Direct Effects of Inflammatory Cytokines on Mouse Uterine Contraction.

PROBLEM: Uterine contractions signal labor onset, with elevated pro-inflammatory cytokines playing a pivotal role. Prior studies have explored their effects on prostaglandins, oxytocin, and signaling pathways, but have overlooked their direct effects on uterine contractions. Here, we aim to investigate the direct effects of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) on contractions to ascertain if they have immediate observable effects like those reported for lipopolysaccharide (LPS) and other effects. METHOD OF STUDY: Tension recordings were used to assess the direct effects of cytokines and/or LPS on mouse uterine contractions. Calcium imaging was employed to observe calcium oscillations in cytokine-pretreated myometrial smooth muscle cells (MSMCs) in response to oxytocin. The release of inflammatory cytokines and chemokines from uterine explants after LPS and/or cytokines application was investigated using Luminex. RESULTS: IL-1ß, IL-6, and TNF-α rapidly enhanced contractions of term pregnant mouse uterus. LPS combined with TNF-α intensified contractions compared to LPS alone, although this effect was not statistically significant in our results (p > 0.050). Pretreatment of MSMCs with IL-1ß, IL-6, or TNF-α increased calcium oscillations in response to oxytocin. LPS and/or cytokine significantly stimulated the release of IL-1ß, IL-6, TNF-α, Chemokine (C-X-C motif) ligand 1 (CXCL1), and monocyte chemoattractant protein-1 (MCP1) from uterine explants in vitro. CONCLUSIONS: Inflammatory cytokines have short-term and long-term effects on mouse uterine contractions, which together contribute to progressively stronger contractions during labor.

TICRR Overexpression Enhances Disease Aggressiveness and Immune Infiltration of Cutaneous Melanoma.

Objective: To investigate the role of the TopBP1 interacting checkpoint and replication regulator (TICRR) in cutaneous melanoma (CM) as a prognostic biomarker and therapeutic target. Methods: TICRR expression in tumour samples was explored using the TCGA and the GTEx database. The Kaplan-Meier survival curve, nomogram model and risk score curve were established to evaluate the prognostic role of TICRR in CM. Tissue samples of CM patients were obtained to validate the TICRR expression further. Several experiments in vitro were conducted to investigate the effect of TICRR upon CM aggressiveness and to explore underlying mechanisms. Results: TICRR was overexpressed in CM tissue and was correlated with poor prognosis of CM patients. The knockdown of TICRR decreased the proliferation, migration, and invasion of CM cells, whereas overexpression produced the opposite effect. Furthermore, TICRR suppression substantially attenuated the activation of PI3K/AKT/mTOR signalling, while the PI3K/AKT inhibitor LY294002 could partially reverse the aggressiveness-enhancing effect induced by TICRR overexpression. It was further confirmed that TICRR was closely related to immune cell infiltration activities by using immune infiltration and immunofluorescence analysis. Conclusion: TICRR overexpression may enhance CM aggressiveness by activating the PI3K/Akt/mTOR pathway and promoting immune infiltration. TICRR was verified as a potential prognostic biomarker and therapeutic target for CM.

Carbamoylation at C-8 position of natural 3-arylcoumarin scaffold for the discovery of novel PARP-1 inhibitors with potent anticancer activity.

Structural modification based on natural privileged scaffolds has proven to be an attractive approach to generate potential antitumor candidates with high potency and specific targeting. As a continuation of our efforts to identify potent PARP-1 inhibitors, natural 3-arylcoumarin scaffold was served as the starting point for the construction of novel structural unit for PARP-1 inhibition. Herein, a series of novel 8-carbamyl-3-arylcoumarin derivatives were designed and synthesized. The antiproliferative activities of target compounds against four BRCA-mutated cancer cells (SUM149PT, HCC1937, MDA-MB-436 and Capan-1) were evaluated. Among them, compound 9b exhibited excellent antiproliferative effects against SUM149PT, HCC1937 and Capan-1 cells with IC50 values of 0.62, 1.91 and 4.26 µM, respectively. Moreover, 9b could significantly inhibit the intracellular PARP-1/2 activity in SUM149PT cells with IC50 values of 2.53 nM and 6.45 nM, respectively. Further mechanism studies revealed that 9b could aggravate DNA double-strand breaks, increase ROS production, decrease mitochondrial membrane potential, arrest cell cycle at G2/M phase and ultimately induce apoptosis in SUM149PT cells. In addition, molecular docking study demonstrated that the binding mode of 9b with PARP-1 was similar to that of niraparib, forming multiple hydrogen bond interactions with the active site of PARP-1. Taken together, these findings suggest that 8-carbamyl-3-arylcoumarin scaffold could serve as an effective structural unit for PARP-1 inhibition and offer a valuable paradigm for the structural modification of natural products.

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens.

Weak antigens represented by MUC1 are poorly immunogenic, which greatly constrains the development of relevant vaccines. Herein, we developed a multifunctional lipidated protein as a carrier, in which the TLR1/2 agonist Pam3CSK4 was conjugated to the N-terminus of MUC1-loaded carrier protein BSA through pyridoxal 5'-phosphate-mediated transamination reaction. The resulting Pam3CSK4-BSA-MUC1 conjugate was subsequently incorporated into liposomes, which biomimics the membrane structure of tumor cells. The results indicated that this lipidated protein carrier significantly enhanced antigen uptake by APCs and obviously augmented the retention of the vaccine at the injection site. Compared with the BSA-MUC1 and BSA-MUC1 + Pam3CSK4 groups, Pam3CSK4-BSA-MUC1 evoked 22- and 11-fold increases in MUC1-specific IgG titers. Importantly, Pam3CSK4-BSA-MUC1 elicited robust cellular immunity and significantly inhibited tumor growth. This is the first time that lipidated protein was constructed to enhance antigen immunogenicity, and this universal carrier platform exhibits promise for utilization in various vaccines, holding the potential for further clinical application.

Elucidating the role of EPPK1 in lung adenocarcinoma development.

BACKGROUND: We recently found that epiplakin 1 (EPPK1) alterations were present in 12% of lung adenocarcinoma (LUAD) cases and were associated with a poor prognosis in early-stage LUAD when combined with other molecular alterations. This study aimed to identify a probable crucial role for EPPK1 in cancer development. METHODS: EPPK1 mRNA and protein expression was analyzed with clinical variables. Normal bronchial epithelial cell lines were exposed to cigarette smoke for 16 weeks to determine whether EPPK1 protein expression was altered after exposure. Further, we used CRISPR-Cas9 to knock out (KO) EPPK1 in LUAD cell lines and observed how the cancer cells were altered functionally and genetically. RESULTS: EPPK1 protein expression was associated with smoking and poor prognosis in early-stage LUAD. Moreover, a consequential mesenchymal-to-epithelial transition was observed, subsequently resulting in diminished cell proliferation and invasion after EPPK1 KO. RNA sequencing revealed that EPPK1 KO induced downregulation of 11 oncogenes, 75 anti-apoptosis, and 22 angiogenesis genes while upregulating 8 tumor suppressors and 12 anti-cell growth genes. We also observed the downregulation of MYC and upregulation of p53 expression at both protein and RNA levels following EPPK1 KO. Gene ontology enrichment analysis of molecular functions highlighted the correlation of EPPK1 with the regulation of mesenchymal cell proliferation, mesenchymal differentiation, angiogenesis, and cell growth after EPPK1 KO. CONCLUSIONS: Our data suggest that EPPK1 is linked to smoking, epithelial to mesenchymal transition, and the regulation of cancer progression, indicating its potential as a therapeutic target for LUAD.

Skeletal Editing of Benzene Motif: Photopromoted Transannulation for Synthesis of DNA-Encoded Seven-Membered Rings.

In this report, we present a photopromoted, metal-free transannulation of phenyl azides for the synthesis of DNA-encoded seven-membered rings. The transformation is efficiently achieved through a skeletal editing strategy targeting the benzene motif coupled with a Reversible Adsorption to Solid Support (RASS) strategy. A variety of valuable DNA-encoded seven-membered ring compounds, including DNA-encoded 3H-azepines, azepinones, and unnatural amino acids, are now accessible. Crucially, this DNA-compatible protocol can also be applied for the introduction of complex molecules, as exemplified by Lorcaserin and Betahistine. The selective conversion of readily available phenyl rings into high-value seven-membered rings offers a promising avenue for the construction of diversified and drug-like DNA-encoded library.

[Retracted] Effect of RhoC on the epithelial­mesenchymal transition process induced by TGF­ß1 in lung adenocarcinoma cells.

Following the publication of the above article, a concerned reader drew to the Editor's attention that the Transwell cell invasion assay data featured in Figs. 3 and 5, and the cell microscopic/morphological images shown in Fig. 4A and C, were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Oncology Reports, or which under consideration for publication at around the same time (several of which have now been retracted). In addition, overlapping sections of data were noted within Figs. 3 and 5, such that data which were intended to represent the results from differently performed experiments had apparently been derived from the same original source(s). In view of the fact that certain of these data had already apparently been published prior to the submission of this article for publication, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 36: 3105­3112, 2016; DOI: 10.3892/or.2016.5146].

[Effects of Polystyrene Microplastics Combined with Cadmium Contamination on Soil Physicochemical Properties and Physiological Ecology of Lactuca sativa].

Contaminants such as microplastics (MPs) and heavy metals are commonly found in soils, both of which are extremely difficult to degrade and can easily form compound contamination, altering the physicochemical properties of the soil and thus potentially changing the growth and physiological and ecological characteristics of plants. In order to study the effects of the combined contamination of soil MPs and heavy metals on soil properties and plant growth, polystyrene microplastics (PS-MPs) with a particle size of 3 µm and the heavy metal cadmium were selected in the study. The changes in the physicochemical properties of soil and their effects on lettuce (Lactuca sativa) seed germination and seedling growth were studied at various exposure concentrations of PS-MPs (0, 10, 50, 100, 200, and 400 mg·kg-1) and combined with different Cd contamination concentrations (0, 1.2, and 6.0 mg·kg-1), respectively. The results showed that soil organic matter (SOM), available phosphorus (AP), alkali-hydrolysable nitrogen (AHN), and available kalium (AK) showed significant decreases as the intensity of PS-MPs combined with Cd contamination increased. Simultaneously, PS-MPs combined with Cd contamination also significantly reduced the germination rate of lettuce seeds, but low concentrations of PS-MPs slowed down the effect of Cd (6.0 mg·kg-1) contamination on lettuce seeds, and high concentrations of PS-MPs enhanced the effect of Cd (6.0 mg·kg-1). The fresh weight, dry weight, and plant height of lettuce seedlings showed an increasing and then decreasing trend with increasing exposure to PS-MPs. Chlorophyll content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) showed a decreasing trend, whereas malondialdehyde (MDA) content showed an overall increasing trend under different Cd concentrations. The main physicochemical indicators of the soil were negatively correlated with MDA of lettuce seedlings, whereas other indicators of the seedlings were positively correlated. The combined contamination of PS-MPs and Cd could affect the germination of plant seeds and the physiological and ecological characteristics of seedlings by changing the physicochemical properties of the soil. Both exposure to single PS-MPs contaminants and the combination of PS-MPs with Cd inhibited the germination of lettuce seeds and affected the physiological activities of their seedlings, and the inhibition was significantly increased with increasing exposure. Low exposure to PS-MPs or the combination of PS-MPs with Cd contamination exhibited a promotive effect on lettuce seedling growth. High exposure to PS-MPs combined with Cd contamination exhibited significant ecological effects on lettuce seedlings, and high exposure to PS-MPs exacerbated the ecotoxicological effects of Cd contaminants on lettuce seedlings, and PS-MPs and Cd exhibited synergistic effects. The results can provide some reference for assessing the ecological effects of MPs and heavy metal pollution in soil-plant systems.

Clinical Microfluidic Chip Platform for the Isolation of Versatile Circulating Tumor Cells.

Circulating tumor cells (CTCs) are significant in cancer prognosis, diagnosis, and anti-cancer therapy. CTC enumeration is vital in determining patient disease since CTCs are rare and heterogeneous. CTCs are detached from the primary tumor, enter the blood circulation system, and potentially grow at distant sites, thus metastasizing the tumor. Since CTCs carry similar information to the primary tumor, CTC isolation and subsequent characterization can be critical in monitoring and diagnosing cancer. The enumeration, affinity modification, and clinical immunofluorescence staining of rare CTCs are powerful methods for CTC isolation because they provide the necessary elements with high sensitivity. Microfluidic chips offer a liquid biopsy method that is free of any pain for the patients. In this work, we present a list of protocols for clinical microfluidic chips, a versatile CTC isolating platform, that incorporate a set of functionalities and services required for CTC separation, analysis, and early diagnosis, thus facilitating biomolecular analysis and cancer treatment. The program includes rare tumor cell counting, clinical patient blood preprocessing, which includes red blood cell lysis, and the isolation and recognition of CTCs in situ on microfluidic chips. The program allows the precise enumeration of tumor cells or CTCs. Additionally, the program includes a tool that incorporates CTC isolation with versatile microfluidic chips and immunofluorescence identification in situ on the chips, followed by biomolecular analysis.

Complete miRNA-15/16 loss in mice promotes hematopoietic progenitor expansion and a myeloid-biased hyperproliferative state.

Dysregulated apoptosis and proliferation are fundamental properties of cancer, and microRNAs (miRNA) are critical regulators of these processes. Loss of miR-15a/16-1 at chromosome 13q14 is the most common genomic aberration in chronic lymphocytic leukemia (CLL). Correspondingly, the deletion of either murine miR-15a/16-1 or miR-15b/16-2 locus in mice is linked to B cell lymphoproliferative malignancies. However, unexpectedly, when both miR-15/16 clusters are eliminated, most double knockout (DKO) mice develop acute myeloid leukemia (AML). Moreover, in patients with CLL, significantly reduced expression of miR-15a, miR-15b, and miR-16 associates with progression of myelodysplastic syndrome to AML, as well as blast crisis in chronic myeloid leukemia. Thus, the miR-15/16 clusters have a biological relevance for myeloid neoplasms. Here, we demonstrate that the myeloproliferative phenotype in DKO mice correlates with an increase of hematopoietic stem and progenitor cells (HSPC) early in life. Using single-cell transcriptomic analyses, we presented the molecular underpinning of increased myeloid output in the HSPC of DKO mice with gene signatures suggestive of dysregulated hematopoiesis, metabolic activities, and cell cycle stages. Functionally, we found that multipotent progenitors (MPP) of DKO mice have increased self-renewing capacities and give rise to significantly more progeny in the granulocytic compartment. Moreover, a unique transcriptomic signature of DKO MPP correlates with poor outcome in patients with AML. Together, these data point to a unique regulatory role for miR-15/16 during the early stages of hematopoiesis and to a potentially useful biomarker for the pathogenesis of myeloid neoplasms.

Cancer-associated fibroblasts in early-stage lung adenocarcinoma correlate with tumor aggressiveness.

Lung adenocarcinoma (LUAD) is the predominant type of lung cancer in the U.S. and exhibits a broad variety of behaviors ranging from indolent to aggressive. Identification of the biological determinants of LUAD behavior at early stages can improve existing diagnostic and treatment strategies. Extracellular matrix (ECM) remodeling and cancer-associated fibroblasts play a crucial role in the regulation of cancer aggressiveness and there is a growing need to investigate their role in the determination of LUAD behavior at early stages. We analyzed tissue samples isolated from patients with LUAD at early stages and used imaging-based biomarkers to predict LUAD behavior. Single-cell RNA sequencing and histological assessment showed that aggressive LUADs are characterized by a decreased number of ADH1B+ CAFs in comparison to indolent tumors. ADH1B+ CAF enrichment is associated with distinct ECM and immune cell signatures in early-stage LUADs. Also, we found a positive correlation between the gene expression of ADH1B+ CAF markers in early-stage LUADs and better survival. We performed TCGA dataset analysis to validate our findings. Identified associations can be used for the development of the predictive model of LUAD aggressiveness and novel therapeutic approaches.

Tumoral Densities of T-Cells and Mast Cells Are Associated With Recurrence in Early-Stage Lung Adenocarcinoma.

Introduction: Lung cancer is the deadliest cancer in the United States and worldwide, and lung adenocarcinoma (LUAD) is the most prevalent histologic subtype in the United States. LUAD exhibits a wide range of aggressiveness and risk of recurrence, but the biological underpinnings of this behavior are poorly understood. Past studies have focused on the biological characteristics of the tumor itself, but the ability of the immune response to contain tumor growth represents an alternative or complementary hypothesis. Emerging technologies enable us to investigate the spatial distribution of specific cell types within the tumor nest and characterize this immune response. This study aimed to investigate the association between immune cell density within the primary tumor and recurrence-free survival (RFS) in stage I and II LUAD. Methods: This study is a prospective collection with retrospective evaluation. A total of 100 patients with surgically resected LUAD and at least 5-year follow-ups, including 69 stage I and 31 stages II tumors, were enrolled. Multiplexed immunohistochemistry panels for immune markers were used for measurement. Results: Cox regression models adjusted for sex and EGFR mutation status revealed that the risk of recurrence was reduced by 50% for the unit of one interquartile range (IQR) change in the tumoral T-cell (adjusted hazard ratio per IQR increase = 0.50, 95% confidence interval: 0.27-0.93) and decreased by 64% in mast cell density (adjusted hazard ratio per IQR increase = 0.36, confidence interval: 0.15-0.84). The analyses were reported without the type I error correction for the multiple types of immune cell testing. Conclusions: Analysis of the density of immune cells within the tumor and surrounding stroma reveals an association between the density of T-cells and RFS and between mast cells and RFS in early-stage LUAD. This preliminary result is a limited study with a small sample size and a lack of an independent validation set.

Platinum and Frustrated Lewis Pairs on Ceria as Dual-Active Sites for Efficient Reverse Water-Gas Shift Reaction at Low Temperatures.

The low-temperature reverse water-gas shift (RWGS) reaction faces the following obstacles: low activity and unsatisfactory selectivity. Herein, the dual-active sites of platinum (Pt) clusters and frustrated Lewis pair (FLP) on porous CeO2 nanorods (Ptcluster /PN-CeO2 ) provide an interface-independent pathway to boost high performance RWGS reaction at low temperatures. Mechanistic investigations illustrate that Pt clusters can effectively activate and dissociate H2 . The FLP sites, instead of the metal and support interfaces, not only enhance the strong adsorption and activation of CO2 , but also significantly weaken CO adsorption on FLP to facilitate CO release and suppress the CH4 formation. With the help of hydrogen spillover from Pt to PN-CeO2 , the Ptcluster /PN-CeO2 catalysts achieved a CO yield of 29.6 %, which is very close to the thermodynamic equilibrium yield of CO (29.8 %) at 350 °C. Meanwhile, the Ptcluster /PN-CeO2 catalysts delivered a large turnover frequency of 8720 h-1 . Moreover, Ptcluster /PN-CeO2 operated stably and continuously for at least 840 h. This finding provides a promising path toward optimizing the RWGS reaction.

Integrated Multi-omics Analysis of Early Lung Adenocarcinoma Links Tumor Biological Features with Predicted Indolence or Aggressiveness.

Lung adenocarcinoma (LUAD) is a heterogeneous group of tumors associated with different survival rates, even when detected at an early stage. Here, we aim to investigate the biological determinants of early LUAD indolence or aggressiveness using radiomics as a surrogate of behavior. We present a set of 92 patients with LUAD with data collected across different methodologies. Patients were risk-stratified using the CT-based Score Indicative of Lung cancer Aggression (SILA) tool (0 = least aggressive, 1 = most aggressive). We grouped the patients as indolent (x ≤ 0.4, n = 14), intermediate (0.4 > x ≤ 0.6, n = 27), and aggressive (0.6 > x ≤ 1, n = 52). Using Cytometry by time of flight (CyTOF), we identified subpopulations with high HLA-DR expression that were associated with indolent behavior. In the RNA sequencing (RNA-seq) dataset, pathways related to immune response were associated with indolent behavior, while pathways associated with cell cycle and proliferation were associated with aggressive behavior. We extracted quantitative radiomics features from the CT scans of the patients. Integrating these datasets, we identified four feature signatures and four patient clusters that were associated with survival. Using single-cell RNA-seq, we found that indolent tumors had significantly more T cells and less B cells than aggressive tumors, and that the latter had a higher abundance of regulatory T cells and Th cells. In conclusion, we were able to uncover a correspondence between radiomics and tumor biology, which could improve the discrimination between indolent and aggressive LUAD tumors, enhance our knowledge in the biology of these tumors, and offer novel and personalized avenues for intervention. Significance: This study provides a comprehensive profiling of LUAD indolence and aggressiveness at the biological bulk and single-cell levels, as well as at the clinical and radiomics levels. This hypothesis generating study uncovers several potential future research avenues. It also highlights the importance and power of data integration to improve our systemic understanding of LUAD and to help reduce the gap between basic science research and clinical practice.

900 MHZ electromagnetic field exposure relieved AD-like symptoms on APP/PS1 mice: A potential non-invasive strategy for AD treatment.

BACKGROUND: Evidence shows that microwaves radiation may have various biological effects on central nervous system. Role of electromagnetic fields in neurodegenerative diseases, especially AD, has been widely studied, but results of these studies are inconsistent. Therefore, the above effects were verified again and the mechanism was preliminarily discussed. METHODS: Amyloid precursor protein (APP/PS1) and WT mice were exposed to long-term microwave radiation for 270 days (900 MHz, SAR: 0.25-1.055 W/kg, 2 h/day, alternately), and related indices were assessed at 90, 180 and 270 days. Cognition was evaluated by Morris water maze, Y maze and new object recognition tests. Congo red staining, immunohistochemistry and ELISA were used to analyze Aß plaques, Aß40 and Aß42 content. Differentially expressed proteins in hippocampus between microwave-exposed and unexposed AD mice were identified by proteomics. RESULTS: Spatial and working memory was improved in AD mice after long-term 900 MHz microwave exposure compared with after sham exposure. Microwave radiation (900 MHz) for 180 or 270 days did not induce Aß plaque formation in WT mice but inhibited Aß accumulation in the cerebral cortex and hippocampus in 2- and 5-month-old APP/PS1 mice. This effect mainly occurred in the late stage of the disease and may have been attributed to downregulation of apolipoprotein family member and SNCA expression and excitatory/inhibitory neurotransmitter rebalance in the hippocampus. CONCLUSIONS: The present results indicated that long-term microwave radiation can retard AD development and exert a beneficial effect against AD, suggesting that 900 MHz microwave exposure may be a potential therapy for AD.

Discovery of novel benzamide derivatives bearing benzamidophenyl and phenylacetamidophenyl scaffolds as potential antitumor agents via targeting PARP-1.

Poly(ADP-ribose) polymerase-1 (PARP-1) plays a crucial role in DNA damage repair and has been identified as a promising therapeutic target in cancer therapy. As a continuation of our efforts on the development of novel PARP-1 inhibitors with potent anticancer activity, a series of benzamide derivatives containing the benzamidophenyl and phenylacetamidophenyl scaffolds were designed and synthesized based on the structure optimization of our previously reported compound IX. All target compounds were screened for their in vitro antiproliferative activities against human colorectal cancer cells (HCT116, DLD-1 and SW480) and human normal colonic epithelial cells (NCM460). Among them, compound 13f exhibited the most potent anticancer activity against HCT116 cells and DLD-1 cells with IC50 = 0.30 µM and 2.83 µM, respectively. Moreover, 13f displayed significant selectivity in inhibiting HCT116 cancer cells over the normal NCM460 cells. Furthermore, 13f exhibited excellent PARP-1 inhibitory effect with IC50 = 0.25 nM. Besides, 13f was found to effectively inhibit colony formation and migration of HCT116 cells. Studies on the mechanisms revealed that 13f could arrest cell cycle at G2/M phase, accumulate DNA double-strand breaks, reduce mitochondrial membrane potential and ultimately induce apoptosis in HCT116 cells. In addition, molecular docking study indicated that 13f could combine firmly with the catalytic pocket of PARP-1 through multiple hydrogen bond interactions. Collectively, these findings demonstrated that 13f could serve as a promising anticancer candidate and deserves further investigation.

Repair of multiple hand defects with superficial circumflex iliac artery perforator flap.

BACKGROUND: Reconstruction and repair of multiple defects in the hand is a combination of function, sensation and aesthetics. The reconstruction using the superficial circumflex iliac artery perforator flap has become popular, which overcomes the inherent shortcomings of traditional inguinal flaps by preserving the deep fascia. In this report, we present our experience in the design and clinical application of the superficial circumflex iliac artery perforator flap, which we used to repair multiple defects in the hand. METHODS: From January 2015 to December 2020, 41 patients received free superficial circumflex iliac artery perforator flap to repair multiple hand defects. All flaps were carefully designed according to the hand defect including 21 single and 20 bilobed flaps. The area of ​​the donor area is 2.5 cm × 3.0cm∼8.0 cm × 6.5 cm. We followed up all patients regularly and completed standardized assessments of outcomes based on post-reconstruction hand function and esthetic scores. RESULTS: 41 cases of flaps survived completely.3 cases of vascular crisis was relieved after surgical exploration, 1 case of mild distal necrosis was healed after dressing change, 1 case of pigmentation happened. There were 41 patients, 27 males and 14 females, with an average age of 40.5 years (4 to 59 years old). The defects included 20 cases opisthenars and 21 cases palms. The wounds were irregular, with exposed or damaged tendons, nerves or bones. All flaps were followed for a mean of 10.5 months (3 to 15 months). The functional and esthetic outcomes were satisfactory for all flaps without complications such as hand spasms, adhesions and scar contractures CONCLUSION: The superficial circumflex iliac artery perforator flap's donor site was concealed, relatively stable perforators, easy dissection. Recipient site condition was good and acceptable for the patients. It is a significant choice for multiple hand defects.

Development and Validation of a Prognostic Nomogram for Lung Adenocarcinoma: A Population-Based Study.

Purpose: To establish an effective and accurate prognostic nomogram for lung adenocarcinoma (LUAD). Patients and Methods. 62,355 LUAD patients from 1975 to 2016 enrolled in the Surveillance, Epidemiology, and End Results (SEER) database were randomly and equally divided into the training cohort (n = 31,179) and the validation cohort (n = 31,176). Univariate and multivariate Cox regression analyses screened the predictive effects of each variable on survival. The concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) were used to examine and validate the predictive accuracy of the nomogram. Kaplan-Meier curves were used to estimate overall survival (OS). Results: 10 prognostic factors associated with OS were identified, including age, sex, race, marital status, American Joint Committee on Cancer (AJCC) TNM stage, tumor size, grade, and primary site. A nomogram was established based on these results. C-indexes of the nomogram model reached 0.777 (95% confidence interval (CI), 0.773 to 0.781) and 0.779 (95% CI, 0.775 to 0.783) in the training and validation cohorts, respectively. The calibration curves were well-fitted for both cohorts. The AUC for the 3- and 5-year OS presented great prognostic accuracy in the training cohort (AUC = 0.832 and 0.827, respectively) and validation cohort (AUC = 0.835 and 0.828, respectively). The Kaplan-Meier curves presented significant differences in OS among the groups. Conclusion: The nomogram allows accurate and comprehensive prognostic prediction for patients with LUAD.