Skilled reaching test for shoulder function assessment in a rat model of rotator cuff tear: a pilot study.

BACKGROUND: Functional assessments are crucial to evaluate treatment outcomes in clinical and animal studies on rotator cuff injuries. While gait analysis is commonly used to assess animal models of rotator cuff tears, it is less relevant for human patients as the human shoulder is typically assessed in a non-weight-bearing condition. The present study introduces the skilled reaching test as a shoulder functional assessment tool for rats, which allows for evaluation without weight bearing. METHODS: In the control group, 8 male Sprague-Dawley rats received rotator cuff tear surgery without repair. In the rotator cuff repair group, 20 rats received rotator cuff repair at 4 weeks post rotator cuff tear. For the skilled reaching test, rats were trained to extend their forelimbs to fetch food pellets, and the number of trials, number of attempts and the success rate were recorded. The gait analysis and skilled reaching test were performed at baseline, 4 weeks post-tear, 1, 2, 4, and 8 weeks post-repair. The repeated measures analysis of variance was used to evaluate the effects of time on the shoulder function. The significance level was set at 0.05. RESULTS: The skilled reaching test required 216 h to conduct, while the gait analysis took 44 h. In the rotator cuff repair group, gait performance significantly deteriorated at 1 week post-repair and restored to 4 weeks post-tear levels at 4 weeks post-repair. Regarding the skilled reaching test, the number of attempts, number of trials and the success rate decreased at 1 week post-repair. Subsequently, there was a brief rebound in performance observed at 2 weeks post-repair, followed by a continued decline in the number of attempts and trials. By 8 weeks post-repair, only the success rate had restored to levels similar to those observed at 4 weeks post-tear. CONCLUSION: The skilled reaching test can detect functional deficiencies following rotator cuff tear and repair, while it requires high time and labour costs.

Comparative short-term effectiveness of non-surgical treatments for insertional Achilles tendinopathy: a systematic review and network meta-analysis.

BACKGROUND: The incidence of Achilles tendinopathy has risen over the past decades. Insertional Achilles tendinopathy is characterised by tissue degeneration of the Achilles tendon from its insertion in the calcaneus to up to 2 cm proximally. This clinical condition is accompanied by pain, loss of function and diminished exercise tolerance. Numerous conservative treatment modalities are available to participants with insertional Achilles tendinopathy, including eccentric exercises, extracorporeal shockwave therapy, laser therapy, cryotherapy, therapeutic ultrasound, and orthotics. Eccentric exercise and extracorporeal shockwave therapy may reduce pain in participants with non-calcified insertional Achilles tendinopathy. However, no specific treatment is recommended over another due to the low methodological quality of trials. Given the lack of standard or preferred non-surgical treatment and the potential risks of surgical treatment, there is an imminent need to reassess different non-surgical treatments based on the newest evidence. Thus, this systematic review aims to evaluate the clinical effectiveness of the various non-surgical treatments for insertional Achilles tendinopathy. METHODS: AMED EBSCOhost, CINAHL, EBSCOhost, EMBASE, PEDro, PubMed, Web of Science, and Clinicaltrials.gov were searched from 1992 to 14th October 2022, randomised controlled trials of adults with insertional Achilles tendinopathy investigating non-surgical treatments compared with each other or no treatment, placebo/sham control. Two reviewers independently screened and extracted the data. Random effects of network meta-analysis immediately after treatments were used to report comparative treatment effects. The surface under the cumulative ranking probabilities was calculated to assess the relative ranking of treatments. RESULTS: Nine trials (total n = 464 participants) were included. This review recommended the combination of eccentric exercise and soft tissue therapy to manage insertional Achilles tendinopathy. With the highest SUCRA values of 84.8, and the best mean rank of 1.9, Eccentric exercise plus soft tissue treatment ranked as the most effective treatment for short-term pain. CONCLUSIONS: This is the first NMA of non-surgical treatment focusing on short-term pain control for IAT which eccentric exercise plus soft-tissue therapy was found to be the most effective treatment combination. However, the overall confidence in non-surgical treatments from all included trials was very low. No recommendation of the best treatment option can be made from this review.

Bilateral impairments of quadriceps neuromuscular function occur early after anterior cruciate ligament injury.

The study aimed to investigate the impairments in quadriceps neuromuscular function, including strength, rate of torque development (RTD) and activation failure (QAF) early after an ACL injury. A cross-sectional study was conducted. Thirty physically active patients with a primary ACL injury within three months, aged 18 to 40 years old, and who were scheduled for ACL reconstruction were included. Thirty matched healthy controls were also recruited. All the outcomes were measured on an isokinetic dynamometer with knee flexion at 45°. Quadriceps strength was measured by maximal voluntary isometric contractions (MVIC). Early (RTD0-50) and late (RTD100-200) phases of RTD were retrieved from the MVIC test from 0 to 50 ms and 100-200 ms, respectively. QAF was quantified by the central activation ratio (CAR) measured by superimposed burst technique. The results of Mann-Whitney U test showed that compared with the healthy limbs, the injured limbs of the ACL group showed lower quadriceps strength (P < 0.001), RTD0-50 (P < 0.001) and RTD100-200 (P < 0.001); the uninjured limbs showed lower quadriceps strength (P = 0.009), RTD0-50 (P = 0.006) as well as greater QAF (P = 0.010). To conclude, bilateral quadriceps suffered from neuromuscular impairments early after an ACL injury.

Associations of patient characteristics, rate of torque development, voluntary activation of quadriceps with quadriceps strength, and knee function before anterior cruciate ligament reconstruction.

Good preoperative knee function (KF) and quadriceps strength (QS) relate to good prognoses after anterior cruciate ligament reconstruction (ACLR). This study aimed to investigate the associations between patient characteristics, rate of torque development (RTD), voluntary activation (VA) of the quadriceps against preoperative KF and QS. A cross-sectional study was conducted. Forty patients with a primary, unilateral ACL injury who had finished the preoperative rehabilitation and scheduled for an ACLR were included. KF was evaluated using the International Knee Documentation Committee score. QS was measured by maximal voluntary isometric contractions. RTD was divided into the early (RTD0-50) and the late (RTD100-200) phases. Quadriceps VA was measured using the superimposed burst technique. Our results showed that patients with poor preoperative KF had more deficits in RTD0-50 (P = 0.025), higher BMI(P = 0.043), and more meniscus injuries (MI) (P = 0.001) than those with good KF. Patients with asymmetrical QS showed lower BMI (P = 0.020) and shorter time from injury (TFI) (P = 0.027) than those with symmetrical QS. Additionally, a higher pre-injury Tegner score combined with greater RTD100-200 contributed to greater QS on the injured limb (R2 = 0.357, P = 0.001). To conclude, BMI, TFI, concomitant MI, pre-injury physical activity level, and quadriceps RTD are related to QS and KF before ACLR.

Knee wobbling during the single-leg-squat-and-hold test reflects dynamic knee instability in patients with anterior cruciate ligament injury.

We propose using the single-leg squat-and-hold (SLSH) task with kinematic analysis to objectively measure dynamic knee stability after anterior cruciate ligament (ACL) injury. There are three objectives of this study: to compare the knee kinematics of ACL-deficient patients and healthy controls by capturing knee wobbling during the SLSH task, to detect kinematic changes after ACL reconstruction, and to correlate the kinematic variables with self-reported knee function. Twenty-five ACL-deficient participants and 18 healthy matched participants were recruited. The knee kinematics involving both the magnitudes and frequency of motion fluctuation was captured during SLSH by 3D motion analysis system (Vicon). Compared to the limbs of the control participants, the ACL involved limbs exhibited a greater range of flexion-extension (4.33 ± 1.96 vs. 2.73 ± 1.15; p = 0.005) and varus-valgus (2.52 ± 0.99 vs. 1.36 ± 0.42; p < 0.001). It also inhibited higher frequency of flexion-extension (4.87 ± 2.55 vs. 2.68 ± 1.23; p = 0.003) and varus-valgus (3.83 ± 2.59 vs. 1.42 ± 0.55; p < 0.001). The range of flexion-extension (4.50 ± 2.24 vs. 2.90 ± 1.01; p = 0.018), frequency of flexion-extension (4.58 ± 2.53 vs. 3.05 ± 1.80; p = 0.038) and varus-valgus (3.46 ± 2.11 vs. 1.80 ± 1.23; p = 0.022) was reduced after ACL reconstruction. Increased frequency of knee varus-valgus was correlated with lower IKDC score (r = -0.328; p = 0.034). Knee wobbling was more prominent in ACL-deficient patients, which was associated with poor knee function. SLSH task with kinematic analysis appears to be a potential assessment method for monitoring dynamic knee stability after ACL injury.

Differential MMP 1 and MMP 13 expression in proliferation and ligamentization phases of graft remodeling in anterior cruciate ligament reconstruction.

Purpose: Graft remodeling in anterior cruciate ligament reconstruction (ACLR) demonstrates three distinct phases: necrosis, proliferation and ligamentization. Biological enhancement involves modulating these processes, but the cellular activities related to extracellular matrix remodeling have not been investigated. We hypothesized that changes in matrix metalloproteinases (MMPs) 1 and 13 expression are involved in the transition of proliferation phase to ligamentization phase of graft remodeling.Materials and methods: Thirty-three rats underwent ACLR. Tendon grafts were harvested at week 1 (necrosis), 2 (proliferation), or 12 (ligamentization) post-operation for histological examination (n = 3), or for isolation of graft-derived cells (n = 8) for flow cytometry, proliferation assay, cell invasion assay, measurement of gene expression related to matrix remodeling (Col1A1, Col3A1, MMP1, tissue inhibitor of marix metalloproteinase 1 (TIMP1), and MMP13) and total MMP activities.Results: Increased cellularity in tendon graft was contributed by active cell proliferation and migration at week 2 post-operation, while decreased cellularity were paralleled by increased apoptosis at week 12. All genes measured (Col1A1, Col3A1, MMP1, TIMP1, and MMP13) increased significantly in week 2 cells compared to week 1 cells. MMP1 expression subsided at week 12, while MMP13 expression kept increasing till 12 weeks post-operation. Total MMP activities was 3-fold higher in cultured graft-derived cells from week 2 as compared to cells from week 12. Two distinct processes of graft remodeling were identified, characterized by increased MMP1 expression with cell proliferation and increased MMP13 expression with cell apoptosis.Conclusions: Unfavorable matrix remodeling during the proliferation phase is found with increased MMP1, while remodeling leading to ligamentization is associated with increased MMP13 expression.

A systematic review of inflammatory cells and markers in human tendinopathy.

BACKGROUND: This article systematically reviews the current evidence regarding inflammation in Tendinopathy with the aim to increase understanding of a potential common pathophysiology. METHODS: Following the PRISMA statements, the terms: (tendinopathy OR (tendons AND rupture)) AND (inflammation OR (inflammation AND cells) OR immune system OR inflammation mediators OR bacteria) were used. One thousand four hundred thirty-one articles were identified which was screened down to 53. RESULTS: 39/53 studies mentioned inflammatory cells but had contradicting conclusions. Macrophages were the most common cell type and inflammatory markers were detectable in all the articles which measure them. CONCLUSIONS: The included studies show different conclusions, but this heterogeneity is not unexpected since the clinical criteria of 'tendinopathy' encompass a huge clinical spectrum. Different 'tendinopathy' conditions may have different pathophysiology, and even the same clinical condition may be at different disease stages during sampling, which can alter the histological and biochemical picture. Control specimen sampling was suboptimal since the healthy areas of the pathological-tendon may actually be sub-clinically diseased, as could the contralateral tendon in the same subject. Detection of inflammatory cells is most sensitive using immunohistochemistry targeting the cluster of differentiation markers, especially when compared to the conventional haematoxylin and eosin staining methods. The identified inflammatory cell types favour a chronic inflammatory process; which suggests a persistent stimulus. This means NSAID and glucocorticoids may be useful since they suppress inflammation, but it is noted that they may hinder tendon healing and cause long term problems. This systematic review demonstrates a diversity of data and conclusions in regard to inflammation as part of the pathogenesis of Tendinopathy, ranging from ongoing or chronic inflammation to non-inflammatory degeneration and chronic infection. Whilst various inflammatory markers are present in two thirds of the reviewed articles, the heterogenicity of data and lack of comparable studies means we cannot conclude a common pathophysiology from this systematic review.

Is Pre-operative Quadriceps Strength a Predictive Factor for the Outcomes of Anterior Cruciate Ligament Reconstructions.

Persistent quadriceps weakness prevents patients from returning to sports after ACL reconstruction. Pre-operative quadriceps strength was indicated as an important factor for the outcomes of ACL reconstruction. However, the existing evidence is controversial. Therefore, this systematic review was conducted to summarize and evaluate the relationship between pre-operative quadriceps strength and the outcomes following ACL reconstruction, and to summarize the predictive value of pre-operative quadriceps strength for satisfactory post-operative outcomes. Pubmed, WOS, Embase, CINAHL and SportDiscus were searched to identify eligible studies according to PRISMA guidelines. Relevant data was extracted regarding quadriceps strength assessment methods, pre-operative quadriceps strength, participants treatment protocols, post-operative outcomes, follow-up time points and the relevant results of each individual study. Twelve cohort studies (Coleman methodology score: 62±10.4; from 44-78) with 1773 participants included. Follow-up period ranged from 3 months to 2 years. Moderate evidence supports the positive association between pre-operative quadriceps strength and post-operative quadriceps strength; weak evidence supports the positive association between pre-operative quadriceps strength and post-operative functional outcomes. By now, there is no consensus on the predictive value of pre-operative quadriceps strength for achieving satisfactory quadriceps strength after ACLR. To conclude, pre-operative quadriceps strength should be taken into consideration when predict patient recovery of ACLR.

Motion Task Selection for Kinematic Evaluation After Anterior Cruciate Ligament Reconstruction: A Systematic Review.

PURPOSE: To examine the different motion tasks and the protocols used to objectively quantify dynamic stability in terms of knee kinematics at different stages of anterior cruciate ligament reconstruction (ACLR) recovery. METHODS: A systematic search was done using OVID in Embase, Cochrane Central Register of Controlled Trials, Medline, PsychINFO, and AMED. A combination of the following keywords and their variations were used: anterior cruciate ligament, motion tasks (e.g., jump, hop, gait), and stability. The inclusion criteria were as follows: (1) ACLR subjects were recruited, (2) at least 1 motion task was performed and kinematics data were recorded, and (3) uninjured subjects or the contralateral uninjured limbs were included as a control group. Exclusion criteria were as follows: (1) non-English language publications, (2) retrospective studies and review articles, (3) animal studies, and (4) cadaveric studies. RESULTS: The search returned 2,195 studies, and 56 were included in this review according to the criteria. A total of 1,086 ACLR subjects were included. Pivoting, landing, walking, running, stair negotiation, and squats were assessed using optoelectronic motion capture, electrogoniometry, or video-radiography. CONCLUSIONS: The appropriate selection of motion tasks is an integral factor in dynamic stability testing as it evokes different kinematic outcomes in relation to the different stages of ACLR recovery. Stair negotiation and landing tasks are best performed during the early stages of recovery, and landing and pivoting are recommended 6 months after ACLR surgery. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II studies.

A Systematic Review of Anterior Cruciate Ligament Femoral Footprint Location Evaluated by Quadrant Method for Single-Bundle and Double-Bundle Anatomic Reconstruction.

PURPOSE: To unravel the standard position of anterior cruciate ligament (ACL) femoral origin and deduce practical arthroscopic localization and postsurgical evaluation method. METHODS: Two independent reviewers searched PubMed using the terms ACL, footprint, femur, etc. We included studies published since January 1, 2000, in which the results were measured by Bernard's quadrant method. This method consists of 4 distances, including total diameter of lateral condyle along Blumensaat's line (distance t), maximum intercondylar notch height (distance h), distance from center of footprint to proximal border (distance x), and distance from center of footprint to Blumensaat's line (distance y). The data of included studies were combined to calculate theoretical centers and standard area for both ACL as a whole bundle and as anteromedial (AM) and posterolateral (PL) bundles individually. Finally, we translated the combined data to arthroscopic localization and postsurgical evaluation. RESULTS: A total of 13 studies were included. The theoretical centers of ACL as a whole bundle is 28.4% ± 5.1% (x) of distance t and 35.7% ± 6.9% (y) of distance h, whereas AM bundle is 24.2% ± 4%, 21.6% ± 5.2% (x, y) and PL bundle is 32.8% ± 4.7%, 46.7% ± 4.9% (x, y), respectively. The standard area of ACL footprint is a circle with a center of 27.53%, 35.85% (x, y), and a radius of 4.58%, 9.2% (x, y), respectively. Translation of combined data shows that under arthroscopy, for single-bundle ACL reconstruction, the midpoint of distance from border of proximal to distal articular cartilage is the center of anatomic femoral socket. CONCLUSIONS: Combined data unravel the standard position of ACL femoral origin. It can be used by clinicians to localize anatomic tunnel both in surgery and postsurgical evaluation. For single-bundle ACL reconstruction, the midpoint of lateral femoral condyle corresponds to anatomic socket. LEVEL OF EVIDENCE: Level V, systematic review of anatomic studies.

A portable affective computing system for identifying mate preference.

Recognizing an individual's preference state for potential romantic partners based on electroencephalogram (EEG) signals holds significant practical value in enhancing matchmaking success rates and preventing romance fraud. Despite some progress has been made in this field, challenges such as high-dimensional feature space and channel redundancy limited the technology's practical application. The aim of this study is to explore the most discriminative EEG features and channels, in order to enhance the recognition performance of the system, while maximizing the portable and practical value of EEG-based systems for recognizing romantic attraction. To achieve this goal, we first conducted an interesting simulated dating experiment to collect the necessary data. Next, EEG features were extracted from various dimensions, including band power and asymmetry index features. Then, we introduced a novel method for EEG feature and channel selection that combines the sequential forward selection (SFS) algorithm with the frequency-based feature subset integration (FFSI) algorithm. Finally, we used the random forest classifier (RFC) to determine a person's preference state for potential romantic partners. Experimental results indicate that the optimal feature subset, selected using the SFS-FFSI method, attained an average classification accuracy of 88.42%. Notably, these features were predominantly sourced from asymmetry index features of electrodes situated in the frontal, parietal, and occipital lobes.

Banxia Xiexin decoction modulates gut microbiota and gut microbiota metabolism to alleviate DSS-induced ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine prescription for treating ulcerative colitis (UC). However, its potential mechanism of action is still unclear. AIM OF THE STUDY: Reveal the correlation between the beneficial impacts of BXD on UC and the composition of the gut microbiota. MATERIALS AND METHODS: The major constituents of BXD were identified using the HPLC-DAD technique. An experimental model of UC was induced in male C57BL/6 mice by administering dextran sodium sulfate (DSS). A total of 48 mice were divided into different groups, including control, model, high-dose BXD treatment, medium-dose BXD treatment, low-dose BXD treatment, and a group treated with 5-amino acid salicylic acid (5-ASA). Body weight changes and disease activity index (DAI) scores were documented; colon length, colon index, spleen index, and thymus index scores were determined; myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) activities were assessed; and histological staining with hematoxylin-eosin and alcian blue/phosphate Schiff was performed. The immunofluorescence technique was employed to examine the presence of ZO-1 and occludin in the colon tissue. 16S rRNA sequencing was employed to assess the gut microbiota's diversity and metabolomics was utilized to examine alterations in metabolites within the gut microbiota. The impact of BXD on the gut microbiota was confirmed through fecal microbiota transplantation (FMT). RESULTS: BXD exhibited a positive impact on UC mice, particularly in the high-dose BXD treatment group. The BXD group experienced weight recovery, decreased DAI scores, improved colon length, and restored of spleen and thymus index scores compared to the DSS group. Additionally, BXD alleviated colon damage and the inflammatory response while restoring intestinal barrier function. FMT in BXD-treated mice also showed therapeutic effects in UC mice. At the phylum level, the relative abundance of Desulfobacterota, Deferribacterota and Actinobacteriota increased; at the genus level, g__norank__f__Muribaculaceae, Dubosiella, Akkermansia, and Lactobacillus increased, whereas Faecalibaculum, Alloprevotella, Turicibacter, and g_Paraprevotella decreased. g__norank_f__Muribaculaceae was positively correlated with body weight and colon length and negatively with colon index scores, splenic index scores, and MPO levels; Alloprevotella was positively correlated with splenic index scores, histological scores, and TNF-α levels and negatively with thymus index scores and thymus index scores. Faecalibaculum was positively correlated with colon index scores and MPO levels. Metabolic investigations revealed 58 potential indicators, primarily associated with the metabolism of amino acids, purines, and lipids. Alloprevotella, g_Paraprevotella, and Bifidobacterium were strongly associated with metabolic pathways. CONCLUSION: BXD showed beneficial therapeutic effects in UC mice. The mechanism may be by promoting the balance and variety of gut microbiota, as well as regulating the metabolism of amino acids, purines, and lipids.

Analysis of Clinical Trials Using Anti-Tumor Traditional Chinese Medicine Monomers.

The potential anti-cancer effect of traditional Chinese medicine (TCM) monomers has been widely studied due to their advantages of well-defined structure, clear therapeutic effects, and easy quality control during the manufacturing process. However, clinical trial information on these monomers is scarce, resulting in a lack of knowledge regarding the research progress, efficacy, and adverse reactions at the clinical stage. Therefore, this study systematically reviewed the clinical trials on the anti-cancer effect of TCM monomers registered in the Clinicaltrials.gov website before 2023.4.30, paying special attention to the trials on tumors, aiming to explore the research results and development prospects in this field. A total of 1982 trials were started using 69 of the 131 TCM monomers. The number of clinical trials performed each year showed an overall upward trend. However, only 26 monomers entered into 519 interventional anti-tumor trials, with vinblastine (194, 37.38%) and camptothecin (146, 28.13%) being the most used. A total of 45 tumors were studied in these 519 trials, with lymphoma (112, 21.58%) being the most frequently studied. Clinical trials are also unevenly distributed across locations and sponsors/collaborators. The location and the sponsor/collaborator with the highest number of performed trials were the United States (651,32.85%) and NIH (77). Therefore, China and its institutions still have large room for progress in promoting TCM monomers in anti-tumor clinical trials. In the next step, priority should be given to the improvement of the research and development ability of domestic enterprises, universities and other institutions, using modern scientific and technological means to solve the problems of poor water solubility and strong toxic and side effects of monomers, so as to promote the clinical research of TCM monomers.

Prenylated Flavonoids in Sophora flavescens: A Systematic Review of Their Phytochemistry and Pharmacology.

Sophora flavescens has been widely used in traditional Chinese medicine for over 1700 years. This plant is known for its heat-clearing, damp-drying, insecticidal, and diuretic properties. Phytochemical research has identified prenylated flavonoids as a unique class of bioactive compounds in S. flavescens. Recent pharmacological studies reveal that the prenylated flavonoids from S. flavescens (PFS) exhibit potent antitumor, anti-inflammatory, and glycolipid metabolism-regulating activities, offering significant therapeutic benefits for various diseases. However, the pharmacokinetics and toxicological profiles of PFS have not been systematically studied. Despite the diverse biological effects of prenylated flavonoid compounds against similar diseases, their structure-activity relationship is not yet fully understood. This review aims to summarize the latest findings regarding the chemical composition, drug metabolism, pharmacological properties, toxicity, and structure-activity relationship of prenylated flavonoids from S. flavescens. It seeks to highlight their potential for clinical use and suggest directions for future related studies.

Identification and immunological role of cuproptosis in osteoporosis.

Background: osteoporosis is a skeletal disorder disease features low bone mass and poor bone architecture, which predisposes to increased risk of fracture. Copper death is a newly recognized form of cell death caused by excess copper ions, which presumably involve in various disease. Accordingly, we intended to investigate the molecular clusters related to the cuproptosis in osteoporosis and to construct a predictive model. Methods: we investigated the expression patterns of cuproptosis regulators and immune signatures in osteoporosis based on the GSE56815 dataset. Through analysis of 40 osteoporosis samples, we investigated molecular clustering on the basis of cuproptosis--related genes, together with the associated immune cell infiltration. The WGCNA algorithm was applied to detect cluster-specific differentially expressed genes. Afterwards, the optimum machine model was selected by calculating the performance of the support vector machine model, random forest model, eXtreme Gradient Boosting and generalized linear model. Nomogram, decision curve analysis, calibration curves, and the GSE7158 dataset was utilizing to confirm the prediction efficiency. Results: Differences between osteoporotic and non-osteoporotic controls confirm poorly adjusted copper death-related genes and triggered immune responses. In osteoporosis, two clusters of molecules in connection with copper death proliferation were outlined. The assessed levels of immune infiltration showed prominent heterogeneity between the different clusters. Cluster 2 was characterized by a raised immune score accompanied with relatively high levels of immune infiltration. The functional analysis we performed showed a close relationship between the different immune responses and specific differentially expressed genes in cluster 2. The random forest machine model showed the optimum discriminatory performance due to relatively low residuals and root mean square errors. Finally, a random forest model based on 5 genes was built, showing acceptable performance in an external validation dataset (AUC = 0.750). Calibration curve, Nomogram, and decision curve analyses also evinced fidelity in predicting subtypes of osteoporosis. Conclusion: Our study identifies the role of cuproptosis in OP and essentially illustrates the underlying molecular mechanisms that lead to OP heterogeneity.

Prophylactic application of dexmedetomidine reduces the incidence of Emergence delirium in children: A systematic review and Meta-analysis.

BACKGROUND: Emergence delirium (ED) is a common postoperative cognitive dysfunction in children. ED may cause distress to patients and their families in the early post-anesthesia period and have long-term adverse effects on children. THE PRIMARY PURPOSE: was to verify whether dexmedetomidine can reduce the occurrence of ED in children. RESEARCH TYPE: Systematic review and meta-analysis of RCTs. DATA ACQUISITION: A search was conducted on Web of Science, WHO Trials, Cochrane Library, Clinical Trials.gov, and PubMed for all published studies from inception to 23 Oct.2022. ELIGIBILITY CRITERIA: Randomized clinical trials that met the following criteria: patients aged 1-18 years, study site in the PACU (Post-anesthesia care unit), incidence of ED as the primary outcome, and prophylactic use of dexmedetomidine defined as injected before admission to the PACU. RESULTS: A total of 7 randomized trials were included (6 studies during eye and neck surgery, 1 during hernia surgery), involving 512 patients (257 (50.1%) with dexmedetomidine, and 250 (49.9%) with control. ED was observed in 17.51% of the patients treated with dexmedetomidine and in 43.14% of those receiving control (risk ratio (RR) = 0.40, 95 % confidence interval [CI] [0.30 - 0.55], P < 0.00001). Additionally, the prophylactic application of dexmedetomidine also reduced the occurrence of Post-Operating Nausea and Vomiting (RR = 0.24, 95%CI [0.12 - 0.49], P = 0.0001) and PACU stay time after extubation (mean difference (MD) = -1.57, 95%CI [-3.07 to -0.07], P = 0.04). However, sensitivity analysis of RCTs showed that our effect estimates were not stable (MD = -1.78, 95%CI [-4.18 - 0.62], P = 0.15). CONCLUSION: The prophylactic use of dexmedetomidine was associated with a reduction of ED. However, our findings only apply to eye and neck surgery. TRIAL REGISTRATION: PROSPERO: CRD42022371840.

Biomimetic triphasic silk fibroin scaffolds seeded with tendon-derived stem cells for tendon-bone junction regeneration.

The regeneration of tendon and bone junctions (TBJs), a fibrocartilage transition zone between tendons and bones, is a challenge due to the special triphasic structure. In our study, a silk fibroin (SF)-based triphasic scaffold consisting of aligned type I collagen (Col I), transforming growth factor ß (TGF-ß), and hydroxyapatite (HA) was fabricated to mimic the compositional gradient feature of the native tendon-bone architecture. Rat tendon-derived stem cells (rTDSCs) were loaded on the triphasic SF scaffold, and the high cell viability suggested that the scaffold presents good biocompatibility. Meanwhile, increased expressions of tenogenic-, chondrogenic-, and osteogenic-related genes in the TBJs were observed. The in vivo studies of the rTDSC-seeded scaffold in a rat TBJ rupture model showed tendon tissue regeneration with a clear transition zone within 8 weeks of implantation. These results indicated that the biomimetic triphasic SF scaffolds seeded with rTDSCs have great potential to be applied in TBJ regeneration.

Effect of graft tensioning on mechanical restoration in a rat model of anterior cruciate ligament reconstruction using free tendon graft.

PURPOSE: Initial graft tensioning is important in anterior cruciate ligament reconstruction (ACLR), but its effect on graft healing is still not clear. Since all previous animal studies on graft tensioning used bone-patellar tendon-bone, this study aimed to investigate the effect of initial graft tensioning on ACLR using tendon graft. METHODS: Fifty-five Sprague-Dawley rats underwent ACLR using flexor digitorum longus tendon graft. A constant force of 2 or 4 N was applied during graft fixation. At 0, 2, and 6 weeks, knee samples were harvested (n = 6) for static knee laxity test and graft pull-out test. Histological examination was performed at 2 and 6 weeks post-injury (n = 4). RESULTS: At time zero, knee laxity was restored by ACLR with 2 or 4 N tensioning as compared to ACL-deficient group (p < 0.001), and the 4 N group exhibited a better restoration as compared to 2 N group (p = 0.031). At week 2 post-operation, the 4 N group still exhibited a better restoration in knee laxity (p = 0.001) and knee stiffness (p = 0.002) than the 2 N group; the graft pull-out force (p = 0.032) and stiffness (p = 0.010) were also higher. At week 6 post-operation, there was no significant difference between the 2 and 4 N group in knee laxity and graft pull-out strength. Histological examination showed that the beneficial effect of higher initial graft tension may be contributed by maintenance of graft integrity at mid-substance and reduction in adverse peri-graft bone changes in the femoral tunnel region. CONCLUSIONS: A higher initial graft tension favours the restoration of knee laxity and promotes graft healing in ACLR using free tendon graft in the rat model.

Mining association rules between the granulation feasibility and physicochemical properties of aqueous extracts from Chinese herbal medicine in fluidized bed granulation.

Fluidized bed granulation (FBG) is a widely used granulation technology in the pharmaceutical industry. However, defluidization caused by the formation of large aggregates poses a challenge to FBG, particularly in traditional Chinese medicine (TCM) due to its complex physicochemical properties of aqueous extracts. Therefore, this study aims to identify the complex relationships between physicochemical characteristics and defluidization using data mining methods. Initially, 50 types of TCM were decocted and assessed for their potential influence on defluidization using a set of 11 physical properties and 10 chemical components, utilizing the loss rate as an evaluation index. Subsequently, the random forest (RF) and Apriori algorithms were utilized to uncover intricate association rules among physicochemical characteristics and defluidization. The RF algorithm analysis revealed the top 8 critical factors associated with defluidization. These factors include physical properties like glass transition temperature (Tg) and dynamic surface tension (DST) of DST100ms, DST1000ms, DST10ms and conductivity, in addition to chemical components such as fructose, glucose and protein contents. The results from Apriori algorithm demonstrated that lower Tg and conductivity were associated with an increased risk of defluidization, resulting in a higher loss rate. Moreover, DST100ms, DST1000ms and DST10ms exhibited a contrasting trend in the physical properties Specifically, defluidization probability increases when Tg and conductivity dip below 29.04℃ and 6.21 ms/m respectively, coupled with DST10ms, DST100ms and DST1000ms values exceeding 70.40 mN/m, 66.66 mN/m and 61.58 mN/m, respectively. Moreover, an elevated content of low molecular weight saccharides was associated with a higher occurrence of defluidization, accompanied by an increased loss rate. In contrast, protein content displayed an opposite trend regarding chemical properties. Precisely, the defluidization likelihood amplifies when fructose and glucose contents surpass 20.35 mg/g and 34.05 mg/g respectively, and protein concentration is less than 1.63 mg/g. Finally, evaluation criteria for defluidization were proposed based on these results, which could be used to avoid this situation during the granulation process. This study demonstrated that the RF and Apriori algorithms are effective data mining methods capable of uncovering key factors affecting defluidization.

Clinical effectiveness of pulsed electromagnetic field therapy as an adjunct treatment to eccentric exercise for Achilles tendinopathy: a randomised controlled trial.

BACKGROUND: The Achilles tendon is the largest and strongest tendon in the human body. Achilles tendinopathy (AT) is a common clinical problem with Achilles overuse. Eccentric exercise is often used as an initial treatment for these patients. Most patients with AT experienced moderate to severe pain, limiting the incentive to perform eccentric exercise. It is difficult for them to complete eccentric exercise for 3 months consecutively to obtain significant improvements. Using PEMF as an adjunct, there could be immediate pain relief and improved response to eccentric exercise by modulating the mechanical properties of the Achilles tendon. Participants may experience less pain while performing eccentric exercises to increase compliance with the rehabilitation programme. METHODS: This prospective randomised double-blinded, placebo-controlled trial aims to investigate the treatment effects of PEMF for participants with AT. All participants are randomised into two groups: the intervention group (n = 20; active PEMF treatment and eccentric exercise) and the control group (n = 20; sham treatment and eccentric exercise). Researchers perform self-reported, functional and ultrasonographic outcomes during baseline assessment, 4 weeks, 8 weeks follow-ups, and 3 and 6 months follow-ups after the commencement of the PEMF treatment. DISCUSSION: AT is a common clinical condition affecting athletes and sedentary populations. It is essential to investigate treatment adjuncts to improve rehabilitation outcomes for these patients. This trial may demonstrate the effectiveness of PEMF in relieving pain, improving function, and restoring mechanical changes of the tendon in participants with AT. TRIAL REGISTRATION: ClinicalTrials.gov NCT05316961. Registered on 7th April 2022.