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.

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.

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.

Iron-Based Nanovehicle Delivering Fin56 for Hyperthermia-Boosted Ferroptosis Therapy Against Osteosarcoma.

Background: Although systemic chemotherapy is a standard approach for osteosarcoma (OS) treatment, its efficacy is limited by the inherent or acquired resistance to apoptosis of tumor cells. Ferroptosis is considered as an effective strategy capable of stimulating alternative pathways of cancer cell demise. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy. Methods and Results: A novel nanovehicle composed of arginine-glycine-aspartate (RGD) modified mesoporous silica-coated iron oxide loading Fin56 was rationally prepared (FSR-Fin56). With the RGD-mediated targeting affinity, FSR-Fin56 could achieve selective accumulation and accurate delivery of cargos into cancer cells. Upon exposure to NIR light, the nanovehicle could generate localized hyperthermia and disintegrate to liberate the therapeutic payload. The released Fin56 triggered the degradation of GPX4, while Fe3+ depleted the intracellular GSH pool, producing Fe2+ as a Fenton agent. The local rise in temperature, in conjunction with Fe2+-mediated Fenton reaction, led to a rapid and significant accumulation of ROS, culminating in LPOs and ferroptotic death. The outstanding therapeutic efficacy and safety of the nanovehicle were validated both in vitro and in vivo. Conclusion: The Fin56-loaded FSR nanovehicle could effectively disturb the redox balance in cancer cells. Coupled with NIR laser irradiation, the cooperative CDT and PTT achieved a boosted ferroptosis-inducing therapy. Taken together, this study offers a compelling strategy for cancer treatment, particularly for ferroptosis-sensitive tumors like osteosarcoma.

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.

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.

Traumatic brain injury stimulates sympathetic tone-mediated bone marrow myelopoiesis to favor fracture healing.

Traumatic brain injury (TBI) accelerates fracture healing, but the underlying mechanism remains largely unknown. Accumulating evidence indicates that the central nervous system (CNS) plays a pivotal role in regulating immune system and skeletal homeostasis. However, the impact of CNS injury on hematopoiesis commitment was overlooked. Here, we found that the dramatically elevated sympathetic tone accompanied with TBI-accelerated fracture healing; chemical sympathectomy blocks TBI-induced fracture healing. TBI-induced hypersensitivity of adrenergic signaling promotes the proliferation of bone marrow hematopoietic stem cells (HSCs) and swiftly skews HSCs toward anti-inflammation myeloid cells within 14 days, which favor fracture healing. Knockout of ß3- or ß2-adrenergic receptor (AR) eliminate TBI-mediated anti-inflammation macrophage expansion and TBI-accelerated fracture healing. RNA sequencing of bone marrow cells revealed that Adrb2 and Adrb3 maintain proliferation and commitment of immune cells. Importantly, flow cytometry confirmed that deletion of ß2-AR inhibits M2 polarization of macrophages at 7th day and 14th day; and TBI-induced HSCs proliferation was impaired in ß3-AR knockout mice. Moreover, ß3- and ß2-AR agonists synergistically promote infiltration of M2 macrophages in callus and accelerate bone healing process. Thus, we conclude that TBI accelerates bone formation during early stage of fracture healing process by shaping the anti-inflammation environment in the bone marrow. These results implicate that the adrenergic signals could serve as potential targets for fracture management.

Programmable DNA Hydrogel Provides Suitable Microenvironment for Enhancing TSPCS Therapy in Healing of Tendinopathy.

Tendon stem/progenitor cells (TSPCs) therapy is a promising strategy for enhancing cell matrix and collagen synthesis, and regulating the metabolism of the tendon microenvironment during tendon injury repair. Nevertheless, the barren microenvironment and gliding shear of tendon cause insufficient nutrition supply, damage, and aggregation of injected TSPCs around tendon tissues, which severely hinders their clinical application in tendinopathy. In this study, a TSPCs delivery system is developed by encapsulating TSPCs within a DNA hydrogel (TSPCs-Gel) as the DNA hydrogel offers an excellent artificial extracellular matrix (ECM) microenvironment by providing nutrition for proliferation and protection against shear forces. This delivery method restricts TSPCs to the tendons, significantly extending their retention time. It is also found that TSPCs-Gel injections can promote the healing of rat tendinopathy in vivo, where cross-sectional area and load to failure of injured tendons in rats are significantly improved compared to the free TSPCs treatment group at 8 weeks. Furthermore, the potential healing mechanism of TSPCs-Gel is investigated by RNA-sequencing to identify a series of potential gene and signaling pathway targets for further clinical treatment strategies. These findings suggest the potential pathways of using DNA hydrogels as artificial ECMs to promote cell proliferation and protect TSPCs in TSPC therapy.

Amplification of oxidative stress with a hyperthermia-enhanced chemodynamic process and MTH1 inhibition for sequential tumor nanocatalytic therapy.

During chemodynamic therapy (CDT), tumor cells can adapt to hydroxyl radical (˙OH) invasion by activating DNA damage repairing mechanisms such as initiating mutt homologue 1 (MTH1) to mitigate oxidation-induced DNA lesions. Therefore, a novel sequential nano-catalytic platform MCTP-FA was developed in which ultrasmall cerium oxide nanoparticle (CeO2 NP) decorated dendritic mesoporous silica NPs (DMSN NPs) were used as the core, and after encapsulation of MTH1 inhibitor TH588, folic acid-functionalized polydopamine (PDA) was coated on the periphery. Once endocytosed into the tumor, CeO2 with multivalent elements (Ce3+/4+) could transform H2O2 into highly toxic ˙OH through a Fenton-like reaction to attack DNA as well as eliminating GSH through a redox reaction to amplify oxidative damage. Meanwhile, controllable release of TH588 hindered the MTH1-mediated damage repair process, further aggravating the oxidative damage of DNA. Thanks to the excellent photothermal performance of the PDA shell in the near-infrared (NIR) region, photothermal therapy (PTT) further improved the catalytic activity of Ce3+/4+. The therapeutic strategy of combining PTT, CDT, GSH-consumption and TH588-mediated amplification of DNA damage endows MCTP-FA with powerful tumor inhibition efficacy both in vitro and in vivo.

New Classification Based on CT and Its Value Evaluation for Fractures of the Lateral Process of the Talus.

This study aimed to develop a comprehensive classification system for fractures of the lateral process of the talus (LPTF) based on CT, and to evaluate its prognostic value, reliability and reproducibility. We retrospectively reviewed 42 patients involving LPTF with an average follow-up of 35.9 months for clinical and radiographic evaluations. In order to develop a comprehensive classification, a panel of experienced orthopedic surgeons discussed the cases. All fractures were classified according to Hawkins, McCrory-Bladin and new proposed classifications by 6 observers. The analysis of interobserver and intraobserver agreements was measured using kappa statistics. The new classification included 2 types based on presence of concomitant injuries or not, with type I consisting of 3 subtypes and type II of 5 subtypes. Average AOFAS score was 91.5 in the type Ia of new classification, 86 in type Ib, 90.5 in type Ic, 89 in type IIa, 76.7 in type IIb, 76.6 in type IIc, 91.3 in type IId, and 83.5 in type IIe. Interobserver and intraobserver reliability of the new classification system were almost perfect (κ = 0.776 and 0.837, respectively), showing a higher interobserver and intraobserver reliability compared to the Hawkins classification (κ 0.572 and 0.649, respectively) as well as McCrory-Bladin classification (κ = 0.582 and 0.685, respectively). The new classification system is a comprehensive one that takes into account concomitant injuries and shows good prognostic value with clinical outcomes. It is more reliable and reproducible and could be a useful tool for decision-making on treatment options for LPTF.

Decreased medial posterior tibial slope is associated with an increased risk of posterior cruciate ligament rupture.

PURPOSE: It remains unclear whether there is an association between posterior cruciate ligament (PCL) rupture and the medial posterior tibial slope (MTS) or lateral posterior tibial slope (LTS). The present case-control study aimed to investigate a possible association between primary PCL rupture and MTS or LTS measured by magnetic resonance imaging (MRI). METHODS: A retrospective case-control study was conducted. Patients with primary PCL ruptures but not with anterior cruciate ligament injuries, were 1:1 matched by age and sex to a control group with no evidence of knee ligament injuries. Knee MRI was used to measure the MTS and LTS. In addition, the receiver operating characteristic (ROC) analysis was performed to identify an optimal cut-off value of the MTS and/or LTS. RESULTS: In total, 46 patients with PCL ruptures (32 males, 14 females) and 46 controls (32 males, 14 females) were included in this study. The MTS was significantly lower in the patients with PCL ruptures (3.0° ± 2.2°) than in the control group (5.1° ± 2.3°, p < 0.001). The mean LTS/MTS ratio was significantly higher in patients with PCL ruptures (2.6 ± 2.5) than in the control group (1.3 ± 1.3, p = 0.001). However, the LTS was not significantly different between patients with PCL ruptures and the controls (4.4° ± 2.3° vs. 5.3° ± 2.6°, n.s.). After the MTS was determined to be a significant predictor, the ROC analysis was performed. The ROC analysis revealed the most accurate MTS cut-off of < 3.9°, with a sensitivity of 76.1% and a specificity of 73.9%. CONCLUSION: A decreased MTS and an increased LTS/MTS ratio are associated with an increased risk of primary PCL rupture. People with MTS < 3.9° are particularly at risk for PCL ruptures, and prevention and intervention programs for PCL ruptures should be developed and targeted towards them. LEVELS OF EVIDENCE: Level III.

Characterizing the tumor microenvironment at the single-cell level reveals a novel immune evasion mechanism in osteosarcoma.

The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma (OS). However, the landscape and dynamics of immune cells in OS are poorly characterized. By analyzing single-cell RNA sequencing (scRNA-seq) data, which characterize the transcription state at single-cell resolution, we produced an atlas of the immune microenvironment in OS. The results suggested that a cluster of regulatory dendritic cells (DCs) might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells. We also found that major histocompatibility complex class I (MHC-I) molecules were downregulated in cancer cells. The findings indicated a reduction in tumor immunogenicity in OS, which can be a potential mechanism of tumor immune escape. Of note, CD24 was identified as a novel "don't eat me" signal that contributed to the immune evasion of OS cells. Altogether, our findings provide insights into the immune landscape of OS, suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.

Proximal femoral bionic nail (PFBN)-an innovative surgical method for unstable femoral intertrochanteric fractures.

PURPOSE: Intertrochanteric femoral fractures (IFF) are one of the most common traumatic conditions, but there are no established treatment methods for this condition due to implant failure and re-operation rates. The proximal femoral bionic nail (PFBN), which is a new design of the cephalomedullary nail, was developed by our team. The objective of this study was to assess the clinical and radiographic outcomes of PFBN in patients with unstable IFF. METHODS: From October 2020 to August 2021, 12 patients diagnosed with unstable IFF (31-A2, 3) were treated with PFBN at the Third Hospital of Hebei Medical University. We evaluated the clinical therapeutic effects of this treatment by measuring peri-operative indicators and post-operative complications. Clinical outcomes, specific radiographic parameters, and post-operative complications were collected and analyzed within the first post-operative year. RESULTS: The average age of the patients was 72.4 ± 16.1 years (five males and seven females). The mean operation time was 90.4 ± 16.0 min, whereas the operation time of 31-A2 fractures (83.1 ± 12.2 min) was shorter than that of 31-A3 fractures (105.0 ± 12.9 min) (p < 0.05). The blood loss was 175 ml (range: 50 to 500 ml), and the length of hospitalization was 10.0 ± 1.9 days. The prognosis evaluation was assessed at three, six and 12 months after the operation; for these time points, the Harris hip scores were 69.6 ± 4.1, 77.8 ± 3.8, and 82.6 ± 4.6, respectively, and the Parker-Palmer scores were 5.3 (5.0, 7.0), 6.3 (5.3, 7.0), and 7.8 (7.0, 8.0), respectively. CONCLUSION: PFBN has shown advantages in the treatment of unstable IFF (particularly in geriatric patients) and possesses both stability and safety. This innovative method may provide a new option for treating unstable IFFs.

Cascade-Enhanced Catalytic Nanocomposite with Glutathione Depletion and Respiration Inhibition for Effective Starving-Chemodynamic Therapy Against Hypoxic Tumor.

Background: Although chemodynamic therapy (CDT) has attracted enormous attention in anti-tumor studies for converting endogenous hydrogen peroxide (H2O2) into toxic hydroxyl radicals (•OH) by Fenton-type reaction, the treating effects of using CDT alone is still unsatisfying. Recently, glucose oxidase (GOx) was reported to be co-delivered with Fenton agent for synergistic starvation therapy (ST) and CDT. However, the overexpressed glutathione (GSH) and hypoxia in tumor microenvironment (TME) restrict the therapeutic efficacy of ST/CDT. Methods and Results: In this work, a novel nanoplatform composed of GOx plus Fenton agent (Cu2+) encapsulated core and metformin (MET)-loaded manganese dioxide nanosheets (MNSs) shell was prepared and further functionalized by arginine-glycine-aspartate (RGD). With the RGD-mediated affinity with cancer cells, the nanocomposite (GOx-CuCaP@MNSs-MET@PEG-RGD, GCMMR) could accomplish targeting delivery and TME-activated release of cargos. The intracellular GSH was depleted by MnO2/Cu2+ and abundant H2O2 was generated along with the GOx-induced glucose deprivation, which process was further enhanced by MET-mediated hypoxia relief via inhibiting mitochondria-associated respiration. Subsequently generated •OH from Cu+-mediated Fenton-like reaction exerts severe intracellular oxidative stress and cause apoptosis. Moreover, significant inhibition of tumor growth was detected in a subcutaneous xenograft model of osteosarcoma (OS) after GCMMR treatment. Conclusion: The excellent therapeutic efficacy and biosafety of the nanoplatform were confirmed both in vitro and in vivo. Collectively, this study provides an appealing strategy with catalytic cascade enhancement on targeted ST/CDT for cancer treatment, especially for hypoxic solid tumors.

Synthesis of dual-stimuli responsive metal organic framework-coated iridium oxide nanocomposite functionalized with tumor targeting albumin-folate for synergistic photodynamic/photothermal cancer therapy.

The synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted considerable attention in the field of cancer therapy because of its excellent anti-tumor effect. This work provides a novel pH/NIR responsive therapeutic nanoplatform, IrO2@ZIF-8/BSA-FA (Ce6), producing a synergistic effect of PTT-PDT in the treatment of osteosarcoma. Iridium dioxide nanoparticles (IrO2 NPs) with exceptional catalase-like activity and PTT effects were synthesized by a hydrolysis method and decorated with zeolitic imidazolate framework-8 (ZIF-8) shell layer to promote the physical absorption of Chlorin e6 (Ce6), and further functionalized with bovine serum albumin-folate acid (BSA-FA) for targeting tumor cells. The IrO2@ZIF-8/BSA-FA nanocomposite indicated an outstanding photothermal heating conversion efficiency of 62.1% upon laser irradiation. In addition, the Ce6 loading endows nanoplatform with the capability to induce cell apoptosis under 660 nm near-infrared (NIR) laser irradiation through a reactive oxygen species (ROS)-mediated mechanism. It was further testified that IrO2@ZIF-8/BSA-FA can function as a catalase and convert the endogenous hydrogen peroxide (H2O2) into oxygen (O2) to improve the local oxygen pressure under the acidic tumor microenvironment (TME), which could subsequently amplified PDT-mediated ROS cell-killing performance via relieving hypoxia microenvironment of tumor. Both in vitro and in vivo experimental results indicated that the nanomaterials were good biocompatibility, and could remarkably achieve tumor-specific and enhanced combination therapy outcomes as compared with the corresponding PTT or PDT monotherapy. Taken together, this work holds great potential to design an intelligent multifunctional therapeutic nanoplatform for cancer therapy.

Platinum-based nanocomposites loaded with MTH1 inhibitor amplify oxidative damage for cancer therapy.

Photodynamic therapy (PDT) is a promising therapeutic strategy for tumor ablation by generating highly toxic reactive oxygen species (ROS) to damage DNA and other biomacromolecules. However, the local hypoxic microenvironment of the tumor and the presence of ROS-defensing system, such as the mobilization of mutt homolog 1 (MTH1) to sanitize ROS-oxidized nucleotide pool, severely limit the efficiency of PDT. Therefore, a novel tumor ablation strategy was developed that not only focused on the enhancement of ROS generation but also weakened the ROS-defensing system by inhibiting MTH1 enzyme activity. In our work, a simple one-step reduction approach was applied to enable platinum nanoparticles (Pt NPs) with catalase activity to grow in situ in the nanochannels of mesoporous silica nanoparticles (MSNs). After physical encapsulation of photosensitizer chlorin e6 (Ce6) and MTH1 inhibitor TH588, the drug loading nanoplatform was modified with an arginine-glycine-aspartic acid (RGD) functionalized liposome shell, resulting in the fabrication of amplified oxidative damage nanoplatform MSN-Pt@Ce6/TH588 @Liposome-RGD (MPCT@Li-R). The prepared MPCT@Li-R NPs could continuously catalyze the decomposition of hydrogen peroxide (H2O2) into oxygen (O2) in tumor, thus promoting the generation of singlet oxygen during PDT process for improved oxidative damage of bases. Simultaneously, acid responsive released TH588 hindered MTH1-mediated scavenging of oxidative bases, further aggravating DNA oxidative damage. Consequently, this cascade therapy strategy exhibited excellent tumor suppression efficiency both in vitro and in vivo.

Glenoid bony morphology along long diameter is associated with the occurrence of recurrent anterior shoulder dislocation: a case-control study based on three-dimensional CT measurements.

PURPOSE: The purpose of our study is to compare the anatomic parameters of proximal humerus, glenoid, and glenohumeral joint between patients with recurrent anterior shoulder dislocation (RASD) and patients without RASD with the assistance of three-dimensional (3D) CT scans. METHODS: Sixty patients were included in the study and divided into group RASD and group control. 3D-CT models of shoulder joint for each included patient were reconstructed and multiple anatomic parameters were measured. RESULTS: There were no statistically significant differences between the two groups in morphological parameters of humerus and glenohumeral joints. Long diameter of glenoid was 3.50 ± 0.34 cm for patients in group RASD and 3.31 ± 0.32 cm in group control (p = 0.039). There was a statistically significant difference in the ratio of long to short diameter of glenoid (p < 0.001). Ratio of humeral head height to glenoid long diameter (Hhh/Gld) was 1.02 ± 0.07 in group RASD, significantly lower than 1.09 ± 0.08 in group control (p = 0.001). Longitudinal depth of glenoid was significantly higher in group RASD (p = 0.013). CONCLUSION: The glenoid morphology along long diameter is closely correlated with the stability of glenohumeral joint, including glenoid long diameter and glenoid longitudinal depth. It is especially noteworthy that the value of Hhh/Gld decreases in patients with RASD. The difference of Hhh/Gld between the two groups reminds us that the correlation of bony structure along long diameter between glenoid and humeral head plays an important role in RASD.

Single-stage arthroscopic-assisted treatment of anteromedial tibial plateau fracture with posterolateral corner injury: a retrospective study.

BACKGROUND: Anteromedial tibial plateau fracture with posterolateral corner (PLC) injury is a relatively rare combined injury in the clinic. In addition, there is no unified treatment scheme for this combined injury. The purpose of this study was to evaluate the clinical and imaging results of single-stage arthroscopic-assisted surgery for anteromedial tibial plateau fracture with PLC injury, and to explore the advantages of this surgical technique. METHOD: In this retrospective study, a total of 9 patients (7 males and 2 females) were included, aged 24-64 years (average 40.7 years), treated in our Department of Orthopedics from January 2016 to January 2021. In the preoperative evaluations, there were 9 cases of anteromedial tibial plateau fractures with PLC injuries, 6 cases of concomitant PCL injuries, 6 cases of concomitant medial or lateral meniscus injuries, and 2 cases of concomitant fibular head avulsion fractures. All patients underwent single-stage arthroscopic-assisted surgery. RESULTS: All patients were followed up, and the average follow-up period was 15.2 months (range 12-18 months). The average operation time was 135.6 min (range 100-160 min), and the average surgical blood loss was 87.2 ml (range 60-110 ml). The anatomical reduction was achieved in 9 cases, and the anatomical reduction rate was 100%. The average fracture healing time was 13.1 weeks (range 12-16 weeks). At the last follow-up, the average VAS score was 1 (range 0-2); the average Lysholm function score was 90.7 (range 86-95), and the average IKDC score was 91.4 (range 88-95); the average knee extension angle of all patients was 0° and the average knee flexion angle was 128.3° (average 120-135°); The posterior drawer test, the Lachman test and the dial test were negative for all cases. None of the patients had operation-related complications. CONCLUSION: Single-stage arthroscopy-assisted surgery in the treatment of anteromedial tibial plateau fracture with PLC injury can achieve good clinical outcomes, restore the stability of the knee joint, and reduce the risk of severe lower extremity dysfunction.

Comparison of the Effect of Rhombic and Inverted Triangle Configurations of Cannulated Screws on Internal Fixation of Nondisplaced Femoral Neck Fractures in Elderly Patients.

OBJECTIVE: To investigate whether four-screw fixation in rhombic configuration could improve the clinical outcomes and decrease the complication rate compared with three-screw fixation in inverted triangle configuration in elderly patients with nondisplaced femoral neck fractures. METHOD: From January 2018 to January 2019, 91 elderly patients with nondisplaced femoral neck fractures who were treated with a cannulated screw system were reviewed retrospectively. The inverted triangle configuration was applied in 51 patients and rhombic configuration in 40 patients. The demographic and perioperative information of the patients were extracted from medical records and surgical records. Variables including incision size, surgical blood loss, surgical time, fluoroscopy time, hospital stays, fracture union time, postoperative visual analogue scale (VAS) scores, and complications were compared between the two groups. Also, Harris hip score at the final follow-up was used to evaluate the functional outcomes. RESULTS: All patients were followed up from 24 to 36 months, with an average of 29.75 months. The average age of patients was 72.37 ± 7.16 years. No significant differences were found between the two groups with regard to patients' age, gender, affected side, Garden classification, Pauwels classification and comminution of posterior wall (P > 0.05). We found shorter incision size (P < 0.001), less blood loss (P = 0.020), less surgical time (P = 0.026), and shorter fluoroscopy time (P < 0.001) in inverted triangle configuration group. However, shorter hospital stays (P = 0.001) and fracture union time (P = 0.002) were found in the rhombic configuration group. The VAS scores were lower in the rhombic configuration group at the first (P < 0.001) and third months (P = 0.010), but no significant difference was found at the sixth month (P = 0.075). Meanwhile, the total complication rate was relatively lower in the rhombic configuration group compared to the inverted triangle configuration group (P = 0.041). Harris hip score presented no significant difference between the two groups at final follow-up (P = 0.078). No wound infection or cortical perforation occurred in either group. CONCLUSION: Four-screw fixation in rhombic configuration was superior to three-screw fixation in inverted triangle configuration in the treatment of nondisplaced femoral neck fractures in elderly patients in terms of less early postsurgical pain, shorter fracture union time, and lower complication rate.