Objective:To investigate the effect of DKK1 on linearly patterned programmed cell necrosis (LPPCN) and vasculogenic mim-icry (VM) and the related molecular mechanism in non-small cell lung cancer (NSCLC). Methods:A total of 173 human NSCLC speci-mens were collected to detect LPPCN by H&E staining, detect VM with CD31/PAS double staining, and investigate DKK1 and related protein expression by immunohistochemistry. The clinical pathological significance of LPPCN, VM, and DKK1 and the correlation of them were analyzed. Human NSCLC H460-DKK1 cells were engrafed in nude mice to evaluate the influence of DKK1 up-regulation on VM and LPPCN in vivo. Results:Approximately, 14.45%(25/173) of NSCLC had VM and 49.71%(86/173) had LPPCN. 25.6%(22/86) of NSCLC cases in LPPCN-positive group formed VM. Both of VM and LPPCN were all correlated with poor differentiation, late TNM stage, easy recurrence and metastasis and poor prognosis in NSCLC. DKK1 expression in the VM-positive group and the LPPCN-positive group was higher than that in the VM-negative group and the LPPCN-negative group, respectively. DKK1, LPPCN, and VM were positive-ly correlated with VE-cadherin, MMP-2,β-catenin nuclear expression and Twist1. H460-DKK1 transplantation tumor model confirmed that DKK1 promotes the expression of VM and LPPCN and related proteins in NSCLC. Conclusion:The increase of theβ-catenin and Twist1 expression induced by DKK1 may promote the formation of LPPCN and VM in NSCLC.

[Objective] To retrospectively analyze the outcome of unrelated umbilical cord blood transplantation in the treatment of aggressive-phase chronic myeloid leukemia.[Methods] Fourteen consecutive patients with aggressive-phase chronic myeloid leukemia were treated with unrelated umbilical cord blood transplantation,thirteen patients were treated with myeloablative unrelated CBT and one patients were treated with nonmyeloablative unrelated CBT.All patients received standard cyclosporine A (CsA) and mycophenolate mofetil(MMF) as a graft-versus-host disease (GVHD) prophylaxis.[Results] 14 patients were all successfully engrafted.The median times for their neutrophil returning to ≥0.5×109/L and for platelet returning to ≥20×109/L were 22.8 days and 37.8 days,respectively.Acute GVHD occurred in 10 of 13 evaluable patients.The grading of acute GVHD was gradeⅡ-Ⅳin 6 patients(46.2 ％).Chronic GVHD occurred in 7 of 11 evaluable patients(63.6％).Relapse occurred in 2 of 15 patients,lextramedullary relapse was included.9 of 14 patients were alive and event-free after CBT.The probability of OS rate at 5 years was 64.3 ％,the probability of DFS rate at 5 years was 5,7.1％.[Conclusion]Unrelated umbilical cord blood transplantation is effective in the treatment of aggressive-phase chronic myeloid leukemia.

Objective To evaluate the effectiveness and safety of gefitinib retreatment beyond progression(GRBP)in non-small cell lung cancer(NSCLC)patients with rare EGFR mutations.Methods We retrospectively analyzed six rare-EGFR-mutation NSCLC patients from Jan 2011 to Dec 2015.Those patients had previous disease control and then disease progression according to Response Evaluation Criteria in Solid Tumors version 1.1(RECIST v1.1)after taking oral gefitinib 250 mg once a day.After that,continuing gefitinib was decided by clinicians′ experience at the same treatment option.The primary endpoints were response rate(RR),overall survival(OS),the first and second progression-free survival(PFS-1 and PFS-2).Safety was assessed according to the NCI-CTCAE version 4.0.Results After initial treatment of gefitinib,4 patients achieved partial response(PR)and 2 patients showed stable disease(SD),with RR being 66.7％.The median PFS-1 and PFS-2 were 10 months(95％CI 6.6-13.4)and 9 months(95％CI 6.9-11.1),respectively.The median OS time was 28 months(95％CI 10.4-45.6).The most common treatment-related adverse events were fatigue,diarrhea,rash,itching and elevated transaminases.Conclusion In our study,gefitinib retreatment beyond disease progression is effective with a manageable tolerability profile.

The effect of electroacupuncture (EA) on TRPM7 mRNA expression of focal cerebral ischemia in rats and further the role of EA in the relationship between TRPM7 and trkA pathway was investigated. Thirty SD rats were randomly divided into 5 groups : normal group, ischemia/reperfusion group, EA treated group (ischemic rats with EA treatment), TE infusion group (ischemic rats with EA treatment and TE buffer infusion), AS-ODN group (ischemic rats with EA treatment and antisense trkA oligonucleotide infusion). The stroke animal model was established by the modified method of middle cerebral artery occlusion. Antisense trkA oligonucleotide that blocked NGFs effects was injected into cerebroventricle before EA. The TRPM7 mRNA was detected by RT-PCR method. The results showed that there were low TRPM7 mRNA levels in cortex and hippocampus in normal group. Compared with normal group, TRPM7 mRNA expression was increased significantly in ischemia/reperfusion group (P<0.05). A significant reduction in the expression of TR-PM7 mRNA was found in EA treated group in contrast to ischemia/reperfusion group (P<0.05). The expression of TRPM7 mRNA in AS-ODN group was remarkably increased compared with EA treated group and TE infusion group (P<0.05). The results indicated that TRPM7 channels in the ischemic cortex and hippocampus in rats might play a key role in ischemic brain injury. EA could reverse the overexpression of TRPM7 in cerebral ischemia/reperfusion rats. And the inhibitory effect of EA on TRPM7 channels might be through trkA pathway.

Recombinant adeno-associated viral (rAAV) vectors are promising vectors for human gene therapy. However, AAV-mediated gene transduction can be hampered because of the pre-existing neutralized natural antibodies (NAbs) in primates. We evaluated transduction efficiency of rAAV6 expressing human alpha-1-anti-trypsin (hAAT) vectors in murine models, and found that these vectors showed stable and high levels of transgene expression. Fluorescence imaging showed that AAV6 expressing enhanced green fluorescent protein (eGFP) by intravenous administration predominantly targeted the liver, but led to self-limited hepatitis. Besides, our study evaluated epidemiology of anti-AAV6 NAb in non-human primates (NHPs) by NAb assay in vitro. The result indicated that 52.17% of NHPs had detectable NAb at 1:5 dilution rate. In vivo passive transfer experiment showed that AAV6 specific neutralizing antibody, even though with low NAb titer, could significantly inhibit rAAV6 transduction.
Adoptive Transfer ; Animals ; Antibodies, Neutralizing ; immunology ; Dependovirus ; genetics ; metabolism ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; alpha 1-Antitrypsin ; genetics ; metabolism

Summary: The effect of electroacupuncture (EA) on TRPM7 mRNA expression of focal cerebral ischemia in rats and further the role of EA in the relationship between TRPM7 and trkA pathway was investigated. Thirty SD rats were randomly divided into 5 groups : normal group, ischemia/reperfusion group, EA treated group (ischemic rats with EA treatment), TE infusion group (ischemic rats with EA treatment and TE buffer infusion),AS-ODN group (ischemic rats with EA treatment and antisense trkA oligonucleotide infusion). The stroke animal model was established by the modified method of middle cerebral artery occlusion. Antisense trkA oligonucleotide that blocked NGF's effects was injected into cerebroventricle before EA. The TRPM7 mRNA was detected by RT-PCR method. The results showed that there were low TRPM7 mRNA levels in cortex and hippocampus in normal group. Compared with normal group, TRPM7 mRNA expression was increased significantly in ischemia/reperfusion group (P<0.05). A significant reduction in the expression of TRPM7 mRNA was found in EA treated group in contrast to ischemia/reperfusion group (P<0.05). The expression of TRPM7 mRNA in AS-ODN group was remarkably increased compared with EA treated group and TE infusion group (P<0.05). The results indicated that TRPM7 channels in the ischemic cortex and hippocampus in rats might play a key role in ischemic brain injury. EA could reverse the overexpression of TRPM7 in cerebral ischemia/reperfusion rats. And the inhibitory effect of EA on TRPM7 channels might be through trkA pathway.

In the present paper, in-situ preparation of silver nanoparticles have been conducted in 3D network structure of BC membrane through liquid phase chemical deoxidization method. The characterization of products was investigated using scanning electron microscopy (SEM), infrared spectroscopy (IR), energy dispersion spectrometry (SEM-EDS). The absorbing water capacity and preserving water capacity of substitutes and the antibacterial capacities of antibacterial agent-loaded artificial skin were tested. The results showed the silver nanoparticles were approximately spherical particles with an average diameter of 45nm, and were noted to have excellent sterilizing efficacy the efficiency of against Escherichia coli, yeast and Candida albicans.
Anti-Bacterial Agents ; pharmacology ; Bacteria ; chemistry ; Candida albicans ; drug effects ; Cellulose ; chemistry ; Escherichia coli ; drug effects ; Humans ; Metal Nanoparticles ; chemistry ; Microbial Sensitivity Tests ; Silver ; Skin, Artificial

The role of catecholamine (CA) in the pathogenesis and development of macular edema of central serous chorioretinopathy (CSC) was studied, and its relations with visual acuity were investigated. Plasma concentrations of epinephrine (E) and norepinephrine (NE) were determined in 30 consecutive eyes with CSC. Central macular thickness analysis was done by RTA and all the data were compared with normal eyes and analyzed with SAS software package. Plasma concentrations of E and NE were increased to (569 +/- 123) ng/L and (721 +/- 104) ng/L respectively in active CSC patients, significantly higher than those in normal subjects (P < 0.01), and decreased to normal in convalescent stage. RTA analysis revealed that the retinal thickness of CSC patients was increased at active and recovery stage as compared with normal subjects; and the plasma concentration of E was significantly correlated with central macular thickness (t = 2.173, P < 0.05). Also, central macular thickness measured by RTA was significantly correlated with the visual acuity (r = -0.8046, P < 0.001) in CSC eyes. RTA analysis might be useful to quantitatively detect and evaluate prognosis in CSC patients. The plasma concentration of E, which was highly correlated with macular edema, might play an important role in the early damage and the pathogenesis of CSC.
Adult ; Chorioretinitis ; blood ; etiology ; Edema ; Epinephrine ; blood ; physiology ; Female ; Fluorescein Angiography ; Humans ; Macula Lutea ; pathology ; Male ; Middle Aged ; Norepinephrine ; blood ; physiology ; Retina ; pathology ; Visual Acuity

OBJECTIVE: To explore the genetic etiology of a child suspected for β-ketothiolase deficiency by neonatal screening. METHODS: All coding exons and flanking sequences of the ACAT1 gene were subjected to targeted capture and high-throughput sequencing. Suspected variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child was found to harbor compound heterozygous variants of the ACAT1 gene, namely c.121-3C>G and c.275G>A (p. Gly92Asp). The c.121-3C>G variant was also detected in his father and two sisters, while the c.275G>A (p. Gly92Asp) was a de novo variant. A c.334+ 172C>G (rs12226047) polymorphism was also detected in his mother and two sisters. Sanger sequencing has verified that the c.275G>A (p. Gly92Asp) and c.334+172C>G (rs12226047) variants are located on the same chromosome. Bioinformatics analysis suggested both c.121-3C>G and c.275G>A (p.G92D) variants to be damaging. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.275G>A variant of the ACAT1 gene was predicted to be pathogenic (PS2+ PM2+ PM3+ PP3+PP4), the c.121-3C>G variant to be likely pathogenic (PM2+ PM3+ PP3+PP4). CONCLUSION The c.121-3C>G and c.275G>A variants of the ACAT1 gene probably underlay the pathogenesis of the child. Above finding has enriched the variant spectrum of the ACAT1 gene.
Acetyl-CoA C-Acetyltransferase/genetics* ; Acetyl-CoA C-Acyltransferase/genetics* ; Amino Acid Metabolism, Inborn Errors/genetics* ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Infant, Newborn ; Male ; Mutation

Objective:Medical post-doctors are important young talents in the field of medical research, to whom the management and training play an important roles in promoting the development of medical research. To improve the academic capacity and training quality of medical post-doctor, this article analyzed the status and problems of post-doctor management, and put forward countermeasures in a grade A tertiary pubic hospital in Beijing.Methods:Questionnaire survey and in-depth interview were used to survey the source, training mode, stress and satisfaction among 17 postdocs from 2016 to 2020.Results:The source of postdocs was limited, and there were a few interdisciplinary postdocs. After scientific research training, many postdocs can significantly improve their scientific research capacity; Most of the postdocs were under great pressure, which is mainly caused by scientific research and economic pressure. Key disciplines and cooperative supervisors are scientific research talents, which have high academic requirements for postdocs. Most postdocs are satisfied with their salary. Cooperative supervisors generally give full play to scientific research and clinical guidance, but lack of mental health guidance; Most postdocs have a low sense of belonging.Conclusions:The article proposed following measurements, including intensity propaganda, strengthen three-level management, enhance the sense of belonging, strengthen the management of cooperative supervisors, pay more attention to psychological counseling, relieve pressure, to improve the scientific research capacity and quality of medical postdocs.