Objective To investigate the role of IL-11 and CTGF in bone metastasis of breast cancer.Methods A total of 180 pathologically confirmed breast cancer patients in Tianjin Medical University Cancer Institute and Hospital were enrolled,90 of which had bone metastasis.Twenty healthy people who took physical examination at the same period were adopted as controls,excluding those with endocrine or metabolic disease or other chronic diseases.Peripheral blood samples were collected and ELISA was employed to detect IL-11 and CTGF expression.Forty paraffin-embedded breast cancer tissue sections from those with bone metastasis and forty tissue sectioned from those without bone metastasis were detected for IL-11 and CTGF expression with immunohistochemisty.Results Serum IL-11 level was (242.9 ±56.3) μg/L in the group with bone metastasis and (85.9 ± 35.7) μg/L in the group without bone metastasis,with a significant difference (F =43.532,P ＜0.01).Serum level of CTGF was (15.6 ±7.4) μg/L in the group with bone metastasis and (15.0 ± 7.0) μg/L in the group without bone metastasis,with no significant difference (F =3.007,P ＞ 0.05).The rate of positive immunohistochemical staining for IL-11 in the group with bone metastasis (57.5％) was significantly higher than that in the group without bone metastasis (14.3％) (x2 ＝ 36.626,P ＜ 0.01).There was no significant difference in the positive rate of CTGF expression between the group with bone metastasis (17.5％) and the group without metastasis (14.3％) (x2 =0.370,P ＞ 0.05).Conclusions IL-11 expression is correlated with bone metastasis of breast cancer.Breast cancer patients with high IL-11 expression are more prone to develop bone metastasis.

Objective:To construct and evaluate a novel tissue-engineered bone composed of murine stromal cell-derived factor 1(mSDF-1), simvastatin (SIM) and collagen scaffold (Bio-Oss?), serving as a cell-homing approach for bone formation .Methods: In the study , 32 ICR mice were randomly divided into 4 groups,each group including 8 mice.The drug-loaded collagen scaffolds were implanted subcutaneously onto the cranium of each mouse according to the groups: ( 1 ) 1 ∶50 ( volume ratio ) dimethyl sulfoxide ( DMSO ) /phosphate-buffered saline ( PBS ) solution +collagen scaffold ( blank control group ); ( 2 ) 10 -3 mol/L SIM solution +collagen scaffold ( SIM group ); ( 3 ) 200 mg/L mSDF-1solution +collagen scaffold (mSDF-1 group); and (4) 10 -3mol/L SIM +200 mg/L mSDF-1 solution +collagen scaffold ( SIM +mSDF-1 group) .One week after implantation , the mice were trea-ted by injecting the same drug solution mentioned above around the scaffold once a day for two days .The specimens were harvested 6 weeks after implantation and the bone formation was evaluated by soft X-ray analysis , HE staining and immunohistochemical staining .Angiogenesis of each group was checked by calculation of vessels in each tissue section .Results:Six weeks after implantation , the collagen scaffolds were retrieved.The value of gray scale for the SIM +mSDF-1 group[(421 836.5 ±65 425.7) pixels] was significantly higher than that of the blank control group [(153 345.6 ±45 222.2)pixels, P<0.01], the SIM group [(158 119.2 ±100 284.2) pixels, P<0.01], and the mSDF-1 group[(255 529.5 ± 152 142.4) pixels, P <0.05 ]; HE staining analysis revealed that significant bone formation was achieved in the SIM +mSDF-1 group; The immunohistochemical staining showed the existence of os-teopontin and osteocalcin in the SIM +mSDF-1 group; There were more vessels in the SIM +mSDF-1 group[(46 ±8)vessels/mm2] than in the blank control group [(23 ±7) vessels/mm2, P<0.01], and the SIM group[(24 ±6) vessels/mm2 , P<0.01].Conclusion:The novel tissue-engineered bone com-posed of mSDF-1, SIM and collagen scaffolds has the potential to form bone subcutaneously in vivo.It re-presents a novel method of in vivo bone re-generation without seed cell delivery .

Artemisinin and its derivative is a kind of efficient,quick and low toxicity of anti-malarial drug.In recent years,we find that artemisinin drugs can not only against malaria,but also have pharmacological effects of immunosuppression,antiviral and anticancer.A number of studies have confirmed that artemisinin and its derivatives have the radiosensitization effects in nasopharyngeal carcinoma,cervical cancer,lung cancer and glioma,and their mechanisms are related to decreasing Weel protein expression,increasing Cyclin B1 protein expression,blocking G2-M phase and cell apoptosis.

Objective:To construct a novel biomimetic calcium phosphate (BioCaP) scaffold loaded with bone morphogenetic protein-2 (BMP-2),and to investigate its role in the osteogenesis of human adipose-derived stem cells (hASCs) in vitro and in vivo.Methods:The BioCaP scaffold coprecipitated with BMP-2 (BMP-2-BioCaP) was constructed in this study.Field emission scanning electron microscopy (SEM) was used to analyze the morphology of the surfaces.The release kinetics was measured to evaluate the slow-release characteristics in vitro.BMP-2-BioCaP was immersed in proliferation medium (PM) or osteogenic medium (OM),respectively.The supernatants were collected and used to culture hASCs in vitro.Cell numbers were determined using the cell-counting kit-8 (CCK-8) to assess the cell proliferation.After 7 and 14 days,alkaline phosphatase (ALP) staining and quantification were performed to test the activity of ALP.After 14 and 21 days,the calcification deposition was determined by alizarin red S (ARS) staining and quantification.The expressions of the osteoblast-related genes were tested on day 4 and day 14.In the in vivo study,6 nude mice were used and implanted subcutaneously into the back of the nude mice for 4 groups:(1) BioCaP scaffold only,(2) BioCaP scaffold + hASCs,(3) BMP-2-BioCaP scaffold,(4) BMP-2-BioCaP scaffold + hASCs (test group).After 4 weeks of implantation,hematoxylin-eosin (HE) staining was performed to evaluate the in vivo osteogenesis of hASCs.Results:SEM observations showed that BioCaP and BMP-2-BioCaP scaffold were entirely composed of straight,plate-like and sharp-edged crystal units,and the length of the crystal units varied between 5 and 10 μm.Release kinetics analysis demonstrated that BMP-2 incorporated with BioCaP could be released at certain concentration and last for more than 21 days,and the accumulative protein release could reach 20％.CCK-8 assays showed that cell proliferation was not significantly affected by BMP-2BioCaP.ALP activity was higher by the induction of OM + BMP-2-BioCaP than of the other groups (P ＜0.01).More mineralization deposition and more expressions of osteoblast-related genes such as Runt-related transcription factor 2 (RUNX2),ALP,osteopontin (OPN) and osteocalcin (OC) were determined in the OM + BMP-2-BioCaP group at different time points (P ＜0.01).HE staining showed that,in the test group and BMP-2-BioCaP scaffold group,the extracellular matrix (ECM) with eosinophilic staining were observed around hASCs,and newly-formed bone-like tissues could be found in ECM around the scaffold materials.Moreover,compared with the BMP-2-BioCaP scaffold group,more bone-like tissues could be observed in ECM with typical structure of bone tissue in the test groups.No obvious positive results were found in the other groups.Conclusion:BMP-2-BioCaP scaffold could achieve slow-release of BMP-2 and promote the osteogenic differentiation of hASCs in vitro and in vivo.The novel tissue-engineered bone composed of hASCs and BMP-2-BioCaPis promising for the repair of bone defect.

Objective To explore the changes of end-tidal carbon dioxide tension (PETCO2) and continued invasive arterial blood pressure during cardiopulmonary resuscitation (CPR) in children of pediatric intensive care unit (PICU) and the correlation between them. Methods A total of 63 pediatric patients with CPR of PICU in Zhengzhou Children's Hospital from January 2016 to January 2017 were included. The pediatric patients were divided into successful group (n=49) and losing group (n=14) according to the results of CPR. This study analyzed the changes of PETCO2and invasive arterial blood pressure during CPR in children of pediatric patients in two groups 0 min, 5 min, 10 min, 20 min, 30 min, 1 h, 3 h, 12 h, 24 h during CPR and explored the correlation between them. The study used SPSS 17.0 software for data analysis. Results The PETCO2, invasive systolic pressure, invasive diastolic pressure and mean invasive arterial blood pressure of pediatric patients in successful group all raised and remained stable 30 min after CPR. Otherwise, those values of pediatric patients in losing group during CPR raised momently and droped rapidly, and then could not be measured after 30 min. The PETCO2pediatric patients in successful group 5 min, 10 min, 20 min and 30 min during CPR was higher than that in losing group with significant differences (P<0.05). The invasive systolic pressure, invasive diastolic pressure and mean invasive arterial blood pressure of pediatric patients 20 min and 30 min during CPR in successful group were all higher than those in losing group with significant differences (P<0.05). The PETCO2was positively associated with the mean invasive arterial blood pressure (P<0.05). Conclusions The PETCO2and invasive arterial blood pressure can be the predictors of CPR outcomes from pediatric patients and provide a basis for successful rescues. They are worth to be used widely in pediatric CPR.

OBJECTIVETo investigate the apoptosis of NK cells induced by the erythroleukemia cell line K562 in vitro.

METHODSPrimary NK cells isolated from the peripheral blood of healthy donors by magnetic-activated cell sorting were cultured with stem cell medium containing recombinant human interleukin-2 (rhIL-2). The NK cells and K562 cells were mixed and co-cultured at different E:T ratios for different time lengths. The apoptosis of NK cells and K562 cells were detected using PE-AnnexinV/7-AAD labeling and flow cytometry.

RESULTSThe purity of isolated NK cells reached (93.99∓4.22)%. At the same E: T ratio, the apoptotic rate of NK cells induced by K562 cells increased significantly with time. As the E:T ratio reduced, the apoptotic rate of the NK cells increased and their cytotoxic activity against K562 cells was attenuated.

CONCLUSIONK562 cells can induce the apoptosis of activated NK cells, which is one of the probable mechanisms of immune escape of tumors.

BACKGROUNDTo evaluate three new chemotherapeutic regimens for non-small cell lung cancer (NSCLC) by pharmacoeconomic analysis in guiding rational use of drugs.

METHODSOne hundred and one cases of NSCLC in clinic stage III or IV were treated by one of the three chemotherapeutic schemes-PC: paclitaxel (135mg/m²,d1)+DDP; TC: docetetaxel (75mg/m²,d1)+DDP; VC: vinorelbine (25mg/m²,d1 and d8)+DDP, DDP were given at 80mg/m² in 3 groups. Pharmacoeconomic cost-effectiveness analysis was used to compare the efficacy of the three regimens.

RESULTSThe response rate was 46.9%, 48.6% and 47.1% and median survival duration was 7.8, 7.5 and 7.6 months for PC, TC and VC regimen respectively, with 1-year survival rate of 37.5%, 37.1% and 38.2% respectively. There was remarkable difference in the response rate and median survival duration between PC and TC, but no statistical difference was observed between PC and VC. There was no statistical difference in 1-year survival rate among the three regimens. The average cost of one patient for one therapeutic cycle was RMB 15840.5, 15831.1 and 9401.8 Yuan respectively. Escalation of 1% of response rate costed RMB 337.75, 325.74 and 199.61 Yuan respectively. Prolongation of 1 month of median survival duration costed RMB 2030.83, 2110.97 and 1237.08 Yuan respectively. Escalation of 1% of one year survival rate costed RMB 422.41 , 426.71 and 246.12 Yuan respectively.

CONCLUSIONSAmong these three new chemotherapeutic regimens for the advanced patients with NSCLC, the expenditure of VC is much cheaper than PC and TC. The cost effectiveness of VC is the lowest among the three regimens.

Objective:To investigate the region-specific characteristics of the gut microbiota and evaluate the association of speci?c gut microbes with type 2 diabetes mellitus (T2DM) from the Dongxiang Group in Gansu province, Northwest China.Methods:Fifty-three participants who was born in Dongxiang Autonomous County (Gansu Province) from April 2020 to January 2021 were enrolled, including 25 patients with T2DM recruited from the outpatient departments of internal medicine at The People′s Hospital of Dongxiang County(T2DM group) and 28 healthy controls recruited from the health screening center (HC group). Gut microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol.Results:A total of 936 operational taxonomic units (OTU) were obtained in the two groups. Of note, the HC and T2DM groups had 633 OTU in common. The alpha and beta diversity were different between the two groups ( P<0.05). Shannon index was significantly higher than that in the HC group, and Simpson index was significantly lower than that in the HC group, displacement multivariate analysis of variance was used to compare β diversity between the two groups, and the difference was statistically significant ( P<0.05). At the Phylum level, firmicutes and actinomycetes in T2DM group were significantly higher than those in the HC group (37.97% vs. 22.89%, 5.09% vs. 2.08%), and the differences were statistically significant ( P<0.05). The abundance of Bacteroidetes was significantly decreased (68.00% in T2DM group and 49.75% in HC group), and the difference was statistically significant ( P<0.05). At the genus level, there were 20 genera statistically significant differences between the two groups. The abundance of Bifidobacterium, Escherichia, Shigella, and Tyzzerella_4 levels were significantly increased in the T2DM group, but Prevotella_9, Erysipelotrichaceae_UCG-003, and Roseburia levels were significantly decreased in the T2DM group compared to those in the HC group. Conclusions:There is a significant difference in the gut microbiota between patients with T2DM and healthy individuals of the Dongxiang group in Northwest China. So as to preliminary exploration the intestinal flora characteristics of T2DM in the Dongxiang group.The findings of this study provide a theoretical basis for the prevention and control of T2DM in Dongxiang group in the future.

Objective:To investigate the factors affecting postoperative short-term improvement of consciousness level in patients with prolonged disorders of consciousness after severe traumatic brain injury (sTBI).Methods:A case-control study was conducted to analyze the clinical data of 55 patients with prolonged disorders of consciousness after sTBI admitted to Beijing Tiantan Hospital Affiliated to Capital Medical University and Seventh Medical Center of PLA General Hospital from September 2021 to September 2022. There were 33 males and 22 females, with the age range of 13-68 years [(43.0±15.5)years]. All patients were assessed for the consciousness level using the coma recovery scale-revision (CRS-R) preoperatively and within 48 hours postoperatively. A total of 33 patients were observed in vegetative state and 22 in minimally conscious state preoperatively. The consciousness level was found to be improved in 26 patients (consciousness- improved group), but not improved in the remaining 29 patients (consciousness-unimproved group). Indicators were documented including gender, age, cause of injury, Glasgow coma score (GCS) on admission, course of injury, preoperative consciousness level, operation mode, operation time, intraoperative fluid replenishment, intraoperative urine volume, intraoperative bleeding volume, American Society of Anesthesiologists grade, analgesic regimen and sedation maintenance drugs. A univariate analysis was conducted first to assess those indicators′ correlation with postoperative short-term improvement of consciousness level in patients with prolonged disorders of consciousness after sTBI. Multivariate Logistic regression analysis was then used to determine the independent risk factors for their postoperative short-term improvement of consciousness level.Results:Univariate analysis showed that GCS on admission, course of injury, preoperative consciousness level and analgesic regimen were correlated with short-term improvement of postoperative consciousness level in patients with prolonged disorders of consciousness after sTBI (all P<0.05), whereas gender, age, cause of injury, operation mode, operation time, intraoperative fluid replenishment, intraoperative urine volume, intraoperative bleeding volume, American Society of Anesthesiologists grade and sedation maintenance drugs showed no relation to the improvement of postoperative consciousness level (all P>0.05). Multivariate Logistic regression analysis showed that the GCS &ge;7 points on admission ( OR=0.06, 95% CI 0.01, 0.36, P<0.01), preoperative minimally conscious state ( OR=0.09, 95% CI 0.02, 0.40, P<0.01) and intraoperative use of Sufentanil combined with Remifentanil ( OR=0.07, 95% CI 0.01, 0.43, P<0.01) were significantly correlated with postoperative improvement of consciousness level. Conclusion:The GCS on admission (&ge;7 points), preoperative minimally conscious state and intraoperative use of Sufentanil combined with Remifentanil are independent risk factors affecting short-term postoperative improvement of consciousness level in patients with prolonged disorders of consciousness after sTBI.

Objective:To understand the pathogens and molecular-epidemiologic characteristics of viral meningo-encephalitis in Zhejiang province during 2002 to 2018.Methods:All the samples were collected from suspected patients admitted to the hospitals under the monitoring program. Of the total samples, 2 173 were cerebrospinal fluids while the other 455 were stool specimens. Cerebrospinal fluid (CSF) samples were subject to real-time qPCR for the detection of Human enterovirus (HEV), Mumps virus (MuV), Herpes simplex virus (HSV), Cytomegalovirus (CMV) and Japanese encephalitis virus (JEV). Stool sample were subject to real-time qPCR for HEV. ELISA was used to detect the IgM antibodies in CSF, in the 5 kinds of virus mentioned above. VP1 genes from all RNA-positive specimen were amplified, sequenced, for typing and for evolution analysis.Results:871 (40.1 %) of the 2 173 samples were detected as HEV nucleic acid positive during 2002 to 2018. 654 (38.1 %) of the 1 718 CSF sample were HEV nucleic acid positive while 217 (47.7 %) of the 455 stool sample were HEV nucleic acid positive. Among the total positive nucleic acid sample, 670 of them were VP1 sequence positive, including 5 HEV-A and 665 HEV-B. There were 23 HEV serotypes, including Coxsackievirus (CV) CVA4, CVA6, CVA9, CVA10, CVB1-5, Echovirus (EchoV; E) E3, E4, E6,E7, E9, E11, E14, E16, E18, E21, E25, E30, E33 and EV-71. The top three serotypes went to E30, E6 and CVB5. These three serotypes presented enhanced viral activity in every several years. 795 CSF samples were detected as virus nucleic acid positive, including 374 HEV, 6 MuV, 5 HSV and 5 CMV, from 2012 to 2015 and in 2018. 5 kinds of IgM antibodies were detected simultaneously in 368 CSF samples, including 2 HEV positive, 6 JEV positive and 1 MuV positive for 5 viruses, respectively. Except for EV-71, there were 517 EchoV and 152 CV viruses presented, with the ratio of 3.4∶1. These two kinds of viruses alternately changed for each predominant epidemic strains in every 3-5 years. Based on VP1, results from the phylogenetic tree showed that HEV from Zhejiang province clustered into HEV-A and HEV-B clades respectively. E30 developed both h and i sub-genotypes. Conclusions:HEV-B seemed the main pathogen for viral meningo-encephalitis in Zhejiang province. Ratio of positive detection on EchoV was significantly higher than that on CV. These two kinds of virus alternately presented changing tendency in every several years. Predominant epidemic strains E30, CVB5 and E6 were presenting enhanced viral activity, also in every several years. High correlation was found in both HEV viral activity from the surveillance sites and in time line of the viral meningo-encephalitis outbreaks.