Features and clinical significance of tertiary lymphoid structure in cutaneous squamous cell carcinoma.

BACKGROUND: Tertiary lymphoid structure (TLS) plays an important role in antitumour immunity, largely reflecting the prognosis. However, its clinical implication in cutaneous squamous cell carcinoma (cSCC) remains unknown. OBJECTIVES: To explore the features of TLS in cSCC and its association with clinicopathological characteristics. METHODS: Two independent RNA-seq data of cSCC were used to investigate the tumour immune microenvironment, as well as TLS-related chemokines and cytokines. The density and location of TLSs were assessed in a total of 82 cSCC patients, and the clinicopathologic association was examined. RESULTS: Bioinformatics analysis showed that a large amount of immune cell infiltration and significant up-regulation of TLS-related chemokines were observed in cSCC. Histologically, TLSs appeared as highly organized structures in 72 (87.8%) cases with different levels of density and maturation, among which 14 cases were in low-density group and 58 cases were in high-density group. Clinically, the presence of TLS was prominently associated with better degree of histopathological grades and higher level of sun exposure. Furthermore, the presence of intratumoral TLS was associated with lower lymphovascular invasion. CONCLUSIONS: TLS is highly organized in cSCC, and the presence of TLS is a positive prognostic factor for cSCC, which will provide a theoretical basis for the future diagnostic and therapeutic value in cSCC.

[Preparation and in vitro evaluation of fused deposition modeling 3D printed verapa-mil hydrochloride gastric floating formulations].

OBJECTIVE: To explore the feasibility of preparing gastric floating formulations by fused de-position modeling (FDM) 3D printing technology, to evaluate the in vitro properties of the prepared FDM 3D printed gastric floating formulations, and to compare the influence of different external shapes of the formulation with their in vitro properties. METHODS: Verapamil hydrochloride and polyvinyl alcohol (PVA) were used as the model drug and the excipient, respectively. The capsule-shaped and hemisphere-shaped gastric floating formulations were then prepared by FDM 3D printing. The infill percentages were 15%, the layer heights were 0.2 mm, and the roof or floor thicknesses were 0.8 mm for both the 3D printed formulations, while the number of shells was 3 and 4 for capsule-shaped and hemisphere-shaped formulation, respectively. Scanning electron microscopy (SEM) was used to observe the morpho-logy of the surface and cross section of the formulations. Gravimetric method was adopted to measure the weights of the formulations. Texture analyzer was employed to evaluate the hardness of the formulations. High performance liquid chromatography method was used to determine the drug contents of the formulations. The in vitro floating and drug release behavior of the formulations were also characterized. RESULTS: SEM showed that the appearance of the FDM 3D printed gastric floating formulations were both intact and free from defects with the filling structure which was consistent with the design. The weight variations of the two formulations were relatively low, indicating a high reproducibility of the 3D printing fabrication. Above 800.0 N of hardness was obtained in two mutually perpendicular directions for the two formulations. The drug contents of the two formulations approached to 100%, showing no drug loss during the 3D printing process. The two formulations floated in vitro without any lag time, and the in vitro floating time of the capsule-shaped and hemisphere-shaped formulation were (3.97±0.41) h and (4.48±0.21) h, respectively. The in vitro release of the two formulations was significantly slower than that of the commercially available immediate-release tablets. CONCLUSION: The capsule-shaped and hemisphere-shaped verapamil hydrochloride gastric floating formulations were prepared by FDM 3D printing technology successfully. Only the floating time was found to be influenced by the external shape of the 3D printed formulations in this study.

A whole genome sequence association study for puberty in a large Duroc × Erhualian F2 population.

A large proportion of gilts and sows are culled from reproduction populations because of anestrus and pubertal reproductive failure. Selecting early onset of puberty gilts has a favorable effect on sows' reproductivity. However, age at puberty is hard to be routinely measured in commercial herds. With molecular genetic predictors, identifying individuals that have a propensity for early onset of puberty can be simplified. We previously performed genome scanning and a genome-wide association study for puberty in an F2 resource population using 183 microsatellites and 62 125 SNPs respectively. The detection power and resolution of identified quantitative trait loci were very low. Herein, we re-sequenced 19 founders of the F2 resource population in high coverage, and whole genome sequences of F2 individuals were imputed to perform an association study for reproductive traits. A total of 2339 SNPs associated with pubertal reproductive failure were identified in the region of 30.94-40.74 Mb on SSC7, with the top one, positioned at 33.36 Mb, explaining 16% of the phenotypic variances. We improved the magnitude of the P-value by 10E+5 to 10E+7 using the whole genome sequence rather than using low/middle density markers as in previous studies, and we narrowed down the QTL confidence interval to 5.25 Mb. Combining the annotation of gene function, RAB23 and BAK1 were perceived as the most compelling candidate genes. The identified loci may be useful in culling sows failing to show estrus by marker-assisted selection to increase reproductive efficiency of swine herds.

Functional proteomics to identify critical proteins in signal transduction pathways.

Reversible protein phosphorylation plays a crucial role in the regulation of signaling pathways that control various biological responses, such as cell growth, differentiation, invasion, metastasis and apoptosis. Proteomics is a powerful research approach for fully monitoring global molecular responses to the activation of signal transduction pathways. Identification of different phosphoproteins and their phosphorylation sites by functional proteomics provides informational insights into signaling pathways triggered by all kinds of factors. This review summarizes how functional proteomics can be used to answer specific questions related to signal transduction systems of interest. By examining our own example on identifying the novel phosphoproteins in signaling pathways activated by EB virus-encoded latent membrane protein 1 (LMP1), we demonstrated a functional proteomic strategy to elucidate the molecular activity of phosphorylated annexin A2 in LMP1 signaling pathway. Functional profiling of signaling pathways is promising for the identification of novel targets for drug discovery and for the understanding of disease pathogenesis.

A clinical analysis of 836 cases with electric injury.

Eight hundred thirty-six patients with electric injury were admitted to Shanghai Power Hospital from 1972 to 1998. The majority of electric injury patients were young or middle-aged industrial workers from both cities and rural areas. These patients were classified into three categories depending on the type of electric injury: (1) electric shock; (2) electric contact burn injury; (3) electric arc burn. In our study of wound management, we focused on three areas: first, the choice of operation time in electric burn injury; second, the methods of wound management on the injured extremities, especially the hands and upper limbs; third, functional site wounds that included some exposed blood vessels. Nerves and tendons were covered and repaired by various flaps. Through the analysis of 836 electric injury cases, we summarized our experience of treating electric injury with the purpose of increasing our knowledge in the area of electric injury prevention and treatment.