Impact of CSF3R Mutation on Treatment Response and Survival of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CSF3R mutation in acute myeloid leukemia (AML) and analyze its clinical characteristics and prognosis.@*METHODS@#A retrospective study was conducted in 212 patients with AML who were newly diagnosed in the Second Hospital of Shanxi Medical University from January 1th 2018 to June 30th 2021, including 22 patients with CSF3R mutations as mutation group and 190 patients with CSF3R wild type ［66 cases of them were screened by propensity score matching (PSM), as control group］. The early efficacy and survival between the two groups were compared.@*RESULTS@#The median age of patients in the mutation group was 50(17-73) years old, and the ratio of male to female was 1.2:1 The main types were AML with maturation (11 cases) and acute myelomonocytic leukemia (9 cases). Prognostic stratification was carried out according to the risk stratification system of the European leukemia network in 2017, with 16 cases (72.73%) in the middle and high-risk group. At the initial diagnosis, the median count of white blood cell (WBC) was 44.75(1.30-368.71)×109/L, among which 15 cases (68.18%) were >10×109/L, and the median count of platelet (PLT) was 24(4-55)×109/L. CSF3R T618I (68.18%) was a common mutation site, which had concomitant gene mutations, in which CEBPA mutation was the most common (10 cases, 45.45%), but only existed in CSF3R T618I mutation. The CR/CRi rate was 68.18% and 71.21% in the mutant group and the control group (P >0.05), the median over all survival time was 15 months and 9 months (P >0.05), and the median disease-free survival time was 8 months and 4 months (P >0.05), respectively.@*CONCLUSION@#Most AML patients with CSF3R mutation are middle-aged patients, the main types are AML with maturation and acute myelomonocytic leukemia, and most of them have middle and high-risk prognosis. CSF3R mutation may not be an independent prognostic marker for newly diagnosed AML patients.

Applicability of Seven Glomerular Filtration Rate Evaluation Formulas in Dose Adjustment of High Concentration of Methotrexate Chemotherapy in Children with ALL / 中国实验血液学杂志

OBJECTIVE@#To investigate the diagnostic efficacy of seven glomerular filtration rate (GFR) evaluation formulas Schwartz2009, Schwartz1976, Counahan-Barratt, Filler, CKD-EPIscysc, Cockrofi-Gault, CKD-EPIScysC-Scr in high concentration of methotrexate (HDMTX) chemotherapy dose adjusted cut-off point (GFR ≤85 ml/min) in children with acute lymphoblastic leukemia (ALL).@*METHODS@#One hundred and twenty-four children with ALL were included in the study. GFR determined by renal dynamic imaging (sGFR) was used as the standard to evaluate the accuracy, consistency of eGFR calculated by seven formulas and sGFR, and the diagnostic efficacy of each formula when the sGFR ≤85 ml/min boundary.@*RESULTS@#All of the accuracy of eGFR estimated by Schwartz2009 were greater than 70% in the 0-3, >4 and ≤6, >6 and ≤9, >9 and ≤16 years old group and male group, and the consistency exceeded the professional threshold. When the sensitivity of the ROC curve sGFR ≤85 ml/min was 100% of CKD-EPIscysc in the 0-3, >3 and ≤4 years old group, Filler in the >3 and ≤4 years old group, and Cockrofi-Gault in the >6 and ≤9 years old group, the specificity was 73.02%, 78.95%, 78.95%, 69.32%, respectively, and the AUC under the ROC curve was the largest (P<0.05).@*CONCLUSION@#Schwartz2009 formula predicts the highest accuracy of eGFR in the 7 glomerular filtration rate. CKD-EPIscysc, Filler, and Cockrofi-Gault formulas have more guiding signi-ficance for the adjustment of HDMTX chemotherapy in pre-adolescence in children with ALL when sGFR ≤85 ml/min.

Advances in gut microbiomes and immunology of IgG4-related hepatobiliary and pancreatic diseases / 中华肝脏病杂志

IgG4-related disease (IgG4-RD) is an immune-mediated condition associated with chronic fibroinflammatory lesions that can affect nearly any organ. IgG4-related hepatobiliary and pancreatic diseases are IgG4-RD involving the hepatobiliary and pancreatic system, which is characterized with elevated serum IgG4 concentrations, large numbers of IgG4 positive lymphoplasma cells infiltration in affected organs, storiform fibrosis, and imaging changes of organ morphology. Due to the lack of reliable biomarkers, histopathology is still an important basis for diagnosis. The pathogenesis of IgG4-related hepatobiliary and pancreatic diseases has not been clarified. This review focuses on the recent advances in intestinal microecology-immunology, host genetics-immunity and recurrence monitoring of IgG4-related hepatobiliary and pancreatic diseases.

Association between alcohol related knowledge, attitude,practice and alcohol use disorder among high school students / 中国学校卫生

Objective@#To analyze the relationship between alcohol related knowledge, attitude,practice and alcohol use disorder among high school students, and to provide reference for alcohol abuse intervention.@*Methods@#The study adopted stratified cluster sampling. A total of 811 high school students from 4 high schools in Changning District were selected to conduct a questionnaire survey on alcohol related knowledge, attitude,practice and alcohol dependence. The software SPSS 20.0 was used for statistical analysis.@*Results@#There were 279 (34.4%) high school students with mild alcohol use disorder and 29 (3.6%) with severe alcohol use disorder. The average score of high school students alcohol related knowledge, attitude,practice scores were (9.56±3.55) ( 4.96± 2.36) and (2.81±1.29),respectively. High school students alcohol related knowledge, attitude,practice were negatively correlated with alcohol use disorder score ( r =-0.10, -0.39, -0.71, P <0.01). Multivariate Logistic regression indicated that the total score of alcohol related KAP ( OR=0.86, 95%CI =0.83-0.89) and the family economic level (high level: OR=2.05, 95%CI =1.26-3.32) were positively associated with mild alcohol use disorder. The total score of alcohol related KAP ( OR=0.76, 95%CI =0.70-0.83) and school type ( OR=3.72, 95%CI =1.51-9.18) were positively associated with severe alcohol use disorder ( P <0.05).@*Conclusion@#There is a correlation between low alcohol related KAP and alcohol use disorder, alcohol related health education should be strengthened, especially among vocational school students and students from high family economic level.

Discussion for Quality Control of Chinese Patent Drugs from Quality Difference Among Different Dosage Forms of Liuwei Dihuang Preparations / 中国实验方剂学杂志

Objective:Through comprehensive evaluation and analysis of the quality of Liuwei Dihuang （LWDH） preparations from different manufacturers and combining factors such as production technology， the key factors in the quality control of LWDH preparations are explored to provide a reference for improving the quality control level of LWDH preparations. Method:Morroniside， loganin and paeonol as quality control markers of LWDH products were determined by high performance liquid chromatography （HPLC）， the mobile phase was acetonitrile （A） -0.3% phosphoric acid aqueous solution （B） for gradient elution （0-5 min， 5%-8%A； 5-20 min， 8%A； 20-35 min， 8%-20%A； 35-45 min， 20%-60%A； 45-55 min， 60%A）， the detection wavelength of paeonol was at 274 nm， and the detection wavelengths of morroniside and loganin were at 240 nm. The quality characteristics of LWDH preparations with different dosage forms （big candied pills， water-honeyed pills， concentrated pills， hard capsules and soft capsules） from different manufacturers were analyzed. Combined these results with their actual production processes， the key-points of quality control in the whole production process were discussed. Result:The contents of three index ingredients in 128 batches of LWDH preparations were all in conformity with the standards of the 2015 edition of <italic>Chinese Pharmacopoeia</italic>， however， the content limit of some dosage forms in the current standard was unreasonable. For example， although the daily dose of crude drugs for big candied pills were almost twice the dose of water- honeyed pills （15.00， 8.57 g， respectively）， they got exactly the same daily limits of the contents for both the quality markers. What′s more， these two formulations had the same process， so the differences between the process obviously could not be the reason of these differences. Conclusion:It is recommended that for the products with different dosage forms should have a similar content limits， if there are no obvious distinctions between their production processes. Which may benefit the quality control of the products with multi-dosage forms. The research on the quality standards of proprietary Chinese medicines should deeply study the existing characteristics of the quality standards， and fully respect the laws of the quality attributes of traditional Chinese medicines and the rules of the production process of Chinese patent medicines.

Analysis of the correlation between lymphocyte subsets and severity of corona virus disease 19 / 北京大学学报(医学版)

OBJECTIVE@#To understand the differences in lymphocyte subsets in patients with different clinical classifications of corona virus disease 19 (COVID-19).@*METHODS@#Eighty-one patients with COVID-19 who were admitted to the isolation ward under the responsibility of three medical aid teams in the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from February 8, 2020 to March 28, 2020, were selected to collect clinical data. According to the relevant diagnostic criteria, the disease status of the patients was classified into moderate cases (n=35), severe cases (n=39) and critical cases (n=7) when lymphocyte subset testing was performed. Their blood routine tests, lymphocyte subsets and other indicators were tested to compare whether there were differences in each indicator between the patients of different clinical classification groups.@*RESULTS@#The differences in the absolute count of total lymphocytes, T-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and natural killer (NK) cells among the three groups of patients were all statistically significant (P < 0.05), and the critical cases were significantly lower than the moderate and severe cases in the above indicators, and the indicators showed a decreasing trend with the severity of the disease. In 22 patients, the six indicators of the absolute count of T-lymphocytes, B-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and NK cells, CD4+/CD8+ ratio were all within the normal reference range in the first test, and 59 patients had abnormalities of the above indicators, with the absolute count of NK cells and CD8+ T lymphocytes decreasing most frequently (61%, 56%). The patients with the absolute count of NK cells and CD8+ T lymphocytes below the normal reference range were one group, and the remaining abnormal patients were the other group. There were more critical cases in the former group (moderate : severe : critical cases were 4 : 8 : 7 vs. 19 : 21 : 0, respectively, P=0.001), and all the deaths were in this group (6 cases vs. 0 case, P=0.001). The absolute B lymphocyte count was below the normal reference range in 15 patients, and the remaining 64 cases were within the normal range. The ratio of moderate, severe and critical cases in the reduced group was 4 : 7 : 4, and the ratio of critical cases was more in normal group which was 30 : 31 : 3, and the difference between the two groups was statistically significant (P=0.043).@*CONCLUSION@#The more critical the clinical subtype of patients with COVID-19, the lower the absolute count of each subset of lymphocytes.

Observation on the distribution of nerve fibers and neural cells morphology in Aspidogaster conchiola / 中国血吸虫病防治杂志

Objective To understand the distribution of nerve fibers and the types of neural cells in Aspidogaster conchiola. Methods Whole worms were subjected to silver staining, histochemical staining and hematoxylin-eosin (HE) staining, and the nervous systems of the worms were observed. Results There were 3 types of neural cells in the worm head near the cerebral ganglion, including unipolar, bipolar and multipolar neurons, which were divided into 7 types according to the morphology. There was a nerve network on the surface of pharynx and intestinal tract, as well as the reproductive organ, including testis, ovary, lower uterus and penis sac. The nerve network was consisted of circular and longitudinal nerve fibers, and the structure of the nerve network around the mouth was similar to central nerve. Conclusions The structure of the A. conchiola central nervous system is very complicated, and the neural networks may be associated with the physiologic activity of the worm. Different neural cells may have diverse functions.

Effects of Chinese herbal medicine of tonifying spleen and stomach on learning and memory ability and PKA/ERK/p-CREB pathway in hippocampus of SAMP8 mice / 中草药

Objective: To study the effects of prescriptions including Ginseng Decoction, Xixin Decoction, and Dabuyuan Decoction for tonifying spleen and stomach on learning and memory ability and PKA/ERK/p-CREB pathway in hippocampus of SAMP8 mice, and explore the mechanism in the prevention and treatment of Alzheimer's disease (AD). Methods: Three-month-old SAMP8 mice were randomly divided into model group, Donepezil Hydrochloride group, prescription group of Tonifying Spleen and Stomach Yuanqi Prescription (Ginseng, Xixin Decoction, and Dabuyuan Decoction). Moreover, three-month-old SAMR1 mice were recruited as a normal control group, six groups in total. Related indices were detected after 10 weeks continuous gastrogavage. The spatial learning-memory deficit of mice was detected by Morris water maze test. The expression levels of PKA protein in hippocampal region of mice were detected by immunohistochemistry, and the expression levels of ERK and p-CREB protein in hippocampal region of mice were detected by immunofluorescence. The protein expression levels of PKA, ERK, and p-CREB in hippocampus were detected by Western blotting. Results: Compared with the model group, the escape latency of the prescription group of tonifying spleen and stomach was decreased (P < 0.05, P < 0.01), while the swimming time and the times of crossing the platform in the target quadrant were increased (P < 0.01). Results of immunohistochemistry showed that the protein expression of PKA was significantly increased and the expression of ERK and p-CREB in hippocampal region was significantly increased (P < 0.05, P < 0.01). The results of Western blotting were consistent with those of immunohistochemistry and immunofluorescence (P < 0.05, P < 0.01). Conclusion: The Tonifying Spleen and Stomach Yuanqi Prescription showed obvious improvement on the spatial learning-memory deficit in SAMP8 mice, which might be associated with affecting the PKA/ERK/p-CREB pathway in hippocampal region.

Quality Control of Zhenqi Fuzheng Granule Based on Multi-component Determination / 中国实验方剂学杂志

Objective: To estimate the overall quality characteristics of Zhenqi Fuzheng granules (ZQFZ),which were composed of Ligustri Lucidi Fructus and Astragali Radix and collected from different manufacturers (their final preparations included two types,contained sugar and sugar free) by established HPLC methods,in order to propose an appropriate quality-control strategy for promoting the quality control specification of ZQFZ.Method: The quantification of the 6 components (rhodioloside,calycosin-7-O-β-D-glucoside,specnuezhenide,ononin,calycosin and astragaloside IV) were performed on a C18 column with two chromatographic systems.Chromatographic system Ⅰ:methanol and water were adopted as mobile phase with gradient elution,the flow rate was 1.0 mL·min-1,and optimum detection waves were at 224,250 and 275 nm respectively.Chromatographic system Ⅱ:methanol and water (80:20) were adopted as mobile phase with gradient elution at the flow rate of 1.0 mL·min-1,and the detector parameters were set as follows:the drift tube temperature was 75℃,and the carrier gas flow rate was 1.5 L·min-1.Both column temperatures were at 30℃.All of the 80 batches of ZQFZ from different manufacturers were determined and analyzed.Result: All of the six markers could be detected in 80 batches of ZQFZ,but their contents were quite different.The results of the one-way ANOVA showed significant differences between manufacturer 4 and other three manufacturers in sugar-containing preparations (P PConclusion: It is of great significance to increase relevant quality control markers of Ligustri Lucidi Fructus in ZQFZ,such as rhodioloside and specnuezhenide,for standardizing production and improving quality level.

Jar-TTA, a natural diterpenoid derivatives, induces apoptosis in human esophageal cancer cells through dual inhibition of glycolysis and oxidative phosphorylation / 中国药理学通报

Aim To investigate the effects of Jar-TTA in dual inhibition of glycolysis/oxidative phosphoryla-tion in human esophageal cancer cells and explore the related molecular mechanism. Methods The effect of Jar-TTA on the esophageal cancer cell EC 109 and KYSE-150 viability was examined using MTT assay. The effect of Jar-TTA in apoptosis morphology and mitochondrial membrane potential ( MMP) was observed by a fluorescence microscopy. The apoptosis of cell lines treated with Jar-TTA, the quantitative analysis of MMP falling, as well as the glucose uptake was ana-lyzed by flow cytometry. The mitochondrial OXPHOS and glycolysis of EC 109 cells in response to Jar-TTA were analyzed using a Seahorse XFp extracellular flux analyzer by real-time measurements of the oxygen consumption rate (OCR, indicative of mitochondrial OXPHOS) and extracellular acidification rate(ECAR, indicative of glycolysis). The expression of the proteins related with glycolysis were detected by Western blot. Results Jar-TTA caused strong antiproliferation in EC 109 and KYSE-150 cells in a concentration-dependent manner. 2 , 4 and 8 jimol • L"1 Jar-TTA treat-ments of EC 109 cells for 24 h resulted in a significant increase of early apoptosis population up to (27. 9 ± 6. 1)%, (71.1 ±9.3)% and (65. 0 ±9.5)%, respectively , compared to control treated cells (5. 6 ± 3.2)%. The mitochondrial OXPHOS and glycolysis were significantly inhibited in EC 109 incubated by 4 and 8 p,mol • L"1 Jar-TTA for 2 h. In addition, Jar-TTA induced the drop of MiMP. Furthermore, the glucose uptake and the expression of GLUT4 and LDHA were distinctly inhibited in EC 109 treated by Jar-TTA. Conclusions Jar-TTA induces apoptosis of human e-sophageal cancer cells through dual inhibition of glycolysis and oxidative phosphorylation, which is related with the drop of MMP collapse, the decrease of glucose uptake and the down-regulation of GLUT4 and LDHA in EC 109 treated by Jar-TTA.

Antitumor activityand mechanism of JD20,a newly synthetic analog of natural ent-kaurane diterpenoid / 中国药理学与毒理学杂志

OBJECTIVE To study the anti-tumor activity and molecular mechanism of natural diter-pene derivative JD20 in vitro. METHODS Screening the sensitive of gastric carcinoma cell lines to JD20 by cytotoxicity test for 24 h.Cell morphology was evaluated by using DAPI.After staining of can-cer cells with PI or annexin V-FITC/PI respectively,the cell cycle and apoptosis induced by JD20 were detectded by flow cytometry. The change in cell membrane potential was detected by JC-1 test kit. Western blot method was used to detect the apoptosis-related protein. RESULTS The novel natural kaurane diterpene derivative JD20 had a significant inhibitory effect on tumor cells and was particularly active on gastric cancer cell lines HGC-27 (IC50=4.72 ± 1.37 μmol·L- 1) and MGC-803 (IC50=7.36 ± 0.86 μmol·L-1).Further studies found that JD20 resulted in thecell cycle arrest in the G2/M phase,and induced a significant apoptosis in HGC-27. In addition, JD20 also caused the drop of mitochondrial membrane potential of HGC-27 within a short time (3 h). Furthermore, the Western blotting analysis showed that JD20 could induce the up-regulation of p53,Bax and Bim protein expression in gastric can-cer cells,and the releasing of cytochrome c from the mitochondria into the cytoplasm,as well as the ac-tivation of casepase-9/3.CONCLUSION The natural kaurane diterpene derivative JD20 can inhibit the proliferation of various human cancer cells by blocking the cell cycle and inducing apoptosis, and its mechanism of inducing apoptosis may be related to the mitochondria-mediated apoptosis pathway.

NQO1 dependent non-canonical necroptosis mediated by ROS and RIP1/RIP3 in parallel in glioma cancer cells / 中国药理学与毒理学杂志

OBJECTIVE Glioblastomas(GBM)are the most malignant brain tumors in humans and have a very poor prognosis. New therapeutics are urgently needed. Here, we reported 2-methoxy-6-acetyl-7-methyljuglone (MAM)-induced cell death in U87 and U251 glioma cancer cells. METHODS Cells were cultured and treated with MAM, the cell viability was determined by MTT assay and LDH assay. Intracellular reactive oxygen species (ROS) generation was observed by DCF fluorescence. The protein expression was determined by Western blotting. RESULTS MAM induced glioma cancer cell death without caspase activation. The cell death induced by MAM was attenuated by the pharmacological or genetic blockage of necroptosis signaling,including RIP1 inhibitor necrostatin-1s (Nec-1s)and siRNA-mediated gene silencing of RIP1 and RIP3,but was unaffected by caspase inhibitor z-vad-fmk or necrosis inhibitor 2-(1H-Indol-3-yl)-3-pentylamino-maleimide (IM54). MAM treated U87 and U251 glioma cancer cells induced RIP1/RIP3 complex formation, ROS level increased, ATP concentration decreased and loss of plasma membrane integrity, further confirmed this process was necroptosis.The essential role of ROS was confirmed by the protective effect of ROS scavenger NAC. Interestingly, MAM induced necroptosis both triggered by RIP1/RIP3 complex and ROS generation. Moreover, MAM induced necroptosis through cytosolic calcium (Ca2 +) accumulation and sustained c-Jun N-terminal kinase (JNK) activation. Both calcium chelator BAPTA-AM and JNK inhibitor SP600125 could attenuate cell death. Further, we found there exists a feedback loop between RIP1 and JNK activation.Finally,MAM induced necroptosis was inhibited by dicoumarol(a NQO1 inhibitor). Dicoumarol exposed glioma cancer cells were resistant to RIP1/RIP3 complex formation and ROS generation. MAM induced necroptosis was independent of MLKL. CONCLUSION MAM induced non-canonical necroptosis through the NQO1-dependent ROS and RIP1/RIP3 pathway.This study also provided new insights into the molecular regulation of necroptosis in human glioma cancer cells and a promising approach for GBM treatment.

Anti-esophagus cancer activity and mechanism of DN3,a novel natural diterpenoid derivative,as a dual inhibitor of glycolysis and oxidative phosphorylation / 中国药理学与毒理学杂志

OBJECTIVE To probe into the anti-esophagus cancer activity and mechanisms of DN3, a novel natural diterpenoid derivative. METHODS The anti-tumor activity in vitro of DN3 was evaluated by MTT, and by using human esophageal carcinoma cells xenografted into athymic mice model in vivo. The specific mechanisms of DN3, as a dual inhibitor of glycolysis and oxidative phos-phorylation(OXPHOS)were explored through cell and molecular biology techniques.For instance,the manner of cancer cell death induced by DN3 was characterized by hoechst33342, FITC-Annexin V/PI staining and flow cytometric analysis,then these changes of glucose consumption,glucose uptake and lactate production in glycolysis, as well as oxygen consumption rate (OCR) and ATP content in OXPHOS caused by DN3 were performed separately through related kits and SeahorseBioscience XF24 Extra-cellular Flux Analyzer.Furthermore,in order to obtain a clear understanding of the inhibition of DN3 to glycolysis and OXPHOS, these regulatory factors were investigated by Western blot, such as PI3K/AKT, c-Myc and p53 of glycolysis, Bax and HK2 of mitochondrial function. RESULTS DN3 inhibited the growth of esophagus cancer cell EC9706, EC109 and EC1 cells in a dose and time dependent manner,but showed no significant effects on human esophageal epithelial cells(HEECs).DN3 caused significant G2/M arrest of esophagus cancer cell lines and induced apoptosis of these cell lines, which indicated DN3 inhibited the growth of esophagus cancer cell through blocking cell cycle and inducing apoptosis in a dose and time-dependent manner. Importantly, 8 μM DN3 decreased the extracellular acidification rate (ECAR) by 45% in EC109, which indicated glycolysis was inhibited by DN3. Mean-while, DN3 decreased the oxygen consumption rate (OCR) and the OCR linked to intracellular ATP production in EC109 cells,but that was not obvious in HEECs,so which indicated that DN3 could selec-tively block OXPHOS of cancer cells. In addition, the accumulation of reactive oxygen species (ROS) and the drop of mitochondrial membrane potential (MMP) were also observed in EC109 incubated by DN3,which suggested mitochondrial biological function was disturbed.Furthermore,the expression of PI3K/AKT, c-Myc and HK2 related to glycolysis were down-regulated by DN3, but the p53 and Bax were up-regulated in esophageal carcinoma cells. The changes of these enzymes accounted for the decreased glycolysisand OXPHOS in esophageal carcinoma cells treated by DN3. CONCLUSION The new compound DN3 has a strong anti-esophageal carcinoma activity,and it is tolerable that DN3 is seen as a dual inhibitor of glycolysis and oxidative phosphorylation.

Metabolic heterogeneity of gastric cancer cell lines / 中国药理学与毒理学杂志

OBJECTIVE Gastric cancer is one of the most common malignant tumors,and the inci-dence rate is the highest in all kinds of tumors in China. However,it remains unclear that how signifi-cantly gastric cells are dependent on glycolysis,and which type of gastric cells are sensitive to glycolysis inhibition. In this study, several kind of gastric cancer cell lines were used as the research object, and the metabolic characteristics of different cell lines were systematically analyzed to provide theoretical support for the accurate treatment of gastric cancer. METHODS We examined the energy metabolism of four gastric cancer cell lines(MGC-803,SGC-7901,HGC-27 and BGC-823)by using glycolysis inhibitor, 2-deoxy-D-glucose(2-DG)and inhibitor of oxidative phosphorylation,oligomycin.Oxygen consumption rates(OCR)and L-lactate were also measured with an XF96 Analyzer(Seahorse Biosciences)to deter-mine the significance of metabolism of oxidative phosphorylation and aerobic glycolysisin gastric cells. In addition, western blot was used to detect the contribution of AMP-activated protein kinase (AMPK), and anti-apoptotic proteins(Bcl-2 and survivin)to clarify the mechanism of death or survival of gastric cancer cells treated by 2-DG or oligomycin. RESULTS In this study, it was shown that the growth of gastric cell lines were suppressed by 2-DG.However,the sensitivity to 2-DG was quite different among cell lines:IC 50 of 2-DG was from 3.28 mmol·L-1(MGC-803)to 15.57 mmol·L-1(BGC-823).MGC-803 was relatively sensitive to 2-DG (IC 50:3.28 mmol·L-1), consumed more glucose and produced more lactate (waste product of glycolysis) than the three other cell lines. Consequently, MGC-803 could be more dependent on glycolysis than other cell lines, which was further confirmed by the fact that glucose (+)FCS(-)medium showed more growth and survival than glucose(-)FCS(+)medium.Alternatively, BGC-823, most resistant to 2-DG (IC50: 15.57 mmol·L- 1), was most sensitive to oligomycin, and showed more growth and survival in glucose(-)FCS(+)medium than in glucose(+)FCS(-)medium. Thus,we had reasons to think BGC-823 cells depended on oxidative phosphorylation for energy production. In BGC-823,AMPK,which is activated when ATP becomes limiting,was rapidly phosphorylated by 2-DG, and expression of Bcl-2 was augmented,which might result in resistance to 2-DG.Interestingly,AMPK phosphorylation and augmentation of Bcl-2 expression by 2-DG were not observed in MGC-803,which is 2-DG sensitive. CONCLUSION There is a large metabolic difference between gastric cancer cell lines,which will facilitate the future gastric cancer therapy by targeting metabolic pathways.

Platelet-rich plasma combined with surgical hip joint dislocation:An effective option for femoral head necrosis in the peri-collapse stage / 医学研究生学报

Objective Reports are rarely seen about the application of platelet-rich plasma (PRP) combined with surgical dislocation of head and neck fenestration (HNF) in the treatment of osteonecrosis of the femoral head (ONFH) in the peri-collapse stage. The purpose of this study was to investigate the clinical effects of PRP combined with surgical dislocation of HNF in the treatment of ONFH. Methods Using PRP combined with surgical dislocation of HNF,we treated 18 ONFH patients with 22 hips involved,in-cluding 7 cases of ARCO stage Ⅱc,10 cases of stage Ⅲa,and 5 cases of stage Ⅲb, and followed them up for 12.40±3.12 months. We evaluated the clinical results and compared the Harris scores and radiographic manifestations obtained before and after surgery. Results The overall Harris scores of the patients at 12 months after surgery were significantly higher than the baseline(86.84±6.44 vs 73.73±5.42,P=0.04),(87.73±2.43 vs 74.23±7.30,P<0.05) in the stageⅡc group,(85.22±7.63 vs 72.82±5.31,P<0.05) in the stageⅢa group,and(78.86±5.91 vs 69.37±6.13,P<0.05) in the stageⅢb group. The rate of excellence was 90.91% and that of im-provement was 95.45%.There were no such postoperative complications as nonunion,infection,or osteothrombosis. Conclusion PRP com-bined with surgical dislocation of HNF exhibited an excellent short-term effect in the treatment of ONFH in the peri-collapse stage, which has provided a new option for the management of the disease.

Nontargeted metabolomic analysis of Anoectochilus roxburghii at different cultivation stages / 中国中药杂志

Anoectochilus roxburghii is a traditional Chinese medicine and natural health products. In the modern cultivation system, A. roxburghii is micropropagated in tissue culture, and the plants are transferred to soil cultivation for months. However, it remains unclear about the necessity of soil cultivation for the accumulation of health beneficial compounds. In this paper, we performed nontargeted metabolomic analysis using GC-TOF-MS and UPLC-Q-TOF-MS, on A. roxburghii plants at tissue culture stage or after 3 months of soil cultivation. The results showed that the primary metabolites such as alcohols and organic acids are abundant in the tissue culture plants. In contrast, polysaccharide, nucleoside, esters and secondary metabolites such as flavonoids, terpenoids were significantly accumulated in cultivated seedlings. Flavonoids and polysaccharides are considered as the principle effective components in A. roxburghii. Soil cultivation period is therefore essential for the accumulation of these metabolites.

Dynamic Characteristics of Serum Hepatitis B Surface Antigen in Chinese Chronic Hepatitis B Patients Receiving 7 Years of Entecavir Therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The ultimate goal of hepatitis B treatment is hepatitis B surface antigen (HBsAg) seroclearance. Several factors have been suggested to be associated with the rate of HBsAg reduction in antiviral-naive or lamivudine therapy cohorts. However, there are few studies evaluating the factors during long-term entecavir (ETV) therapy. In the present study, we aimed to evaluate the factors to predict the outcome of ETV therapy for 7 years.</p><p><b>METHODS</b>A total of 47 chronic hepatitis B (CHB) patients treated with ETV monotherapy were included in this study. Liver biochemistry, hepatitis B virus (HBV) serological markers, serum HBV DNA, and HBsAg titers were tested at baseline, 3 months, 6 months, and yearly from 1 to 7. The associations between factors and HBsAg reduction were assessed using multivariate tests with repeated measure analysis of variance.</p><p><b>RESULTS</b>At baseline, serum HBsAg levels showed a positive correlation with baseline HBV DNA levels (r = 0.625, P < 0.001). The mean HBsAg titers after ETV treatment were significantly lower than the baseline titers (P ranges from 0.025 to 0.000,000,6). The HBsAg reduction rate during the 1st year was greater compared to after 1 year of treatment (P < 0.05). Multivariate test showed that hepatitis B e antigen (HBeAg) seroclearance and/or HBsAg reduction ≥0.5 log10 IU/ml at 6 months had a high negative predictive value (96.77%) for HBsAg seroclearance (P = 0.002, P = 0.012, respectively).</p><p><b>CONCLUSIONS</b>The HBsAg reduction rate during the 1st year was greater than that after 1 year of treatment. Further, HBeAg status and HBsAg levels at month 6 are the optimal factors for the early prediction of HBsAg seroclearance after long-term ETV therapy in CHB patients.</p>

Papers published in PLoS One by hospitals in China / 中华医学图书情报杂志

Objective To study the reasons why PLoS One has set off an upsurge in China especially in hospitals, the academic level of papers published in PLoS One, and how to correctly judge the SCI-covered papers published by hospitals.Methods Papers published in PLoS One by hospitals in China were retrieved.The number of papers published in PLoS One by hospitals in China, the institutions that published the papers in PLoS One, and the num-ber of fund-supported papers were analyzed.Results A total of 9739 papers were published in PLoS One by hospitals in China from 2007 to October 2015, with an average cited frequency of 5.29.The majority of authors who published the papers were from affiliated hospitals of scientific research institutions and teaching hospitals of colleges and uni-versities.Of the 9739 papers, 87.78%were supported by funds from different foundations.Conclusion Nothing is strike about the academic level of papers published in PLoS One by hospitals in China with their average cited fre-quency lower than that (8.14) in our country.The SCI-covered papers published by hospitals should not be con-sidered as the only criterion in assessing the performances of staff in hospitals.

Practice and thinking of translational medicine in the perspective of research-based medicine / 中华医院管理杂志

Translational medicine,as an important form of research-based medicine,is key to research hospitals.Analysis in the paper holds that such hospitals should highlight top-level design in its medical system building,rely on characteristic and advantageous disciplines,target research outcome applications,take the pathway of overlapping and fusion,and the synergy mechanism as the guarantee. The paper introduced the efforts of the hospitals'experiences in innovative clinical practice of research during the development of the translational medicine system,in an organized,planned,targeted,and measurable manner.It is concluded that the innovative outcomes of the effort help elevate medical competence of the hospital as a whole.

Umbilical cord blood-derived mesenchymal stem cells ameliorate graft-versus-host disease following allogeneic hematopoietic stem cell transplantation through multiple immunoregulations / 华中科技大学学报（医学）（英德文版）

Although mesenchymal stem cells (MSCs) are increasingly used to treat graft-versus-host disease (GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs (UCB-hMSCs) on GVHD patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK cells, Treg cells and dendritic cells (DCs) and cytokines including interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4(+) and CD8(+) Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.