[Predictive Value of LIPI and iSEND Immune Scoring System 
in Immunotherapy of Advanced Non-small Cell Lung Cancer].

BACKGROUND: This study retrospectively analyzed the application value of lung cancer immunotherapy prognostic index (LIPI) and iSEND immune scoring system in advanced non-small cell lung cancer (NSCLC) patients treated with immunotherapy in China, in order to find guidance for clinical development of NSCLC treatment plan. METHODS: The clinical data of 178 patients with advanced NSCLC treated with immunotherapy were analyzed retrospectively. LIPI and iSEND immune scores were performed, receiver operating characteristic (ROC) curves were drawn, and the predictive values of two models for objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) were compared. Kaplan-Meier method was used for survival analysis, and Cox regression analysis method was used for univariate analysis and multivariate analysis. RESULTS: The area under the curver (AUC) of ORR, DCR and PFS predicted by iSEND immune score were 0.616, 0.634 and 0.631 respectively; LIPI were 0.789, 0.750 and 0.732 respectively, which were higher than iSEND immune score (P<0.05). The median PFS of patients in LIPI score groups 0, 1 and 2 were 9.9 months, 6.1 mon and 3.7 mon respectively; The median PFS of patients with good, moderate and poor iSEND immune scores were 9.9 mon, 7.0 mon and 3.5 mon respectively, with statistically significant differences (P<0.001). In the immunotherapy subgroup, the median PFS of patients with different LIPI and iSEND immune scores was also statistically significant. Cox regression analysis showed that the derived neutrophil to lymphocyte ratio (dNLR), lactic dehydrogenase (LDH) and PFS were independently correlated (P<0.05). CONCLUSIONS: LIPI and iSEND immune scoring system can effectively predict the efficacy and prognosis of advanced NSCLC treated with immunotherapy, and LIPI has higher predictive value than iSEND immune scoring system.

Modified Embedded-Atom Interatomic Potential Parameters of the Ti-Cr Binary and Ti-Cr-N Ternary Systems.

The second nearest-neighbor modified embedded-atom method (2NN MEAM) potential parameters of the Ti-Cr binary and Ti-Cr-N ternary systems are optimized in accordance with the 2NN MEAM method. The novel constructed potential parameters can well reproduce the multiple fundamental physical characteristics of binary and ternary systems and reasonably agree with the first-principles calculation or experimental data. Thus, the newly constructed 2NN MEAM potential parameters can be used for atomic simulations to determine the underlying principle of the hardness enhancement of TiN/CrN multilayered coatings.

Research on the dynamic heat transfer of stratified air conditioning zone building surfaces in large space scale rig based on low supply-middle return.

Radiation heat and convection heat exist on stratified air conditioning zone building surfaces in large space, and they have significant impact on cooling load calculation and thermal comfort analysis. Actually, heat transfer in large space is usually under non-steady condition. Based on an actual large space, a 1:4 scale model experiment rig is built as research object, which has: typical sloping ceiling structure, columnar low supply air, middle return air, inner surfaces periodic heat flow simulation system, heat measurement, and control system. For stratified air conditioning zone building surfaces in large space, radiation heat transfer calculation model is presented based on Gebhart radiation model and radiation heat is calculated by matrix calculation. Convection heat transfer calculation formula is presented based on inner surfaces temperatures and indoor air temperatures. Taking two periodic heat flow experiment conditions, building surfaces temperatures and indoor air temperatures of stratified air conditioning zone in large space were collected, taking model calculation program to compute dynamic radiation heat and convection heat. The result indicated the dynamic characteristics of radiation heat and convection heat of stratified air conditioning zone building surfaces in large space. It provided some important information for dynamic heat transfer research in stratified air conditioning zone building surfaces in large space.

Principles of rodent surgery for the new surgeon.

For both scientific and animal welfare reasons, training in basic surgical concepts and techniques should be undertaken before ever seeking to perform surgery on a rodent. Students, post-doctoral scholars, and others interested in performing surgery on rodents as part of a research protocol may not have had formal surgical training as part of their required coursework. Surgery itself is a technical skill, and one that will improve with practice. The principles of aseptic technique, however, often remain unexplained or untaught. For most new surgeons, this vital information is presented in piecemeal fashion or learned on the job, neither of which is ideal. It may also make learning how to perform a particular surgery difficult, as the new surgeon is learning both a surgical technique and the principles of asepsis at the same time. This article summarizes and makes recommendations for basic surgical skills and techniques necessary for successful rodent surgery. This article is designed to supplement hands-on training by the user's institution.

Zebrafish foxe3: roles in ocular lens morphogenesis through interaction with pitx3.

Foxe3 is a winged helix/forkhead domain transcription factor necessary for mammalian and amphibian lens development. Human FOXE3 mutations cause anterior segment dysgenesis and cataracts. The zebrafish foxe3 cDNA was PCR amplified from 24 h post-fertilization (hpf) embryo cDNA. The zebrafish foxe3 gene consists of a single exon on chromosome 8 and encodes a 422 amino acid protein. This protein possesses 44% and 67% amino acid identity with the human FOXE3 and Xenopus FoxE4 proteins, respectively. A polyclonal antiserum was generated against a bacterial fusion protein containing the Foxe3 carboxyl terminus. The purified antiserum detects zebrafish Foxe3 on immunoblots, in embryo wholemounts, and frozen tissue sections. The zebrafish Foxe3 protein is first detected in the lens at 31hpf and is restricted to the nucleated cell population, including the epithelial and elongating fiber cells. Knockdown of Foxe3 protein using an antisense morpholino results in small lenses with multilayered epithelial cells and fiber cell dysmorphogenesis. The morphants posses normal retinas, although retinal cell proteins, including rhodopsin, are abnormally expressed in the morphant lens tissue. Functional interactions between foxe3 and pitx3 during lens development were assessed by RT-PCR and comparison of Foxe3 and Pitx3 protein expression in both foxe3 and pitx3 morphants. Immunoblots and immunohistochemistry reveal Pitx3 is expressed in the foxe3 morphant lens, while Pitx3 knockdown results in the elimination of Foxe3 expression. These data demonstrate that Foxe3 is necessary for lens development in zebrafish and that foxe3 lies genetically downstream of pitx3 in a zebrafish lens development pathway.

Molecular cloning of three zebrafish lin7 genes and their expression patterns in the retina.

The vertebrate retina develops from an undifferentiated sheet of neuroepithelial cells, whose differentiation requires the generation and maintenance of the correct cellular polarity. To examine the role of cell polarity in retinal development, we cloned three zebrafish lin7 genes (lin7a, lin7b, and lin7c), which each encodes a protein candidate that is required for generation/maintenance of neuroepithelial cell junctions. These three zebrafish Lin7 proteins share over 78% amino acid identity and contain both L27 and PDZ domains that are present in all Lin7 homologs. Immunoblots revealed that the Lin7b and Lin7c proteins were first expressed in the developing eye by 24hr postfertilization (hpf), while Lin7a was not detected in the eye until 72 hpf. At 33 hpf, the Lin7 proteins localized at, or slightly apical of, the actin-associated adherens junctions in the retinal neuroepithelium. This subcellular distribution required the expression of the Nok protein. In the absence of Nok, the Lin7 proteins failed to localize to either the ectopic adherens junctions or the cell membrane. At 4 days postfertilization, in situ hybridisation revealed that all three lin7 genes were expressed in both the ganglion cell layer and the bipolar cell region of the inner nuclear layer. The lin7a gene was also expressed in the amacrine and horizontal cell regions of the inner nuclear layer, while lin7c was also expressed in the outer nuclear layer. In the adult retina, where Lin7a is the predominant form expressed, the Lin7 proteins were localized to the outer and inner plexiform layers, the bipolar and horizontal cells of the inner nuclear layer, and the ganglion cells. These results suggest that the three zebrafish Lin7 proteins possess partially redundant, yet essential, roles in retinal development.

The zebrafish Pard3 ortholog is required for separation of the eye fields and retinal lamination.

The vertebrate retina develops from a sheet of neuroepithelial cells. Because adherens and tight junctions are critical for epithelial and neuronal differentiation in a variety of eukaryotic systems, we examined the role of Par-3, a PDZ scaffold protein that is critical in cellular membrane junction formation. We cloned the zebrafish Par-3 ortholog (pard3), which encodes two Pard3 proteins (150 and 180 kDa) that differ in their carboxyl-terminus. Immunohistochemistry revealed that Pard3 localized to the apical region of the retinal and brain neuroepithelium, partially overlapping the adherens junction-associated actin bundles. After retinal lamination, the Pard3 protein was restricted to the outer limiting membrane and the outer and inner plexiform layers in the retina. Reducing Pard3 expression with antisense morpholinos caused loss of the retinal pigmented epithelia, disruption of retinal lamination, and cell death in the ventral diencephalon, which resulted in cyclopia. Overexpressing Pard3 by injection of wild-type pard3 mRNA resulted in cyclopia and eyeless embryos. Thus, Pard3 plays a critical role in the origination and separation of zebrafish eye fields and retinal lamination.