Objective To evaluate the role of spinal phosphatidyl-inositol 3-kinase/Akt (PI3k/Akt) signaling pathway in the maintenance of bone cancer pain (BCP) in rats and its relationship with microglial activation.Methods Forty healthy female Sprague-Dawley rats,weighing 180-200 g,were randomly divided into 5 groups (n =8 each):sham operation group (group S) ; PI3K inhibitor LY294002 group (group L) ; group BCP; BCP + dimethyl sulfoxide (DMSO) group (group BCP + D) ; BCP + LY294002 group (group BCP + L).BCP was induced by inoculating Walker 256 mammary gland carcinoma cells into the medullary cavity of the left tibia.At 7-9 days after inoculation,LY294002 2.5 μg/10 μl was injected intrathecally in L and BCP + L groups,normal saline 10 μl was injected intrathecally in S and BCP groups,and 5％ DMSO 10 μl was injected intrathecally in BCP+ D group once a day.Mechanical paw withdrawal threshold (MWT) was measured at 1 day before inoculation and 1,3,5,7,8 and 9 days after inoculation.The rats were sacrificed after MWT was measured on day 9 after inoculation and the L4-6 segments of the spinal cord were removed to determinate the activation of spinal microglia using immunofluorescence.Results Compared with group S,MWT was significantly decreased,and the activation of spinal microglia was increased in BCP,BCP + D and BCP+ L groups.Compared with BCP and BCP + D groups,MWT was significantly increased,and the activation of spinal microglia was decreased in BCP + D group.Conclusion Spinal PI3K/Akt signaling pathway is involved in the maintenance of BCP possibly through activating microglia in spinal dorsal horns of rats.

Aim To investigate the effect of intrathecal injection of PI3 K inhibitor LY294002 on pain behav-iour and expression of p-Akt in spinal dorsal horns in bone cancer pain( BCP) rats. Methods Forty female SD rats weighing 180~200 g were randomly divided in-to five groups ( n =8 each ):(Ⅰ) sham group;(Ⅱ) sham+LY294002 group;(Ⅲ) BCP group;(Ⅳ) BCP+DMSO group;( V) BCP+LY294002 group. BCP rat model was induced by inoculating Walker 256 mamma-ry gland carcinoma cells into the medullary cavity of the left tibia. Rats received i. t. injections of either PI3 K inhibitor LY294002 10μL ( 2. 5 g · L-1 ) or 5%DMSO 10 μL at the time of d 7~9 after the operation. Mechanical withdrawal threshold( MWT) test was per-formed before and after i. t. injections on d7(till 8h). The rats were sacrificed after inoculation and the L4~6 segments of the spinal cords were removed for immu-nohistochemistry to determinate the expression changes of spinal p-Akt. Results Compared with I group, the rats inⅢ,Ⅳ,Ⅴgroup showed obvious mechanical hy-peralgesia. The MWT of V group increased apparently from 2nd hour to 4th hour(P<0. 05),and reached the peak in 3rd hour(P<0. 01). Compared with I group, the expression of p-Akt in the spinal cord in Ⅲ,Ⅳgroup increased obviously ( P <0. 01 ) . Compared withⅢ,Ⅳ group,i. t. injections of LY294002 obviously cut down the expression of p-Akt in the spinal cord ( P <0. 05). Conclusion PI3K/Akt singaling pathway may take part in the development of bone cancer pain.

Objective To analyze the significance of postoperative radiotherapy for lymph node positive patients after radical resection of esophageal carcinoma.Methods Two hundred and sixty patients with esophageal squamous cell cancer,aged ≤70,with the performance status score of0 -1,who had undergone radical resection were divided into 2 equal groups:surgery alone group (Group A ) and surgery plus radiotherapy group (Group B).Group A was classified into 3 sub-groups:Group A1 (n =42)without lymph node involvement,Group A2 (n =43 ) with 1 to 3 involved lymph nodes,and Group A3(n =45) with ≥4 involved lymph nodes.Group B was classified into 3 sub-groups:Group B1 (n =43 )without lymph node involvement,Group B2 (n =44) with 1 to 3 involved lymph nodes,and Group B3(n =43 ) with ≥4 involved lymph nodes.The patients were followed up till death.Results The 1-,3-,and 5-year overall survival rates of Group A were 71.5％,35.4％ and 20％,respectively,all significantly lower than those in Group B (76.2％,48.5％ and 36.2％,respectively,x2 =7.822,P ＜0.05).The 1-,3-,and 5-year survival rates of Groups A1 were 83.3％,52.3％,and 38.1％,respectively,all not significantly different from those of Group B1 (81.3％,58.1％,and 46.5％,respectively,x2 =0.283,P ＞ 0.05 ).The 1-,3-,and 5-year survival rates of Groups A2 were 69.8％,34.9％,and 18.6％,respectively,all significantly lower than those of Group B2 (77.3％,47.7％,and 40.9％,respectively,x2 =4.188,P ＜ 0.05).The 1-,3-,and 5-year survival rates of Groups A3 were 62.2％,20％,and 4.4％,respectively,all significantly lower than those of Group B3 ( 69.8％,39.5％,and 20.9％,respectively,x2 =6.168,P ＜ 0.05).The 5-year metastatic lymph node rates of Groups A1 to A3 were 30.9％,53.4％,and 66.7％,respectively,all significantly higher than those of Groups B1 to B3 ( 11.6％,22.7％,and 30.2％,respectively,x2 =4.753,8.741,and 11.682,respectively,all P ＜0.05).The 5-year distant metastasis rates of Groups A1 to A3 were 11.9％,20.9％,and 31.1％,respectively,all not significantly different from those of Groups B1 to B3 (13.9％,20.4％,and 25.6％,respectively,x2 =0.079,0.003,and 0.203,respectively,all P ＞ 0.05 ).Conclusions Postoperative radiotherapy increases the survival rate of lymph node positive patients,but shows little efficacy on the lymph node negative patients.It reduces the occurrence of lymph node metastasis,even in the lymph node negative patients,and does not increase the morbidity of complications,especially that of anastomotic stenosis.The number of metastatic lymph node is one of the important factors affecting the survival of esophageal carcinoma.Distant metastasis increases along with the number of metastatic lymph nodes.

Objective To evaluate the feasibility , toxicity and clinical efficacy of intensity-modulated radiotherapy using the simultaneous integrated boost (SIB- IMRT) and concurrent chemotherapy for advanced nasopharyngeal carcinoma. Methods Thirty nsopharyngeal carcinoma were treated with full course IMRT including nasopharynx and full neck to supraclavicle. The radiotherapy dosage is 68 Gy to the target. Concurrent chemotherapy was given, and the regimen was DDP 40 mg/m2/weekly.Results The mean dose of covering gross tumor volume(PGTV) (D95) in the nasopharynx was 70.48 Gy, and the mean volume of PGTV1 receiving the 95 % dose(V95) was 98. 46 %. The mean dose of PGTV1, PGTV2, PCTV1 and PCTV2 in the targets were 70.8 Gy, 66.4 Gy, 62.3 Gy and 54.8 Gy. According to the evaluation, the acute skin,mucositis and salivary toxicity with grade Ⅲ in those patients were 3.3 %, 10 %, 6.6 %. The patients developed different blood toxicity, but didn't affect their treatment. The median follow-up time was 6.5 months, and disease free survival rate was 100 %. Conclusion SIB-IMRT yields well dose distribution and acceptable toxicity in advanced stage nasopharyngeal carcinoma. The preliminary clinical result is encouraging.

Objective To analyze the association of Crohn's disease(CD)with vitamin D receptor(VDR) gene polymorphisms. Methods After collecting 326 CD patients and 464 healthy controls,the four single nucleotide polymorphisms of VDR (FokI, BsmI, ApaI and TaqI) were examined by a SNaPshot technique. Results Compared with those in controls,the frequencies of mutant allele(A)and genotype(GA+AA)of BsmI were significantly decreased in CD patients(both P=0.001). The similar conclusions were also drawn for the mutant allele(C)and genotype(TC+CC)of TaqI(both P<0.05). In further stratified analysis,compared with those in controls,the mutant alleles and genotypes of BsmI and TaqI were significantly reduced in stenotic type CD patients (all P<0.0083). The analyses of linkage disequilibrium(LD)and haplotype showed that BsmI,ApaI and TaqI were in a strong LD,and the formed haplotype AAC was significantly lower in CD patients than that in controls (P <0.05). Conclusions VDR(BsmI and TaqI)polymorphisms are significantly related with the reduced susceptibility to CD,especially for patients with stenotic CD. Moreover,the haplotype AAC might engender a reduced risk of CD.

Objective To evaluate the role of c-Jun N-terminal kinase (JNK)/monocyte chemoattractant protein-1 (MCP-1) signaling pathway in the spinal cord in the maintenance of bone cancer pain (BCP) in rats.Methods Fifty female Sprague-Dawley rats,weighing 150-180 g,were randomly divided into 5 groups (n =10 each) using a random number table:sham operation group (group S),sham operation + JNK inhibitor SP600125 (group SP),BCP group,BCP + dimethyl sulfoxide (DMSO) group,and BCP+ SP600125 group (group BCP+ SP).BCP was induced by injecting Walker 256 mammary gland cancer cells into the bone marrow of the left tibia.On 10-12 days after BCP,SP600125 10 μg(10 μ1) was injected intrathecally once a day in SP and BCP + SP groups,and 5％ DMSO 10 μl was injected intrathecally once a day in BCP + DMSO group.Mechanical paw withdrawal threshold (MWT) was measured at 1 day before BCP and 3,6,9,10,11 and 12 days after BCP.After measurement of MWT at 12 days after BCP,the rats were sacrificed and L4-6 segments of the spinal cord were removed for determination of MCP-1 expression by using immuno-histochemistry and Western blot.Results Compared with S group,MWT was significantly decreased at 6-12 days after BCP,MCP-1 expression was upregulated in BCP,BCP + DMSO and BCP + SP groups (P ＜ 0.01),and no significant change was found in the parameters mentioned above in SP group (P ＞ 0.05).Compared with BCP group,MWT was significantly increased at 10-12 days after BCP,MCP-1 expression was down-regulated in BCP + SP group (P ＜ 0.01),and no significant change was found in the parameters mentioned above in BCP + DMSO group (P ＞ 0.05).Conclusion JNK/MCP-1 signaling pathway in the spinal cord may be involved in the maintenance of BCP in rats.

Objective To develop a rapid quantitative detecting assay for point-of-care testing ( POCT ) of N-terminal pro-brain natriuretic peptide ( NT-proBNP ) in serum by the fluorescence immunochromatographic technology.Methods Applying double-antibody sandwich assay to establish the quantitative NT-proBNP kit.The performance of quantitative NT-proBNP kit was evaluated by the sensitivity , specificity, accuracy, precision, stability and clinical effectiveness.It compared the research kit and conference kit by the parallel experience in the 1 056(605 males, 451 females)serum specimen collected from Guangdong Provincial People′s Hospital, Sun Yat-sen Memorial Hospital and Children′s Hospital of Zhengzhou between February 2013 to April 2014.Statistical significance of the results was assessed by correlation analysis , linear regression , receive operating characteristic ( ROC) curve analysis , negative and positive consistent.Results The report range of the NT-proBNP kit was 18-35 000 ng/L.The coefficient of variation ( CV) values for low , median and high concentration calibrators respectively were all less than 15%.Common interfering substances in human serum specimens such as bilirubin , triglyceride and cholesterol were found no significant affect on NT-proBNP antigen detection and the CV were no more than 15%.According to the results of detection for calibrators , the shelf time of the NT-proBNP diagnostic kit should be longer than 12 months.The NT-proBNP kit and reference kit had good correlation ( Y=1.048 9X developed reference +121.54, R2 =0.956 6, n=1 056) to detect the target protein through the parallel experiments and the deviation of the quantitative results of clinical serum samples showed no statistical significance (Z=0.88, P=0.379>0.05).The clinical assays of two different diagnostic kits showed good consistency based on the ROC curve evaluation which is compared by two cut-off values (300 and 450 ng/L).The areas under ROC curve were 0.981 and 0.978 respectively.Conclusions A novel NT-proBNP chromatographic quantitative immunofluorescence detection method was developed in this study .The performance evaluation data indicated that the kit is suitable for rapid detection of serum NT -proBNP.

OBJECTIVETo assess the association of vascular endothelial growth factor (VEGF) gene polymorphisms with susceptibility to Crohn's disease (CD) in a Chinese population.

METHODSFor 275 CD patients and 495 controls, the genotypes of VEGF gene rs699947 and rs3025039 loci were determined with a SNaPshot method.

RESULTSThe allelic and genotypic frequencies of the rs699947 and rs3025039 loci did not differ between the two groups (all P>0.05). By stratification analysis, allele A and genotype CA+AA of rs699947 were more frequent in patients with colonic CD compared with the controls (P=0.006, 95%CI:1.143-2.234; P=0.005, 95%CI:1.203-2.900, respectively). Compared with the controls, the allele A and genotype CA+AA of rs699947 were less frequent in patients with ileal lesions including ileal CD and ileocolonic CD (P=0.033, 95%CI:0.524-0.974;P=0.043, 95%CI:0.481-0.989, respectively). The frequency of TT homozygote of rs3025039 was lower in patients with non-stricturing and non-penetrating CD compared with the controls (P=0.036, 95%CI:0.016-0.870).

CONCLUSIONPolymorphisms of the VEGF gene rs699947 locus may contribute to an increased risk for colonic CD, but may play a protective role in patients with ileal lesion. Individuals carrying the TT genotype for VEGF rs3025039 locus may be less susceptible to non-stricturing and non-penetrating CD.

OBJECTIVE To analyze a neonate with multiple malformations and to correlate its genotype with phenotype. METHODS The karotypes of the child and her parents were subjected to G-banding chromosome analysis, and array comparative genomic hybridization (array-CGH) was used for fine mapping of the aberrant region. RESULTS The karyotype of the child was ascertained as 46,XX,del(18)(p11.2). Array CGH has identified a 9.8 Mb deletion at 18p11.32-p11.22. The patient has presented features such as holoprosencephaly, choanal atresia, heart defect, and craniofacial dysmorphisms. CONCLUSION The de novo 18p deletion probably underlies the main clinical manifestations of the child.
Abnormalities, Multiple ; genetics ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 18 ; Female ; Humans ; Infant, Newborn ; Phenotype

Objective:To retrieve, evaluate and integrate relevant evidence on the management of the developmentally supportive environment in the neonatal intensive care unit(NICU), and to provide clinical references.Methods:Evidence on NICU environmental management was retrieved from Guidelines International Network, Joanna Briggs Institute, National Institute for Health and Care Excellence, Scottish Intercollegiate Guide Network, National Guideline Clearinghouse, Registered Nurses′ Association of Ontario, Yimaitong and other Websites, BMJ Best Practice, UpToDate, Cochrane Library, PubMed, Embase, Wanfang Database, CNKI and other database.The evidence included guidelines, evidence summaries, best clinical practice manuals, expert consensus and systematic reviews.The date limit was from the establishment of the databases to March 31, 2021.Results:Totally 16 articles were involved, including 4 guidelines, 9 systematic reviews, and 3 expert consensus.Finally, 20 pieces of best evidence on four aspects were su-mmarized: sound, light, touch, and smell.There were 11 A-level recommendations and 9 B-level recommendations.The evidence suggested that health care workers should reduce noise and protect premature infants from being exposed to bright light, noxious gases, and negative touch stimuli.Besides, benign auditory and olfactory stimuli, circadian light, and mother-infant skin-to-skin contact should be used to promote the development of premature infants.Conclusions:This study is a summary of the recommendations on NICU environmental management.It is well-designed and has achieved fruitful results, showing great significance for reducing environmental stress of premature infants in the NICU.However, the current recommended methods for providing benign stimulation require validation of more high-quality, well-designed research.It is recommended that medical staff should selectively apply the evidence to clinical practice according to the actual situation.