Single-Dose Radial Extracorporeal Shock Wave Therapy Modulates Inflammation During Meniscal Tear Healing in the Avascular Zone.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) promotes tissue healing by modulating inflammation, which has implications for meniscal tear healing in the avascular zone. PURPOSE: To evaluate the effects of a single dose of radial ESWT on the healing process and inflammation of the meniscus and knee joints after meniscal tears in the avascular zone. STUDY DESIGN: Controlled laboratory study. METHODS: Avascular tears were induced in the medial meniscus (MM) of 72 Sprague-Dawley rats. One week postoperatively, the rats received a single session of radial ESWT with a Power+ handpiece (ESWT group; n = 36) or with a fake handpiece (sham-ESWT group; n = 36). The rats were then euthanized at 2, 4, or 8 weeks postoperatively. The MMs were harvested for analysis of healing (hematoxylin-eosin, safranin O-Fast Green, and collagen type 2 staining) and inflammation (interleukin [IL]-1ß and IL-6 staining). Lateral menisci and synovia were obtained to evaluate knee joint inflammation (enzyme-linked immunosorbent assay of IL-1ß and IL-6). Cartilage degeneration was assessed in the femurs and tibial plateaus using safranin O-Fast Green staining. RESULTS: The ESWT group showed significantly better meniscal healing scores than the sham-ESWT group at 4 (P = .0066) and 8 (P = .0050) weeks postoperatively. The IL-1ß level was significantly higher in the sham-ESWT group than in the ESWT group at 2 (MM: P = .0009; knee joint: P = .0160) and 8 (MM: P = .0399; knee joint: P = .0001) weeks. The IL-6 level was significantly lower in the sham-ESWT group than in the ESWT group at 2 (knee joint: P = .0184) and 4 (knee joint: P = .0247) weeks but higher at 8 weeks (MM: P = .0169; knee joint: P = .0038). The sham group had significantly higher osteoarthritis scores than the ESWT group at 4 (tibial plateau: P = .0157) and 8 (femur: P = .0048; tibial plateau: P = .0359) weeks. CONCLUSION: A single dose of radial ESWT promoted meniscal tear healing in the avascular zone, modulated inflammatory factors in the menisci and knee joints in rats, and alleviated cartilage degeneration. CLINICAL RELEVANCE: Radial ESWT can be considered a potential option for improving meniscal tear healing in the avascular zone because of its ability to modulate inflammation.

Three-Dimensional Imaging and Quantitative Analysis of Blood Vessel Distribution in The Meniscus of Transgenic Mouse after Tissue Clearing.

OBJECTIVE: Blood supply to the meniscus determines its recovery and is a reference for treatment planning. This study aimed to apply tissue clearing and three-dimensional (3D) imaging in exploring the quantitative distribution of blood vessels in the mouse meniscus. MATERIALS AND METHODS: In this experimental study, tissue clearing was performed to treat the bilateral knee joints of transgenic mice with fluorescent vascular endothelial cells. Images were acquired using a light sheet microscope and the vascular endothelial cells in the meniscus was analysed using 3D imaging. Quantitative methods were employed to further analyse the blood vessel distribution in the mouse meniscus. RESULTS: The traditional three-equal-width division of the meniscus is as follows: the outer one-third is the red-red zone (RR), the inner one-third is the white-white zone (WW), and the transition area is the red-white zone (RW). The division revealed significant signal differences between the RW and WW (P<0.05) zones, but no significant differences between the RR and RW zones, which indicated that the division might not accurately reflect the blood supply of the meniscus. According to the modified division (4:2:1) in which significant differences were ensured between the adjacent zones, we observed that the width ratio of each zone was 38 ± 1% (RR), 24 ± 1% (RW), and 38 ± 2% (WW). Furthermore, the blood supply to each region was verified. The anterior region had the most abundant blood supply. The fluorescence count in the anterior region was significantly higher than in the central and posterior regions (P<0.05). The blood supply of the medial meniscus was superior to the lateral meniscus (P<0.05). CONCLUSION: Analysis of the blood supply to the mouse meniscus under tissue clearing and 3D imaging reflect quantitative blood vessel distribution, which would facilitate future evaluations of the human meniscus and provide more anatomical references for clinicians.

Regional Alterations of Macroscopy and Histology in Meniscus in an ACL Transection Rabbit Model.

BACKGROUND: Although meniscal injury is common after anterior cruciate ligament (ACL) injury, the underlying process in different meniscal regions remains unclear. PURPOSE: To investigate macroscopic and histological alterations in different meniscal regions in an ACL transection (ACLT) rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: ACLT was performed on New Zealand White rabbits. Both the medial meniscus (MM) and the lateral meniscus (LM) of the ACLT knees were obtained at 8 (n = 6) and 26 (n = 6) weeks postoperatively. MM and LM collected from nonoperated knees were considered 0 weeks (n = 6) postoperatively. Menisci were then divided into posterior, central, and anterior regions for macroscopic (width) and histological (hematoxylin and eosin, safranin O/fast green, collagen type 2 [COL2]) analysis. RESULTS: The macroscopic widths of MM and LM increased and then decreased over 26 weeks postoperatively, with all 3 MM widths at 8 weeks significantly wider than at 0 weeks (posterior: P < .01; central: P < .05; anterior: P < .05). In the MM, chondrocyte-like cell density increased and then decreased postoperatively, whereas in the LM, it decreased and then remained almost unchanged. Cell density was significantly higher in the central MM region at 8 weeks than at 0 weeks (P < .05). Glycosaminoglycan (GAG) and COL2 percentages of MM and LM decreased from 0 to 8 weeks and then returned to nearly normal levels at 26 weeks postoperatively. In the MM, the GAG percentage in the posterior (P < .05) and central (P < .01) regions and the COL2 percentage in the posterior region (P < .05) was significantly lower at 8 weeks than at 0 weeks. CONCLUSION: After ACLT in rabbit meniscus, the extracellular matrix (ECM) initially decreased and then increased to almost normal. Additionally, there were significant differences in the ECM percentage in the posterior and central regions of the MM in comparison with other meniscal regions between 0 and 8 weeks postoperatively. CLINICAL RELEVANCE: The results indicate that the time for meniscal injury after ACL injury is important, and attention should be paid to the posterior and central regions of the MM after ACLT.

Radial extracorporeal shockwave therapy reduces pain and promotes proximal tendon healing after rotator cuff repair: Randomized clinical trial.

BACKGROUND: Extracorporeal shockwave therapy (ESWT) is widely used to treat soft tissue disorders, but evidence for its application after rotator cuff (RC) repair is lacking. OBJECTIVES: To investigate the effect of ESWT on short-term functional and structural outcomes after RC repair. METHODS: Thirty-eight individuals were randomly assigned to the ESWT group (n = 19) or control group (n = 19) 3 months after RC repair. Both groups underwent 5 weeks of advanced rehabilitation and participants in the ESWT group additionally received 2000 pulses of shockwave therapy every week for 5 weeks. The primary outcome was pain measured on a visual analog scale (VAS). Secondary outcomes were range of motion (ROM), Constant score, University of California Los Angeles score (UCLA), American Shoulder and Elbow Surgeons form (ASES), and Fudan University shoulder score (FUSS). Changes in signal/noise quotient (SNQ), muscle atrophy and fatty infiltration were analyzed from MRI. All participants underwent clinical and MRI examinations 3 months (baseline) and 6 months (follow-up) post repair. RESULTS: A total of 32 participants completed all assessments. Pain and function improved in both groups. At 6 months post repair, pain intensity was lower and ASES scores higher in the ESWT than in the control group (all p-values < 0.01). SNQ near the suture anchor site decreased significantly from baseline to follow-up in the ESWT group (p = 0.008) and was significantly lower than that in the control group (p = 0.036). Muscle atrophy and the fatty infiltration index did not differ between groups. CONCLUSION: ESWT and exercise more effectively reduced early shoulder pain than rehabilitation alone and accelerated proximal supraspinatus tendon healing at the suture anchor site after RC repair. However, ESWT may not be more effective than advanced rehabilitation in terms of functional outcomes at the short-term follow-up.

Real-Time In Vivo Detection and Monitoring of Bacterial Infection Based on NIR-II Imaging.

Treatment according to the dynamic changes of bacterial load in vivo is critical for preventing progression of bacterial infections. Here, we present a lead sulfide quantum dots (PbS QDs) based second near-infrared (NIR-II) fluorescence imaging strategy for bacteria detection and real-time in vivo monitoring. Four strains of bacteria were labeled with synthesized PbS QDs which showed high bacteria labeling efficiency in vitro. Then bacteria at different concentrations were injected subcutaneously on the back of male nude mice for in vivo imaging. A series of NIR-II images taken at a predetermined time manner demonstrated changing patterns of photoluminescence (PL) intensity of infected sites, dynamically imaging a changing bacterial load in real-time. A detection limit around 102-104 CFU/ml was also achieved in vivo. Furthermore, analysis of pathology of infected sites were performed, which showed high biocompatibility of PbS QDs. Therefore, under the guidance of our developed NIR-II imaging system, real-time detection and spatiotemporal monitoring of bacterial infection in vivo can be achieved, thus facilitating anti-infection treatment under the guidance of the dynamic imaging of bacterial load in future.

Moxibustion for stable chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis.

BACKGROUND: There is no optimal treatment to alleviate the decline of lung function in the stable phase of chronic obstructive pulmonary disease (COPD). The effectiveness of moxibustion as an adjunctive treatment for COPD in the stable phase has been reported clinically, but the conclusions on efficacy and safety have not been unified. This study will systematically evaluate the efficacy and safety of moxibustion on the treatment of COPD in the stable phase, providing clinical-based evidence. METHODS: We will systematically search 7 literature databases and 2 clinical trial registration platforms. The searching time will be conducted from the establishment of databases to March 31, 2021, regardless of language. We will include the randomized controlled trial (RCT) evaluation of moxibustion combined with basic therapy vs basic therapy alone for the treatment of stable COPD. We will assess the risk of bias for individual RCTs using the Cochrane Handbook 5.1.0 evaluation tool. The primary outcome is forced expiratory volume in 1 second/forced vital capacity. The secondary outcomes include forced expiratory volume in 1 second, forced vital capacity, six-minute walking distance, COPD assessment test score, maximum ventilation, response to treatment, and incidence of adverse events. We will collect the effective data of individual RCT through systematic analysis of the random effect model. Heterogeneity will be tested by Cochran Q test and I-squared statistics. Two subgroup analyses will be performed to explore the sources of heterogeneity based on clinical experience. Excluding RCTs with a high risk of bias, fixed-effect model will be used for sensitivity analysis to test the robustness of the meta-analysis results. The publication bias will be assessed by funnel plot and Egger test. RESULTS: This study will provide systematic evidence on the efficacy and safety of moxibustion on the treatment of patients with stable COPD through strict quality assessment and reasonable data synthesis. We hope that the results will be submitted to a peer-reviewed journal for publication. CONCLUSION: This systematic review will provide the best current evidence for the adjuvant treatment of stable COPD with moxibustion. INPLASY REGISTRATION NUMBER: INPLASY202140047.

Using bioinformatics approach identifies key genes and pathways in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a chronic and irreversible respiratory disease with a high incidence worldwide and no specific treatment. Currently, the etiology and pathogenesis of this disease remain largely unknown. In main purpose of this study, bioinformatics analysis was used to uncover key genes and pathways related to idiopathic pulmonary fibrosis (IPF). Gene expression profiles of GSE2052 and GSE35145 were obtained. After combining the 2 chip groups; then, we normalized the data, eliminating batch difference. R software was used to process and to screen differentially expressed genes (DEGs) between the IPF and normal tissues. Then, functional enrichment analysis of these DEGs was carried out, and a protein-protein interaction network (PPI) was also constructed. A total of 276 DEGs (152 up and 134 down-regulated genes) were identified in the IPF lung samples. The PPI network was established with 227 nodes and 763 edges. The top 10 hub genes were CAM1, CDH1, CXCL12, JUN, CTGF, SERPINE1, CXCL1, EDN1, COL1A2, and SPARC. Analyzing the PPI network modules with close interaction, the 3 key modules in the whole PPI network were screened out. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched for the module containing DEGs contained the viral protein interaction with cytokine and the cytokine receptor, the TNF signaling pathway, and the chemokine signaling pathway. The identified key genes and pathways may play an important role in the occurrence and development of IPF, and may be expected to be biomarkers or therapeutic targets for the diagnosis of IPF.