Mitigating Critical Peripheral Nerve Deficit Therapy with Reactive Oxygen Species/Ca2+-Responsive Dynamic Hydrogel-Mediated mRNA Delivery.

Critical peripheral nerve deficiencies present as one of the most formidable conundrums in the realm of clinical medicine, frequently culminating in structural degradation and derangement of the neuromuscular apparatus. Engineered extracellular vesicles (EVs) exhibit the potential to ameliorate nerve impairments. However, the advent of Wallerian degeneration (WD), an inexorable phenomenon that ensues post peripheral nerve injury, serves as an insurmountable impediment to the direct therapeutic efficacy of EVs. In this investigation, we have fashioned a dynamic network for the conveyance of PTEN-induced kinase 1 (PINK1) mRNA (E-EV-P@HPCEP) using an adaptive hydrogel with reactive oxygen species (ROS)/Ca2+ responsive ability as the vehicle, bearing dual-targeted, engineered EVs. This intricate system is to precisely deliver PINK1 to senescent Schwann cells (SCs) while concurrently orchestrating a transformation in the inflammatory-senescent milieu following injury, thereby stymying the progression of WD in peripheral nerve fibers through the stimulation of autophagy within the mitochondria of the injured cells and the maintenance of mitochondrial mass equilibrium. WD, conventionally regarded as an inexorable process, E-EV-P@HPCEP achieved functionalized EV targeting, orchestrating a dual-response dynamic release mechanism via boronate ester bonds and calcium chelation, effectuating an enhancement in the inflammatory-senescent microenvironment, which expedites the therapeutic management of nerve deficiencies and augments the overall reparative outcome.

Ultrastable PLGA-Coated 177Lu-Microspheres for Radioembolization Therapy of Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) is a highly effective localized radionuclide therapy that has been successfully used to treat hepatocellular carcinoma (HCC). Extensive research has been conducted on the use of radioactive microspheres (MSs) in TARE, and the development of ideal radioactive MSs is crucial for clinical trials and patient treatment. This study presents the development of a radioactive MS for TARE of HCC. These MSs, referred to as 177Lu-MS@PLGA, consist of poly(lactic-co-glycolic acid) (PLGA) copolymer and radioactive silica MSs, labeled with 177Lu and then coated with PLGA. It has an extremely high level of radiostability. Cellular experiments have shown that it can cause DNA double-strand breaks, leading to cell death. In vivo radiostability of 177Lu-MS@PLGA is demonstrated by microSPECT/CT imaging. In addition, the antitumor study has shown that TARE of 177Lu-MS@PLGA can effectively restrain tumor growth without harmful side effects. Thus, 177Lu-MS@PLGA exhibits significant potential as a radioactive MS for the treatment of HCC.

The induced membrane technique for the management of infected segmental bone defects.

Aims: The aim of the present study was to assess the outcomes of the induced membrane technique (IMT) for the management of infected segmental bone defects, and to analyze predictive factors associated with unfavourable outcomes. Methods: Between May 2012 and December 2020, 203 patients with infected segmental bone defects treated with the IMT were enrolled. The digital medical records of these patients were retrospectively analyzed. Factors associated with unfavourable outcomes were identified through logistic regression analysis. Results: Among the 203 enrolled patients, infection recurred in 27 patients (13.3%) after bone grafting. The union rate was 75.9% (154 patients) after second-stage surgery without additional procedures, and final union was achieved in 173 patients (85.2%) after second-stage surgery with or without additional procedures. The mean healing time was 9.3 months (3 to 37). Multivariate logistic regression analysis of 203 patients showed that the number (≥ two) of debridements (first stage) was an independent risk factor for infection recurrence and nonunion. Larger defect sizes were associated with higher odds of nonunion. After excluding 27 patients with infection recurrence, multivariate analysis of the remaining 176 patients suggested that intramedullary nail plus plate internal fixation, smoking, and an allograft-to-autograft ratio exceeding 1:3 adversely affected healing time. Conclusion: The IMT is an effective method to achieve infection eradication and union in the management of infected segmental bone defects. Our study identified several risk factors associated with unfavourable outcomes. Some of these factors are modifiable, and the risk of adverse outcomes can be reduced by adopting targeted interventions or strategies. Surgeons can fully inform patients with non-modifiable risk factors preoperatively, and may even use other methods for bone defect reconstruction.

FeS2-modified MXene nanocomposite platform for efficient PTT/CDT/TDT integration through enhanced GSH consumption.

Hypoxic microenvironment and glutathione (GSH) accumulation in tumours limit the efficacy of cytotoxic reactive oxygen species (ROS) anti-tumour therapy. To address this challenge, we increased the consumption of GSH and the production of ROS through a novel nanoplatform with the action of inorganic nanoenzymes. In this study, we prepared mesoporous FeS2 using a simple template method, efficiently loaded AIPH, and assembled Ti3C2/FeS2-AIPH@BSA (TFAB) nanocomposites through self-assembly with BSA and 2D Ti3C2. The constructed TFAB nanotherapeutic platform enhanced chemodynamic therapy (CDT) by generating toxic hydroxyl radicals (˙OH) via FeS2, while consuming GSH to reduce the loss of generated ˙OH via glutathione oxidase-like (GSH-OXD). In addition, TFAB is able to stimulate the decomposition of AIPH under 808 nm laser irradiation to produce oxygen-independent biotoxic alkyl radicals (˙R) for thermodynamic therapy (TDT). In conclusion, TFAB represents an innovative nanoplatform that effectively addresses the limitations of free radical-based treatment strategies. Through the synergistic therapeutic strategy of photothermal therapy (PTT), CDT, and TDT within the tumor microenvironment, TFAB nanoplatforms achieve controlled AIPH release, ROS generation, intracellular GSH consumption, and precise temperature elevation, resulting in enhanced intracellular oxidative stress, significant apoptotic cell death, and notable tumor growth inhibition. This comprehensive treatment strategy shows great promise in the field of tumor therapy.

Discovery of Sovleplenib, a Selective Inhibitor of Syk in Clinical Development for Autoimmune Diseases and Cancers.

Herein we describe the medicinal chemistry efforts that led to the discovery of the clinical-staged Syk inhibitor sovleplenib (41) via a structure-activity relationship investigation and pharmacokinetics (PK) optimization of a pyrido[3,4-b]pyrazine scaffold. Sovleplenib is a potent and selective Syk inhibitor with favorable preclinical PK profiles and robust anti-inflammation efficacy in a preclinical collagen-induced arthritis model. Sovleplenib is now being developed for treating autoimmune diseases such as immune thrombocytopenic purpura and warm antibody hemolytic anemia as well as hematological malignancies.

Multifunctional Hydrogel Enhances Inflammatory Control, Antimicrobial Activity, and Oxygenation to Promote Healing in Infectious Wounds.

Chronic infected wounds often fail to heal through normal repair mechanisms, and the persistent response of reactive oxygen species (ROS) and inflammation is a major contributing factor to the difficulty in their healing. In this context, we developed an ROS-responsive injectable hydrogel. This hydrogel is composed of ε-polylysine grafted (EPL) with caffeic acid (CA) and hyaluronic acid (HA) grafted with phenylboronic acid (PBA). Before the gelation process, a mixture CaO2@Cur-PDA (CCP) consisting of calcium peroxide (CaO2) coated with polydopamine (PDA) and curcumin (Cur) is embedded into the hydrogel. Under the conditions of chronic refractory wound environments, the hydrogel gradually dissociates. HA mimics the function of the extracellular matrix, while the released caffeic acid-grafted ε-polylysine (CE) effectively eliminates bacteria in the wound vicinity. Additionally, released CA also clears ROS and influences macrophage polarization. Subsequently, CCP further decomposes, releasing Cur, which promotes angiogenesis. This multifunctional hydrogel accelerates the repair of diabetic skin wounds infected with Staphylococcus aureus in vivo and holds promise as a candidate dressing for the healing of chronic refractory wounds.

Microenvironment-responsive smart hydrogels with antibacterial activity and immune regulation for accelerating chronic wound healing.

Current therapeutic strategies for chronic refractory wounds remain challenge owing to their unfavorable wound microenvironment and poor skin regeneration ability. Thus far, a regimen for effective chronic refractory wounds management involves bacterial elimination, alleviation of oxidative stress, inhibition of inflammatory response, and promotion of angiogenesis. In this work, an injectable glycopeptide hydrogel based on phenylboronic acid-grafted ϵ-polylysine (EPBA) and poly (vinyl alcohol) (PVA) with pH/reactive oxygen species (ROS) dual-responsive properties was prepared, which exerted intrinsic antibacterial and antioxidant properties. ROS-responsive micelles (MIC) loaded with herb-derived Astragaloside IV (AST) are introduced into the hydrogel before gelation. Attributed to the acidic condition and oxidative stress microenvironment of wound bed, the hydrogel gradually disintegrates, and the released EPBA could help to eliminate bacterial. Meanwhile, the subsequential release of AST could help to achieve anti-oxidation, anti-inflammatory, proangiogenic effects, and regulation of macrophage polarization to accelerate chronic wound healing. In addition, the wound repair mechanism of composite hydrogel accelerating skin regeneration was assessed by RNA-sequencing, exploring a range of potential targets and pathway for further study. Collectively, this multifunctional hydrogel dressing, matching different healing stages of tissue remodeling, holds a great potential for the treatment of chronic refractory wounds.

Mechanistic Investigation into Single-Electron Oxidative Addition of Single-Atom Cu(I)-N4 Site: Revealing the Cu(I)-Cu(II)-Cu(I) Catalytic Cycle in Photochemical Hydrophosphinylation.

Understanding the valency and structural variations of metal centers during reactions is important for mechanistic studies of single-atom catalysis, which could be beneficial for optimizing reactions and designing new protocols. Herein, we precisely developed a single-atom Cu(I)-N4 site catalyst via a photoinduced ligand exchange (PILE) strategy. The low-valent and electron-rich copper species could catalyze hydrophosphinylation via a novel single-electron oxidative addition (OA) pathway under light irradiation, which could considerably decrease the energy barrier compared with the well-known hydrogen atom transfer (HAT) and single electron transfer (SET) processes. The Cu(I)-Cu(II)-Cu(I) catalytic cycle, via single-electron oxidative addition and photoreduction, has been proven by multiple in situ or operando techniques. This catalytic system demonstrates high efficiency and requires room temperature conditions and no additives, which improves the turnover frequency (TOF) to 1507 h-1. In particular, this unique mechanism has broken through the substrate limitation and shows a broad scope for different electronic effects of alkenes and alkynes.

Highly Bioadaptable Hybrid Conduits with Spatially Bidirectional Structure for Precision Nerve Fiber Regeneration via Gene Therapy.

Peripheral nerve deficits give rise to motor and sensory impairments within the limb. The clinical restoration of extensive segmental nerve defects through autologous nerve transplantation often encounters challenges such as axonal mismatch and suboptimal functional recovery. These issues may stem from the limited regenerative capacity of proximal axons and the subsequent Wallerian degeneration of distal axons. To achieve the integration of sensory and motor functions, a spatially differential plasmid DNA (pDNA) dual-delivery nanohydrogel conduit scaffold is devised. This innovative scaffold facilitates the localized administration of the transforming growth factor ß (TGF-ß) gene in the proximal region to accelerate nerve regeneration, while simultaneously delivering nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) to the distal region to mitigate Wallerian degeneration. By promoting autonomous and selective alignment of nerve fiber gap sutures via structure design, the approach aims to achieve a harmonious unification of nerve regeneration, neuromotor function, and sensory recovery. It is anticipated that this groundbreaking technology will establish a robust platform for gene delivery in tissue engineering.

Identification of angiogenesis-related subtypes, the development of a prognosis model, and features of tumor microenvironment in colon cancer.

Angiogenesis is associated with tumor progression, prognosis, and treatment effect. However, the angiogenesis' underlying mechanisms in the tumor microenvironment (TME) still remain unclear. Understanding the dynamic interactions between angiogenesis and TME in colon adenocarcinoma (COAD) is necessary. We downloaded the transcriptome data and corresponding clinical data of colon cancer patients from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. We identified two distinct angiogenesis-related molecular subtypes (subtype A and subtype B) and assessed the clinical features, prognosis, and infiltrating immune cells of patients in the two subtypes. According to the prognostic differential genes, we defined two different gene clusters to further explore the correlation between angiogenesis and tumor heterogeneity. Then, we construct the prognostic risk scoring model angiogenesis-related gene (ARG-score) including seven genes (ARMCX2, latent transforming growth factor ß binding protein 1, ADAM8, FABP4, CCL11, CXCL11, ITLN1) using Lasso-multivariate cox method. We analyzed the correlation between ARG-score and prognosis, clinicopathological features, TME, molecular feature, cancer stem cells (CSCs), and microsatellite instability (MSI) status. To assess the application value of ARG-score in clinical treatment, immunophenotype score was used to predict patients' immunotherapy response in colon cancer. We found the mutations of ARGs in TCGA-COAD dataset from genetic levels and discussed their expression patterns based on TCGA and GEO datasets. We observed important differences in clinicopathological features, prognosis, immune feature, molecular feature between the two molecular subgroups. Then, we established an ARG-score for predicting OS and validated its predictive capability. A high ARG-score characterized by higher transcription level of ARGs, suggested lower MSI-high (MSI-H), lower immune score, and worse clinical stage and survival outcome. Additionally, the ARG-score was remarkably related to the CSCs index and immunotherapy sensitivity. We found two new molecular subtypes and two gene clusters based on ARGs and established an ARG-score. Multilayered analysis revealed that ARGs were remarkably correlated to the heterogeneity of colon cancer patients and explained the process of tumorigenesis and progression better. The ARG-score can help us better assess patients' survival outcomes and provide guidance for individualized treatment.

Preclinical Pharmacology Characterization of Sovleplenib (HMPL-523), an Orally Available Syk Inhibitor.

Spleen tyrosine kinase (Syk) is an intracellular tyrosine kinase involved in the signal transduction in immune cells mainly. Its aberrant regulation is associated with diversified allergic disorders, autoimmune diseases and B cell malignancies. Therefore, inhibition of Syk is considered a reasonable approach to treat autoimmune/inflammatory diseases and B cell malignancies. Here we described the preclinical characterization of sovleplenib, a novel, highly potent and selective, oral Syk inhibitor, in several rodent autoimmune disease models. Sovleplenib potently inhibited Syk activity in a recombinant enzymatic assay and Syk-dependent cellular functions in various immune cell lines and human whole blood in vitro. Furthermore, sovleplenib, by oral administration, demonstrated strong in vivo efficacies in murine models of immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and chronic graft-versus-host disease (cGVHD), and a rat model of collagen induced arthritis (CIA) respectively, in a dose-dependent manner. Collectively, these results clearly supported sovleplenib as a therapeutic agent in the treatment of autoimmune diseases. Sovleplenib is being globally developed for ITP (Phase III, NCT05029635, Phase Ib/II, NCT03951623), wAIHA (Phase II/III, NCT05535933) and B-cell lymphoma (Phase I, NCT02857998, NCT03779113). SIGNIFICANCE STATEMENT: Syk is a key mediator of signaling pathways downstream of a wide array of receptors important for immune functions, including the B cell receptor, immunoglobulin receptors bearing Fc receptors. Inhibition of Syk could provide a novel therapeutic approach for autoimmune diseases and hematologic malignancies. The manuscript describes the preclinical pharmacology characterization of sovleplenib, a novel Syk inhibitor, in enzymatic and cellular assays in vitro and several murine autoimmune disease models in vivo.

Self-adhesive wearable poly (vinyl alcohol)-based hybrid biofuel cell powered by human bio-fluids.

Advancement of wearable microelectronics demands their power source with continuous energy supply, skin-integration and miniaturization. In light of poly (vinyl alcohol) (PVA) hydrogel with nontoxicity, good biocompatibility and low cost, an advanced wearable PVA-based hybrid biofuel cells (HBFCs) with high self-adhesiveness was developed. Through the reaction between PVA molecules and succinic anhydride (SAA), the carboxylated PVA (PVA/SAA) was obtained, and by incorporation with PDA as crosslinker, the self-adhesive PVA/SAA-DA hydrogel electrolytes formed by dual covalent and hydrogen bonding. With increasing SAA and PDA content, the pore size decreased, and a uniform and dense network formed, endowing the hydrogel with a relatively high absorption capacity of PBS solution of lactate as cell fuel. Meanwhile the various functional groups of hydrogel, including catechol, quinone, amino and hydroxyl groups, contributed to impressive tissue adhesion strength against pigskin under dry and wet conditions. The PVA/SAA-DA hydrogel displayed high conductive property, and the integrated PVA-based HBFC generated open circuit voltage of 0.50 V and maximum power density of 128.76 µW/cm2 in 20 mM lactate solution, which was optimized to be 0.57 V/224.85 µW/cm2 when the pore size was enlarged. The power retention reached above 70% in one week, showing long-term stability of HBFC. The PVA-based HBFC was further adhered to human skin without extra adhesive tapes to scavenge human sweat as biofuel, and the maximum power density reached 85.34 µW/cm2, while by connected with a DC-DC converter, the HBFC could power watch, exhibiting promising application potentials as wearable electronic device to provide bioelectricity.

Association between different types of preoperative anemia and tumor characteristics, systemic inflammation, and survival in colorectal cancer.

Background: Patients with colorectal cancer often have anemia and other symptoms after diagnosis, especially in patients with advanced colorectal cancer. This study explored the association between different types of preoperative anemia and tumor characteristics and inflammatory response in patients with colorectal cancer and to evaluate the prognosis of patients with different types of anemia before operation. Methods: The clinical data of 95 patients with colorectal cancer treated in the Fourth Hospital of Hebei Medical University from February 2016 to January 2018 were retrospectively analyzed. According to the hemoglobin concentration (Hb), mean corpuscular volume (MCV), mean hemoglobin content (MCH) and mean hemoglobin concentration (MCHC), the patients were divided into the non-anemia group, normal cell anemia group, and small cell anemia group. The three groups' general data, oncological characteristics, and mGPS scores were compared. The patients were followed up for five years, and the survival analysis was carried out. The cox proportional hazard regression model was used to analyze the prognostic factors of patients with colorectal cancer. Results: The preoperative anemia rate of patients with colorectal cancer was 43.15% (41/95). There were significant differences in gender, weight loss, CA724, tumor location, tumor size, TNM stage, mGPS score, and positive expression rate of Ki-67 among different anemia groups. There was a significant difference in survival time among a non-anemia group, small cell anemia group, and normal cell anemia group (P < 0.05). Multivariate analysis showed that tumor size, TNM stage, distant metastasis, mGPS score, Ki-67 positive expression rate, and anemia type were independent risk factors affecting the prognosis of colorectal cancer patients (P < 0.05). Conclusion: The oncological characteristics of colorectal cancer patients with different types of preoperative anemia are different. Preoperative anemia and systemic inflammatory status are independent risk factors for the prognosis of colorectal cancer patients.

NOP58 induction potentiates chemoresistance of colorectal cancer cells through aerobic glycolysis as evidenced by proteomics analysis.

Introduction: The majority of individuals diagnosed with advanced colorectal cancer (CRC) will ultimately acquire resistance to 5-FU treatment. An increasing amount of evidence indicates that aerobic glycolysis performs a significant function in the progression and resistance of CRC. Nevertheless, the fundamental mechanisms remain to be fully understood. Methods: Proteomic analysis of 5-FU resistant CRC cells was implemented to identify and determine potential difference expression protein. Results: These proteins may exhibit resistance mechanisms that are potentially linked to the process of aerobic glycolysis. Herein, we found that nucleolar protein 58 (NOP58) has been overexpressed within two 5-FU resistant CRC cells, 116-5FuR and Lovo-5FuR. Meanwhile, the glycolysis rate of drug-resistant cancer cells has increased. NOP58 knockdown decreased glycolysis and enhanced the sensitivity of 116-5FuR and Lovo-5FuR cells to 5FU. Conclusion: The proteomic analysis of chemoresistance identifies a new target involved in the cellular adaption to 5-FU and therefore highlights a possible new therapeutic strategy to overcome this resistance.

Highly Biocompatible Polyester-Based Piezoelectric Elastomer with Antitumor and Antibacterial Activity for Ultrasound-Enhanced Piezoelectric Therapy.

Currently, the use of piezoelectric materials to provide sustainable and noninvasive bioelectric stimulation to eradicate tumor cells and accelerate wound healing has raised wide attention. The development of a multifunctional piezoelectric elastomer with the ability to perform in situ tumor therapy as well as wound repair is of paramount importance. However, current piezoelectric materials have a large elastic modulus and limited stretchability, making it difficult to match with the dynamic curvature changes of the wound. Therefore, by copolymerizing lactic acid, butanediol, sebacic acid, and itaconic acid to develop a piezoelectric elastomer (PLBSIE), we construct a new ultrasound-activated PLBSIE-based tumor/wound unified therapeutic platform. Excitedly, it showed outstanding piezoelectric performance and high stretchability, and the separated carrier could react with water to generate highly cytotoxic reactive oxygen species (ROS), contributing to effectively killing tumor cells and eliminating bacteria through piezoelectric therapy. In addition, ultrasound-triggered piezoelectric effects could promote the migration and differentiation of wound-healing-related cells, thus accelerating wound healing. Herein, such a piezoelectric elastomer exerted a critical role in postoperative tumor-induced wound therapy and healing with the merits of possessing multifunctional abilities. Taken together, the developed ultrasound-activated PLBSIE will offer a comprehensive treatment for postoperative osteosarcoma therapy.

The role of bacteria and its derived biomaterials in cancer radiotherapy.

Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics. It has made significant progress in breaking the limitations of monotherapy and effectively eradicating tumors, especially when combined with traditional therapy, such as radiotherapy. According to their different biological characteristics, bacteria and their derivatives can not only improve the sensitivity of tumor radiotherapy but also protect normal tissues. Moreover, genetically engineered bacteria and bacteria-based biomaterials have further expanded the scope of their applications in radiotherapy. In this review, we have summarized relevant researches on the application of bacteria and its derivatives in radiotherapy in recent years, expounding that the bacteria, bacterial derivatives and bacteria-based biomaterials can not only directly enhance radiotherapy but also improve the anti-tumor effect by improving the tumor microenvironment (TME) and immune effects. Furthermore, some probiotics can also protect normal tissues and organs such as intestines from radiation via anti-inflammatory, anti-oxidation and apoptosis inhibition. In conclusion, the prospect of bacteria in radiotherapy will be very extensive, but its biological safety and mechanism need to be further evaluated and studied.

Inhibition of IKKß via a DNA-Based In Situ Delivery System Improves Achilles Tendinopathy Healing in a Rat Model.

BACKGROUND: The inhibition of IKKß by the inhibitor 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridine carbonitrile (ACHP) is a promising strategy for the treatment of Achilles tendinopathy. However, the poor water solubility of ACHP severely hinders its in vivo application. Moreover, the effective local delivery of ACHP to the tendon and its therapeutic effects have not been reported. PURPOSE: To investigate the therapeutic effects of IKKß inhibition via injection of ACHP incorporated into a DNA supramolecular hydrogel in a collagenase-induced tendinopathy rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Dendritic DNA, a Y-shaped monomer, and a crosslinking monomer were mixed with ACHP and self-assembled into an ACHP-DNA supramolecular hydrogel (ACHP-Gel). The effects of ACHP-Gel in tendon stem/progenitor cells were investigated via RNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 120 collagenase-induced rats were randomly assigned to 5 groups: blank, phosphate-buffered saline (PBS), DNA-Gel, ACHP, and ACHP-Gel. Healing outcomes were evaluated using biomechanic and histologic evaluations at 4 and 8 weeks. RESULTS: ACHP-Gel enhanced the solubility of ACHP and sustained its release for ≥21 days in vivo, which significantly increased the retention time of ACHP and markedly reduced the frequency of administration. RNA sequencing and qRT-PCR showed that ACHP effectively downregulated genes related to inflammation and extracellular matrix remodeling and upregulated genes related to tenogenic differentiation. The cross-sectional area (P = .024), load to failure (P = .002), stiffness (P = .039), and elastic modulus (P = .048) significantly differed between the ACHP-Gel and PBS groups at 8 weeks. The ACHP-Gel group had better histologic scores than the ACHP group at 4 (P = .042) and 8 weeks (P = .009). Type I collagen expression (COL-I; P = .034) and the COL-I/collagen type III ratio (P = .015) increased while interleukin 6 expression decreased (P < .001) in the ACHP-Gel group compared with the ACHP group at 8 weeks. CONCLUSION: DNA supramolecular hydrogel significantly enhanced the aqueous solubility of ACHP and increased its release-retention time. Injection frequency was markedly reduced. ACHP-Gel suppressed inflammation in Achilles tendinopathy and promoted tendon healing in a rat model. CLINICAL RELEVANCE: ACHP-Gel injection is a promising strategy for the treatment of Achilles tendinopathy in clinical practice.

Change in quality of life and return to work and sports after isolated closing-wedge distal femoral osteotomy.

PURPOSE: To analyze return to work and sports, and health-related quality of life (HRQoL) after closing-wedge distal femoral osteotomy (CWDFO) for valgus deformity and lateral compartmental osteoarthritis. METHODS: Thirty-three patients underwent isolated CWDFO in our center between January 2018 and June 2020 were enrolled, of whom 32 and 23 patients were included in the return-to-work and return-to-sports analyses, respectively. Short Form-36 (SF-36), Tegner score, Knee injury and Osteoarthritis Outcome Score (KOOS) and visual analog scale (VAS) pain score were compared preoperatively and postoperatively. And postoperative complications were recorded. RESULTS: Overall, 33 patients were contacted at a mean follow-up of 37.94 ± 6.68 months, with a median age of 35 years (range: 26-63 years) at the surgery time. The physical component summary of SF-36 (p < 0.001) increased significantly at 1 year postoperatively. All patients returned to work, including 96.86% who returned to the same level of work in 1.89 ± 0.98 months, and to sports, including 78.26% who returned to the same sport level in 6.50 ± 2.05 months. Rates of returning to work (p = 0.215) and sports (p = 0.165) did not differ with work/sports intensity. Tegner scores (p = 0.025) and VAS pain scores (p < 0.001) decreased, and KOOS (p < 0.001) increased at 1 year postoperatively. Revision/conversion surgery was not required. In all, 30.43% patients reported a subjective decrease in sports ability; 82.61% patients considered their sports ability acceptable. CONCLUSION: Patients returned to work/sports after isolated CWDFO, and had increased HRQoL. Patients playing high-impact sports had lower rates of returning to the same sport level, and may require preoperative counseling. LEVEL OF EVIDENCE: IV, Case series.

Treatment of infected bone defects with the induced membrane technique.

Aims: This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes. Methods: A comprehensive search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases between 1 January 2000 and 31 October 2021. Studies with a minimum sample size of five patients with infected bone defects treated with the induced membrane technique were included. Factors associated with nonunion, infection recurrence, and additional procedures were identified using logistic regression analysis on individual patient data. Results: After the screening, 44 studies were included with 1,079 patients and 1,083 segments of infected bone defects treated with the induced membrane technique. The mean defect size was 6.8 cm (0.5 to 30). After the index second stage procedure, 85% (797/942) of segments achieved union, and 92% (999/1,083) of segments achieved final healing. The multivariate analysis with data from 296 patients suggested that older age was associated with higher nonunion risk. Patients with external fixation in the second stage had a significantly higher risk of developing nonunion, increasing the need for additional procedures. The autografts harvested from the femur reamer-irrigator-aspirator increased nonunion, infection recurrence, and additional procedure rates. Conclusion: The induced membrane technique is an effective technique for treating infected bone defects. Internal fixation during the second stage might effectively promote bone healing and reduce additional procedures without increasing infection recurrence. Future studies should standardize individual patient data prospectively to facilitate research on the affected patient outcomes.

The PFNA in treatment of intertrochanteric fractures with or without lateral wall fracture in elderly patients: a retrospective cohort study.

BACKGROUND: There is no consensus about intertrochanteric fractures with lateral wall treated with intramedullary nail-proximal femoral nail antirotation (PFNA). The aim of the present study was to compare function outcomes between lateral wall and no lateral wall fractures after surgery by PFNA. METHODS: This retrospective study evaluated patients with or without lateral wall fractures who underwent PFNA between January 2015 and June 2018. The operative time, intraoperative blood loss, time to fracture healing, complications and functional outcomes qualified by Harris hip score and Parker - Palmer mobility score (PPMS) were compared between the two groups. RESULTS: Two groups were comparable with regard to patient age, sexual distribution, mechanism of injury, fracture type, body mass index (BMI), Time to surgery, American Society of Anesthesiologists (ASA) score and quality of reduction. The incomplete group had a longer operation time (54.1 ± 8.74 min vs. 51.0 ± 9.86 min) and more intraoperative blood loss (228.4 ± 48.8 ml vs. 151.3 ± 43.5 ml) in comparison with the control group (P < 0.01). Regarding functional outcome, the HHSs of the two groups were 76.2 ± 11.6 vs 75.6 ± 12.5 at the 3 months (P = 0.603), 81.9 ± 9.4 vs 82.6 ± 8.7 at the six months (P = 0.224), 83.8 ± 6.6 vs 84.5 ± 6.0 at the twelve months 85.2 ± 5.5 vs 86.0 ± 5.8 at the twenty-four months (P > 0.05), respectively. Similar results were obtained about PPMS. We found no difference in Weight bearing time, Time of fracture healing, and Complications between incomplete group and intact group. CONCLUSIONS: There is no substantial difference in functional results or complication rates for intertrochanteric fractures with lateral wall fractures, except from increased blood loss and operation time. We believe that an intramedullary nail will be sufficient to repair an intertrochanteric fracture with or without a lateral wall fracture.