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.

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.

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.

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.

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.

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.

Exploring the effect of the "quaternary regulation" theory of "peripheral nerve-angiogenesis-osteoclast-osteogenesis" on osteoporosis based on neuropeptides.

Osteoporosis is a common bone metabolic disease among the middle-aged and elderly, with its high incidence rate and a major cause of disability and mortality. Early studies found that bone metabolic homeostasis is achieved through osteogenesis-osteoclast coupling. Although current anti-osteoporosis drugs can attenuate bone loss caused by aging, they present specific side effects. With the discovery of CD31hi Emcnhi blood vessels in 2014, the effect of H-type blood vessels on bone metabolism has been valued by researchers, and the ternary regulation theory of bone metabolism of "Angiogenesis-Osteoclast-Osteogenesis" has also been recognized. Nowadays, more studies have confirmed that peripheral nerves substantially impact bone metabolism. However, due to the complex function of peripheral nerves, the crosstalk mechanism of "Peripheral nerve-Angiogenesis-Osteoclast-Osteogenesis" has not yet been fully revealed. Neuropeptide serves as signaling molecules secreted by peripheral nerves that regulate blood vessels, osteoblasts, and osteoclasts' functions. It is likely to be the breakthrough point of the quaternary regulation theory of "Peripheral nerve-Angiogenesis-Osteoclast-Osteogenesis". Here, we discuss the effect of peripheral nerves on osteoporosis based on neuropeptides.

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.

Persistent quadriceps muscle atrophy after anterior cruciate ligament reconstruction is associated with alterations in exercise-induced myokine production.

Purpose: Persistent quadriceps muscle atrophy is observed in a subset of patients following anterior cruciate ligament reconstruction (ACLR) despite the completion of comprehensive rehabilitation. Critically, quadriceps muscle atrophy correlates with muscle weakness and quadriceps strength deficits. The aim of this study was to examine the effect of resistance exercise on myokine levels and muscle atrophy status in ACLR patients with persistent quadriceps muscle atrophy. Methods: Sixteen participants between the ages of 18-39 with a Tegner score of >6 and who had undergone ACLR with hamstring graft were recruited for the study. Quadriceps muscle thicknesses were ascertained by ultrasonography and isokinetic strength assessments were made prior to commencing a single bout of resistance exercise training (RET). Blood samples were taken before and after RET and assayed for myokine expression. Self-reported activity level and knee function questionnaires were completed and recorded. Results: Clustering by quadriceps muscle size measurements created a non-atrophy group of 9 subjects and an atrophy group of 7 subjects. There were no significant between-group differences in anthropometric measurements, time post operation and knee function questionnaires, but the atrophic group comprised of patients with lower pre-injury sporting levels. The atrophy group exhibited significant lower side-to-side muscle thickness ratios and a decreasing trend in quadriceps strength deficits. Serum brain-derived neurotrophic factor (BDNF) was up-regulated in response to RET in non-atrophy group, but a negative fold change was detected in the atrophy group. Conclusion: The dysregulation in myokines plays an important role in patients failing to regain muscle mass after ACLR leading to persistent quadriceps muscle atrophy, which may potentiate greater strength deficits and poor functional recovery.

Vitamin D deficiency in athletes: Laboratory, clinical and field integration.

Vitamin D deficiency is highly prevalent in athletes. Increased utilisation and storage depletion may be key contributing factor. We found a higher prevalence of vitamin D inadequacy (deficiency/ insufficiency) in power than endurance sport athletes, which may be related to vitamin D utilisation and reserve in skeletal muscles.

Platelet-rich plasma pretreatment protects anterior cruciate ligament fibroblasts correlated with PI3K-Akt-mTOR pathway under hypoxia condition.

Background: /Objective: Biological factors such as platelet-rich plasma (PRP) combined with anterior cruciate ligament (ACL) primary repair technology are used to treat ACL injury. However, the protective mechanism of PRP for ACL fibroblasts under hypoxia condition is still unknown. The aim of this study was to investigate the protective effect of PRP on ACL fibroblasts under hypoxia condition and illustrate the mechanism of PRP regulating the ACL fibroblasts under hypoxia condition. Methods: The cells were divided into three groups: control group, hypoxia group and PRP pretreatment group. Lethal dose (LD) 50 for hypoxia induction time and the maximum efficacy of PRP concentration were confirmed by CCK-8 assay. The ability of cell apoptosis, cell proliferation, and cell migration were tested by flow cytometry, scratch assay and transwell assay, respectively. Extracellular matrix (ECM) synthesis and hypoxia-inducible factor 1α (HIF-1α) were identified by immunofluorescence staining, Masson's staining and transmission electron microscope analysis. Inflammatory cell infiltration was assessed by hematoxylin and eosin staining as well as immunofluorescence staining. Western blot analysis and real-time PCR were performed to assess the associated gene and protein expression, respectively. The ratio of phosphorylated/total PI3K, Akt and mTOR were also assessed by western blot analysis. Results: ① LD 50 of hypoxia was 48 â€‹h and the maximum efficacy of PRP concentration was 600 â€‹× â€‹109/L. ② ANNEXIN V-FITC/PI flow cytometry showed that the hypoxia condition significantly increased the apoptosis of cells (P â€‹< â€‹0.001) whereas PRP pretreatment significantly decreased the apoptosis of cells under hypoxia (P â€‹< â€‹0.001). The expressions of gene and protein of Bax, Bcl-2, cleaved-caspase 3 were consistent with the results of flow cytometric analysis. ③ Cell cycle analysis for flow cytometry showed the inhibitory effect of hypoxia and promotive effect of PRP pretreatment. ④ Immunofluorescence staining (HIF-1α, collagen I and III) showed the positive effect of hypoxia and negative effect of PRP on these parameters. Real-time PCR showed that type I and III collagen were 2.1 folds and 2.5 folds higher after 48 â€‹h hypoxia induction compared to the control group. PRP pretreatment significantly reduced the type I and III collagen mRNA expression of the hypoxia induced ACL fibroblasts to 78.5% and 77.7% at 48 â€‹h compared to hypoxia group (P â€‹< â€‹0.001), respectively.⑤ Cell migration assay showed that hypoxia condition significantly restrained cell migration compared with the control group. PRP could alleviate the inhibitory effect of hypoxia on fibroblasts. ⑥ Western blot analysis showed the ratio of phosphorylated/total PI3K, Akt and mTOR in hypoxia group increased to 31%, 20% and 44/% compared to control group, respectively. ⑦ The results of in vivo analysis was in accordance with the results of in vitro analysis. Conclusion: PRP can protect ACL fibroblasts via decreasing apoptosis and increasing cell viability, cell migration and cell proliferation under hypoxia condition. And such PRP protective effect was correlated with PI3K/Akt/mTOR pathway. The translational potential of this article: PRP can be used to treat patients with ACL tear by injection under arthroscopy or ultrasound guiding.

Application of suture anchors for a clinically relevant rat model of rotator cuff tear.

Current rat model of rotator cuff (RC) tear could not mimic the suture anchor (SA) repair technique in the clinical practice. We designed a novel SA for RC repair of rats to establish a clinically relevant animal model. Small suture anchors that fit the rat shoulder were assembled. 60 rats were assigned to the transosseous (TO) repair group or SA repair group (n = 30/group). Micro-computed tomography (Micro-CT) scanning, biomechanical test and histological analysis were implemented at 2, 4, and 8-week post-repair. The failure load and stiffness in the SA group were significantly higher than those of TO group at 4-week post-repair. Micro-computed tomography analysis showed the bone mineral density and trabecular thickness of the SA group were significantly lower than those of TO group. The SA group showed a better insertion continuity at 4-week post-repair compared to TO group. No significant difference in gait parameters was found between groups. Therefore, SA repair is applicable for the rat model of RC tears. The SA repair achieved superior RC tendon healing, but more extensive initial bone damage compared to TO repair, while the shoulder function was comparable. This model could replicate the current repair technique in the clinical situation and be considered for future preclinical studies on healing enhancement for RC tears. Statement of Clinical Significance: With high clinical relevance, this model may facilitate the translation from an animal study into clinical trials.

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.

Cross-Cultural Adaptation of Chinese Victorian Institute of Sports Assessment-Achilles (VISA-A) Questionnaire for Achilles Tendinopathy.

Background: Victorian Institute of Sports Assessment (VISA-A) is a patient-reported outcome for assessing symptoms severity associated with Achilles tendinopathy (AT). It is a valid and reliable tool that has been used widely for measuring and monitoring treatment outcomes for AT. This clinical measurement study aims to develop a Chinese version of the VISA-A questionnaire. The study objective is to adapt the VISA-A questionnaire cross-culturally and assess its psychometric property for Chinese-speaking individuals. Methods: VISA-A was translated and adapted cross-culturally according to international guidelines for self-reported questionnaires. During the establishment of Chinese VISA-A, there are 5 stages involved in the creation process, including translation, synthesis, reverse translation, review, and pretesting, which are performed by professionals in various fields, including orthopaedic surgeons, physiotherapists, and professional translators. Results: A total of 60 participants were recruited to complete the Chinese VISA-A and 36-Item Short Form Health Survey (SF-36) questionnaires. The overall test-retest reliability was 0.98 (intraclass correlation coefficient = 0.97-0.99). The correlation between Chinese VISA-A and physical function subscale (r = 0.70) was strong and statistically significant. There were moderate correlations between Chinese VISA-A, limitations to role of physical function subscale (r = 0.30), and bodily pain subscale (r = 0.42), which were also statistically significant. There were statistically significant differences in Chinese VISA-A scores between healthy control and pathologic group (P < .001), at-risk group, and pathologic group (P < .001) respectively. Conclusion: Chinese VISA-A demonstrated good reliability and validity for measuring symptom severity in patients with AT. Chinese VISA-A can be recommended as a self-reported measure for monitoring symptoms severity and treatment progress of patients with Achilles tendinopathy.Level of Evidence: Level II, cohort study.

Timing of postoperative weightbearing in the treatment of traumatic chondral injuries of the knee in athletes - A systematic review of current concepts in clinical practice.

BACKGROUND: Surgery aims to stimulate healing and enable a safe return to sport in athletes with symptomatic cartilage lesions of the knee. Timing of postoperative weightbearing is crucial, balancing a stimulation of the healing and avoiding reinjury.To explore current concepts of timing to partial and full weightbearing and rate of return to sport in athletes after articular cartilage surgery of the knee.Systematic Review of studies with level of evidence I-III. METHODS: Four databases (Pubmed, Web of Science, Scopus and Embase) were searched using a predetermined keyword strategy. Two independent reviewers screened results according to inclusion and exclusion criteria. Modified Coleman Methodology Score (mCMS) was used for the quality assessment. RESULTS: 5294 records were found. Data from ten studies was extracted after duplicate removal, title and abstract screening and full-text evaluation. Eight of the ten studies included a detailed rehabilitation protocol, including 336 out of a total athletic population of 401. 62% began partial weightbearing (PWB) 1-2 weeks postoperatively, while 38% began within 3-4 weeks. The studies that had a later PWB all returned to full weightbearing (FWB) within 6-8 weeks. One study with early PWB returned to early FWB, while the other two returned 10-12 weeks postoperatively. "Return to Sport" (RTS) was the most common reported outcome measure, with most studies reporting RTS at 80% or higher. CONCLUSION: There is no clear evidence that the timing of weightbearing (WB) affects the outcome and return to sport in athletes after surgery for focal full-thickness cartilage lesions of the knee. On the other hand, there seems to be no adverse effects in adopting an early WB strategy, currently defined differently by different authors. Further studies directly comparing the timing of WB for specific surgical procedures in athletes and with relevant control groups is recommended. There is a need for a consensus in regard to more exactly defining "early" vs "late" weightbearing in relation to a universal and precisely defined state of healing.

Effects of Deficits in the Neuromuscular and Mechanical Properties of the Quadriceps and Hamstrings on Single-Leg Hop Performance and Dynamic Knee Stability in Patients After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Understanding the role of neuromuscular and mechanical muscle properties in knee functional performance and dynamic knee stability after anterior cruciate ligament reconstruction (ACLR) may help in the development of more focused rehabilitation programs. PURPOSE: To compare the involved and uninvolved limbs of patients after ACLR in terms of muscle strength, passive muscle stiffness, muscle activation of the quadriceps and hamstrings, hop performance, and dynamic knee stability and to investigate the association of neuromuscular and mechanical muscle properties with hop performance and dynamic knee stability. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHOD: The authors studied the quadriceps and hamstring muscles in 30 male patients (mean ± SD age, 25.4 ± 4.1 years) who had undergone unilateral ACLR. Muscle strength was measured using isokinetic testing at 60 and 180 deg/s. Passive muscle stiffness was quantified using ultrasound shear wave elastography. Muscle activation was evaluated via electromyographic (EMG) activity. Hop performance was evaluated via a single-leg hop test, and dynamic knee stability was evaluated via 3-dimensional knee movements during the landing phase of the hop test. RESULTS: Compared with the uninvolved limb, the involved limb exhibited decreased peak torque and shear modulus in both the quadriceps and hamstrings as well as delayed activity onset in the quadriceps (P < .05 for all). The involved limb also exhibited a shorter hop distance and decreased peak knee flexion angle during landing (P < .05 for both). Decreased peak quadriceps torque at 180 deg/s, the shear modulus of the semitendinosus, and the reactive EMG activity amplitude of the semimembranosus were all associated with shorter hop distance (R 2 = 0.565; P < .001). Decreased quadriceps peak torque at 60 deg/s and shear modulus of the vastus medialis were both associated with smaller peak knee flexion angle (R 2 = 0.319; P < .001). CONCLUSION: In addition to muscle strength deficits, deficits in passive muscle stiffness and muscle activation of the quadriceps and hamstrings were important contributors to poor single-leg hop performance and dynamic knee stability during landing. Further investigations should include a rehabilitation program that normalizes muscle stiffness and activation patterns during landing, thus improving knee functional performance and dynamic knee stability.

Effects of Whole-Body Vibration Therapy on Quadriceps Function in Patients With Anterior Cruciate Ligament Reconstruction: A Systematic Review.

CONTEXT: Quadriceps dysfunction is common for patients after anterior cruciate ligament reconstruction (ACLR). Whole-body vibration (WBV) could effectively treat quadriceps dysfunction. OBJECTIVE: To summarize WBV protocols for patients with ACLR and to evaluate the effects of WBV on quadriceps function. DATA SOURCES: PubMed, CINAHL, SportDiscus, Web of Science, Medline, and Embase were searched from inception to January 2020. STUDY SELECTION: Randomized controlled trials recruiting patients with ACLR, using WBV as intervention, and reporting at least 1 of the following outcomes, strength, rate of torque development (RTD), and voluntary activation ratio of quadriceps, were included. STUDY DESIGN: Systematic review. EVIDENCE LEVEL: Level 3. METHODS: This systematic review was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality of evidence was determined by PEDro criteria and GRADE system. Participant characteristics, interventions, and the relevant results of the included studies were extracted and synthesized in a narrative way. RESULTS: In total, 8 studies were included. Of these, 2 studies had serious risk of bias. Five of 8 studies implemented a series of WBV program ranging from 2 to 10 weeks in duration, while the other 3 studies implemented a single session of WBV. Eight WBV protocols were reported. The reported outcomes consisted of quadriceps strength, RTD, and central activation ratio. WBV protocols were heterogeneous. Low quality of evidence supported that exclusive conventional rehabilitation was more effective than exclusive WBV therapy in increasing quadriceps strength. Low quality of evidence supported that WBV combined with conventional rehabilitation was more beneficial in increasing quadriceps strength when compared with conventional rehabilitation alone. Very low quality of evidence supported the efficacy of a single session of WBV on quadriceps function. CONCLUSIONS: There is no standardized WBV protocol for patients with ACLR, and the effectiveness of WBV in rehabilitation on quadriceps function remains inconclusive.

Are muscle weakness and stiffness risk factors of the development of rotator cuff tendinopathy in overhead athletes: a systematic review.

BACKGROUND: Underlying muscle weakness and stiffness may increase the risk of developing rotator cuff tendinopathy. This systematic review aims to assess existing prospective studies to summarize whether muscle weakness and stiffness are risk factors for the development of rotator cuff tendinopathy in overhead athletes. METHODS: A systematic search was performed using PRISMA guidelines. Prospective studies measuring muscle strength or stiffness and the incidence of rotator cuff tendinopathy were included. Quality assessment was performed with the Newcastle-Ottawa quality assessment scale. RESULTS: The search yielded six studies, with a total of 523 trained overhead athletes followed up for one season. External rotation (ER) and internal rotation (IR) strength were described as protective factors against the development of rotator cuff tendinopathy. Athletes who did not sustain shoulder injuries had statistically stronger eccentric IR (p < 0.01) and ER (p < 0.05) strength in the pre-season assessment. Muscle stiffness indicated by limited range of motion of <106° for shoulder ER was described as a risk factor with an odds ratio of 1.12 (p < 0.001). Imbalance between ER and IR strength was reported as risk factors for shoulder injuries in two studies, with a relative risk of 2.57 (p < 0.05) reported in one study. Supraspinatus weakness was also reported as a risk factor for shoulder injuries in one study. CONCLUSION: Limited evidence support ER, IR weakness, limited ER range of motion, and very limited evidence support imbalance in ER/IR strength, and supraspinatus weakness as risk factors for rotator cuff tendinopathy in overhead athletes. No existing studies investigated the general population on this topic. Future cohort studies may improve on existing evidence with investigations on the general public, a longer follow-up time, clearly documented injury history, and a stringent diagnosis to rotator cuff tendinopathy.

Decreased passive muscle stiffness of vastus medialis is associated with poorer quadriceps strength and knee function after anterior cruciate ligament reconstruction.

BACKGROUND: Muscle deficits of the quadriceps and hamstrings are common after anterior cruciate ligament reconstruction, and increase the risk of knee reinjury. Muscle stiffness is an important factor for dynamic joint stability. However, the changes in quadriceps and hamstring muscle stiffness and its influence after anterior cruciate ligament reconstruction remain unclear. METHOD: Twenty-five male subjects with anterior cruciate ligament reconstruction and twenty-one matched healthy subjects participated in this study. The passive muscle stiffness of the quadriceps and hamstrings was assessed by shear modulus using ultrasound shear wave elastography. The isokinetic muscle strengths of the quadriceps and hamstrings were tested. Knee function was evaluated by the International Knee Documentation Committee and Lysholm score. Muscle stiffness was compared between limbs via non-parametric tests. Correlation analysis was used to detect the relationship between muscle stiffness, isokinetic muscle strength and knee functional scores. FINDINGS: The involved limb exhibited significantly decreased shear modulus in the vastus medialis compared to the dominant limbs(z = -3.585;P = 0.001;ES = 1.13) and non-dominant limbs(z = -3.551;P = 0.002;ES = 1.24) of healthy controls. The shear modulus of ST was also significantly lower in the involved limb when compared with the contralateral limbs(z = -3.996;P < 0.001;ES = 1.33), dominant limbs(z = -4.477;P < 0.001;ES = 1.65) and non-dominant limbs(z = -4.234;P = 0.001;ES = 1.43) of healthy controls. The shear modulus of the vastus medialis was associated with quadriceps peak torque at 60°/s(r = 0.470; p < 0.001) and knee functional score(r = 0.459; p = 0.021). INTERPRETATION: The passive muscle stiffness of the vastus medialis decreased after anterior cruciate ligament reconstruction, which is associated with poorer quadriceps strength and knee function. The effect of modulation of muscle stiffness on improving knee function warrants future investigation.