Superior labrum anterior posterior (SLAP) injury is a major challenge for orthopedic surgeons, due to the poor healing ability of the injured labrum. Although arthroscopic surgery is the gold standard for the treatment of SLAP injury, there are still disputes about the adaptation of different surgical techniques, the choice of anchors during operation, knotted or knotless anchors, and fixation methods. The authors believe that arthroscopic repair of SLAP lesions is effective for young patients with intact glenoid labrum(<35 years old) or with extensive activity, where single and knotless anchor is preferred. For the older patients(≥35 years old) with degeneration and wear of glenoid labrum, biceps tenodesis is more preferable, and interference screw fixation technique is recommended. As for patients with failed SLAP repair, biceps tenodesis can achieve a high success rate as a revision surgery. By review of the relevant literature in recent years, this paper summarizes the adaptation of different surgical methods of arthroscopic treatment of SLAP injury, intraoperative anchoring techniques, fixation methods and other improved surgical techniques.

The surgical treatment of massive rotator cuff tears is a clinical challenge for orthopaedic surgeons. Moreover, tendon retraction, adhesions and fatty infiltration after rotator cuff tear will further increase the difficulty of surgical repair. Therefore, it has become a hotspot and difficulty to repair massive rotator cuff tears with a better way in current research. In recent years, with the continuous development of arthroscopic techniques, shoulder arthroscopic surgery has become the gold standard for the treatment of massive rotator cuff tears, but the adaptations, effects and combined application of different surgical methods are still controversial. The author believes that arthroscopic debridement of shoulder joint and acromioplasty or tuberoplasty could relieve shoulder pain in the short-term for elderly patients with lower functional requirements;long biceps tenotomy or tenodesis is effective for patients with biceps long head tendon injury; complete repair is still the first line treatment for massive rotator cuff tears, but partial repair is possible for massive rotator cuff tears that could not be completely repaired;patch augmentation technology could bring good results for young patients with high functional requirements;for patients with limited internal and external rotation of the shoulder joint and high functional requirements, tendon transfers surgery is recommended;superior capsular reconstruction is more advantageous for young patients with no obvious glenohumeral arthritis, better deltoid muscle strength and higher functional requirements. In addition, subacromial spacer implantation has become a current research hotspot due to its advantages of small trauma, low cost and relative safety, and its long-term effect still needs to be further confirmed.

Biofunctional surface-modification surpassed critical limitation of graphene oxide (GO) in biocompatibility and drug delivery efficiency, contributing to versatile biomedical applications. Here, a protein corona-bridged GO nanoplatform with high drug loading, longstanding hyperthermia, and controllable drug release, was engineered for amplified tumor therapeutic benefits. Structurally, GO surface was installed with phenylboronic acid (PBA) layer, on which iRGD conjugated apolipoprotein A-I (iRGD-apoA-I) was coordinated via boron electron-deficiency, to form the sandwich-like GO nanosheet (iAPG). The GO camouflaging by iRGD-apoA-I corona provided multimodal high doxorubicin (DOX) loading by π-π stacking and coordination, and generated a higher photothermal transformation efficiency simultaneously. In vitro studies demonstrated that iAPG significantly improved drug penetration and internalization, then achieved tumor-targeted DOX release through near-infrared (NIR) controlled endo/lysosome disruption. Moreover, iAPG mediated site-specific drug shuttling to produce a 3.53-fold enhancement of tumor drug-accumulation compared to the free DOX in vivo, and induced deep tumor penetration dramatically. Primary tumor ablation and spontaneous metastasis inhibition were further demonstrated with negligible side effects under optimal NIR. Taken together, our work provided multifunctional protein corona strategy to inorganic nanomaterials toward advantageous biomedical applications.

Increasing knowledge of drug delivery properties, tumor profiles and their relationship promotes precise administration regimens, representing a promising pattern to personalized tumor treatment. Herein, we propose a regulatory hydrogel depot toward metastatic cancer by establishing mathematical models between tumor characteristics and administration regimens. Specifically, a thermo-sensitive PLGA-PEG-PLGA polymer is introduced as injectable hydrogel matrix, of which the administration volume and frequency are manipulated elaborately according to tumor size and gel-degradation kinetics. Structurally, doxorubicin (Dox) and arginine-terminated nanoparticles containing KIAA1199 specific shRNA (shKIAARPDNs) are incorporated into hydrogels, thereby formulating a topical and sustained drug depot to achieve synergy treatment. For dual-targeting therapy, Dox interdicts DNA replication/transcription, and shKIAA persistently silences KIAA1199 protein to modulate aggressive phenotypes. After individual peritumoral injection, Gel/shKIAARPDNs/Dox demonstrates desirable distribution patterns and gel degradation kinetics with enhanced tumor penetration. Moreover, a preferable inhibition of tumor proliferation and metastasis is confirmed after twice treatment in 12 days, indicating better therapeutic efficacy with less dosage and frequency. Consequently, the controllable administration regimen inspired mathematical models of thermosensitive hydrogel provides an intelligent platform for personalized treatment to metastatic cancer.

Rotator cuff tendon–bone healing often leads to scarring and low biomechanical strength, resulting in a tendency to re-tear. This study examined whether combining autologous osteochondral transplantation and periosteum transplantation increases fibrocartilage transition zone regeneration and improves biomechanical fixation. A total of 48 New Zealand white rabbits were divided into the periosteum, autologous osteochondral, combination of autologous osteochondral and periosteum, and control groups. The supraspinatus tendon was cut from the greater tuberosity and repaired by different transplants. A total of 12 rabbits were used for histological examination (haematoxylin and eosin staining, Masson’s staining and Safranin-O staining) at 4, 8 and 12 weeks after the repair, and 36 rabbits were used for biomechanical tests (maximal failure load and stiffness). At 4 weeks following the operation, each group had a large tendon–bone gap with a small number of disordered collagen fibres. At 8 weeks, the tendon–bone gap was smaller than that before the operation, and the tendon–bone gap in each experimental group was smaller with neater and denser collagen fibres and chondrocytes than in the control group, with the osteochondral combined periosteum group having the best results. At 12 weeks, the typical tendon–bone transitional structure was observed in the osteochondral combined periosteum group, and more collagen fibres and chondrocytes were generated in each group. The osteochondral combined periosteum group had the largest staining area and the largest amount of cartilage. The maximum tensile strength and stiffness of each group increased over time. There was no significant difference in each group’s maximum tensile strength and stiffness at 4 weeks after the operation. However, the maximum tensile strength and stiffness of the osteochondral combined periosteum group at 8 and 12 weeks after operation were significantly higher than those of other groups (P < 0.05). Histological and biomechanical results show that autologous osteochondral transplantation combined with periosteum transplantation can effectively promote the regeneration of fibrous cartilage in the tendon–bone junction of the rotator cuff. It is concluded that this technique is a new treatment method to promote tendon–bone healing in the rotator cuff.

Background The aim of this literature review was to identify preoperative risk factors associated with recurrent instability after Bankart repair. Methods The PubMed, Web of Science, Embase, and Cochrane Library databases were searched for potentially eligible articles. Two reviewers independently screened the titles and abstracts using prespecified criteria. Articles were included if they clearly stated the risk factors for recurrence after Bankart repair. Data on patient characteristics and recurrence rate were collected from each study. A random-effects model was used for the meta-analysis and the statistical analysis was performed using Review Manager 5.4 software. Results Nineteen studies that included 2922 participants met the inclusion criteria. The overall pooled prevalence of recurrent instability was 15.3% (range 6.9–42). The mean follow-up duration was 40.5 months (18–108). Twenty-one risk factors were identified, 10 of which were explored quantitatively. Statistically significant risk factors for recurrent instability following a Bankart procedure were age under 20 years (odds ratio [OR] 4.24, 95% confidence interval [CI] 2.8–96.23, p < 0.00001), a Hill-Sachs lesion (OR 3.61, 95% CI 2.06–6.33, p < 0.00001), a glenoid bone lesion (OR 2.8, 95% CI 1.96–4.01, p < 0.00001), shoulder hyperlaxity (OR 4.55, 95% CI 2.19–9.44, p < 0.0001), and an off-track lesion (OR 5.53, 95% CI 2.21–13.86, p = 0.0003). There was moderate evidence indicating that male sex (OR 1.6, 95% CI 1.07–2.37, p = 0.02) and playing contact sports (OR 1.54, 95% CI 0.96–2.45, p = 0.07) were further risk factors. Dominant side, a superior labrum from anterior to posterior (SLAP) lesion, and more than five preoperative dislocations were not found to be risk factors. Conclusions Patients younger than 20 years of age, a Hill–Sachs lesion, a glenoid bone lesion, shoulder hyperlaxity, and an off-track lesion appear to be significant predictors of recurrent instability following a Bankart procedure. Factors such as male sex and playing contact sports were associated with recurrent instability. Dominant side, a SLAP lesion, and more than five preoperative dislocations were not significant risk factors.

Despite the remarkable success of immunotherapies over the past decade, their effectiveness against triple-negative breast cancer (TNBC) is limited to a small subset of patients, mainly due to the low immunogenicity and unfavorable tumor microenvironment. In this study, we successfully constructed a programmed site-specific delivery nanosystem for the combined delivery of transforming growth factor beta (TGF-β) receptor inhibitor LY3200882 (LY) and PD-L1 siRNA (siPD-L1) to boost anti-tumor immunotherapy. As expected, LY in the outer layer of the nanosystem was released by stimulation of MMP2, and dramatically down-regulated the expression of extracellular matrix (ECM) in the tumor-associated fibroblasts (TAFs), and thus promoted the infiltration of effector T cells and penetration of nanomedicines. Simultaneously, the blockade of TGF-β by LY also triggered immunogenic cell death (ICD) of tumor cells and induced the maturation of dendritic cells. Moreover, the programmed design provided the siPD-L1/protamine cationic inner core with easier access to tumor cells and TAFs after MMP2-stimulated breakup of the outer layer, down-regulating the expression of PD-L1 in both types of cells. Notably, the synergistic effect of LY and siPD-L1 remarkably enhanced the tumor antigen presentation and immunosuppressive microenvironment remodeling, thus efficiently inhibiting the TNBC growth, metastasis, and recurrence. Therefore, the programmed site-specific delivery nanosystem is a promising drug delivery platform for boosting anti-tumor immunotherapy efficacy for TNBC.

The incidence of re-tearing after rotator cuff repair is very high. The main reason is that the tendon-osseous junction after the operation is scar healed. In response to this problem, research in recent years has focused on the application of grafts, including cell transplantation, periosteum transplantation, cartilage transplantation, and biosynthetic transplantation. Cell transplantation is mainly a variety of stem cells from different sources. The current research has confirmed that it can achieve better results. The combined application of exosomes and stem cells may be the future development direction. Periosteum transplantation is a promising intervention method, but few clinical applications at present, and there are problems such as limited sources of materials and secondary trauma from the materials. Tissue engineered periostium and artificial bionic periostium may be alternatives to periosteal;cartilage transplantation can promote the regeneration of cartilage at the tendon-osseous junction and facilitate tendon-bone healing. However, there are also limited materials and secondary damage. There is no better solution to this problem. The slow degradation of inorganic composites and the poor effect of single use limit its application; biological derivatives have immunogenicity, poor biomechanics and other issues, there is currently no proper solution; organic synthetic grafts pay more attention to simulating the structure of the physiological tendon-osseointegration zone, and show good results in tendon-bone healing, and have good application prospects. In addition, most of the above-mentioned application research of different grafts stays at the cellular and animal level, and more research is needed in clinical application. This article briefly reviews the application status, advantages, disadvantages and development trends of the above-mentioned different grafts, in order to provide certain guidance for the clinical treatment of rotator cuff tears.

The surgical treatment of recurrent anterior shoulder dislocation is a difficult problem in the field of sports injury medicine. The main reason focus on dynamic and osseous constraints of shoulder joint could not recover well. At present, arthroscopic surgery is used at home and abroad, and could receive statisfied postoperative effect, but the choice of specific surgical methods is still controversial. According to presence and size of glenoid and humeral skull defects, different treatments should be selected in clinic. The author recommends that no articular glenoid defect or glenoid defect <20%, choose Bankart surgery;articular glenoid defect <20% with Hill-Sachs bone defect <40%, choose Bankart surgery combined with remplissage surgery or ASA surgery;Glenoid defect 20% to 25%, choose "Sling";Glenoid defect 25% to 40%, choose Bristow-Latarjet; Glenoid or Hill-Sachs bone defect>40% or Bristow-Latarjet if the surgical repair fails, bone grafting is used. In addition, if (humeral avulsion of glenohumeral ligaments, HAGL) injury existed, HAGL injury repair should be used. In addition to considering the important factor of bone defects, it is necessary to combine patient's age, exercise level and surgeon's technique to comprehensively select the bestsurgical method.

SummaryMicroRNA168 (MIR168) is a key miRNA that targets the main RNA‐induced silencing complex component Argonaute 1 (AGO1) to regulate plant growth and environmental stress responses. However, the regulatory functions of MIR168 need to be further elucidated in rice. In this paper, we generated clean OsMIR168a deletion mutants by CRISPR‐Cas9 strategy. We then phenotypically and molecularly characterized these mutants. The rice OsMIR168a mutants grew rapidly at the seedling stage, produced more tillers and matured early. Compared to the wild‐type plants, the mutants were shorter at maturity and produced smaller spikelets and seeds. Analysis of gene expression showed that the transcription levels of OsMIR168a’s target genes such as OsAGO1a, OsAGO1b and OsAGO1d were elevated significantly in the OsMIR168a mutants. Intriguingly, OsAGO18, a member of a new AGO clade that is conserved in monocots, was confirmed to be a target of OsMIR168a not only by informatic prediction but also by expression analysis and a cell‐based cleavage assay in the OsMIR168a mutants. Many protein‐coding genes and miRNAs showed differential expression in the OsMIR168a mutants, suggesting OsMIR168a exerts a major transcriptional regulatory role, likely through its potential target genes such as OsAGO1s and OsAGO18. KEGG enrichment analysis of these differentially expressed genes pointed to OsMIR168a’s involvement in important processes such as plant hormone signalling transduction and plant–pathogen interaction. These data collectively support that the complex regulation module of OsMIR168a‐OsAGO1/OsAGO18‐miRNAs‐target genes contributes to agronomically important traits, which sheds light on miRNA‐mediated crop breeding.

Abstract BackgroundGenerally, the treatment of recurrent anterior shoulder instability is a challenge in the orthopedics with various treatment methods. There is a high recurrence rate for those patients with high activity and glenoid bone lesion less than 20% after Bankart procedure. The authors present a novel surgical technique using autologous osteochondral transplantation (AOT) method for recurrent anterior shoulder instability.MethodsBetween 2019 to 2021, 7 patients (five man and two women; mean age 35.1 years (range 17–55 years)) with recurrent anterior shoulder instability and glenoid bone lesion of 20% or less were treated with AOT method. All patients were available for follow-up at a mean of 25.4 months (range, 16 to 32 months), including Rowe score, Oxford Shoulder Score (OSS), Simple Shoulder Test (SST), and 3-dimensional computed tomography examination.ResultsThe mean preoperative and postoperative Rowe score were calculated to be 25.7 ± 6.7 (range, 20–35) and 90.6 ± 2.4 (range, 85–95), respectively (p < 0.01). The mean preoperative and postoperative Oxford score were 36.4 ± 5.6 (range, 30–40) and 54.6 ± 2.4 (range, 50–57), respectively (p < 0.01). The mean preoperative and postoperative SST score were 6.9 ± 0.7 (range, 6–8) and 11.5 ± 0.7 (range, 11–12), respectively (p < 0.01). The average final forward flexion was 176° (affected shoulder), compared with 177° on the non-affected shoulder (P = 0.81). The average final abduction in external rotation was 86.6° (affected shoulder), compared with 89° on the non-affected shoulder (P = 0.31). Analysis of Computed Tomography (CT) data at an average 1 years postoperative showed that a mean glenoid bony gain of 16.7% was observed (range, 11.2%-19%, SD 3.6).ConclusionThis technique can be a useful option, particularly in patients with glenoid bone defect less than 20%. In addition, AOT technique may be considered as alternative to the Latarjet procedure. Nonetheless, further biomechanical and clinical studies are needed to determine the effect of this procedure to more commonly utilized techniques.Level of EvidenceLevel IV; Case series

The complex blood environment, heterogenic enhanced permeability and retention (EPR) effect, and dense matrix comprise the primary “leakage obstacles” impeding specific accumulation and penetration of nanodrugs against solid tumors, thus forming a key bottleneck for their clinical application. Herein, we present a biomineralization-inspired dasatinib (DAS) nanodrug (CIPHD/DAS) that sequentially permeates all of the abovementioned hindrances for efficient treatment of solid tumors. CIPHD/DAS exhibited a robust hybrid structure constructed from an iRGD-modified hyaluronic acid-deoxycholic acid organic core and a calcium phosphate mineral shell. In vitro and in vivo data demonstrated the mechanism of sequential tumoral infiltration was based on mineral-stiffened blood circulation with decreased premature drug leakage, iRGD-endowed tumor-specific transendothelial transport for “first-order promotion of accumulation” and DAS-mediated restoration of fibrotic stromal homeostasis for “second-order promotion of penetration”. Resultantly, CIPHD/DAS showed remarkable distal drug availability in desmoplastic 4T1/CAFs orthotropic mouse models and significantly suppressed tumor growth and metastasis. This optimized strategy with sequential permeabilization of the capital “leakage obstacles” validates a promising paradigm to conquer the “impaired delivery and penetration” associated bottleneck of nanodrugs in the clinical treatment of solid tumors.

The rate of rotator cuff injury repair and retear is high in elderly patients due to the combination of different degrees of osteoporosis. To solve this problem, many surgeons try to reduce retear rate of rotator cuff injuries in these patients by increasing the initial fixation strength of anchors and changing local bone conditions. The rapid advances of tissue engineering have made it possible to use growth factors as an aid. However, repair of rotator cuff injury with osteoporosis is still a great challenge for clinical workers. How to better increase anchor fixation strength, improve micro-environment of tendon and bone healing, reduce the rotator cuff retear rate have become the research focus in recent years. The paper reviewed literatures on the relationshipbetween osteoporosis and rotator cuff injury, effect of osteoporosis in rotator cuff tendon healing, methods of reducing osteoporosis on rotator cuff tendon healing, in order to guide clinical treatment, improve operative effect and postoperative satisfaction.

Retraction of ‘A multifunctional self-dissociative polyethyleneimine derivative coating polymer for enhancing the gene transfection efficiency of DNA/polyethyleneimine polyplexes in vitro and in vivo’ by Cheng Wang, et al., Polym. Chem., 2015, 6, 780–796.

Modulation of tumor microenvironment (TME) has been indicated as an approach to improve efficacy of cancer therapy. Here, we proposed a nano co-delivery based combination therapy of paclitaxel (PTX) and silybin (SB) which can employ the synergistic effects through chemotherapy sensitization and microenvironment modulation. A dextran-based amphiphilic polymer (Dex-DOCA) was successfully developed for in vivo co-delivery and thus “synchronizing” the biodistribution, transport and release of PTX and SB. Resultantly, Dex-DOCA exhibited an excellent encapsulating efficiency for both PTX and SB with adjustable loading ratio for an optimal synergistic antitumor activity. Moreover, the co-loaded nanoparticles efficiently discharged the two drugs at the prospective dosage ratio specifically in acid endo/lysosome mimic environments. The results of in vitro cytotoxicity and cell apoptosis assays further confirmed the SB sensitized PTX potency. Finally, in vivo investigation demonstrated that the co-loaded nanoparticles could effectively accumulate in tumor sites by passive targeting, and inhibit tumor growth through an enhanced intratumoral penetration (resulted from stromal components eradication and tumor vessels normalization associated TME modulation), as well as a sensitization effect of SB on PTX cytotoxic chemotherapy.

Poor tumor penetration is a major challenge for the use of nanoparticles in anticancer therapy. Moreover, the inability to reach hypoxic tumor cells that are distant from blood vessels results in inadequate exposure to antitumor therapeutics and contributes to development of chemoresistance and increased metastasis. In the present study, we developed iRGD-modified nanoparticles for simultaneous tumor delivery of a photosensitizer indocyanine green (ICG) and hypoxia-activated prodrug tirapazamine (TPZ). The iRGD-modified nanoparticles loaded with ICG and TPZ showed significantly improved penetration in both 3D tumor spheroids in vitro and orthotopic breast tumors in vivo. ICG-mediated photodynamic therapy upon irradiation with a near-IR laser induced hypoxia, which activated antitumor activity of the codelivered TPZ for synergistic cell-killing effect. In vivo studies demonstrated that the nanoparticles could efficiently deliver the drug combination in 4T1 orthotopic tumors. Primary tumor growth and metast...

Neutrophil membrane-functionalized black phosphorus achieved a positive feedback loop in a continuous “administrated-therapy” circle to progressively improve the tumor therapeutic efficiency.

Background: Lung cancer is the primary cause of cancer-related death worldwide. A redox-sensitive nanocarrier system was developed for tumor-targeted drug delivery and sufficient drug release of the chemotherapeutic agent paclitaxel (PTX) for improved lung cancer treatment. Methods: The redox-sensitive nanocarrier system constructed from a hyaluronic acid-disulfide-vitamin E succinate (HA-SS-VES, HSV) conjugate was synthesized and PTX was loaded in the delivery system. The physicochemical properties of the HSV nanoparticles were characterized. The redox-sensitivity, tumor-targeting and intracellular drug release capability of the HSV nanoparticles were evaluated. Furthermore, in vitro and in vivo antitumor activity of the PTX-loaded HSV nanoparticles was investigated in a CD44 over-expressed A549 tumor model. Results: This HSV conjugate was successfully synthesized and self-assembled to form nanoparticles in aqueous condition with a low critical micelle concentration of 36.3 mu g mL(-1). Free PTX was successfully entrapped into the HSV nanoparticles with a high drug loading of 33.5% (w/w) and an entrapment efficiency of 90.6%. Moreover, the redox-sensitivity of the HSV nanoparticles was confirmed by particle size change of the nanoparticles along with in vitro release profiles in different reducing environment. In addition, the HA-receptor mediated endocytosis and the potency of redox-sensitivity for intracellular drug delivery were further verified by flow cytometry and confocal laser scanning microscopic analysis. The antitumor activity results showed that compared to redox-insensitive nanoparticles and Taxol (R), PTX-loaded redox-sensitive nanoparticles exhibited much greater in vitro cytotoxicity and apoptosis-inducing ability against CD44 over-expressed A549 tumor cells. In vivo, the PTX-loaded HSV nanoparticles possessed much higher antitumor efficacy in an A549 mouse xenograft model and demonstrated improved safety profile. In summary, our PTX-loaded redox-sensitive HSV nanoparticles demonstrated enhanced antitumor efficacy and improved safety of PTX. Conclusion: The results of our study indicated the redox-sensitive HSV nanoparticle was a promising nanocarrier for lung cancer therapy.

Photothermal therapy is a promising approach for antitumor application although regrettably restricted by available photothermal agents. Physical entrapment of organic near-infrared dyes into nanosystems was extensively studied to reverse the dilemma. However, problems still remained, such as drug bursting and leakage. We developed here an amphiphilic prodrug conjugate by chemically modifying indocyanine green derivative (ICG-COOH) and paclitaxel (PTX) to hyaluronic acid (HA) backbone for integration of photothermal-chemotherapy and specific tumor imaging. The prepared ICG-HA-PTX conjugates could self-assemble into nanomicelles to improve the stability and reduce systemic toxicity of the therapeutic agents. The high local concentration of ICG-COOH in nanomicelles resulted in fluorescence self-quenching, leading to no fluorescence signal being detected in circulation. When the nanomicelles reached the tumor site via electron paramagnetic resonance effect and HA-mediated active targeting, the overexpressed esterase in tumor cells ruptured the ester linkage between drugs and HA, achieving tumor-targeted therapy and specific imaging. A series of in vitro and in vivo experiments demonstrated that the easily prepared ICG- HA-PTX nanomicelles with high stability, smart release behavio r, and excellent tumor targeting ability showed formidable synergy in tumor inhibition, which provided new thoughts in developing an organic near-infrared-dye-based multifunctional delivery system for tumor theranostics.