and plate cloning assay. At the same time, we found that E2F1 is also highly expressed in liver cancer, using bioinformatics technology to analyze the correlation between SKA1 and E2F1 expression, further detecting the binding site of E2F1 in the SKA1 promoter region, and using dual luciferase technology to detect E2F1 against SKA1. Transcriptional activation.Results:KA1 was highly expressed in liver cancer tissues, and the overall survival rate of liver cancer patients with high SKA1 expression was 49.8%, lower than that of patients with low SKA1 expression, showing a negative correlation. E2F1 is also highly expressed in liver cancer tissues, and the survival time of patients with liver cancer with high E2F1 expression is significantly lower than that in the low expression group, which was negatively correlated with poor prognosis. SKA1 overexpression could increase the proliferation ability of liver cancer cells by nearly 50%. SKA1 is regulated by the E2F1 transcription factor, and the E2F1 transcription factor is combined with the SKA1 promoter to transcriptionally activate the expression of SKA1 in liver cancer cells.Conclusion:E2F1 transcriptional activation of SKA1 promotes proliferation of hepatoma cells, leading to poor prognosis in patients with liver cancer

Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Objective:To evaluate the effect of stellate ganglion block on nighttime sleep quality in the patients with primary sleep disorders.Methods:Sixty patients of both sexes with primary sleep disorders, of American Society of Anesthesiology physical status Ⅰ or Ⅱ, aged 18-64 yr, weighing 40-75 kg, were randomized to 2 groups ( n=30 each): control group (group C) and stellate ganglion block group (group S). In group S, 0.2% ropivacaine 5 ml was injected into the surface of the right longus colli muscle where the the stellate ganglion was located under ultrasound guidance once a day for 7 consecutive days starting from 1 h before bedtime.While the equal volume of normal saline was given instead in group C. Patients′ Subjective Sleep Quality was assessed using the Pittsburgh Sleep Quality Index Questionnaire before treatment (T 0) and 1-7 days after treatment.The objective sleep quality was evaluated with polysomnography.A bispectral index(BIS)monitor and a cerebral and regional blood oxygen monitoring system were used to monitor the BIS value and regional cerebral oxygen saturation (rSO 2) during sleep, which were recorded once every 30 min, and the 7-day average was calculated.The patients′ daytime advanced cognitive function was assessed for 3 consecutive days after the end of treatment (T 8-10), including the Continuous Attention Test and the Behavioral Test for Performing Defect Syndrome, and the 3-day average value was calculated.Venous blood samples were collected at T 0 and T 8 to measure the plasma noradrenaline, cortisol, and serotonin concentrations by high-performance liquid chromatography. Results:Compared with group C, the individual and total scores of Pittsburgh Sleep Quality Index were significantly decreased, the sleep latency, awakening time and fast wave sleep latency were shortened, the number of awakening was increased, the total sleep time was prolonged, the sleep efficiency and proportion of fast wave sleep were increased, S 1-S 2 ratio in slow-wave sleep was decreased, S 3-S 4 ratio was increased, BIS value was decreased, rSO 2 was increased, each parameter of Continuous Attention Test was decreased and each parameter of Behavioral Test for Performing Defect Syndrome was increased after treatment, and plasma noradrenaline level was decreased at T 8 in group S ( P<0.05). Conclusion:Stellate ganglion block can improve nighttime sleep quality in patients with primary sleep disorders.

Objective To investigate the clinical significances of additional chromosome abnormalities and t(15;17) in acute promyelocytic leukemia (APL). Methods A total of 90 newly diagnosed APL patients in the Affiliated Hospital of Qingdao University from January 2007 to June 2014 were analyzed retrospectively. Patients with different chromosome karyotypes were divided into four groups: additional chromosome number abnormalities group (16 cases), additional chromosome structural abnormalities group (14 cases), additional chromosome number and structural abnormalities group (4 cases) and typical chromosome group (56 cases). According to whether the patient contained t(15;17), the patients were divided into group with t (15;17) and group without t (15;17). The short-term efficacy and survival of each group were analyzed and compared. Results The rate of complete remission in additional chromosome number abnormalities group, additional chromosome structural abnormalities group, additional chromosome number and structural abnormalities group and typical t(15;17) chromosome changes group were 56.3％(9/16), 100.0％(14/14), 25.0％(1/4) and 82.1％(46/56), the early mortality rates were 25.0％(4/16), 0 (0/14), 75.0％(3/4) and 8.9％ (5/56) respectively. Among them, the additional number and structural abnormalities group had lower complete remission rate and higher early mortality rate, and compared with other groups, the differences were statistically significant (all P< 0.05). The complete remission rates of the group with t (15;17) and the group without t (15;17) were 80.5％ (66/82) and 50.0％ (4/8), respectively, and the difference was not statistically significant (P= 0.070). Conclusions APL patients with karyotypes with additional number and structural changes have low complete remission rate, high early mortality rate and poor prognosis. Patients with t(15;17)have a high rate of complete remission.

Objective To study and analyze the current situation of patient medication guide in foreign countries, aiming to provide references for the preparation of patient medication guide in China. Methods The current situation of patient medication guide by consulting literatures was mastered. In addition,the design concept of patient medication guide in foreign countries was summarized, the existing problems were analyzed, and the need for improvement was discussed. Results America,Australia,European countries and some Asian countries have developed a mature patient medication guide system under the supervision of the government departments. Patient medication information overseas takes patients ' health literacy into consideration.It employs the concept of information design,focuses on risks and adverse reactions of drugs,and tells patients how to communicate with doctors and pharmacists.At the same time,it has some problems such as improper content and presentation, excessive emphasis on medication risk, not satisfying drug information demand of patients, as well as a lack of medication information for special groups such as the elderly. Conclusion The design,management and practice of patient medication guide in foreign countries set a good example for us.

Objective To investigate the effect of CXCL12 on the secretion of CXCL8 from colon cancer cells and the mechanism of co-regulation of proliferation and metastasis of colon cancer.Methods The expression levels of CXCL8 and CXCl12 in 5 human colon cancer cell lines (DLD-1,HT29,WiDr,CaCo-2,Colo320),fibroblasts,and human umbilical vein endothelial cells (HUVEC) were studied by Western blotting,respectively.ELISA,proliferation and invasion assay were used to explore the role of CXCL12 and CXCL8 for metastatic process of colon cancer and interaction between colon cancer cell and stromal cell in the microenvironment,respectively.Results The expression of CXCL8 was detected in all colon cancer cell lines,fibroblasts and HUVEC,while CXCL12 was expressed only in DLD-1 cell and fibroblast.The secretion level of CXCL8 in CaCo-2,WiDr,HT-29 and HUVEC (2.54-fold vs.control,2.07-fold vs.control,1.87-fold vs.control,2.79-fold vs.control) was enhanced by CXCL12 that derived from fibroblasts(P ＜ 0.01).CXCL8 could significantly promote the proliferation,migration of HUVEC (P ＜0.01).CXCL8 and CXCL12 enhanced proliferation of HUVEC (P ＜ 0.01),invasion of HUVEC and HT-29 (P ＜ 0.01) in a concentration-dependent manner.Conclusion Fibroblasts derived CXCL12 enhanced the CXCL8 secretion in colon cancer cells,and CXCL8 and CXCL12 can promote the proliferation and invasion of colon cancer cells.

OBJECTIVETo investigate the effects of polyunsaturated fatty acids (PUFA) ω-3 and ω-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism.

METHODSThe effects of ω-3, ω-6, PGE2, PGE3 on the proliferation and migration of human umbilical vein endothelial cell (HUVEC) were measured by proliferation and migration assay respectively. The angiogenesis assay in vivo was used to measure the effects of ω-3, ω-6, PGE2 and PGE3 on neovascularization. In all the assays, groups without ω-3, ω-6, PGE2 and PGE3 were designed as the control.

RESULTSWith the increased concentration of ω-6 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs enhanced, and the number of migration cells also increased from 28.2±3.0 to 32.8±2.1, which was higher than control group (21.2±3.2) respectively (both P<0.05). With the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs was inhibited, and the number of migration cells decreased from 15.8±2.0 to 11.0±2.1, which was lower than control group (22.1±3.0) respectively (both P<0.05). In the angiogenesis assay, compared with control group (standard number: 43 721±4 654), the angiogenesis ability of HUVECs was significantly enhanced by ω-6 in concentration-dependent manner (1 μmol/L group: 63 238±4 795, 10 μmol/L group: 78 166±6 123, all P<0.01). Meanwhile, with the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the angiogenesis ability was significantly decreased from 30 129±3 102 to 20 012±1 541(all P<0.01). The proliferation and migration ability of HUVECs were significantly promoted by ω-6 metabolites PGE2 (P<0.05) in a concentration-dependent manner. In contrast, ω-3 metabolites PGE3 significantly inhibited the proliferation and migration ability of HUVECs in a concentration-dependent manner (all P<0.05). After rofecoxib (a COX-2 specific inhibitor) inhibited the expression of COX-2, the expression level of PGE2 was significantly decreased in a dose-dependent manner. In co-culture system, whose gastric cancer cells expressed positive COX-2, ω-6 could increase angiogenesis of gastric cancer cells(P<0.01), but ω-3 could inhibit such angiogenesis(P<0.01). In co-culture system, whose gastric cancer cells did not express COX-2, ω-3 could inhibit the angiogenesis of gastric cancer cells (P<0.05), but ω-6 had no effect on angiogenesis.

CONCLUSIONSThe PUFA ω-6 can enhance the angiogenesis via the promotion of proliferation and migration of HUVECs, and COX-2 and PGE2 may play an important role in this process, whereas, the ω-3 can inhibit the angiogenesis through its middle metabolites PGE3 to inhibit the proliferation and migration of HUVECs. Results of this experiment may provide a new approach to inhibit and prevent the spread of gastric cancer.

Alprostadil ; analogs & derivatives ; pharmacology ; Angiogenesis Inducing Agents ; metabolism ; pharmacology ; Angiogenesis Inhibitors ; pharmacology ; Cell Count ; methods ; Cell Line, Tumor ; drug effects ; physiology ; Cell Migration Assays ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Coculture Techniques ; Cyclooxygenase 2 ; pharmacology ; Dinoprostone ; metabolism ; pharmacology ; Fatty Acids, Omega-3 ; pharmacology ; Fatty Acids, Omega-6 ; metabolism ; pharmacology ; Fatty Acids, Unsaturated ; pharmacology ; Human Umbilical Vein Endothelial Cells ; drug effects ; physiology ; Humans ; Lactones ; pharmacology ; Neovascularization, Pathologic ; physiopathology ; Stomach Neoplasms ; physiopathology ; Sulfones ; pharmacology