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.

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.

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.

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.

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 .

How to accurately predict solution-phase gold nanostar stability.

Unwanted nanoparticle aggregation and/or agglomeration may occur when anisotropic nanoparticles are dispersed in various solvents and matrices. While extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory has been successfully applied to predict nanoparticle stability in solution, this model fails to accurately predict the physical stability of anisotropic nanostructures; thus limiting its applicability in practice. Herein, DLVO theory was used to accurately predict gold nanostar stability in solution by investigating how the choice of the nanostar dimension considered in calculations influences the calculated attractive and repulsive interactions between nanostructures. The use of the average radius of curvature of the nanostar tips instead of the average radius as the nanostar dimension of interest increases the accuracy with which experimentally observed nanoparticle behavior can be modeled theoretically. This prediction was validated by measuring time-dependent localized surface plasmon resonance (LSPR) spectra of gold nanostars suspended in solutions with different ionic strengths. Minimum energy barriers calculated from collision theory as a function of nanoparticle concentration were utilized to make kinetic predictions. All in all, these studies suggest that choosing the appropriate gold nanostar dimension is crucial to fully understanding and accurately predicting the stability of anisotropic nanostructures such as gold nanostars; i.e., whether the nanostructures remain stable and can be used reproducibly, or whether they aggregate and exhibit inconsistent results. Thus, the present work provides a deeper understanding of internanoparticle interactions in solution and is expected to lead to more consistent and efficient analytical and bioanalytical applications of these important materials in the future. Graphical abstract ᅟ.

Application of Indocyanine Green in Flap Surgery: A Systematic Review.

BACKGROUND: The vascularization of the distal portions of transferred tissue represents the most critical factor in the success of reconstructive surgery. In recent years, indocyanine green (ICG) fluorescence imaging techniques have been applied during surgery to evaluate flap perfusion. However, this investigation has found that there is little consensus regarding the standard dose of ICG as well as the pre-operative requirements of ICG allergy testing. The aim of this study is to summarize the applications of ICG to tissue transfers and safe dosing practices and to provide insight to the possible adverse effects of ICG on flap surgery with the goal of helping clinicians apply ICG safely and efficiently to tissue transfer procedures. METHODS: A literature search was performed using, Wiley InterScience, and Springer with the key words, 'Flap,' 'indocyanine green,' 'surgery,' and related mesh words for all publications between 2005 and 2015. Title and abstract screening was performed using predefined in- and exclusion criteria. RESULTS: Seventy-three articles were included. These were classified as "application of ICG in flap surgery" and "the security of applying ICG in flap surgery". CONCLUSIONS: ICG fluorescence imaging preoperatively facilitates the detection of perforators in tissue flaps with thickness <20 mm, aids in the evaluation of flap microcirculation and perfusion, and allows surgeons to select dominant cutaneous nerves while evaluating the quality of vascular anastomoses and locating thromboses. The literature also concluded that potential allergic reactions to ICG should be taken into consideration.

Prefabricated Flaps: Identification of Microcirculation Structure and Supercharging Technique Improving Survival Area.

Background Microcirculation is an important factor frequently overlooked when studying the survival of prefabricated flaps. In the current study, we use different prefabrication techniques for characterizing microcirculation within the flap, with the goal of finding an effective way to improve its survival area. Methods An abdominal prefabricated flap rodent model was created using a two-stage operation. All rats were randomly divided into six groups (n = 10/group): group A, prefabricated femoral vessels; group B, prefabricated femoral artery with a connected superficial inferior epigastric vein (SIEV); group C, connected superficial inferior epigastric artery (SIEA) with a prefabricated femoral vein; group D was similar to group A along with a prefabricated SIEA, and group E was similar to group A along with a prefabricated SIEV; and group F acted as a control group and consisted of an axial flap nourished by superficial inferior epigastric vessels. Flaps were assessed for survival area, blood perfusion area, and capillary density using macroscopic analysis, near-infrared fluorescence imaging (NIFI), and histology. Results The survival area was not significantly different when comparing groups B to C, and D to E. The survival area of groups D and E was larger than that of groups B and C. Groups B through E had a smaller survival area in comparison to group F and a larger survival area than group A. NIFI were consistent with the macroscopic outcomes. The capillary density was not significantly different between groups A to C and groups D to F. Conclusion Both arterial and venous supercharging could potentially improve the survival area of prefabricated flaps.

Bipaddle radial forearm flap for head and neck reconstruction.

BACKGROUND: Although the radial forearm free flap has become a workhorse flap in head and neck reconstruction, the skin grafting of the donor is the main drawback resulting in an unacceptable contour deformity and an unsightly appearance. Several technical modifications have been therefore applied to the radial forearm (RF) flap marking, elevation, and inset to overcome this major shortcoming. In this article, we report our clinical series with the bipaddle RF flap. METHODS: The authors described their 11 cases of head and neck oncologic reconstruction with the bipaddle RF flap. The skin island is designed longer and narrower and split into 2 separate skin paddles each nourished by a proximal and a distal independent perforators raising from the radial artery so that the donor site could be closed directly. The narrow design of the skin paddle and the subsequent splitting in its 2 components applying the "perforator-pedicle propeller flap method" allow for the changing of the flap shape according to the shape of the recipient site defect. RESULTS: From 2007 to 2013, the bipaddle RF flap method was used in 11 patients to restore head and neck defects following cancer ablation. The mean age of the patients was 43 years, ranging from 31 to 50 years. The location of the defects was the tongue (n = 7) and the intraoral region (n = 4). The defect sizes varied from 4 × 5 cm to 5 × 6 cm, and the flap maximum width was 3 cm with mean area of 26.4 cm. The healing was uneventful in all patients with excellent cosmetic and functional results of both donor site and recipient site after 20 months of mean follow-up. CONCLUSIONS: The bipaddle RF free flap is a reliable and versatile option for the reconstruction of a wide range of soft tissue defects of head and neck region. This method allows for a customized resurfacing of the defect because of its large variability in shape and size. The harvesting site is closed primarily, and a second donor site for skin graft is avoided.Clinical Question, Level of Evidence: Therapeutic, IV.

Sebum Production Alteration after Botulinum Toxin Type A Injections for the Treatment of Forehead Rhytides: A Prospective Randomized Double-Blind Dose-Comparative Clinical Investigation.

BACKGROUND: Research has investigated the decrease in human skin sebum after the application of botulinum toxin. Few studies of the mechanism and objective assessments of this phenomenon have been conducted and the correlation between the sebum production and injection dosages or techniques remains unclear. OBJECTIVES: We prospectively investigated the sebum regulation and its gradient around the injection site in patients who received intramuscular injections of botulinum toxin A (BTX-A) for forehead rhytides, comparing two injection doses. METHODS: Forty-two female volunteers with rhytides on the forehead region were randomly assigned to receive 10 or 20 units of BTX-A, which was administered in five standard injection sites. The baseline and post-treatment sebum production was measured using a Sebumeter. RESULTS: Treatment with BTX-A exhibited significant sebum alteration at the injection site of both groups, with a sebum gradient surrounding the injection point. The efficacy did not improve at higher injection doses, with the four-unit regimen generally not being more potent than the two-unit regimen. The sebum production recovered to normal levels at the 16 week follow-up for both treatment groups, indicating that a higher dosage (four units) did not result in a longer duration until relapse compared with the two-unit dose. CONCLUSIONS: We determined that the sebum production has a positive correlation with the distance away from the injection point. Intramuscular injection of BTX-A significantly reduces sebum production at the injection site but increases the sebum production of the surrounding skin at a radius of 2.5 cm at the 2, 4, and 8 week follow-ups. LEVEL OF EVIDENCE: 2 Therapeutic.

Objective breast volume, shape and surface area assessment: a systematic review of breast measurement methods.

BACKGROUND: There are many methods of measuring the breast and their clinical applications are well described in the literature. However, there has been no attempt to compare these various methods to allow the user to have a broad overview of the subject. The authors have attempted to summarise all the available methods to measure the breast in this article to provide a useful reference for all. METHODS: A comprehensive literature search of PubMed was performed, and the resulting articles were screened and reviewed. The data regarding the methods' mechanism, reliability, time and cost were evaluated and compared. RESULTS: A total of 74 articles dating from 1970 to 2013 were included in this study. All of the methods can be classified into those that measure (1) volume, (2) shape and (3) surface area. Each category consists of several methods that work through different mechanisms and they vary in their reliability and feasibility. Based on their mechanism, the volume measurement methods were further grouped into the natural shape methods, the stereological method, the geometrical methods and the mathematical modelling method. CONCLUSIONS: More objective breast evaluation can be achieved if all three dimensions (volume, shape and surface area) are considered. In the volume measurements, 3D modelling and the MRI are the most reliable tools. Linear measurement (geometry) and mathematical modelling are less accurate but are more economical. In the shape measurements, besides the traditional linear measurement, 3D methods that can deliver colour-coded maps and Swanson's 2D photographic measurement system are capable of depicting and tracking breast shape changes after surgery. Although the surface area metric has not been used extensively, it has potential in clinical and research applications. 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.

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.

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.

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.

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.

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.

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.