Rapamycin facilitates the tendon-bone interface healing in an aging rat model of chronic rotator cuff injury.

BACKGROUND: Tendon-bone interface (TBI) healing in chronic rotator cuff injury (CRCI) in older individuals is a common clinical challenge due to cellular senescence, as well as decreased tissue repair and regeneration. Many studies have demonstrated the anti-aging, improved tissue repair, and bone regeneration properties of rapamycin (RPM) in multiple age-related diseases. This study aimed to explore the effects of RPM on TBI healing after CRCI in an aging rat model. METHODS: A CRCI model was established in 60 Sprague-Dawley rats (24 months old). Rats were then randomly allocated into the control, 0.1 µg RPM, and 1 µg RPM groups. At 4 and 8 weeks post-reconstructive surgery, the supraspinatus tendon-humerus complexes were harvested for biomechanical, microimaging, histological, and immunohistochemical evaluations. RESULTS: Biomechanical testing results demonstrated that the failure load, ultimate strength, and stiffness of the two RPM groups were significantly higher than those of the control group at 4 and 8 weeks postoperatively. Microradiographically, both RPM groups had significantly higher values of bone mineral density and the ratio of trabecular bone volume to total volume than controls at each time point. Moreover, the RPM groups had higher histological scores and showed better regenerated TBI, characterized by better organizational tissue, more fibrocartilage cells, and more bone formation. Immunohistochemical evaluations showed that RUNX2-, SOX9-, and SCX-positive cells were significantly more in the two RPM groups than in the controls at each time point. CONCLUSIONS: RPM may effectively enhance CRCI healing after reconstruction by facilitating osteogenesis, tenogenesis, and fibrocartilage reformation at the TBI, as well as improving biomechanical properties.

Controlled-release hydrogel loaded with magnesium-based nanoflowers synergize immunomodulation and cartilage regeneration in tendon-bone healing.

Tendon-bone interface injuries pose a significant challenge in tissue regeneration, necessitating innovative approaches. Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries. In this study, we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions (Mg2+). We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles (Mg-PC) through a self-assembly process and integrated them into a two-component hydrogel. The hydrogel was composed of dopamine-modified hyaluronic acid (Dop-HA) and F127. To ensure controlled release and mitigate the "burst release" effect of Mg2+, we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel. This crosslinking strategy extended the release window of Mg2+ concentrations for up to 56 days. The resulting hydrogel (Mg-PC@Dop-HA/F127) exhibited favorable properties, including injectability, thermosensitivity and shape adaptability, making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites. Furthermore, the hydrogel sustained the release of Mg2+ and Procyanidins, which attracted mesenchymal stem and progenitor cells, alleviated inflammation, and promoted macrophage polarization towards the M2 phenotype. Additionally, it enhanced collagen synthesis and mineralization, facilitating the repair of the tendon-bone interface. By incorporating multilevel metal phenolic networks (MPN) to control ion release, these hybridized hydrogels can be customized for various biomedical applications.

A modular hydrogel bioink containing microsphere-embedded chondrocytes for 3D-printed multiscale composite scaffolds for cartilage repair.

Articular cartilage tissue engineering is being considered an alternative treatment strategy for promoting cartilage damage repair. Herein, we proposed a modular hydrogel-based bioink containing microsphere-embedded chondrocytes for 3D printing multiscale scaffolds integrating the micro and macro environment of the native articular cartilage. Gelatin methacryloyl (GelMA)/alginate microsphere was prepared by a microfluidic approach, and the chondrocytes embedded in the microspheres remained viable after being frozen and resuscitated. The modular hydrogel bioink could be printed via the gel-in-gel 3D bioprinting strategy for fabricating the multiscale hydrogel-based scaffolds. Meanwhile, the cells cultured in the scaffolds showed good proliferation and differentiation. Furthermore, we also found that the composite hydrogel was biocompatible in vivo. These results indicated that the modular hydrogel-based bioinks containing microsphere-embedded chondrocytes for 3D printing multiscale scaffolds could provide a 3D multiscale environment for enhancing cartilage repairing, which would be encouraging considering the numerous alternative applications in articular cartilage tissue engineering.

1D Gradient-Weighted Class Activation Mapping, Visualizing Decision Process of Convolutional Neural Network-Based Models in Spectroscopy Analysis.

Being characterized by the self-adaption and high accuracy, the deep learning-based models have been widely applied in the 1D spectroscopy-related field. However, the "black-box" operation and "end-to-end" working style of the deep learning normally bring the low interpretability, where a reliable visualization is highly demanded. Although there are some well-developed visualization methods, such as Class Activation Mapping (CAM) and Gradient-weighted Class Activation Mapping (Grad-CAM), for the 2D image data, they cannot correctly reflect the weights of the model when being applied to the 1D spectral data, where the importance of position information is not considered. Here, aiming at the visualization of Convolutional Neural Network-based models toward the qualitative and quantitative analysis of 1D spectroscopy, we developed a novel visualization algorithm (1D Grad-CAM) to more accurately display the decision-making process of the CNN-based models. Different from the classical Grad-CAM, with the removal of the gradient averaging (GAP) and the ReLU operations, a significantly improved correlation between the gradient and the spectral location and a more comprehensive spectral feature capture were realized for 1D Grad-CAM. Furthermore, the introduction of difference (purity or linearity) and feature contribute in the CNN output in 1D Grad-CAM achieved a reliable evaluation of the qualitative accuracy and quantitative precision of CNN-based models. Facing the qualitative and adulteration quantitative analysis of vegetable oils by the combination of Raman spectroscopy and ResNet, the visualization by 1D Grad-CAM well reflected the origin of the high accuracy and precision brought by ResNet. In general, 1D Grad-CAM provides a clear vision about the judgment criterion of CNN and paves the way for CNN to a broad application in the field of 1D spectroscopy.

CholecTriplet2021: A benchmark challenge for surgical action triplet recognition.

Context-aware decision support in the operating room can foster surgical safety and efficiency by leveraging real-time feedback from surgical workflow analysis. Most existing works recognize surgical activities at a coarse-grained level, such as phases, steps or events, leaving out fine-grained interaction details about the surgical activity; yet those are needed for more helpful AI assistance in the operating room. Recognizing surgical actions as triplets of combination delivers more comprehensive details about the activities taking place in surgical videos. This paper presents CholecTriplet2021: an endoscopic vision challenge organized at MICCAI 2021 for the recognition of surgical action triplets in laparoscopic videos. The challenge granted private access to the large-scale CholecT50 dataset, which is annotated with action triplet information. In this paper, we present the challenge setup and the assessment of the state-of-the-art deep learning methods proposed by the participants during the challenge. A total of 4 baseline methods from the challenge organizers and 19 new deep learning algorithms from the competing teams are presented to recognize surgical action triplets directly from surgical videos, achieving mean average precision (mAP) ranging from 4.2% to 38.1%. This study also analyzes the significance of the results obtained by the presented approaches, performs a thorough methodological comparison between them, in-depth result analysis, and proposes a novel ensemble method for enhanced recognition. Our analysis shows that surgical workflow analysis is not yet solved, and also highlights interesting directions for future research on fine-grained surgical activity recognition which is of utmost importance for the development of AI in surgery.

Analysis of Therapeutic Effect and Influencing Factors of Ultrasound-Guided Radiofrequency Ablation in the Treatment of Papillary Thyroid Microcarcinoma.

OBJECTIVES: The current study sought to explore the effects of ultrasound (US)-guided radiofrequency ablation (RFA) on papillary thyroid microcarcinoma (PTMC) and influencing factors. METHODS: PTMC patients were assigned to observation (US-guided RFA) and control (surgical operation) groups. A series of operation-related indexes (operation time, intraoperative bleeding, wound closure time, hospital stay, and expenses), visual analogue scale score, lesion size, and thyroid function-related indexes (thyroid-stimulating hormone [TSH], free triiodothyronine*** [FT3], free thyroxine [FT4]), inflammatory factors, and thyroglobulin antibody (TgAb) were assessed and compared. After a 6-month follow-up period, the complications and recurrence were recorded, in addition to analyses of postoperative recurrence cumulative incidence and evaluation of recurrence risk factors. RESULTS: Operation-related indexes of the observation group were relatively decreased compared with the control group. In addition, the lesion volume in the observation group was lower compared to that in the control group at the 6th month after operation, whereas the volume reduction rate was higher. There were no significant differences in regard to thyroid function-related indexes in the observation group before/after operation. After operation, serum TSH levels and inflammatory factors, and TgAb levels were all diminished, while the FT3 and FT4 levels were both elevated in the observation group relative to the control group, and postoperative recurrence cumulative incidence was lower in the observation group. TSH and TgAb were established as the independent risk factors for recurrence after RFA in PTMC patients. CONCLUSIONS: Our findings highlighted that US-guided RFA exhibits better efficacy, safety, and postoperative recovery and lower recurrence risk for PTMC.

Gliotoxin, a natural product with ferroptosis inducing properties.

As one of the mycotoxins produced by Aspergillus fumigatus, gliotoxin has a variety of pharmacological effects, such as anti-tumor, antibacterial, immunosuppressive. Antitumor drugs induce tumor cell death in several forms, including apoptosis, autophagy, necrosis and ferroptosis. Ferroptosis is a recently identified unique form of programmed cell death characterized by iron-dependent accumulation of lethal lipid peroxides, which induces cell death. A large amount of preclinical evidence suggests that ferroptosis inducers may enhance the sensitivity of chemotherapy and the induction of ferroptosis may be an effective therapeutic strategy to prevent acquired drug resistance. In our study, gliotoxin was characterized as a ferroptosis inducer and showed strong anti-tumor activity with IC50 of 0.24 µM and 0.45 µM in H1975 and MCF-7 cells at 72 h, respectively. Gliotoxin may provide a new natural template for the designing of ferroptosis inducers.

6-Heterocyclic carboxylic ester derivatives of gliotoxin lead to LSD1 inhibitors in gastric cancer cells.

Gliotoxin is a representative compound of the epipolythiodioxopiperazine (ETP) class of fungal metabolites. Histone Lysine Specific Demethylase 1 (LSD1) is highly expressed in a variety of cancers. Herein, a series of 6-heterocyclic carboxylic ester derivatives of gliotoxin was designed and synthesized as new LSD1 inhibitors and their biological evaluations in human gastric MGC-803 and HGC-27 cells were carried out. All of the derivatives effectively suppressed the enzymatic activities of LSD1. In particular, compound 4e exhibited excellent LSD1 inhibition with IC50 = 62.40 nM, as well as anti-proliferation against MGC-803 and HGC-27 cells with IC50 values of 0.31 µM and 0.29 µM, respectively. 4e also had a remarkable capacity to inhibit the colony formation, suppress migration and induce the apoptosis of these two cancer cell lines. In sum, our findings identified and characterized the 6-heterocyclic carboxylic ester derivatives of gliotoxin as potent and cellular active LSD1 inhibitors, which may provide a novel chemotype of LSD1 inhibitors for gastric cancer treatment.

Diagnostic Value of Color Doppler Ultrasonography in Subacute Thyroiditis.

In order to explore the clinical effect of color Doppler ultrasonography in the diagnosis of subacute thyroiditis, a method for the diagnosis of subacute thyroiditis by color Doppler ultrasonography was proposed. From November 2019 to November 2020, 90 patients with subacute thyroiditis in our hospital were selected as the experimental group; 90 healthy people were selected as the control group during the same period. Both groups were diagnosed by color Doppler ultrasonography and compared. The experimental results showed that patients with subacute thyroiditis showed mild to moderate enlargement of the involved thyroid gland, and local or diffuse inhomogeneous hypoechoic areas may appear in bilateral or unilateral thyroid glands: irregular edges, unclear boundaries, no "ball feel," mottled changes, and accompanied by tenderness. The blood flow signal around the hypoechoic area is rich, and the internal blood flow signal is less. There was no significant increase in the blood flow velocity of the superior thyroid artery on the affected side. Color Doppler ultrasound not only is simple, economical, and non-invasive but also has a good diagnostic accuracy for subacute thyroiditis, which can provide an important basis for clinical diagnosis and treatment and is worthy of popularization and application.

Spatio-Temporal Causal Transformer for Multi-Grained Surgical Phase Recognition.

Automatic surgical phase recognition plays a key role in surgical workflow analysis and overall optimization in clinical work. In the complicated surgical procedures, similar inter-class appearance and drastic variability in phase duration make this still a challenging task. In this paper, a spatio-temporal transformer is proposed for online surgical phase recognition with different granularity. To extract rich spatial information, a spatial transformer is used to model global spatial dependencies of each time index. To overcome the variability in phase duration, a temporal transformer captures the multi-scale temporal context of different time indexes with a dual pyramid pattern. Our method is thoroughly validated on the public Cholec80 dataset with 7 coarse-grained phases and the CATARACTS2020 dataset with 19 fine-grained phases, outperforming state-of-the-art approaches with 91.4% and 84.2% accuracy, taking only 24.5M parameters.

Effect of secretory leucocyte protease inhibitor on early tendon-to-bone healing after anterior cruciate ligament reconstruction in a rat model.

AIMS: To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction. METHODS: In vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing. RESULTS: SLPI improved the migration ability of BMSCs and upregulated the expression of genes related to osteogenic differentiation of BMSCs in vitro. In vivo, the SLPI group had higher histological scores at the tendon-bone interface by histological evaluation. Micro-CT showed more new bone formation and bone ingrowth around the grafted tendon in the SLPI group. Evaluation of the healing strength of the tendon-bone connection showed that the SLPI group had a higher maximum failure force and stiffness. CONCLUSION: SLPI can effectively promote early tendon-to-bone healing after ACL reconstruction via enhancing the migration and osteogenic differentiation of BMSCs. Cite this article: Bone Joint Res 2022;11(7):503-512.

Nanolayer-Constructed TiO(OH)2 Microstructures for the Efficiently Selective Removal of Cationic Dyes via an Electrostatic Interaction and Adsorption Mechanism.

Efficient removal of organic dyes from contaminated water has become a great challenge and urgent work due to increasingly serious environmental problems. Here, we have for the first time prepared nanolayer-constructed TiO(OH)2 microstructures which can present negative charge by deprotonation of the hydroxyl group to efficiently and selectively remove cationic dyes from aqueous solution through electrostatic interaction and an attraction mechanism. The nanolayer-constructed TiO(OH)2 microstructures achieve a high adsorption capacity of 257 mg g-1 for methylene blue (MB). The adsorption kinetics, thermodynamics, and isotherms of MB over the TiO(OH)2 microstructures have been studied systemically. The experimental measurements and corresponding analyses demonstrate that the adsorption process of MB on TiO(OH)2 microstructures follows a kinetic model of pseudo-second-order adsorption, agrees well with the Langmuir isotherm mode, and is a spontaneous and exothermic physisorption. Fourier transform infrared (FT-IR) spectra confirm that the prepared TiO(OH)2 microstructures possess hydroxyl group which can deprotonate to present negative charge in solution. Further experimental studies evidently demonstrate that the TiO(OH)2 microstructures also can remove other cationic dyes with positive charge such as basic yellow 1, basic green 4, and crystal violet but cannot adsorb anionic dye of methyl orange (MO) with negative charge in aqueous solution. The measurements for FT-IR spectra and the adsorption of cationic and anionic dyes evidently reveal that the adsorption of cationic dyes over the TiO(OH)2 microstructures is achieved by the electrostatic interaction and attraction between TiO(OH)2 and the dye. This work opens a strategy for the design of new absorbents to efficiently remove organic dyes from aqueous solution through an electrostatic attraction-driven adsorption process.

Mechanical stimulation promotes enthesis injury repair by mobilizing Prrx1+ cells via ciliary TGF-ß signaling.

Proper mechanical stimulation can improve rotator cuff enthesis injury repair. However, the underlying mechanism of mechanical stimulation promoting injury repair is still unknown. In this study, we found that Prrx1+ cell was essential for murine rotator cuff enthesis development identified by single-cell RNA sequence and involved in the injury repair. Proper mechanical stimulation could promote the migration of Prrx1+ cells to enhance enthesis injury repair. Meantime, TGF-ß signaling and primary cilia played an essential role in mediating mechanical stimulation signaling transmission. Proper mechanical stimulation enhanced the release of active TGF-ß1 to promote migration of Prrx1+ cells. Inhibition of TGF-ß signaling eliminated the stimulatory effect of mechanical stimulation on Prrx1+ cell migration and enthesis injury repair. In addition, knockdown of Pallidin to inhibit TGF-ßR2 translocation to the primary cilia or deletion of Ift88 in Prrx1+ cells also restrained the mechanics-induced Prrx1+ cells migration. These findings suggested that mechanical stimulation could increase the release of active TGF-ß1 and enhance the mobilization of Prrx1+ cells to promote enthesis injury repair via ciliary TGF-ß signaling.

Efficient pollutant degradation under ultraviolet to near-infrared light irradiation and dark condition using CuSe nanosheets: Mechanistic insight into degradation.

The hydrothermally prepared two-dimensional copper selenide nanosheets (2D CuSe NSs) have been employed for the first time to degrade rhodamine B (RhB) in the presence of hydrogen peroxide (H2O2) under ultraviolet to near-infrared (NIR) light irradiation and dark condition. The experimental measurements demonstrate that 99.7% RhB is degraded under NIR light irradiation for 120 min. Moreover, the experimental tests clearly demonstrate that the 2D CuSe NSs display excellent ability to degrade RhB under dark condition. The different degradation mechanisms under the light irradiation and dark condition have been revealed by the experimental tests through the investigation of H2O2 role and the evaluation of hydroxyl radicals (•OH) and H2O2 concentration during the degradation reaction. Under light irradiation, the H2O2 traps the photogenerated electrons of the CuSe to generate •OH and hydroxide ion (OH-), and the holes react with OH- to produce •OH, making RhB to be degraded efficiently. Under dark conduction, the 2D CuSe NSs react with H2O2 to exhibit Fenton-like process to degrade RhB with a degradation rate of 90.0% within 120 min. This work opens a pathway for developing nanostructures with full-solar-responsive and strong near-infrared photocatalytic activity as well as Fenton-like reaction to efficiently degrade pollutants under light irradiation and dark condition.

Calcitonin Gene-Related Peptide Influences Bone-Tendon Interface Healing Through Osteogenesis: Investigation in a Rabbit Partial Patellectomy Model.

BACKGROUND: Calcitonin gene-related peptide (CGRP), which has been shown to play an important role in osteogenesis during fracture repair, is also widely distributed throughout the tendon and ligament. Few studies have focused on the role of CGRP in repair of the bone-tendon interface (BTI). PURPOSE: To explore the effect of CGRP expression on BTI healing in a rabbit partial patellectomy model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 60 mature rabbits were subjected to a partial patellectomy and then randomly assigned to CGRP, CGRP-antagonist, and control groups. In the CGRP-antagonist group, the CGRP receptor antagonist BIBN4096BS was administered to block CGRP receptors. The patella-patellar tendon complex was harvested at 8 and 16 weeks postoperatively and subjected to radiographic, microlaser Raman spectroscopy, histologic, and biomechanical evaluation. RESULTS: Radiographic data showed that local CGRP expression improved the growth parameters of newly formed bone, including area and volumetric bone mineral density (P < .05 for both). Raman spectroscopy revealed that the relative bone mineral composition increased in the CGRP group compared with in the control group and the CGRP-antagonist group (P < .05 for both). Histologic testing revealed that the CGRP group demonstrated better integration, characterized by well-developed trabecular bone expansion from the residual patella and marrow cavity formation, at the 8- and 16-week time points. Mechanical testing demonstrated that the failure load, ultimate strength, and stiffness in the CGRP group were significantly higher than those in the control group (P < .05 for all), whereas these parameters in the CGRP-antagonist group were significantly lower compared with those in the control group at 16 weeks after surgery (P < .05 for all). CONCLUSION: Increasing the local concentration of CGRP in the early stages of BTI healing enhanced osteogenesis in a rabbit partial patellectomy model and promoted healing of the BTI injury, whereas treatment using a CGRP antagonist had the opposite effect. However, exogenous CGRP expression did not induce novel bone remolding. CLINICAL RELEVANCE: CGRP may have potential as a new therapy for BTI injuries or may be added to postoperative regimens to facilitate healing.

Nanomaterials in Water Applications: Adsorbing Materials for Fluoride Removal.

Fluoride is an important pollutant in many countries, such as China, India, Australia, the United States, Ethiopia, etc [...].

Recombinant human bone morphogenetic protein-4 enhances tendon-to-bone attachment healing in a murine model of rotator cuff tear.

BACKGROUND: Injuries of tendon-to-bone attachments (TBA) are common clinical challenges. Bone morphogenetic protein-4 (BMP-4) is potent in chondrogenesis. However, studies focusing on the influence of BMP-4 on the healing of TBA are scarce. Thus, this study's objective was to explore the effect of BMP-4 on the healing of TBA in a murine model of rotator cuff tear. METHODS: An injury model of the supraspinatus tendon (SST) insertion was established on a total of 120 mature C57 black (BL)/6 mice (12 weeks old), who were then randomly allocated into 3 groups: BMP-4, noggin (an inhibitor of all BMP activities), and control, At weeks 2 and 4 after surgery, the supraspinatus tendon-humerus complexes (SSTHC) were harvested for microradiographic, histologic, immunofluorescent, and biomechanical evaluations. RESULTS: Radiographic data showed that BMP-4 was able to improve the quality of subchondral bone, manifested as higher bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and lower trabecular spacing (Tb.Sp). Histologically, the BMP-4 group at week-2 and -4 showed a better TBA healing interface, characterized by better organizational integration and remodeling, thicker fibrocartilage layer, and more fibrocartilage cells. Immunofluorescence evaluation demonstrated that the number of SOX 9 positive cells in the BMP-4 group was significantly more than that in the control or noggin groups at postoperative weeks 2 and 4 (P<0.05 for all). Mechanical testing results at postoperative weeks 4 demonstrated the failure load, and stiffness in the BMP-4 group were significantly higher (P<0.05 for both), while in the noggin group were significantly lower (P<0.05 for both), compared to the control group. CONCLUSIONS: The BMP-4 might enhance TBA healing by promoting the regeneration of fibrocartilaginous enthesis and mineralization, while this process was inhibited by noggin. Thus, BMP-4 may be a potential therapy to augment TBA healing and finally lead to more rapid rehabilitation and reduce recurrent injury risk.

Effect of Exercise Intensity on the Healing of the Bone-Tendon Interface: A Mouse Rotator Cuff Injury Model Study.

BACKGROUND: Injuries at the bone-tendon interface (BTI) are common findings in clinical practice. Rehabilitation procedures after BTI surgery are important but are controversial. PURPOSE: To investigate the effects of different exercise intensities on BTI healing by means of an established mouse rotator cuff injury model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 150 specific pathogen free male C57BL/6 mice, with supraspinatus insertion injury, were randomly assigned to 1 of 5 groups according to postoperative rehabilitation of different exercise intensities: (1) control group, (2) low-intensity exercise group, (3) moderate-intensity exercise group, (4) high-intensity exercise group, and (5) increasing-intensity exercise group (IG). The specimens were harvested 4 or 8 weeks postoperatively for microarchitectural, histological, molecular biological, and mechanical evaluations. RESULTS: Histological test results showed that the degrees of tissue fusion and polysaccharide protein distribution at the healing interface at 4 and 8 weeks after surgery were significantly better in the IG than in the other 4 groups. Synchrotron radiation micro-computed tomography showed that the quantity of subchondral bone at the enthesis (bone volume/total volume fraction, trabecular thickness, trabecular number) was higher and trabecular separation was lower in the IG than in the other 4 groups. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that the healing interface in the IG expressed more transcription factors, such as sox 9, runx 2, and scleraxis, than the interfaces in the other groups. Although no significant difference was seen in the cross-sectional area between the groups at postoperative weeks 4 and 8 (P > .05), the tensile load, ultimate strength, and stiffness of the specimens in the IG were significantly better than those in the other 4 groups (P < .05). CONCLUSION: The rehabilitation program with increasing-intensity exercise was beneficial for BTI healing. CLINICAL RELEVANCE: The results of this study provide evidence supporting the use of a simple and progressive exercise rehabilitation program after rotator cuff surgery.

Comparative validation of multi-instance instrument segmentation in endoscopy: Results of the ROBUST-MIS 2019 challenge.

Intraoperative tracking of laparoscopic instruments is often a prerequisite for computer and robotic-assisted interventions. While numerous methods for detecting, segmenting and tracking of medical instruments based on endoscopic video images have been proposed in the literature, key limitations remain to be addressed: Firstly, robustness, that is, the reliable performance of state-of-the-art methods when run on challenging images (e.g. in the presence of blood, smoke or motion artifacts). Secondly, generalization; algorithms trained for a specific intervention in a specific hospital should generalize to other interventions or institutions. In an effort to promote solutions for these limitations, we organized the Robust Medical Instrument Segmentation (ROBUST-MIS) challenge as an international benchmarking competition with a specific focus on the robustness and generalization capabilities of algorithms. For the first time in the field of endoscopic image processing, our challenge included a task on binary segmentation and also addressed multi-instance detection and segmentation. The challenge was based on a surgical data set comprising 10,040 annotated images acquired from a total of 30 surgical procedures from three different types of surgery. The validation of the competing methods for the three tasks (binary segmentation, multi-instance detection and multi-instance segmentation) was performed in three different stages with an increasing domain gap between the training and the test data. The results confirm the initial hypothesis, namely that algorithm performance degrades with an increasing domain gap. While the average detection and segmentation quality of the best-performing algorithms is high, future research should concentrate on detection and segmentation of small, crossing, moving and transparent instrument(s) (parts).

Metabolome Analysis Revealed the Mechanism of Exogenous Glutathione to Alleviate Cadmium Stress in Maize (Zea mays L.) Seedlings.

Cadmium (Cd) is one of the major heavy metal pollutants in the environment and imposes severe limitations on crop growth and production. Glutathione (GSH) plays an important role in plant Cd tolerance which is able to scavenge stresses-induced reactive oxygen species (ROS) and is involved in the biosynthesis of phytochelatins (PCs). Our previous study revealed that Cd stress affects maize growth, and the GSH treatment could relieve Cd stress in maize seedlings. In this study, we attempted to characterize the metabolomics changes in maize leaves and roots under Cd stress and exogenous GSH conditions. We identified 145 and 133 metabolites in the leaves and roots, respectively. Cd stress decreased the tricarboxylic acid cycle (TCA cycle) metabolism and increased the amino acid contents in the leaves, while it decreased the amino acid contents, increased the TCA cycle metabolism, the sugar contents, and shikimic acid metabolism in the roots. On the other hand, exogenous GSH increased the GSH content, changed the production of metabolites related to antioxidant systems (such as ascorbic acid-related metabolites and flavonoid-related metabolites), and alleviated lipid peroxidation, thereby alleviating the toxic effect of Cd stress on maize. These findings support the idea that GSH alleviates Cd-induced stress in maize and may help to elucidate the mechanism governing Cd-induced stress and the GSH-driven alleviation effect.