OBJECTIVE To set up normal ranges for indexes in embryo-fetal development toxicity studies in Sprague-Dawley(SD)rats and to establish a background database to provide reference for the embryo-fetal development toxicity evaluation of drugs.METHODS The data on embryonic develop-ment and fetal growth from embryo-fetal development toxicity studies(11 items)conducted by our center between 2013 and 2022 was statistically analyzed,involving 205 pregnant rats and 3037 fetuses in total,with the mean and standard deviation,coefficient of variation and 95%confidence interval calculated.The indexes included body mass,body mass gain and food consumption during pregnancy,pregnancy outcomes(pregnancy rate,average corpora lutea,average Implant sites,average live conceptuses,live conceptuse rate,resorption rate and dead conceptuse rate),fetal growth and development(fetal mass,placental mass and sex ratio),appearance abnormality rate,visceral abnormality rate,and skeletal abnormality rate.RESULTS The mass of pregnant rats trended up during gestation,with significant increases in the late period.Food consumption increased along with gestation.Caesarean section was conducted on gestation day 20,and the pregnancy rate was 93.2%.The average corpora lutea,Implant sites and live conceptuses were 18.0±3.2,15.9±2.8 and 14.8±3.0,respectively.The live conceptuse rate was 93.4%while the total dead embryo rate was 6.6%.The average mass of fetuses and placenta were respectively 3.6±0.3 and(0.6±0.3)g,and the fetal sex ratio(male/female)was 0.94.The incidence of fetal appearance abnormalities was about 0.2%,and that of soft tissue abnormalities was approximately 0.8%.The rate of skeletal abnormalities was about 1.2%,with higher incidence of non-ossification and incomplete ossification mostly identified on sternum and hyoid bone.The numbers of ossifications of metacarpal bones,metatarsal bones and sacrococcygeal vertebrae were 7.0±0.7,8.0±0.1 and 7.4±0.5,respectively.The rate of ossification of sternumⅠtoⅣwas higher,with an average of about 98.6%-99.9%.The ossification rates of sternum Ⅴ and Ⅵ were(68.0±28.4)%and(82.8±23.9)%.CONCLUSION The background database of indexes in the embryo-fetal development toxicity study on SD rats is established for our GLP laboratory,which provides reference for reproductive toxicity studies.

Objective:To analyze the influencing factors and improvement paths of the cultivation of full-time doctoral scientific and technological innovation ability in large public hospitals, and propose countermeasures and suggestions.Methods:This studyed conducted a survey and analysis of 122 doctors from Linyi People′s Hospital in Shandong Province, and completed a current situation study based on the analysis results.Results:There was no significant difference between the two groups in gender, age, degree type, professional category, discipline level, Graduate School type, job type and other indicators. There were significant differences between the two groups in scientific research topic selection ability score, project design ability score, data analysis ability score, data interpretation ability score, project approval in recent 5 years, project level, number of SCI journal papers published in recent 5 years, cumulative impact factors of SCI journal papers, and annual number of academic activities ( P<0.05). Conclusions:The hospital can improve the scientific and technological innovation ability of full-time doctors by setting up a special cultivation plan, establishing an interdisciplinary team, optimizing scientific research management services, improving the evaluation and assessment system, and improving welfare protection.

Objective:To explore the short-term and long-term prognostic outcomes of anatomical liver resection(AR)for patients with perihilar cholangio-carcinoma. Methods:This is a retrospective study.All data were obtained from 4 centers,including The First Affiliated Hospital of Army Medical University,Eastern Hepatobiliary Hospital of Naval Medical University,Sichuan Provincial People's Hospital and Affiliated Hospital of Qinghai University,of a multi-center database.A total of 305 consecutive perihilar cholangiocarcinoma patients receiving radical resection between January 2013 and June 2021 were included in this study.According to the method of liver resection,all patients were divided into the AR group(n=205)and the non-anatomical liver resection(NAR)group(n=100).The baseline characteristics,short-term prognosis and long-term prognosis of the 2 groups were compared. Results:The perioperative transfusion rate and the 30-day complication rate were significantly lower in the AR group than those in the NAR group(P＜0.05).There was no statistically significant difference in the survival rates between the AR and the NAR groups(P＞0.05). Conclusion:The 2 hepatic resection modalities had no obvious effect on the long-term prognosis of perihilar cholangiocarcinoma patients after radical resection,but choosing AR tends to achieve a better short-term prognosis and is worth promoting in clinical practice.

OBJECTIVE To establish a comprehensive and rapid m ethod for the a nalysis of chemical constituents as phthalides and organic acids in Angelica sinensis ，and to provide scientific reference for the quality evaluation and pharmacodynamic substance research of A. sinensis . METHODS The 70％ ethanol extract of A. sinensis was analyzed by ultra high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF/MS）. The determination was performed on ACQUITY UPLC BEH-C 18 column with mobile phase consisted of 0.1％ formic acid solution- acetonitrile（gradient elution ）at the flow rate of 0.3 mL/min. The column temperature was set at 30 ℃，and sample size was 2 µL. The ion source was an electrospray ion source ，using positive ion scanning mode ，and the mass scanning range was m/z 50-1 000. Capillary voltage was 4 000 V； atomizer pressure was 35 psi；cracking voltage was 135 V and the taper hole voltage was 65 V；the temperature of dry gas was 320 ℃；the flow of dry gas was 10 L/min and the flow of sheath gas was 11 L/min；collision energy were 20 and 40 V. Qualitative Analysis 10.0 software was used to obtain the retention time of compounds ，the accurate mass number of excimer ion peaks and secondary fragments. The compounds were analyzed by comparing with the mass spectra of the reference substance ，combined with relevant literature ，mass spectrometry cleavage law and database such as Chemspider ，MassBank，PubChem. RESULTS A total of 72 compounds were identified or deduced from A. sinensis ，including 55 phthalides，13 organic acids and 4 other constituents. CONCLUSIONS The established method is rapid and accurate for the identification of chemical constituents from A. sinensis ，such as organic acids and phthalides ，which provides an efficient and rapid analytical method for the comprehensive characterization of its chemical constituents.

Objective To investigate the synergistic effect of hyperhomocystinemia (HHcy) and smoking on the incidence of Coronary heart disease. Methods A total of 22 043 subjects were enrolled from health care center. Participants were classified into two groups: Non-coronary heart disease group (control group, n = 19 410) and coronary heart disease group(n=2 633).A questionnaire survey,physical examination and blood homocysteine (Hcy)test were carried out among the participants.Results After controlling the confounding factors,multivariable Logistic regression analysis showed that the risk of coronary heart disease in patients with smoking was 4.832 times higher than that of patients with normal waistline. The risk of coronary heart disease in patients with HHcy was 1.019 times higher than that of patients with normal Hcy (OR = 4.832,1.019,P < 0.05).Interaction analysis showed that the risk of patients with HHcy and smoking was 2.473 times higher than that of patients without HHcy and no-smoking.The synergy index between HHcy and smoking on the incidence of Coronary heart disease was 1.739. The pure attributable proportion due to the interaction was 42.9%. Conclusions HHcy and smoking are risk factors for coronary heart disease and there is a positive synergistic effect between HHcy and smoking on the incidence of coronary heart disease.

Objective:To explore therapeutic effect of atorvastatin on inflammatory factor levels and vascular endothelial function in patients with coronary heart disease (CHD).Methods: A total of 112 CHD patients treated in our hospital were selected.According to random number table, they were randomly and equally divided into routine treatment group and atorvastatin group, and both groups were treated for eight weeks.Serum levels of inflammatory factors and vascular endothelial function before and after treatment, angina pectoris and ECG therapeutic effect after treatment, and incidence of adverse reactions during medication were compared between two groups.Results: Compared with before treatment, after treatment, there were significant reductions in serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, C reactive protein (CRP), intercellular adhesion molecule (ICAM)-1 and endothelin (ET)-1, and significant rise in nitric oxide (NO) level, left ventricular ejection fraction (LVEF) and cardiac output (CO) in both groups,P<0.01 all;compared with routine treatment group after treatment, there were significant reductions in serum levels of IL-6 [(157.42±30.13) pg/ml vs.(129.83±27.31) pg/ml], TNF-α [(25.41±2.67) ng/L vs.(21.38±2.13) ng/L], CRP [(19.87±2.78) mg/L vs.(17.13±2.04) mg/L], ICAM-1 [(81.23±19.83) pg/ml vs.(64.31±15.46) pg/ml] and ET-1 [(1.45±0.34) pg/ml vs.(0.87±0.23) pg/ml], and significant rise in NO level [(53.27±5.31) mmol/L vs.(58.72±5.46) mmol/L], LVEF [(52.37±5.38)% vs.(63.19±5.79)%] and CO [(4.58±0.78) L/min vs.(5.13±0.82) L/min] in atorvastatin group, P<0.01 all.Compared with routine treatment group, there were significant rise in total effective rates of angina pectoris (73.22% vs.89.29%) and ECG (66.07% vs.83.93%) in atorvastatin group, P<0.05 both.There were no serious adverse drug reactions in two groups.Conclusion: Atorvastatin can significantly improve inflammation state and vascular endothelial function in patients with coronary heart disease.

OBJECTIVETo study the molecular mechanism of cisplatin to enhance the ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in reversing multidrug resistance in vincristine-resistant human gastric cancer SGC7901/VCR cells.

METHODSMTT assay was used to measure the 50% inhibiting concentration (IC₅₀) and cell survival in SGC7901 and SGC7901/VCR cells after different treatments. SGC7901/VCR cells were treated with different concentrations of DDP, different concentrations of TRAIL alone or in combination, and then the mRNA and protein levels of several genes were determined by RT-PCR, RT-qPCR and Western-blot analysis. After targeted silencing with specific siRNA and transfection of recombinant plasmid c-myc into the SGC7901/VCR cells, the mRNA and protein levels of DR4, DR5 and c-myc were determined by RT-PCR and Western-blot analysis.

RESULTSAfter combined treatment with TRAIL and DDP of the SGC7901/VCR cells, the IC₅₀ of VCR, DDP, ADM, and 5-Fu treatment was significantly decreased compared with the control group or TRAIL-treated group (P < 0.05). After treatment with 0, 10, 50 ng/ml TRAIL in combination with 0.4 µg/ml DDP, the SGC7901/VCR cells showed significantly higher activation of caspase 3, down-regulation of DNA-PKcs/Akt/GSK-3β signaling pathway, and higher inhibition of MDR1(P-gp) and MRP1 than those treated with TRAIL alone (P < 0.01 for all). The mRNA and protein levels of DR4, DR5, c-myc were significantly decreased after silencing c-myc with specific siRNA in the SGC7901/VCR cells (P < 0.01 for all), and were significantly increased after transfection of recombinant plasmid c-myc into the SGC7901/VCR cells (P < 0.01 foe all). After the treatment with 10 ng/ml TRAIL, 0.25 µg/ml DDP + 10 ng/ml TRAIL and 0.5 µg/ml DDP + 10 ng/ml TRAIL, the relative expression level of c-myc protein in the SGC7901/VCR cells was 0.314 ± 0.012, 0.735 ± 0.026, and 0.876 ± 0.028, respectively, and the relative expression of cytochrome C was 0.339 ± 0.036, 0.593 ± 0.020 and 0.735 ± 0.031, respectively, and the relative expression levels of DR4, DR5, active-caspase 3 and active-caspase 9 in the SGC7901/VCR cells were also increased along with increasing DDP concentrations.

CONCLUSIONSThe activation of DNA-PKcs/Akt/GSK-3β signaling pathway and high expression of MDR1 and MRP1 play an important role in the multi-drug resistance properties of SGC7901/VCR cells. After combining with TRAIL, DDP can enhance the expression of DR4 and DR5 through up-regulating c-myc and enhancing the activation of caspase 3 and caspase 9 by facilitating mitochondrial release of cytochrome C. It may be an important molecular mechanism of DDP-induced sensitization of TRAIL to reverse the multidrug resistancein SGC7901/VCR cells.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; pharmacology ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cisplatin ; administration & dosage ; pharmacology ; Down-Regulation ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Fluorouracil ; administration & dosage ; pharmacology ; Formazans ; Genes, myc ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Inhibitory Concentration 50 ; Multidrug Resistance-Associated Proteins ; metabolism ; Neoplasm Proteins ; metabolism ; Plasmids ; Proto-Oncogene Proteins c-myc ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; pharmacology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Stomach Neoplasms ; drug therapy ; pathology ; TNF-Related Apoptosis-Inducing Ligand ; administration & dosage ; pharmacology ; Tetrazolium Salts ; Transfection ; methods

Objective To study the molecular mechanism of cisplatin to enhance the ability of tumor necrosis factor?related apoptosis?inducing ligand ( TRAIL ) in reversing multidrug resistance in vincristine?resistant human gastric cancer SGC7901/VCR cells. Methods MTT assay was used to measure the 50% inhibiting concentration( IC50 ) and cell survival in SGC7901 and SGC7901/VCR cells after different treatments.SGC7901/VCR cells were treated with different concentrations of DDP, different concentrations of TRAIL alone or in combination, and then the mRNA and protein levels of several genes were determined by RT?PCR, RT?qPCR and Western?blot analysis. After targeted silencing with specific siRNA and transfection of recombinant plasmid c?myc into the SGC7901/VCR cells, the mRNA and protein levels of DR4, DR5 and c?myc were determined by RT?PCR and Western?blot analysis. Results After combined treatment with TRAIL and DDP of the SGC7901/VCR cells, the IC50 of VCR, DDP, ADM, and 5?Fu treatment was significantly decreased compared with the control group or TRAIL?treated group (P<0.05). After treatment with 0, 10, 50 ng/ml TRAIL in combination with 0. 4 μg/ml DDP, the SGC7901/VCR cells showed significantly higher activation of caspase 3, down?regulation of DNA?PKcs/Akt/GSK?3β signaling pathway, and higher inhibition of MDR1(P?gp) and MRP1 than those treated with TRAIL alone (P<0.01 for all). The mRNA and protein levels of DR4, DR5, c?myc were significantly decreased after silencing c?myc with specific siRNA in the SGC7901/VCR cells ( P<0. 01 for all ) , and were significantly increased after transfection of recombinant plasmid c?myc into the SGC7901/VCR cells (P<0.01 foe all). After the treatment with 10 ng/ml TRAIL, 0. 25 μg/ml DDP+10 ng/ml TRAIL and 0. 5 μg/ml DDP+10 ng/ml TRAIL, the relative expression level of c?myc protein in the SGC7901/VCR cells was 0.314±0.012, 0.735±0.026, and 0.876±0.028, respectively, and the relative expression of cytochrome C was 0.339±0.036, 0.593±0.020 and 0.735±0.031, respectively, and the relative expression levels of DR4, DR5, active?caspase 3 and active?caspase 9 in the SGC7901/VCR cells were also increased along with increasing DDP concentrations. Conclusions The activation of DNA?PKcs/Akt/GSK?3β signaling pathway and high expression of MDR1 and MRP1 play an important role in the multi?drug resistance properties of SGC7901/VCR cells. After combining with TRAIL, DDP can enhance the expression of DR4 and DR5 through up?regulating c?myc and enhancing the activation of caspase 3 and caspase 9 by facilitating mitochondrial release of cytochrome C. It may be an important molecular mechanism of DDP?induced sensitization of TRAIL to reverse the multidrug resistancein SGC7901/VCR cells.

Objective To study the molecular mechanism of cisplatin to enhance the ability of tumor necrosis factor?related apoptosis?inducing ligand ( TRAIL ) in reversing multidrug resistance in vincristine?resistant human gastric cancer SGC7901/VCR cells. Methods MTT assay was used to measure the 50% inhibiting concentration( IC50 ) and cell survival in SGC7901 and SGC7901/VCR cells after different treatments.SGC7901/VCR cells were treated with different concentrations of DDP, different concentrations of TRAIL alone or in combination, and then the mRNA and protein levels of several genes were determined by RT?PCR, RT?qPCR and Western?blot analysis. After targeted silencing with specific siRNA and transfection of recombinant plasmid c?myc into the SGC7901/VCR cells, the mRNA and protein levels of DR4, DR5 and c?myc were determined by RT?PCR and Western?blot analysis. Results After combined treatment with TRAIL and DDP of the SGC7901/VCR cells, the IC50 of VCR, DDP, ADM, and 5?Fu treatment was significantly decreased compared with the control group or TRAIL?treated group (P<0.05). After treatment with 0, 10, 50 ng/ml TRAIL in combination with 0. 4 μg/ml DDP, the SGC7901/VCR cells showed significantly higher activation of caspase 3, down?regulation of DNA?PKcs/Akt/GSK?3β signaling pathway, and higher inhibition of MDR1(P?gp) and MRP1 than those treated with TRAIL alone (P<0.01 for all). The mRNA and protein levels of DR4, DR5, c?myc were significantly decreased after silencing c?myc with specific siRNA in the SGC7901/VCR cells ( P<0. 01 for all ) , and were significantly increased after transfection of recombinant plasmid c?myc into the SGC7901/VCR cells (P<0.01 foe all). After the treatment with 10 ng/ml TRAIL, 0. 25 μg/ml DDP+10 ng/ml TRAIL and 0. 5 μg/ml DDP+10 ng/ml TRAIL, the relative expression level of c?myc protein in the SGC7901/VCR cells was 0.314±0.012, 0.735±0.026, and 0.876±0.028, respectively, and the relative expression of cytochrome C was 0.339±0.036, 0.593±0.020 and 0.735±0.031, respectively, and the relative expression levels of DR4, DR5, active?caspase 3 and active?caspase 9 in the SGC7901/VCR cells were also increased along with increasing DDP concentrations. Conclusions The activation of DNA?PKcs/Akt/GSK?3β signaling pathway and high expression of MDR1 and MRP1 play an important role in the multi?drug resistance properties of SGC7901/VCR cells. After combining with TRAIL, DDP can enhance the expression of DR4 and DR5 through up?regulating c?myc and enhancing the activation of caspase 3 and caspase 9 by facilitating mitochondrial release of cytochrome C. It may be an important molecular mechanism of DDP?induced sensitization of TRAIL to reverse the multidrug resistancein SGC7901/VCR cells.

OBJECTIVETo study the pathologic characteristics and prognosis in different subtypes of adult medulloblastoma (MB).

METHODSThe clinical information, imaging findings and pathologic characteristics of 151 cases of adult medulloblastomas were retrospectively reviewed and analyzed by chi-square test. The survival data were assessed using the Kaplan-Meier method.

RESULTSAmongst the 151 MB cases studied, there were 73 cases of classic MB, 36 cases of desmoplastic/nodular MB, 39 cases of anaplastic MB and 3 cases of large cell MB. The primary tumors were more frequently located in cerebral hemisphere in desmoplastic/nodular MB than in other subtypes (P=0.000).On the other hand, large cell/anaplastic MB were associated with more frequently local recurrence and distant metastasis (P=0.003). The post-operative overall survival time ranged from 6 to 150 months, with median survival being (103.3±5.7) months (95%CI, 92.52 to 115.09). The median survival of classic MB, desmoplastic/nodular MB and large cell/anaplastic MB was (110.7±7.8) months, (125.5±7.6) months and (57.6±7.6) months, respectively. The differences were statistically significant (P=0.000).

CONCLUSIONSThe three variants of MB show different biologic behavior. Large cell/anaplastic MB represents an independent poor prognostic indicator in adults.

Adolescent ; Adult ; Cerebellar Neoplasms ; classification ; metabolism ; pathology ; radiotherapy ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen ; metabolism ; Male ; Medulloblastoma ; classification ; metabolism ; pathology ; radiotherapy ; surgery ; Middle Aged ; Neoplasm Recurrence, Local ; Phosphopyruvate Hydratase ; metabolism ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Analysis ; Synaptophysin ; metabolism ; Young Adult