Vascularized lymph node flaps can survive on venous blood without an arterial inflow: an experimental model describing the dynamics of venous flow using indocyanine green angiography (With video).

Background: Several surgeons have described studies of free-tissue transfers using veins instead of arteries. These innovative microsurgical techniques can offer several advantages, such as an easier dissection during flap harvesting, and represent an alternative during an accidental surgical mistake or development of new surgical procedures. The purpose of this study was to describe and explore different constructs of vascularized lymph node transfer (VLNT) only based on venous blood flow in a mouse model, evaluate their blood flow microcirculation through indocyanine green (ICG) angiography and investigate the lymphatic drainage function and the lymph nodes' structures. Methods: Five types of venous lymph node flaps (LNF) were created and investigated: Types IA, IB, IC, IIA and IIB were developed by ICG intraoperatively (with videos in the article). Seven weeks later, by applying methylene blue, the recanalization of the lymphatic vessels between the LNF and the recipient site was detected. Lymph nodes were collected at the same time and their structures were analyzed by hematoxylin and eosin staining analysis. Results: All of the venous LNFs developed except Type IC. Seven weeks later, methylene blue flowed into Types IA, IB, IIA and IIB from recipient sites. When comparing with arteriovenous lymph node, the medullary sinus was diffusely distributed in venous lymph nodes. The proportion of cells was significantly reduced (p < 0.05). The artery diameters were significantly smaller (p < 0.05). The veins diameters and lymphatic vessels output in Types IA, IB, IIA and IIB were more dilated (p < 0.05). Conclusions: This research demonstrated that Type IA, IB, IIA and IIB venous LNFs can retrogradely receive venous blood supply; they can survive, produce a lymphatic recanalization and integrate with the surrounding tissue, despite lymph node structural changes. Our results will improve the understanding of the survival mechanism of venous LNFs and will help researchers to design new studies or lymphatic models and eventually find an alternative procedure for the surgical treatment of lymphedema.

In Vivo Precision Evaluation of Lymphatic Function by SWIR Luminescence Imaging with PbS Quantum Dots.

Advancements in lymphography technology are essential for comprehensive investigation of the lymphatic system and its function. Here, a shortwave infrared (SWIR) luminescence imaging of lymphatic vessels is proposed in both normal and lymphatic dysfunction in rat models with PbS quantum dots (PbS Qdots). The lymphography with PbS Qdots can clearly and rapidly demonstrate the normal lymphatic morphology in both the tail and hind limb. More importantly, compared to ICG, SWIR luminescence imaging with PbS Qdots can easily identify the dominant lymphatic vessel and node with higher luminescence signal in rats. Moreover, lymphatic pump is identified as segment contracting sections with a size of ≈1 cm in rat by in vivo SWIR lymphograhy, which propose a direct feature for precise evaluation of lymphatic function. Notably, in vivo SWIR luminescence imaging with PbS Qdots also clearly deciphers the in vivo pattern of morphological and function recovery from lymphatic system in rat model. In summary, SWIR luminescence imaging with PbS Qdots can improve the lymphography and thus deepen the understanding of the morphology and structure of the lymphatic system as well as lymphatic function such as lymphatic pump, which will facilitate the diagnosis of lymphatic dysfunction in the future.

A top-down spectroscopic approach for correlating coating thickness distributions with the dissolution profiles of enterically coated pellets.

Pharmaceutical dosage forms such as tablets and capsules are often coated with a functional polymer to modify the drug release. To obtain the drug release profiles, ensure quality control and predict in-vivo performance, dissolution studies are performed. However, dissolution tests are time-consuming, sample destructive and do not readily allow for at-line or in-line characterization. Rapid assessment of functional coatings is essential for products where a single capsule is comprised of hundreds of functionally-coated pellets and the collective drug release kinetics of the entire capsule depends on contributions from each pellet. Here, single Raman measurements were used to evaluate the coating thickness distributions of a dosage form comprised of small, functionally-coated pellets in capsules. First, the composition and physicochemical properties of pellets were characterized by multivariate analysis assisted Raman mapping of pellet cross-sections. Second, a method of collecting single Raman spectrum with spectral contributions from the coating and API layers was developed and optimized to estimate the thickness of coatings. The coating thicknesses obtained from single Raman measurements of pellets in each capsule revealed thickness distributions that correlated with the dissolution profiles (capsules with one distribution had single stage release and capsules with two distributions had a two-stage release). Finally, an unsupervised multivariate analysis method was demonstrated as a rapid and efficient way to correlate dissolution profiles of enterically coated pellets. In summary, this study presents a non-destructive and rapid characterization method for assessing coating thickness and has the potential to be applied in process analytical technologies to ensure coating uniformity and predict product dissolution rate performance.

Making "cold" tumors "hot"- radiotherapy remodels the tumor immune microenvironment of pancreatic cancer to benefit from immunotherapy: a case report.

Immune checkpoint inhibitors have limited efficacy in metastatic pancreatic cancer due to the complex tumor immune microenvironment (TIME). Studies have shown that radiotherapy can cause cell lesions to release tumor antigens and then take part in the remodeling of the tumor environment and the induction of ectopic effects via regional and systemic immunoregulation. Here, we reported a case of advanced metastatic pancreatic cancer treated with immunotherapy combined with chemotherapy and radiotherapy and a sharp shift of the TIME from T3 to T2 was also observed. One hepatic metastasis within the planning target volume (PTV) was evaluated complete response (CR), the other one was evaluated partial response (PR) and 2 hepatic metastases outside the PTV were surprisingly considered PR. In the study, we found that immunotherapy combined with chemotherapy and radiotherapy achieved significant therapeutic benefits, which may provide a new strategy for the treatment of advanced pancreatic cancer.

Tumor immune microenvironment and immunotherapy efficacy in BRAF mutation non-small-cell lung cancer.

Previous small-size studies reported BRAF-mutated NSCLC patients have comparable sensitivity to immune checkpoint inhibitors (ICIs). However, how BRAF mutation affects the tumor immune microenvironment (TIME) is unknown. We performed Nanostring-panel RNA sequencing to evaluate TIME in 57 BRAF mutated and wild-type (WT) NSCLC specimens (cohort A). The efficacy of ICI monotherapy or combined therapies was determined in 417 patients with WT and BRAF mutated NSCLC (cohort B). We found that BRAF-mutant tumors had similar ratios of CD8+ T cells to Tregs, the balance of cytotoxicity gene expression signatures and immune suppressive features, and similar ICI-response-related biomarkers to WT NSCLC. A similar TIME pattern was observed between the BRAF V600E and Non-V600E subgroups of NSCLC. The further retrospective study confirmed that treatment with ICI monotherapy or combined therapies resulted in similar overall survival (OS) (HR: 0.85; 95% CI, 0.56 to 1.30; p = 0.47) and progress-free survival (PFS) (HR: 1.02; 95% CI, 0.72 to 1.44; p = 0.91) of patients with WT (n = 358) and BRAF mutant (n = 59) NSCLC. Similarly, both patients with BRAF V600E or Non-V600E NSCLC had similar responses to immunotherapy. Our findings support that BRAF mutation did not modulate TIME in NSCLC and therapeutic responses to ICIs. Patients with NSCLC harboring BRAF mutation should not be denied treatment with ICIs.

Double-network composites based on inorganic fillers reinforced dextran-based hydrogel with high strength.

The biodegradable hydrogels with a 3D network structure have potential applications in bone tissue engineering. Here, inspired by natural bone, the novel organic-inorganic composites (GelMPC-x) with high compressive strength are designed via adding magnesium oxide/calcium dihydrogen phosphate (MPC) powders into the oxidized dextran/gelatin (OD/Gel) hydrogel. GelMPC-x composites can trigger the gelation of OD/Gel hydrogel through an acid-alkaline reaction between magnesium oxide and calcium dihydrogen phosphate, thus forming an organic-inorganic double network. The cross-linked network between oxidized dextran and gelatin, and the multiple weak interactions between OD/Gel hydrogel and MPC enable the composites to have remarkable compressive strength (77-652 kPa) at the strain of 44 %. More importantly, the composites with appropriate MPC content possess superior injectability, high porosity, and excellent cytocompatibility. This work provides guidelines for the preparation of oxidized dextran-based composite hydrogels with enhanced mechanical performance.

Intense Pulsed Light Therapy Improves Acne-Induced Post-inflammatory Erythema and Hyperpigmentation: A Retrospective Study in Chinese Patients.

INTRODUCTION: Post-inflammatory erythema (PIE) and post-inflammatory hyperpigmentation (PIH) are the most common acne-related sequelae with no effective treatments. By combining different cut-off filters, intense pulsed light (IPL) therapy can effectively treat these conditions with few side effects. While the safety and effectiveness of IPL for treating post-burn hyperpigmentation is well known, there is little evidence for its benefits for acne-related PIH. In this article, we evaluate the efficacy and safety of IPL for the treatment of acne-related PIE and PIH. METHODS: This retrospective study evaluated 60 patients with more than 6 months of PIE and PIH treated by the same IPL device and similar protocols. The treatment included three to seven sessions at 4-6-week intervals, and three cut-off filters (640 nm, 590 nm and 560 nm) were used sequentially in each session. Using the Global Aesthetic Improvement Scale (GAIS), Cardiff Acne Disability Index (CADI), and Erythema Assessment Scale (EAS), patients were evaluated on the basis of their facial photographs. The facial brown spots and red areas were visualised and analysed using the VISIA-CR system. Six months after the last treatment, the patients were assessed for acne relapse or any side effects.Please check and confirm that the authors and their respective affiliations have been correctly processed and amend if necessary.Checked and confirmed. No further corrections. RESULTS: On the basis of the GAIS, 49 of 60 patients (81.7%) showed complete or partial clearance of erythema and hyperpigmentation. The CADI and EAS scores showed significant improvement (p < 0.01) after IPL treatment compared with pre-treatment. A significant reduction (p < 0.01) in the facial brown spots and red areas was seen after IPL treatment. While no long-term side effects were reported, seven patients (11.7%) experienced acne relapse at follow-up. CONCLUSION: IPL is an effective and safe treatment for acne-related PIE and PIH.

Efficacy and safety of camrelizumab plus apatinib during the perioperative period in resectable hepatocellular carcinoma: a single-arm, open label, phase II clinical trial.

OBJECTIVE: This study aimed to assess the efficacy and safety of camrelizumab plus apatinib in patients with resectable hepatocellular carcinoma (HCC) as neoadjuvant therapy. METHODS: Initially, 20 patients with HCC were screened and 18 patients with resectable HCC were enrolled in this open-label, single-arm, phase II clinical trial. Patients received three cycles of neoadjuvant therapy including three doses of camrelizumab concurrent with apatinib for 21 days followed by surgery. Four to 8 weeks after surgery, patients received eight cycles of adjuvant therapy with camrelizumab in combination with apatinib. Major pathological reactions (MPR), complete pathological reactions (pCR), objective response rate (ORR), relapse-free survival (RFS), and adverse events (AE) were assessed. In addition, cancer tissue and plasma samples were collected before and after treatment, and genetic differences between responding and non-responding lesions were compared by tumor immune microenvironment (TIME) analysis, circulating tumor DNA (ctDNA) analysis and proteomics analysis. RESULTS: In 18 patients with HCC who completed neoadjuvant therapy, 3 (16.7%) and 6 (33.3%) patients with HCC reached ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and modified RECIST criteria, respectively. Of the 17 patients with HCC who received surgical resection, 3 (17.6%) patients with HCC reported MPR and 1 (5.9%) patient with HCC achieved pCR. The 1-year RFS rate of the enrolled patients was 53.85% (95% CI: 24.77% to 75.99%). Grade 3/4 AEs were reported in 3 (16.7%) of the 18 patients, with the most common AEs being rash (11.1%), hypertension (5.6%), drug-induced liver damage (5.6%), and neutropenia (5.6%) in the preoperative phase. The 289 NanoString panel RNA sequencing showed that TIME cell infiltration especially dendritic cells (DCs) infiltration was better in responding tumors than in non-responding tumors. Our results of ctDNA revealed a higher positive rate (100%) among patients with HCC with stage IIb-IIIa disease. When comparing patients with pCR/MPR and non-MPR, we observed more mutations in patients who achieved pCR/MPR at baseline (6 mutations vs 2.5 mutations, p=0.025). Patients who were ctDNA positive after adjuvant therapy presented a trend of shorter RFS than those who were ctDNA negative. Proteomic analysis suggested that abnormal glucose metabolism in patients with multifocal HCC might be related to different sensitivity of treatment in different lesions. CONCLUSION: Perioperative camrelizumab plus apatinib displays a promising efficacy and manageable toxicity in patients with resectable HCC. DCs infiltration might be a predictive marker of response to camrelizumab and apatinib as well as patients' recurrence. ctDNA as a compose biomarker can predict pathological response and relapse. Abnormal glucose metabolism in patients with multifocal HCC may be related to different sensitivity of treatment in different lesions. TRIAL REGISTRATION NUMBER: NCT04297202.

Identification of CXCL5 expression as a predictive biomarker associated with response and prognosis of immunotherapy in patients with non-small cell lung cancer.

BACKGROUND: The breakthrough of immunotherapy has revolutionized the treatment of non-small cell lung cancer (NSCLC). However, only a limited part of patients could derive clinical benefits. To study how immune microenvironment (IME) of patients could influence the therapeutic efficacy of immunotherapy, we evaluated the response patterns of NSCLC patients treated with PD-1 inhibitors and analyzed the molecules related to prognosis and efficacy of immunotherapy. METHODS: Tumor samples were collected from 47 NSCLC patients treated with PD-1 inhibitors. RNA expressions of tumor immune-related 289 genes were analyzed using NanoString nCounter. Immune infiltration and correlation between clinical information and expression of immune-related genes were assessed. RESULTS: Unsupervised clustering analysis revealed two groups infiltrated with different immune cells and differentially expressed genes (DEGs) including CXCL5, CXCL9, IDO1, and LAG3 were found between groups. Stratification based on DEGs indicated that the group with high expression of CXCL5 was characterized by neutrophils. Univariate and multivariate Cox analysis further demonstrated that CXCL5 mRNA expression was positively associated with worse progression free survival (PFS). Logistic analyses indicated high CXCL5 was associated with worse response to immunotherapy. CONCLUSIONS: CXCL5 may be a potential biomarker for prognosis and responsiveness to immunotherapy and may be a novel preventive and therapeutic target for NSCLC.

Electrocatalytic generation and tuning of ultra-stable and ultra-dense nanometre bubbles: an in situ molecular dynamics study.

Electrocatalytic generation of nanometre gas bubbles (nanobubbles) and their tuning are important for many energy and chemical processes. Studies have sought to use indirect or ex situ methods to investigate the dynamics and properties of nanobubbles, which are of fundamental interest. Alternatively, we present a molecular dynamics simulation method, which features in situ and high spatial resolution, to directly address these fundamentals. Particularly, our simulations can quantitatively reproduce the generation of ultra-stable and ultra-dense nanobubbles observed in electrochemical experiments. More importantly, our results demonstrate that the classical nucleation theory is still valid even for the scale down to several nanometres, to predict the dynamics and properties of nanobubbles. This provides general guidelines to design efficient nanocatalysts and nanoelectrodes. In our specific case, nanoelectrodes with wetting angles below 71° can suppress the generation of surface nanobubbles.

Effects of pullulan on the biomechanical and anti-collapse properties of dicalcium phosphate dihydrate bone cement.

In this work, a modified dicalcium phosphate dihydrate (DCPD) bone cement with unique biodegradable ability in a calcium phosphate cement system was prepared by the hydration reaction of monocalcium phosphate monohydrate and calcium oxide and integration with pullulan (Pul), a non-toxic, biocompatible, viscous, and water-soluble polysaccharide that has been successfully used to improve defects in DCPD bone cement, especially its rapid solidification, fragile mechanical properties, and easy collapse. The effect of different contents of Pul on the structure and properties of DCPD were also studied in detail. The modified cement was characterised by X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, ultraviolet-visible absorption, X-ray photoelectron spectroscopy analysis, and rheological property measurements. The results indicated that Pul promoted the hydration formation of DCPD, and interface bonding occurred between Pul and DCPD. With increasing content of Pul, the setting time of the DCPD bone cement increased from 2.6 min to 42.3 min, the compressive strength increased from 0 MPa to 20.4 MPa, and the anti-collapse ability also improved owing to the strong interface bonding, implying that the DCPD bone cement improved by Pul has better potential for application in the field of non-loading bone regenerative medicine compared to unmodified DCPD bone cement.

Infrared thermography-guided designing and harvesting of pre-expanded pedicled flap for head and neck reconstruction.

BACKGROUND: Pre-expanded pedicled flaps possess a more flexible transfer pattern and higher tissue utilization than random flaps, but the perfusion is fully dependent on the chosen axial vessels. A precise mapping of the vessels would assist the surgical design and increase the likelihood of success. The application of Infrared thermography (IRT) has been previously reported for perforator location. The aim of this study is to report the use of IRT in mapping the course and distribution of axial vessels in the pre-expanded flap to guide the designing and harvesting. METHODS: Patients who underwent head and neck reconstruction using pre-expanded flaps were included. After tissue expansion, IRT was used to mark the vessel distribution along the expanded flap. The results were compared with color Doppler ultrasound (CDU) and/or computed tomographic angiography (CTA). The flap was designed and raised based on the pre-operative marking by IRT. The mark was verified intraoperatively. RESULTS: A total of 26 expanded flaps were performed, including 20 pedicled flaps and 6 free flaps. IRT succeeded to map the vessel distribution in all cases. All marked results were verified by CDU, CTA, and intraoperative dissection (26/26, 100%). IRT showed more comprehensive distribution of vascular branches than CDU or CTA, and could be utilized intraoperatively to identify the arteries. CONCLUSION: IRT provides accurate and comprehensive mapping of the axial vessel distribution in the pre-expanded flaps, assisting with flap design and harvest. It is easy to use and non-invasive as an important tool pre- or intraoperatively to ensure the safe elevation.

3D Mesh Releasing Method: A Retrospective Analysis of Fractional CO2 Treatment on Contracture Scars.

BACKGROUND AND OBJECTIVES: There has been reports on fractional CO2 laser successfully improving contracture scars that impair the function of a joint. It seems that certain contracture problems could be solved by laser instead of surgery. However, the clinical application could be difficult when the efficacy of the method remains unknown. The purpose of this study is to report the releasing capacity of the fractional CO2 laser on contracture scars based on a defined treatment method. STUDY DESIGN/MATERIALS AND METHODS: We conducted a retrospective study in patients with limited function in joints caused by contracture scars. Fractional CO2 laser and our "3D mesh releasing" protocol were applied. The primary outcome was the improvement measured in range of motion (ROM) of the relevant joint before all intervention and 6 months after the last treatment. RESULT: From November 2016 to January 2018, 11 joints of 10 cases were treated by the fractional CO2 laser. Patients went through 2.27 (standard deviation [SD] 1.42, 1-5) sessions. The average progress of ROM before and 6 months after all treatments was 19.13° (SD 10.25, P < 0.02). In six cases, we recorded that there was an 8.53° (SD 5.81, P < 0.02) of increase in ROM immediately after the laser session, and the average improvement reached up to 13.58° (SD 8.15, P < 0.02) after 2-3 months during the next follow-up. CONCLUSION: The fractional CO2 laser could achieve functional improvement in contracture scars and it maintained its effect for at least 6 months. The "3D Mesh Releasing" protocol would help to standardize the treatment procedure. This modality has minimal-invasiveness and potentially could become a supplement to the current treatment choices for mild contracture scars. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Developing a biodegradable tricalcium silicate/glucono-delta-lactone/calcium sulfate dihydrate composite cement with high preliminary mechanical property for bone filling.

Bone cements with the feature of easily shaping could ideally match the defect site and prevent the ingrowth of fibrous tissue. In this manuscript, a biodegradable tricalcium silicate (C3S)/glucono-delta-lactone (GDL)/calcium sulfate dihydrate (CSD) organic-inorganic composite cement was fabricated with shorter setting time (less than 15 min) and high preliminary mechanical property (5.27 MPa in the first hour). Many methods were applied to study the physicochemical and biological properties of the cement in vitro. The weight loss in PBS can reach 58% after 12 weeks soaking indicating the better biodegradability. The excellent bioactivity in vitro was emerging after the cement was soaked in the simulated body fluid. The cell experiments showed that suitable concentration of the extract liquid of cement was conducive to the proliferation, differentiation and extracellular matrix calcification of the mouse bone marrow stromal cells. Briefly, the C3S/GDL/CSD composite cement would have the bright capacity for bone filling.

Efficacy and safety of a dual-scan protocol for carbon dioxide laser in the treatment of split-thickness skin graft contraction in a red Duroc pig model.

BACKGROUND: Fractional CO2 laser plays an important role in scar management post split-thickness skin graft by loosening the graft contracture and restoring the smoothness of the surface. However, the optimal treatment protocol remains unknown. This study applied a dual-scan protocol to achieve both releasing and ablation of contracted skin graft. We comprehensively describe this treatment method and compare the efficacy and safety between this dual-scan method and the conventional mono-scan mode. METHODS: A hypercontracted scar model after split-thickness skin grafting in red Duroc pigs was established. All scars meeting the inclusion criteria were randomly divided into four groups: high fluence-low density (HF-LD), low fluence-high density (LF-HD), combined group and control group. The energy per unit area was similar in the HF-LD and LF-HD groups. Two laser interventions were performed at a 6-week interval. The efficacy of the treatment was evaluated by objective measures of scar area, release rate, elasticity, thickness and flatness, while the safety was evaluated based on adverse reactions and melanin index. Collagen structure was observed histologically. The animals were followed up for a maximum of 126 days after modeling. RESULTS: A total of 28 contracted scars were included, 7 in each group. At 18 weeks postoperatively, the HF-LD and the combined groups showed significantly increased scar release rate (p = 0.000) and elasticity (p = 0.036) and decreased type I/III collagen ratio (p = 0.002) compared with the control and LF-HD groups. In terms of flatness, the combined group was significantly better than the HF-LD group for elevations <1 mm (p = 0.019). No significant skin side effects, pigmentation or scar thickness changes were observed at 18 weeks. CONCLUSIONS: Dual-scan protocol could achieve superficial ablation and deep release of contracted split-thickness skin graft in a single treatment, with similar contraction release and texture improvement compared to a single deep scan. Its main advantage is to restore a smoother scar appearance. Adequate laser penetration was necessary for the release of contracted scars.

Elucidation of pH impacts on monosubstituted benzene derivatives using normal Raman and surface-enhanced Raman scattering.

Raman spectral vibrational frequencies are used to probe the local chemical environment surrounding molecules in solution and adsorbed to gold nanostars. Herein, the impacts of functional group protonation on monosubstituted benzene derivatives with amine, carboxylic acid, or hydroxide are evaluated. Changes in binding affinity and orientation are apparent by evaluating systematic variations in vibrational frequencies. Notably, the electron donating abilities of these functional groups influence the vibrational frequency of the ring breathing mode, thus leading to improved spectral interpretation. Furthermore, gold nanostars are used to investigate the impact of molecular protonation on the adsorption of benzoic acid/benzoate to gold. The changes in molecular protonation are measured using zeta potential and the surface-sensitive technique, surface-enhanced Raman scattering. These methods reveal that pH variations induce carboxylate protonation and electron redistribution that weaken molecular affinity, thereby causing the molecule to adopt a perpendicular to parallel orientation with respect to the nanostar surface. Functional group identity influences the ring breathing mode frequency as a function of changes in electron donation from the functional group to the ring in solution as well as molecular affinity to and orientation on gold. This exploitation of vibrational frequencies facilitates the elucidation of molecule behavior in complex systems.

Pre-expanded bipedicled visor flap: an ideal option for the reconstruction of upper and lower lip defects postburn in Asian males.

BACKGROUND: Reconstruction of upper and lower lip subunits is a complicated and elusive challenge. For patients affected by defects involving upper and lower lip subunits, a technique able to reconstruct both aesthetic units with matched colour, sufficient contours and similar texture would be ideal. In this study, we present our experience with upper and lower lip reconstruction using the pre-expanded bipedicled visor flap. METHODS: From January 2014 to January 2017, 12 male patients presenting with defects of the upper and lower lip subunits were treated using this surgical technique. After a period of expansion of the scalp flap of over 6 months, the bipedicled visor flap was raised from both the parietal regions and rotated to resurface the defect. Delay and section of the pedicle were then performed. RESULTS: Twelve male patients with postburn scars aged 22 to 48 years (mean: 34 years) were successfully treated with no major complications. The donor site was closed primarily in all cases. Subsequent flap debulking and minor revisions were performed under local anaesthesia between 6 and 12 months postoperatively. CONCLUSIONS: The pre-expanded bipedicled visor flap provides an effective and reliable option for upper and lower lip reconstruction with excellent colour and texture. It is feasible to achieve these results simultaneously from a single donor site by using a pre-expanded bipedicled visor flap.

The Injection for the Lower Eyelid Retraction: A Mechanical Analysis of the Lifting Effect of the Hyaluronic Acid.

BACKGROUND: It has been reported that the injection of the hyaluronic acid (HA) into the lower lid area could improve lower eyelid retraction. However, the published studies offered few insights into the mechanism of this treatment. When the underlying mechanism is not clear, many surgeons will not trust the method enough to apply it in their clinical practice. The purpose of this article was to propose a possible explanation for the underlying mechanism of the treatment and further verify the method by a series of cases. METHODS: The authors performed a mechanical analysis on the physical impact of HA on the lower eyelid. In the clinical cases, we injected the fillers under the orbicularis muscle to correct lower lid retraction. The results were evaluated by the standardized marginal reflex distance 2 (MRD2) immediately and 9 months later. RESULTS: From October 2013 to October 2015, the injections were carried out in 27 cases (14 post-blepharoplasty and 13 involuntary). In 26 cases (96.3%), the retraction was completely corrected and did not recur through the last follow-up. The average improvement of the standardized MRD2 was 0.84 mm immediately after the injection and 1.19 mm 9 months later. Complications were not reported. CONCLUSION: Lower eyelid retraction could be treated by the injection of HA under the orbicularis muscle. The filler in this situation acted as a lifter because the filler changed the balance of force of the lower lid, forcing it to shift upward to gain the new balance. The 'lifter' mechanism could be applicable to other facial injections that generate elevating effects. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Identification of a Combined RNA Prognostic Signature in Adenocarcinoma of the Lung.

BACKGROUND Adenocarcinoma of the lung is a type of non-small cell lung cancer (NSCLC). Clinical outcome is associated with tumor grade, stage, and subtype. This study aimed to identify RNA expression profiles, including long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA, associated with clinical outcome in adenocarcinoma of the lung using bioinformatics data. MATERIAL AND METHODS The miRNA and mRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database, and lncRNA expression profiles were downloaded from The Atlas of Noncoding RNAs in Cancer (TANRIC) database. The independent dataset, the Gene Expression Omnibus (GEO) accession dataset, GSE81089, was used. RNA expression profiles were used to identify comprehensive prognostic RNA signatures based on patient survival time. RESULTS From 7,704 lncRNAs, 787 miRNAs, and 28,937 mRNAs of 449 patients, four joint RNA molecular signatures were identified, including RP11-909N17.2, RP11-14N7.2 (lncRNAs), MIR139 (miRNA), KLHDC8B (mRNA). The random forest (RF) classifier was used to test the prediction ability of patient survival risk and showed a good predictive accuracy of 71% and also showed a significant difference in overall survival (log-rank P=0.0002; HR, 3.54; 95% CI, 1.74-7.19). The combined RNA signature also showed good performance in the identification of patient survival in the validation and independent datasets. CONCLUSIONS This study identified four RNA sequences as a prognostic molecular signature in adenocarcinoma of the lung, which may also provide an increased understanding of the molecular mechanisms underlying the pathogenesis of this malignancy.

Elucidation of HEPES Affinity to and Structure on Gold Nanostars.

The zwitterion, N-2-hydroxyethylpiperazine- N'-2-ethanesulfonic acid (HEPES), facilitates the formation and stability of gold nanostars; however, little is known about how this molecule interacts with the metal postsynthesis. Herein, restructuring of gold nanostar morphology is induced upon acidification, an effect that depends on both pH and acid composition as well as on the protonation state of HEPES. Changes in molecular protonation are measured using zeta potential and modeled using DFT. The surface-sensitive technique, surface-enhanced Raman scattering (SERS), reveals that pH variations induce reversible activation of the amine and sulfonate groups in HEPES and that electron redistribution weakens its affinity to the metal thus promoting the adsorption and SERS detection of benzene. By selecting a molecule that does not induce significant desorption of the stabilizing agent, binding energies of benzene to gold are measured even though only weak London dispersion and π-π interactions promote adsorption. All in all, this molecular-level insight is expected to facilitate new applications of these nanostructures in ways that have not been possible to date.