Efficacy of Platelet-Rich Plasma Versus Placebo in the Treatment of Tendinopathy: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the efficacy of platelet-rich plasma (PRP) injections versus placebo in the treatment of tendinopathy. DATA SOURCES: We performed a systematic literature search in MEDLINE, Embase, Scopus, CINAHL, Cochrane Library, and ClinicalTrials.gov through November 2020 to identify randomized controlled trials (RCTs) that evaluated the clinical efficacy of PRP versus placebo for the treatment of tendinopathy. Outcomes were analyzed on an intention-to-treat basis with random-effects models. MAIN RESULTS: A total of 13 RCTs were included in this meta-analysis. The pooled analysis showed no significant difference in pain relief at 4 to 6 weeks (standard mean difference [SMD]: -0.18, 95% confidence intervals [CI]: -0.62 to 0.26), 12 weeks (SMD: -0.14, 95% CI: -0.55 to 0.26), and ≥24 weeks (SMD: -0.56, 95% CI: -1.16 to 0.05) or function improvement at 4 to 6 weeks (SMD: 0.11, 95% CI: -0.13 to 0.35), 12 weeks (SMD: 0.18, 95% CI: -0.13 to 0.49), and ≥24 weeks (SMD: 0.26, 95% CI: -0.14 to 0.66) for PRP compared with placebo in the treatment of tendinopathy. The sensitivity analysis indicated no significant difference in pain relief or function improvement at 12 weeks between PRP and placebo for different types of tendinopathies, treatment regimens, leukocyte concentrations, or cointerventions. CONCLUSIONS: Platelet-rich plasma injection was not found to be superior to placebo in the treatment of tendinopathy, as measured by pain relief and functional improvement at 4 to 6, 12, and ≥24 weeks.

Comparative Efficacy of Root Repair versus Partial Meniscectomy and Observation for Patients with Meniscus Root Tears.

The purpose of this study was to (1) compare the efficacy of root repair versus partial meniscectomy and observation for patients with meniscus root tears; (2) compare osteoarthritis (OA) progression and functional outcomes in patients with isolated repair and with adjuvant surgery; and (3) evaluate OA progression and functional outcomes after pullout repair or all-inside repair of meniscus root tears. We performed a systematic literature search in PubMed, Embase, Scopus, and the Cochrane Library up to September 1, 2020, to identify studies that evaluated the efficacy of root repair versus partial meniscectomy and observation in patients with meniscus root tears. Random-effects meta-analysis was used to pool data. A total of nine studies were included in the meta-analysis, with 485 patients comprising 238 in the root repair group, 113 in the partial meniscectomy group, and 134 in the observation group. The mean age of the patients ranged from 46.1 to 64.8 years. Compared with partial meniscectomy, root repair was associated with significantly lower postoperative Kellgren-Lawrence (K-L) grade (mean difference [MD]: -0.62, 95% confidence interval [CI]: -1.00 to -0.23) and progression to arthroplasty rate (odds ratio [OR]: 0.15, 95% CI: 0.04-0.60) at final follow-up. Compared with observation, root repair was associated with significantly lower arthroplasty rate (OR: 0.07, 95% CI: 0.01-0.44) and better International Knee Documentation Committee (IKDC) score (MD: 8.07, 95% CI: 0.72-15.41) at final follow-up. Moreover, significantly lower postoperative K-L grade and progression to arthroplasty rate, as well as higher IKDC and Lysholm scores were seen in favor of root repair in patients with isolated meniscus root tears. Additionally, significantly lower OA progression and higher function scores were found in favor of root repair when the tears were repaired with pullout technique. Current evidence indicates that root repair with pullout technique may be a better choice than partial meniscectomy and observation for patients with isolated meniscus root tears as measured by OA progression, progression to arthroplasty, as well as functional outcomes.

Regional brain dysfunction in insomnia after ischemic stroke: A resting-state fMRI study.

Objective: This study aimed to explore the abnormality of local brain function in patients with post-stroke insomnia (PSI) based on fMRI and explore the possible neuropathological mechanisms of insomnia in patients with PSI in combination with the Pittsburgh sleep quality index (PSQI) score and provide an objective evaluation index for the follow-up study of acupuncture treatment of PSI. Methods: A total of 27 patients with insomnia after stroke were enrolled, and the PSQI was used to evaluate their sleep status. Twenty-seven healthy participants who underwent physical examinations during the same period were selected as controls. Resting-state brain function images and structural images of the two groups of participants were collected, and the abnormal changes in the regional brain function in patients with PSI were analyzed using three methods: regional homogeneity (ReHo), the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF), and a correlation analysis with the PSQI scale score. Results: Compared with the HCs, the ReHo values of the PSI group in the bilateral lingual gyrus, right cuneus, right precentral and postcentral gyri were significantly lower, and the ReHo values of the left supramarginal gyrus were significantly higher. In the PSI group, the ALFF values in the bilateral lingual gyrus were significantly decreased, whereas those in the bilateral middle temporal gyrus, right inferior temporal gyrus, right inferior frontal gyrus, right limbic lobe, right precuneus, left posterior cingulate gyrus, and left middle occipital gyrus were significantly increased. Compared with HCs, the fALFF values of the bilateral lingual gyrus, bilateral inferior occipital gyrus, and bilateral cuneus in the PSI group were significantly higher. The ReHo value of the left supramarginal gyrus in the PSI group was significantly negatively correlated with the total PSQI score. Conclusion: Patients with PSI have abnormal local activities in multiple brain regions, including the visual processing-related cortex, sensorimotor cortex, and some default-mode network (DMN) regions. Over-arousal of the DMN and over-sensitivity of the audiovisual stimuli in patients with PSI may be the main mechanisms of insomnia and can lead to a decline in cognitive function and abnormalities in emotion regulation simultaneously.

Arthroscopic subacromial decompression improves long-term functional outcome in patients with subacromial impingement: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The effect of arthroscopic subacromial decompression for impingement syndrome is still under debate. The purpose of this study was to evaluate short-term and long-term effects of arthroscopic decompression in patients with subacromial impingement. METHODS: A systematic literature search was performed in Pubmed, Embase, Scopus, Cochrane Library, and ClinicalTrials.gov through March 2021 to identify randomized controlled trials (RCTs) that evaluated the clinical effects of arthroscopic decompression versus placebo surgery or exercise therapy for patients with subacromial impingement. Outcomes were analyzed on an intention-to-treat basis with random-effects models. RESULTS: Nine RCTs were included in the meta-analysis. The pooled analysis showed that arthroscopic decompression was associated with significantly better function improvement at 24-36 months and ≥ 60 months (24-36 months: SMD: 0.29, 95% CI: 0.10 to 0.48, P = 0.002; ≥ 60 months: SMD, 0.65, 95% CI, 0.20 to 1.09, P=0.004) compared with control group. Moreover, the effect size of function improvement ≥ 60 months exceeded the minimum clinically important difference (MCID). Additionally, sensitivity analysis indicated that compared with either exercise therapy or placebo surgery, arthroscopic decompression was associated with significantly better function improvement ≥ 60 months follow-up. However, there was no significant difference regarding pain relief at 6 months, 12 months, 24-36 months, ≥ 60 months, and function improvement at 6 months, 12 months for arthroscopic decompression compared with control group. CONCLUSION: After ≥ 60 months of follow-up, arthroscopic decompression in patients with subacromial impingement appears to render better function results than exercise therapy and placebo surgery. LEVEL OF EVIDENCE: I, systematic review and meta-analysis of level I studies.

Effect of overtime pancreaticoduodenectomy on the short-term prognosis of patients.

BACKGROUND: Due to the large number of operations, surgeons sometimes need to work overtime or even stay up late to perform pancreaticoduodenectomy. Fatigue and sleep deprivation can result in an increased error rate at work. There have been numerous studies about the effect of overtime surgery on the prognosis of patients. However, the effect of overtime work for pancreaticoduodenectomy on the prognosis of patients is unclear. This study explores the impact of overtime work for pancreaticoduodenectomy on the prognosis of patients. AIM: To explore the impact of overtime work for pancreaticoduodenectomy on the short-term prognosis of patients. METHODS: This was a single-center, retrospective cohort study. The patients who underwent pancreaticoduodenectomy between January 2017 and December 2019 were included. Patients were stratified by operative start time into the control group (surgery that started between 8:00 and 16:49) and the overtime group (surgery that started between 17:00 and 22:00) and compared intraoperative and postoperative parameters. The following parameters were compared between the overtime group and the control group: Operative time, blood loss, number of lymph nodes removed, duration of treatment in the Intensive Care Unit (ICU), and incidence of complications. RESULTS: From January 2017 to December 2019, a total of 239 patients underwent pancreaticoduodenectomy in the Department of Hepatobiliary Surgery of our institution. Four patients were excluded from this study due to lack of clinical data. A total of 235 patients were included, with 177 in the control group and 58 in the overtime group. There was no difference between the two groups in operative time, blood loss, number of lymph nodes removed, ICU length of stay, hospital length of stay, mortality during hospitalization. Compared with the control group, the overtime group had a higher incidence of pancreatic fistula (32.8% vs 15.8%, P < 0.05). Multivariate analysis showed that overtime work, higher Body Mass Index were independent risk factors for pancreatic fistula (P < 0.05). CONCLUSION: Overtime work for pancreaticoduodenectomy increases the incidence of pancreatic fistula. The effect of overtime surgery on the long-term prognosis of patients' needs to be further studied.

Quadriceps Tendon Autograft Versus Bone-Patellar Tendon-Bone and Hamstring Tendon Autografts for Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis.

BACKGROUND: The best type of autograft for anterior cruciate ligament (ACL) reconstruction remains debatable. HYPOTHESIS: Compared with bone-patellar tendon-bone (BPTB) and hamstring tendon (HT) autografts, the quadriceps tendon (QT) autograft has comparable graft survival as well as clinical function and pain outcomes. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: A systematic literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library to July 2020. Randomized controlled trials (RCTs) and observational studies reporting comparisons of QT versus BPTB or HT autografts for ACL reconstruction were included. All analyses were stratified according to study design: RCTs or observational studies. RESULTS: A total of 24 studies were included: 7 RCTs and 17 observational studies. The 7 RCTs included 388 patients, and the 17 observational studies included 19,196 patients. No significant differences in graft failure (P = .36), the International Knee Documentation Committee (IKDC) subjective score (P = .39), or the side-to-side difference in stability (P = .60) were noted between QT and BPTB autografts. However, a significant reduction in donor site morbidity was noted in the QT group compared with the BPTB group (risk ratio [RR], 0.17 [95% CI, 0.09-0.33]; P < .001). No significant differences in graft failure (P = .57), the IKDC subjective score (P = .25), or the side-to-side stability difference (P = .98) were noted between QT and HT autografts. However, the QT autograft was associated with a significantly lower rate of donor site morbidity than the HT autograft (RR, 0.60 [95% CI, 0.39-0.93]; P = .02). A similar graft failure rate between the QT and control groups was observed after both early and late full weightbearing, after early and late full range of motion, and after using the QT autograft with a bone plug and all soft tissue QT grafts. However, a significantly lower rate of donor site morbidity was observed in the QT group compared with the control group after both early and late full weightbearing, after early and late full range of motion, and after using the QT autograft with a bone plug and all soft tissue QT grafts. No difference in effect estimates was seen between RCTs and observational studies. CONCLUSION: The QT autograft had comparable graft survival, functional outcomes, and stability outcomes compared with BPTB and HT autografts. However, donor site morbidity was significantly lower with the QT autograft than with BPTB and HT autografts.

Altered Hippocampal Subfields Volumes Is Associated With Memory Function in Type 2 Diabetes Mellitus.

Objective: Cognitive impairment in type 2 diabetes mellitus (T2DM) patients is related to changes in hippocampal structure and function. However, the alternation of hippocampal subfields volumes and their relationship with cognitive function are unclear. This study explored morphological alterations in the hippocampus and its subfields in T2DM patients and their relationship with cognitive function. Methods: Thirty T2DM patients and 20 healthy controls (HCs) were recruited and underwent 3-dimensional, high-resolution T1-weighted sequence (3D-T1) and a battery of cognitive tests. Freesurfer 6.0 was performed to segment the hippocampus into 12 subregions automatically. Then relationships between hippocampal subfield volumes and neurocognitive scale scores in the T2DM group were evaluated. Results: Immediate memory scores on the auditory verbal learning test (AVLT) and Montreal Cognitive Assessment (MoCA) scores in T2DM patients were lower than in the HCs. T2DM patients showed that volumes of the bilateral hippocampus were significantly reduced, mainly in the bilateral molecular layer, granule cell and molecular layer of the dentate gyrus (GC-ML-DG), cornu ammonis 4 (CA4), fimbria, and left subiculum and the right hippocampus amygdala transition area (HATA) compared to HCs. In addition, T2DM patients showed the FINS was negatively correlated with volume of left GC-ML-DG (r = -0.415, P = 0.035) and left CA4 (r = -0.489, P = 0.011); the FBG was negatively correlated with volume of right fimbria (r = -0.460, P = 0.018); the HOMA-IR was negatively correlated with volume of left GC-ML-DG (r = -0.367, P = 0.046) and left CA4(r = 0.462, P = 0.010). Partial correlation analysis found that the volume of right HATA in T2DM group was positively correlated with AVLT (immediate) scores (r = 0.427, P = 0.03). Conclusion: This study showed the volumes of multiple hippocampal subfields decreased and they were correlated with FINS, FBG and HOMA-IR in T2DM patients. We hypothesized that decreased hippocampal subfields volumes in T2DM patients was related to insulin resistance and impaired vascular function. In addition, we also found that abnormal hippocampal subfields volumes were related to memory function in T2DM patients, suggesting that reduced volumes in specific hippocampal subfields may be the potential mechanism of memory dysfunction in these patients.

Second-Look Arthroscopic Evaluation of Healing Rates After Arthroscopic Repair of Meniscal Tears: A Systematic Review and Meta-analysis.

BACKGROUND: Evaluation of meniscal healing status after repair is important, as it allows the surgeon to inform patients whether they can increase their activities or return to sports. PURPOSE: To identify the healing rates after arthroscopic repair of meniscal tears via second-look arthroscopic evaluation. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: Searches of PubMed, Embase, Scopus, and the Cochrane databases were conducted to identify relevant studies published before June 1, 2020. Studies were eligible for this meta-analysis if they provided data regarding healing status of the meniscus at second-look arthroscopy. Random-effects meta-analyses were generated to provide pooled meniscal healing estimates. We further performed subgroup analysis to investigate the healing rates of the meniscus under different situations. RESULTS: A total of 41 studies with 1908 individuals were included in the study. The pooled analysis showed the complete healing rate was 74% (95% confidence interval [CI], 67%-80%), the partial healing rate was 10% (95% CI, 6%-16%), and the failure rate was 12% (95% CI, 10%-15%) for arthroscopic repair of meniscal tears via second-look arthroscopic evaluation. Sensitivity analysis demonstrated that no individual study affected the overall healing rate by >1%. Subgroup analysis found higher meniscal healing rates in patients with the following characteristics: age <40 years, male, body mass index <26, red-red tear location, tear in posterior horn, vertical tear, outside-in technique, repair concomitant with anterior cruciate ligament reconstruction, weight-restricted rehabilitation, and time interval from meniscal repair to second-look arthroscopy >12 months. CONCLUSION: In this systematic review, the complete healing rate was 74%, the partial healing rate was 10%, and the failure rate was 12% for arthroscopic repair of meniscal tears via second-look arthroscopic evaluation.

Advances in biomechanical and biochemical engineering methods to stimulate meniscus tissue.

Meniscal injuries can cause cartilage degeneration, which usually leads to the development of osteoarthritis (OA) and results in progressive destruction of the knee joint. Therefore, it is important to identify methods to stop or slow the development of OA after the onset of meniscal defects. The current surgical techniques for meniscal injuries are insufficient to prevent the progression of knee OA, which has accelerated the development of alternative tissue engineering strategies. Much progress has been made in the use of biomechanical and biochemical stimuli in the past decades to engineer neotissue akin to native meniscus. In this review, we focus on the current progress in biomechanical and biochemical stimuli-based strategies applied to meniscal tissue engineering, and explore how these factors influence meniscal regeneration. By understanding the functional mechanism that can stimulate regeneration in the meniscus, we hope that this review will provide a theoretical basis and strategies for meniscus tissue engineering.

Altered Topological Properties of Static/Dynamic Functional Networks and Cognitive Function After Radiotherapy for Nasopharyngeal Carcinoma Using Resting-State fMRI.

OBJECTIVES: The purpose of this study was to (1) explore the changes in topological properties of static and dynamic brain functional networks after nasopharyngeal carcinoma (NPC) radiotherapy (RT) using rs-fMRI and graph theoretical analysis, (2) explore the correlation between cognitive function and changes in brain function, and (3) add to the understanding of the pathogenesis of radiation brain injury (RBI). METHODS: Fifty-four patients were divided into 3 groups according to time after RT: PT1 (0-6 months); PT2 (>6 to ≤12 months); and PT3 (>12 months). 29 normal controls (NCs) were included. The subjects' topological properties were evaluated by graph-theoretic network analysis, the functional connectivity of static functional networks was calculated using network-based statistics, and the dynamic functional network matrix was subjected to cluster analysis. Finally, correlation analyses were conducted to explore the relationship between the altered network parameters and cognitive function. RESULTS: Assortativity, hierarchy, and network efficiency were significantly abnormal in the PT1 group compared with the NC or PT3 group. The small-world variance in the PT3 group was smaller than that in NCs. The Nodal ClustCoeff of Postcentral_R in the PT2 group was significantly smaller than that in PT3 and NC groups. Functional connectivities were significantly reduced in the patient groups. Most of the functional connectivities of the middle temporal gyrus (MTG) were shown to be significantly reduced in all three patient groups. Most of the functional connectivities of the insula showed significantly reduced in the PT1 and PT3 groups, and most of the functional connectivities in brain regions such as frontal and parietal lobes showed significantly reduced in the PT2 and PT3 groups. These abnormal functional connectivities were correlated with scores on multiple scales that primarily assessed memory, executive ability, and overall cognitive function. The frequency F of occurrence of various states in each subject differed significantly, and the interaction effect of group and state was significant. CONCLUSION: The disruption of static and dynamic functional network stability, reduced network efficiency and reduced functional connectivity may be potential biomarkers of RBI. Our findings may provide new insights into the pathogenesis of RBI from the perspective of functional networks.

Effectiveness of Curcuma longa extract versus placebo for the treatment of knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

The aim of this systematic review was to evaluate the efficacy and safety of all types of Curcuma longa extract versus placebo for knee osteoarthritis (OA) treatment. The research was conducted by using the databases of PubMed, Embase, Scopus, and Cochrane Library through April 2021. Randomized controlled trials (RCTs) that compared the effect of Curcuma longa extract with placebo for patients with knee OA were considered eligible. The pooled results were expressed as mean differences or relative risks with 95% confidence intervals. A total of 10 RCTs with 783 patients were eligible for this meta-analysis. The pooled analysis showed that Curcuma longa extract was associated with significantly better pain relief and functional improvement compared with placebo for knee OA. Moreover, the smallest effect sizes of VAS for pain and WOMAC total score exceeded the minimum clinically important differences (MCIDs). Current evidence indicates that, compared with placebo, Curcuma longa extract has more benefit in pain relief and functional improvement for symptomatic knee OA. However, considering the potential heterogeneity in the included studies, more future high-quality RCTs with large sample sizes are necessary to confirm the benefits of Curcuma longa extract on knee OA.

The effect of fascia iliaca block on postoperative pain and analgesic consumption for patients undergoing primary total hip arthroplasty: a meta-analysis of randomized controlled trials.

BACKGROUND: The primary aim of this systematic review and meta-analysis was to compare postoperative pain, analgesic consumption, and complications after fascia iliaca block (FIB) versus control for patients undergoing primary total hip arthroplasty (THA). Second, we compared the outcomes of FIB versus placebo. Finally, we sought to evaluate pain and analgesic consumption after preoperative and postoperative FIB. METHODS: We performed a systematic literature search in MEDLINE, Embase, Scopus, Web of Science, Google Scholar, ClinicalTrials.gov , and CENTRAL through February 2021 to identify randomized controlled trials (RCTs) that evaluated the efficacy of FIB versus control for patients undergoing primary THA. All analyses were conducted on intent-to-treat data with a random-effects model. RESULTS: Twelve RCTs with a total of 815 patients were included. There was no difference in postoperative pain (P = 0.64), analgesic consumption (P = 0.14), or complication rate (P = 0.99) between FIB and control groups. Moreover, no difference in postoperative pain (P = 0.26), analgesic consumption (P = 0.06), or complication rate (P = 0.71) was found between FIB and placebo. Moreover, sensitivity analysis suggested that no significant difference in postoperative pain, analgesic consumption, or complication rate was present between FIB and control in studies that used preoperative and postoperative FIB. CONCLUSION: FIB was not found to be superior to placebo or various anesthetic techniques for patients undergoing primary THA, as measured by postoperative pain, analgesic consumption, and complications.

The potential role of necroptosis in clinical diseases (Review).

As an important type of programmed cell death in addition to apoptosis, necroptosis occurs in a variety of pathophysiological processes, including infections, liver diseases, kidney injury, neurodegenerative diseases, cardiovascular diseases, and human tumors. It can be triggered by a variety of factors, such as tumor necrosis factor receptor and Toll­like receptor families, intracellular DNA and RNA sensors, and interferon, and is mainly mediated by receptor­interacting protein kinase 1 (RIP1), RIP3, and mixed lineage kinase domain­like protein. A better understanding of the mechanism of necroptosis may be useful in the development of novel drugs for necroptosis­related diseases. In this review, the focus is on the molecular mechanisms of necroptosis, exploring the role of necroptosis in different pathologies, discussing their potential as a novel therapeutic target for disease therapy, and providing suggestions for further study in this area.

DNA Nanosieve-Based Regenerative Electrochemical Biosensor Utilizing Nucleic Acid Flexibility for Accurate Allele Typing in Clinical Samples.

Herein, an interface-based DNA nanosieve that has the ability to differentiate ssDNA from dsDNA has been demonstrated for the first time. The DNA nanosieve could be readily built through thiol-DNA's self-assembly on the gold electrode surface, and its cavity size was tunable by varying the concentration of thiol-DNAs. Electrochemical chronocoulometry using [Ru(NH3)6]3+ as redox revealed that the average probe-to-probe separation in the 1 µM thiol-DNA-modified gold electrode was 10.6 ± 0.3 nm so that the rigid dsDNA with a length of ∼17 nm could not permeate the nanosieve, whereas the randomly coiled ssDNA could enter it due to its high flexibility, which has been demonstrated by square wave voltammetry and methylene blue labels through an upside-down hybridization format. After combining the transiently binding characteristic of a short DNA duplex and introducing a regenerative probe (the counterpart of ssDNA), a highly reproducible nanosieve-based E-DNA model was obtained with a relative standard deviation (RSD) as low as 2.7% over seven cycles. Finally, we built a regenerative nanosieve-based E-DNA sensor using a ligation cycle reaction as an ssDNA amplification strategy and realized one-sensor-based continuous measurement to multiple clinical samples with excellent allele-typing performance. This work holds great potential in low-cost and high-throughput analysis between biosensors and biochips and also opens up a new avenue in nucleic acid flexibility-based DNA materials for future applications in DNA origami and molecular logic gates.

Rehabilitation regimen for non-surgical treatment of Achilles tendon rupture: A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To compare re-rupture rate, functional and quality-of-life outcomes, return to sports and work, complications, and resource use in patients treated non-surgically with different rehabilitation regimens for Achilles tendon rupture. DESIGN: Systematic review and meta-analysis. METHODS: We performed a systematic literature search in PubMed, Embase, Scopus and the Cochrane Library through May 2020 to identify randomized controlled trials (RCTs) that included patients treated non-surgically for Achilles tendon rupture. All analyses were stratified according to rehabilitation protocols. RESULTS: Eight RCTs with a total of 978 patients were included. There was no significant difference about re-rupture rate (P=0.38), return to sports (P=0.85) and work (P=0.33), functional outcome (P=0.34), quality of life (P=0.50), and complication rate (P=0.29) between early weight bearing with functional ankle motion and traditional ankle immobilisation with non-weight bearing. Similarly, no significant difference in re-rupture rate (P=0.88), return to sports (P=0.45) and work (P=0.20), functional outcome (P=0.26), and complication rate (P=0.49) was seen between ankle immobilisation with non-weight bearing and early weight bearing without functional ankle motion. CONCLUSIONS: Traditional ankle immobilisation with non-weight bearing was not found to be superior to early weight bearing with or without functional ankle motion for patients treated non-surgically for Achilles tendon rupture. Clinicians may consider early weight bearing in functional brace as a safe and cost-effective alternative to non-weight bearing with plaster casting.

Ultrasensitive Detection of RNA with Single-Base Resolution by Coupling Electrochemical Sensing Strategy with Chimeric DNA Probe-Aided Ligase Chain Reaction.

Accurate and sensitive detection of single-base mutations in RNAs is of great value in basic studies of life science and medical diagnostics. However, the current available RNA detection methods are challenged by heterogeneous clinical samples in which trace RNA mutants usually existed in a large pool of normal wild sequences. Thus, there is still great need for developing the highly sensitive and highly specific methods in detecting single-base mutations of RNAs in heterogeneous clinical samples. In the present study, a new chimeric DNA probe-aided ligase chain reaction-based electrochemical method (cmDNA-eLCR) was developed for RNA mutation detection through the BSA-based carrier platform and the horseradish peroxidase-hydrogen peroxide-tetramethylbenzidine (HRP-H2O2-TMB) system. The denaturing polyacrylamide gel electrophoresis and a fluorophore-labeled probe was ingeniously designed to demonstrate the advantage of cmDNA in ligation to normal DNA templated by RNA with the catalysis of T4 RNA ligase 2 as well as its higher selectivity than DNA ligase system. Finally, the proposed cmDNA-eLCR, compared with the traditional eLCR, showed excellent performance in discriminating single base-mismatched sequences, where the signal response for mismatched targets at a high concentration could overlap completely with that for the blank control. Besides, this cmDNA-eLCR assay had a wide linear range crossing six orders of magnitude from 1.0 × 10-15 to1.0 × 10-10 M with a limit of detection as low as 0.6 fM. Furthermore, this assay was applied to detect RNA in real sample with a satisfactory result, thereby demonstrating its great potential in diagnosis of RNA-related diseases.

Intra-Articular Mesenchymal Stromal Cell Injections Are No Different From Placebo in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

PURPOSE: To evaluate the efficacy and safety of intra-articular mesenchymal stromal cells (MSCs) injections for knee osteoarthritis (OA) treatment. METHODS: We performed a systematic literature search in PubMed, Embase, Scopus, and the Cochrane Library through April 2020 to identify level I randomized controlled trials (RCTs) that evaluated the clinical efficacy of MSCs versus control treatments for knee OA. Outcomes were analyzed on an intention-to-treat basis with random-effects models. RESULTS: A total of 13 RCTs were included in the meta-analysis. Compared with placebo, there was no significant difference in VAS for pain (mean difference [MD] 1.62, 95% confidence interval [CI -0.60 to 3.85), WOMAC pain score (MD 1.88, 95% CI -0.21 to 3.98), WOMAC function score (MD -0.67, 95% CI -6.54 to 5.19), or WOMAC stiffness score (MD 0.64, 95% CI -0.86 to 2.14) for MSCs. Moreover, the smallest treatment effect of VAS for pain, WOMAC pain score, WOMAC function score, and WOMAC stiffness score did not exceed the minimum clinically important difference (MCID). Additionally, there was no significant difference in percentage of patients crossing the MCID threshold between MSC and placebo groups for VAS for pain (relative risk [RR] 0.93, 95% CI 0.55 to 1.57) or WOMAC total score (RR 0.40, 95% CI 0.13 to 1.21). Compared with hyaluronic acid (HA), MSC injection was associated with significantly better improvement in VAS for pain (MD 2.00, 95% CI 0.94 to 3.07), WOMAC pain score (MD 4.58, 95% CI 0.49 to 8.67), WOMAC total score (MD 14.86, 95% CI 10.59 to 19.13), and WOMAC stiffness score (MD 1.85, 95% CI 0.02 to 3.69). However, the smallest treatment effect of VAS for pain, WOMAC pain score, WOMAC function score, and WOMAC stiffness score did not exceed the MCID. Moreover, there was no significant difference in percentage of patients crossing the MCID threshold between MSC and HA groups for WOMAC total score (RR 0.57, 95% CI 0.21 to 1.55). We also found that MSCs did not increase adverse events compared with HA and placebo. CONCLUSIONS: Intra-articular MSC injection was not found to be superior to placebo in pain relief and functional improvement for patients with symptomatic knee OA. However, additional direct testing and combination trials of different type of cells, doses, and number of injections of MSCs are required to further enhance clinical decision making for people with symptomatic knee OA. LEVEL OF EVIDENCE: I, meta-analysis of level I studies.

Recent Progress in 3D Printing of Elastic and High-Strength Hydrogels for the Treatment of Osteochondral and Cartilage Diseases.

Despite considerable progress for the regenerative medicine, repair of full-thickness articular cartilage defects and osteochondral interface remains challenging. This low efficiency is largely due to the difficulties in recapitulating the stratified zonal architecture of articular cartilage and engineering complex gradients for bone-soft tissue interface. This has led to increased interest in three-dimensional (3D) printing technologies in the field of musculoskeletal tissue engineering. Printable and biocompatible hydrogels are attractive materials for 3D printing applications because they not only own high tunability and complexity, but also offer favorable biomimetic environments for live cells, such as porous structure, high water content, and bioactive molecule incorporation. However, conventional hydrogels are usually mechanically weak and brittle, which cannot reach the mechanical requirements for repair of articular cartilage defects and osteochondral interface. Therefore, the development of elastic and high-strength hydrogels for 3D printing in the repairment of cartilage defects and osteochondral interface is crucial. In this review, we summarized the recent progress in elastic and high-strength hydrogels for 3D printing and categorized them into six groups, namely ion bonds interactions, nanocomposites integrated in hydrogels, supramolecular guest-host interactions, hydrogen bonds interactions, dynamic covalent bonds interactions, and hydrophobic interactions. These 3D printed elastic and high-strength hydrogels may provide new insights for the treatment of osteochondral and cartilage diseases.