Complications of Injected Exogenous Growth Factor for Cosmetic Facial Rejuvenation: A Case Series and Sequential Therapy.

BACKGROUND: Exogenous growth factor presents promising soft tissue regeneration, but the complications from injectable exogenous growth factor seem to be growing. However, there is no detailed summary of complications and sequential treatment protocols. It is noted that the injection of exogenous growth factor into the soft tissue is an unreasonable or even illegal procedure, which could cause uncontrollable tissue growth and some other complications. METHODS: A total of 65 patients underwent analysis retrospectively for complications related to the injection of exogenous growth factor from 2017to 2022 at Xijing Hospital in China. Initially the symptoms mainly consisted of redness, skin temperature arisen, itching, tissue hypertrophy, localized swelling, mass, and lump, with later manifestations including ulcerations and purulent discharge. A comprehensive treatment scheme was formulated based on the location and size of the lumps as well as the type of complication. Post-treatment satisfaction was evaluated over a mean 16-month follow-up (range 6-39 months). RESULTS: A total of 65 patients participated in the treatment. Drug injection therapy was initially performed on all patients. If injections were not effective, surgical treatment (debridement/excision/liposuction) was performed. Twenty-eight patients were managed with intralesional injections alone. Patients reported improved satisfaction in 23 cases (82.14%), full symptom resolution in 3 cases (10.72%), and no improvement in 2 cases (7.14%). Surgery was required for 37 patients. Postoperative improved satisfaction was reported in 30 cases (81.08%), full symptom resolution was recorded in 4 cases (10.82%), and no improvement was seen in 3 cases (8.10%). CONCLUSIONS: This study highlights the management of complications arising from exogenous growth factor injections through the implementation of a sequential therapy approach. Specifically, this approach involves the initial administration of drug injection therapy, and if drug injection therapy proves ineffective, then surgical treatment is pursued. In conclusion, the injection of exogenous growth factors into soft tissues should be forbidden. 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 Dose-Dependent Spatiotemporal Response of Angiogenesis Elicited by Zn Biodegradation during the Initial Stage of Bone Regeneration.

Zinc (Zn) plays a crucial role in bone metabolism and imbues biodegradable Zn-based materials with the ability to promote bone regeneration in bone trauma. However, the impact of Zn biodegradation on bone repair, particularly its influence on angiogenesis, remains unexplored. This study reveals that Zn biodegradation induces a consistent dose-dependent spatiotemporal response in angiogenesis,both in vivo and in vitro. In a critical bone defect model, an increase in Zn release intensity from day 3 to 10 post-surgery is observed. By day 10, the CD31-positive area around the Zn implant significantly surpasses that of the Ti implant, indicating enhanced angiogenesis. Furthermore,angiogenesis exhibits a distance-dependent pattern closely mirroring the distribution of Zn signals from the implant. In vitro experiments demonstrate that Zn extraction fosters the proliferation and migration of human umbilical vein endothelial cells and upregulates the key genes associated with tube formation, such as HIF-1α and VEGF-A, peaking at a concentration of 22.5 µM. Additionally, Zn concentrations within the range of 11.25-45 µM promote the polarization of M0-type macrophages toward the M2-type, while inhibiting polarization toward the M1-type. These findings provide essential insights into the biological effects of Zn on bone repair, shedding light on its potential applications.

Synthesis of robust underwater glues from common proteins via unfolding-aggregating strategy.

Underwater adhesive proteins secreted by organisms greatly inspires the development of underwater glue. However, except for specific proteins such as mussel adhesive protein, barnacle cement proteins, curli protein and their related recombinant proteins, it is believed that abundant common proteins cannot be converted into underwater glue. Here, we demonstrate that unfolded common proteins exhibit high affinity to surfaces and strong internal cohesion via amyloid-like aggregation in water. Using bovine serum albumin (BSA) as a model protein, we obtain a stable unfolded protein by cleaving the disulfide bonds and maintaining the unfolded state by means of stabilizing agents such as trifluoroethanol (TFE) and urea. The diffusion of stabilizing agents into water exposes the hydrophobic residues of an unfolded protein and initiates aggregation of the unfolded protein into a solid block. A robust and stable underwater glue can thus be prepared from tens of common proteins. This strategy deciphers a general code in common proteins to construct robust underwater glue from abundant biomass.

α-Helix-Mediated Protein Adhesion.

Proteins have been adopted by natural living organisms to create robust bioadhesive materials, such as biofilms and amyloid plaques formed in microbes and barnacles. In these cases, ß-sheet stacking is recognized as a key feature that is closely related to the interfacial adhesion of proteins. Herein, we challenge this well-known recognition by proposing an α-helix-mediated interfacial adhesion model for proteins. By using bovine serum albumin (BSA) as a model protein, it was discovered that the reduction of disulfide bonds in BSA results in random coils from unfolded BSA dragging α-helices to gather at the solid/liquid interface (SLI). The hydrophobic residues in the α-helix then expose and break through the hydration layer of the SLI, followed by the random deposition of hydrophilic and hydrophobic residues to achieve interfacial adhesion. As a result, the first assembled layer is enriched in the α-helix secondary structure, which is then strengthened by intermolecular disulfide bonds and further initiates stepwise layering protein assembly. In this process, ß-sheet stacking is transformed from the α-helix in a gradually evolving manner. This finding thus indicates a valuable clue that ß-sheet-featuring amyloid may form after the interfacial adhesion of proteins. Furthermore, the finding of the α-helix-mediated interfacial adhesion model of proteins affords a unique strategy to prepare protein nanofilms with a well-defined layer number, presenting robust and modulable adhesion on various substrates and exhibiting good resistance to acid, alkali, organic solvent, ultrasonic, and adhesive tape peeling.

Protein/Polysaccharide Composite toward Multi-in-One Toxin Removal in Blood with Self-Anticoagulation and Biocompatibility.

Biocompatible adsorbents play an essential role in hemoperfusion. Nevertheless, there are no hemoperfusion adsorbents that can simultaneously remove small and medium toxins, including bilirubin, urea, phosphor, heavy metals, and antibiotics. This bottleneck significantly impedes the miniaturization and portability of hemoperfusion materials and devices. Herein, a biocompatible protein-polysaccharide complex is reported that exhibits "multi-in-one" removal efficacy for liver and kidney metabolism wastes, toxic metal ions, and antibiotics. Through electrostatic interactions and polysaccharide-mediated coacervation, adsorbents can be prepared by simply mixing lysozyme (LZ) and sodium alginate (SA) together in seconds. The LZ/SA absorbent presented high adsorption capacities for bilirubin, urea, and Hg2+ of up to 468, 331, and 497 mg g-1 , respectively, and the excellent anti-protein adsorption endowed LZ/SA with a record-high adsorption capacity for bilirubin in the interference of serum albumin to simulate the physiological environment. The LZ/SA adsorbent also has effective adsorption capacity for heavy metals (Pb2+ , Cu2+ , Cr3+ , and Cd2+ ) and multiple antibiotics (terramycin, tetracycline, enrofloxacin, norfloxacin, roxithromycin, erythromycin, sulfapyrimidine, and sulfamethoxazole). Various adsorption functional groups exposed on the adsorbent surface significantly contribute to the excellent adsorption capacity. This fully bio-derived protein/alginate-based hemoperfusion adsorbent has great application prospects in the treatment of blood-related diseases.

Biopolymer coating for particle surface engineering and their biomedical applications.

Surface engineering of particles based on a polymeric coating is of great interest in materials design and applications. Due to the disadvantages of non-biodegradability and undesirable biocompatibility, the application of petroleum-based synthetic polymers coating in the biomedical field has been greatly limited. In addition, there is lack of a universal surface modification method to functionalize particles of different compositions, sizes, shapes, and structures. Thus, it is imperative to develop a versatile biopolymeric coating with good biocompatibility and tunable biodegradability for the preparation of functional particle materials regardless of their surface chemical and physical structures. Recently, the natural polysaccharide polymers (e.g. chitosan and cellulose), polyphenol-based biopolymers (e.g. polydopamine and tannic acid), and proteins (e.g. amyloid-like aggregates) have been utilized in surface modification of particles, and applications of these modified particles in the field of biomedicine have been also intensively exploited. In this review, the preparation of the above three coatings on particles surface are summarized, and the applications of these materials in drug loading/release, biomineralization, cell immobilization/protection, enzyme immobilization/protection, and antibacterial/antiviral are exemplified. Finally, the challenges and the future research directions on biopolymer coating for particles surface engineering are prospected.

Identification and structural elucidation of a new cetrorelix methylene dimer impurity in cetrorelix acetate by using LC-MS/MS.

Cetrorelix, a potent third generation of luteinizing hormone releasing hormone (LHRH) antagonist, is a synthetic decapeptide used for treatment of infertility, prostatic hypertrophy and sexual hormone-dependent tumors. The approved drug of cetrorelix (Cetrotide, Asta Medica AG, Frankfurt, Germany.), was used for prevention of premature ovulation in patients undergoing a controlled ovarian stimulation (COS), followed by oocyte pick-up and assisted reproductive techniques, and has been shown safe and effective in controlled ovarian stimulation. Nevertheless, the study of aggregation products of cetrorelix was rarely reported. A simple liquid chromatography mass spectrometry (LC-MS/MS) method was developed for separation, identification and characterization of a new cetrorelix methylene dimer impurity in cetrorelix. The chromatographic separation was achieved on an XSelect Peptide CSH ™C18 column (150 × 4.6 mm, 3.5 µm particle size) using gradient elution with a mobile phase of ammonium formate buffer (pH 3.0, 20 mM), acetonitrile at a flow rate 1.0 mL min-1, and an ultraviolet detection wavelength of 226 nm. The new cetrorelix methylene dimer impurity was characterized by LC-MS/MS and it characteristic fragment ions were summarized. A simple, fast and accurate method was established for the determination of the molecular weight and structure of the new cetrorelix methylene dimer impurity. In this study, the results showed that the cetrorelix was highly unstable in formaldehyde conditions. In addition, it is proposed that the impact of formaldehyde in the environment on the quality of cetrorelix acetate for Injection should be evaluated during the production process.

Amyloid-like protein aggregates combining antifouling with antibacterial activity.

Infections related to implanted medical devices have placed a heavy burden on public health and require feasible solutions. In this study, a simple approach is reported to fabricate an antifouling and antibacterial dual-functional coating. One-step aqueous supramolecular assembly of bovine serum albumin (BSA) is employed to immobilize ε-polylysine (ε-PL) and form a coating (PTB@ε-PL). Based on amyloid-like protein aggregation through the rapid reduction of the intramolecular disulfide bonds of BSA by tris(2-carboxyethyl) phosphine, a dense PTB@ε-PL nanofilm with controllable thickness and ε-PL loading density can be covered on virtually arbitrary material surfaces by simple aqueous dipping. In vitro and in vivo experiments show that this coating not only exhibits effective antibacterial activity against Gram-positive/Gram-negative bacteria, but also imparts excellent antifouling property to the surface. As a pure biopolymer coating, the PTB@ε-PL nanofilm shows negligible cytotoxicity and hemolysis. In addition, due to the various functional groups exposed on the surface of the nanofilm, the coating shows excellent interfacial bonding stability and can maintain bactericidal and antifouling properties under harsh conditions including ultrasound, autoclaving, organic solvents, and physiological body fluids.

The Prediction of Drug-Disease Correlation Based on Gene Expression Data.

The explosive growth of high-throughput experimental methods and resulting data yields both opportunity and challenge for selecting the correct drug to treat both a specific patient and their individual disease. Ideally, it would be useful and efficient if computational approaches could be applied to help achieve optimal drug-patient-disease matching but current efforts have met with limited success. Current approaches have primarily utilized the measureable effect of a specific drug on target tissue or cell lines to identify the potential biological effect of such treatment. While these efforts have met with some level of success, there exists much opportunity for improvement. This specifically follows the observation that, for many diseases in light of actual patient response, there is increasing need for treatment with combinations of drugs rather than single drug therapies. Only a few previous studies have yielded computational approaches for predicting the synergy of drug combinations by analyzing high-throughput molecular datasets. However, these computational approaches focused on the characteristics of the drug itself, without fully accounting for disease factors. Here, we propose an algorithm to specifically predict synergistic effects of drug combinations on various diseases, by integrating the data characteristics of disease-related gene expression profiles with drug-treated gene expression profiles. We have demonstrated utility through its application to transcriptome data, including microarray and RNASeq data, and the drug-disease prediction results were validated using existing publications and drug databases. It is also applicable to other quantitative profiling data such as proteomics data. We also provide an interactive web interface to allow our Prediction of Drug-Disease method to be readily applied to user data. While our studies represent a preliminary exploration of this critical problem, we believe that the algorithm can provide the basis for further refinement towards addressing a large clinical need.

dbDEPC 3.0: the database of differentially expressed proteins in human cancer with multi-level annotation and drug indication.

Database URL: https://www.scbit.org/dbdepc3/index.php.

A Novel Water-Soluble Fluorescence Probe with Wash-Free Cellular Imaging Capacity Based on AIE Characteristics.

A potential real-time imaging water-soluble fluorescent polymer (P3) is facilely prepared via one-pot method. For P3, tetraphenylethene unit serves as the fluorescent unit, poly(acryloyl ethylene diamine) (a kind of polyelectrolyte) with specific degree of polymerization acts as water-soluble part. 1 H-NMR, gel permeation chromatography (GPC), UV-vis spectroscopy, photoluminescence (PL), and confocal laser scanning microscopy are undertaken to characterize the structure and property of P3. The results of wash-free cellular imaging show that the signal-to-noise ratio is high as the concentration of P3 is 50 µg mL-1 . In addition, the pH-responsive and Cd2+ -responsive are also investigated in this paper. The results coming from pH-responsive show that P3 solution displays significant fluorescence under near neutral. And the result from the cellular imaging shows that intracellular fluorescence intensity enhances with the augment of concentration of Cd2+ , which reveals that P3 can give a hint to resolve the dilemma of traditional fluorescent dyes used as living cellular fluorescent probe.

Biomolecular Network-Based Synergistic Drug Combination Discovery.

Drug combination is a powerful and promising approach for complex disease therapy such as cancer and cardiovascular disease. However, the number of synergistic drug combinations approved by the Food and Drug Administration is very small. To bridge the gap between urgent need and low yield, researchers have constructed various models to identify synergistic drug combinations. Among these models, biomolecular network-based model is outstanding because of its ability to reflect and illustrate the relationships among drugs, disease-related genes, therapeutic targets, and disease-specific signaling pathways as a system. In this review, we analyzed and classified models for synergistic drug combination prediction in recent decade according to their respective algorithms. Besides, we collected useful resources including databases and analysis tools for synergistic drug combination prediction. It should provide a quick resource for computational biologists who work with network medicine or synergistic drug combination designing.

Management of the first confirmed case of avian influenza A H7N9.

In March 2013, the first patient infected with the avian influenza A H7N9 virus was identified in China. The infection progressed rapidly, and the patient died of ARDS. During hospitalization, the patient was suspected of having an infectious respiratory disease, and contingency plans for public health emergencies were promptly started. When the viral infection was identified, strict procedures for disinfection and protection were carried out. None of the health care workers involved in the management of the patient were infected.

[Characterization of vinflunine tartrate liposomes in vitro and in vivo].

Vinflunine tartrate-loaded liposomes (VT-L) with two drug-to-lipid ratios were prepared by pH gradient method. Vesicle size and zeta potential were determined by the Zetasizer Nano ZS. Entrapment efficiency was evaluated by cation exchange resin centrifugalization method. The toxicity and tumor inhibition to nude mouse administrated by VT-L with different drug-to-lipid ratios were investigated and compared with the vinflunine tartrate injection (VT-I). The results showed that the mean particle size, zeta potential and entrapment efficiency of the VT-L with drug-to-lipid ratios of 1 : 5 and 1 : 10 were 124.6 nm and 128.3 nm, -25.3 mV and -22.8 mV, 94.46% and 97.31%, respectively. The VT-L with two different drug-to-lipid ratios has significantly higher anti-tumor effect to nude mouse transplanted human non-small cell lung carcinoma A549 and lower toxicity than VT-I. While there were no significant differences in anti-tumor effect and toxicity between VT-L with two different drug-to-lipid ratios.

Ten-digit replantation with seven years follow-up: A case report.

In this report, we present a case of successful replantation of 10-digit complete amputation and results of postoperative rehabilitation in 7 years follow-up. The rehabilitation program included psychotherapy, physical therapy, sensory re-education, and measurements. At the 7 years postoperatively, the static two-point discriminations of replanted digits ranged from 4 to 11 mm. Grasping powers ranged from 69 to 81 lb, and pinching powers ranged from 13 to 19 lb. The patient returned to the previous employment. Our experience has demonstrated that systemic postoperative rehabilitation and measurements could achieve satisfactory recovery of the sensory and motor functions of multiple-digit replantation.

[Optimization of the formulation of ranolazine hydrochloride sustained-release tablet and its pharmacokinetics in dogs].

Ranolazine hydrochloride sustained-release tablet (RH-ST) was prepared and its release behavior in vitro was studied. The pharmacokinetic characteristics and bioavailability in six Beagle dogs after oral administration of RH-ST and ranolazine hydrochloride common tablets (RH-CT) as reference were compared. Three kinds of matrix, hydroxypropylmethylcellulose (HPMC K4M), ethylcellulose (EC 100cp) and acrylic resins (Eudragit RL100) were selected as functional excipients to keep ranolazine hydrochloride (RH) release for 12 hours. Through orthogonal designs, the polymers were quantified and the optimized cumulative release profile was obtained. The single oral dose of RH-ST 500 mg and RH-CT 333.3 mg was given to six dogs using a two way crossover design. Plasma levels were determined by LC-MS and the absorption fractions were calculated according to Loo-Riegelman formula. The steady-state concentration of RH in plasma of six dogs and its pharmacokinetics behaviors after continuous oral administration of RH-ST and RH-CT at different time intervals were studied by LC-MS. The steady-state pharmacokinetic parameters were computed by software program BAPP2.0. With the increase of the amount of the matrix, the drug release was decreased. The most important factor influencing drug release is the quantity of HPMC K4M. Drug release within the period (from 0 h to 12 h) fitted well into Higuchi model. The correlation coefficient (r) between the dissolution in vitro in release media of the distilled water and the absorptin fraction in vivo was 0.9550. To compare with RH-CT, RH-ST in vivo has a steady and slow release behavior, Tmax was obviously delayed (3.00 +/- 0.50) h and the relative bioavailability was over 80 percentage. The combined use of multiple polymers can decrease the tablet weight effectively, and the drug release rate can be decreased both in vitro and in vivo.