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1.
J Orthop Surg Res ; 19(1): 457, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095889

ABSTRACT

BACKGROUND: There are many adhesion barrier materials, cross-linked or non-cross-linked hyaluronic acid (HA), used during surgeries. PURPOSE: This study investigates the efficacy of cross-linked and non-cross-linked HA in preventing Achilles tendon adhesions. We hypothesized that non-cross-linked HA may be more effective than cross-linked HA in preventing Achilles tendon adhesions following injury and repair. METHODS: Twenty male Sprague Dawley rats, totaling 40 legs, underwent Achilles tendon transection and repair. Following the surgery, they were treated simultaneously with cross-linked and non-cross-linked HA formulations. The rats were divided into four groups: a positive control group, a group treated with BMC non-cross-linked HA gel, a group treated with DEFEHERE cross-linked HA gel, and a group treated with ANIKA cross-linked HA gel. Four weeks after surgery, macroscopic evaluation of peritendinous adhesion and histological analysis were conducted to assess the effectiveness of the treatments. RESULTS: Non-cross-linked BMC HA demonstrated superior efficacy in preventing tendon adhesions compared to cross-linked HA and control groups. Histological analysis confirmed reduced adhesion severity in the non-cross-linked HA group (P < 0.05). The findings support the potential of non-cross-linked HA as a treatment to inhibit tendon adhesions. Further research, including clinical trials, is warranted to validate these results in human subjects. CONCLUSIONS: Non-cross-linked BMC HA had significantly lower tendon adhesions parameters and better healing scores in histological analysis than cross-linked HA and control group did. Non-cross-linked HA holds promise as a potential treatment to inhibit the formation of such adhesions.


Subject(s)
Achilles Tendon , Hyaluronic Acid , Postoperative Complications , Rats, Sprague-Dawley , Animals , Achilles Tendon/injuries , Achilles Tendon/surgery , Tissue Adhesions/prevention & control , Tissue Adhesions/etiology , Male , Rats , Postoperative Complications/prevention & control , Disease Models, Animal , Cross-Linking Reagents , Tendon Injuries/prevention & control , Tendon Injuries/surgery , Treatment Outcome
2.
Am J Sports Med ; : 3635465241262339, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39126190

ABSTRACT

BACKGROUND: The ulnar collateral ligament (UCL) is essential for elbow stability during pitching. In professional baseball, the fastball (FB) is the most commonly used pitch, making postrecovery FB performance after UCL reconstruction (UCLR) a crucial aspect to consider. HYPOTHESES: (1) Pitchers undergoing UCLR would show no significant changes in performance metrics compared with nonoperated pitchers with similar FB velocity and spin rate, and (2) no significant variance would be found in these metrics within the operated pitchers concerning their preinjury anthropometric characteristics and pitching performance metrics. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The study included 91 Major League Baseball (MLB) pitchers who underwent primary UCLR between January 1, 2015, and December 31, 2021. A matched 1:1 control group of MLB pitchers without UCLR injuries was established. Publicly available pitch metrics and anthropometric data were compared between the study and control groups. RESULTS: Disparities in several performance metrics emerged during the first postreturn year (PRY1), including FB use percentage (P = .029), fielder independent pitching (FIP) (P = .021), and standardized FB runs above average per 100 pitches (wFB/C) (P < .001). Subgroup analysis within the UCLR group revealed a negative correlation between presurgery mean FB velocity and its subsequent change (P < .001) and a positive correlation with changes in FIP (P = .025) from the index year to PRY1. A negative correlation was observed between FB use percentage in the index year and its change by PRY1 (P = .002). By the second postreturn year, no significant differences were found in these performance metrics. No factors were significantly related to prolonged recovery time. CONCLUSION: Although FB velocity and spin rate remained consistent, significant differences were observed in FB use percentage, FIP, and wFB/C in PRY1. However, by second postreturn year, these differences were no longer significant. No specific risk factors were identified concerning prolonged recovery time between pre-UCLR FB pitching metrics and the physical anthropometric data. These results suggest that although the short-term postsurgery period may affect more specialized pitching metrics, the basic pitching performance metrics, as hypothesized, remain largely unaffected by UCLR.

3.
BMC Musculoskelet Disord ; 25(1): 625, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39107761

ABSTRACT

BACKGROUND: Anterior cruciate ligament (ACL) graft failure is influenced by factors such as meniscal tears and tibial plateau slope. Combined anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstruction has reduced failure rates; however, its efficacy in high-risk patients remains unclear. This study hypothesized that combined ACL and ALL reconstruction would yield similar clinical outcomes in patients with varying risks of ACL failure. PATIENTS AND METHODS: A total of 76 patients who underwent primary single-bundle ACL reconstruction combined with ALL reconstruction between June 2018 and June 2021 were included. The medial tibial slope (MTS), lateral tibial slope (LTS), and anterior tibial translation (ATT) were measured using magnetic resonance imaging and plain radiography of the knee joint. The meniscal lesions were assessed during surgery. Preoperative clinical assessments and final follow-up were conducted using patient-reported outcome measurements (PROMs), including the International Knee Documentation Committee (IKDC) evaluation, Lysholm knee scoring scale, and Tegner Activity scale. PROMs were collected at least two years postoperatively. RESULTS: The average follow-up was 32.5 ± 7.4 months. There were no significant differences in postoperative IKDC score, Lysholm score, or Tegner activity score between patients with or without medial meniscus injury (p = 0.155, 0.914, and 0.042, respectively), with or without lateral meniscus injury (p = 0.737, 0.569, and 0.942, respectively), medial tibial slope > 12° or ≤ 12° (p = 0.290, 0.496, and 0.988, respectively), or lateral tibial slope > 7.4° or ≤ 7.4° (p = 0.213, 0.625, and 0.922, respectively). No significant correlations were found between anterior tibial translation and postoperative IKDC (R = -0.058, p = 0.365), Lysholm (R = -0.017, p = 0.459), or Tegner activity scores (R = -0.147, p = 0.189). CONCLUSION: Our study demonstrates that single-bundle ACL reconstruction combined with ALL reconstruction provides reliable and comparable clinical outcomes in patients with high-risk factors for ACL graft failure, such as increased tibial slope or meniscal injury. Our results suggest that the indications for ALL reconstruction may be expanded to include patients with a high tibial slope or meniscal injury, because these factors have been shown to contribute to increased rotational instability and high rates of ACL graft failure. Future prospective randomized controlled trials with large patient cohorts and long follow-up periods are needed to validate these findings and establish clear guidelines for patient selection and surgical decision-making. LEVEL OF EVIDENCE: Level 3.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Humans , Anterior Cruciate Ligament Reconstruction/methods , Anterior Cruciate Ligament Reconstruction/adverse effects , Female , Male , Adult , Anterior Cruciate Ligament Injuries/surgery , Risk Factors , Young Adult , Retrospective Studies , Knee Joint/surgery , Knee Joint/diagnostic imaging , Patient Reported Outcome Measures , Tibial Meniscus Injuries/surgery , Tibial Meniscus Injuries/diagnostic imaging , Anterior Cruciate Ligament/surgery , Anterior Cruciate Ligament/diagnostic imaging , Adolescent , Treatment Failure , Follow-Up Studies , Tibia/surgery , Tibia/diagnostic imaging , Middle Aged , Magnetic Resonance Imaging
4.
BMC Musculoskelet Disord ; 25(1): 594, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39069639

ABSTRACT

BACKGROUND: We investigated whether double-bundle (DB) anterior cruciate ligament (ACL) reconstruction (ACLR) combined with anterolateral ligament reconstruction (ALLR) improved clinical and radiological outcomes in patients at high risk of ACL failure. The primary outcome was graft failure, and secondary outcomes included knee stability and patient-reported outcome measures (PROMs). PATIENTS AND METHODS: Fifty-two patients who underwent DB ACLR combined with ALLR were included in this retrospective cohort study. Preoperative risk factors, including femorotibial angle (FTA), lateral tibial slope (LTS), medial tibial slope (MTS), and meniscal tears, were assessed using X-ray and magnetic resonance imaging (MRI). The grade of post-operative pivot shift, Lysholm score, and Tegner activity score were used to assess clinical outcomes. The minimum follow up duration was 2 years. RESULTS: The cohort (mean age, 26.1 ± 9.4 years; 51.9% male) had a mean follow-up duration of 28.9 ± 3.4 months. Preoperatively, 57.8% had lateral meniscus (LM) tears, and 61.0% had a grade 2-3 pivot shift. Postoperatively, no graft failures or revision cases occurred during follow-up. Approximately 90.4% of the patients exhibited a negative pivot shift (p < 0.001), with Lysholm and Tegner activity scores of 92.5 ± 6.1 and 5.1 ± 2.0. The medial meniscus (MM) tear group had a significantly smaller FTA than the intact group (p = 0.043). No significant differences in PROMs were found between the LM tear and intact LM groups or between the high and low MTS or LTS groups (p = n.s.). CONCLUSION: DB ACLR combined with ALLR had satisfactory clinical outcomes in patients at high risk of ACL failure, with no graft failures observed during a mean follow-up duration of 2.4 years. The technique effectively reduced the postoperative pivot shift, regardless of preoperative risk factors. STUDY DESIGN: Level IV, retrospective therapeutic case-series. TRAIL REGISTRATION: ethical approval number, 202300134B0; ethical committee, the Institutional Review Board of Chang Gung Medical Foundation.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Humans , Anterior Cruciate Ligament Reconstruction/methods , Anterior Cruciate Ligament Reconstruction/adverse effects , Female , Male , Retrospective Studies , Adult , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Injuries/diagnostic imaging , Young Adult , Adolescent , Risk Factors , Treatment Failure , Patient Reported Outcome Measures , Follow-Up Studies , Magnetic Resonance Imaging , Knee Joint/surgery , Knee Joint/diagnostic imaging , Knee Joint/physiopathology , Joint Instability/surgery , Joint Instability/diagnostic imaging , Anterior Cruciate Ligament/surgery , Anterior Cruciate Ligament/diagnostic imaging
5.
Curr Issues Mol Biol ; 46(6): 5052-5065, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38920975

ABSTRACT

A low-calcium microenvironment is imperative for spermatozoa maturation within the epididymis. Our previous work has shown that γ-glutamyl carboxylase (GGCX), the carboxylation enzyme of the matrix Gla protein (MGP), plays an essential role in epididymal calcium homeostasis and sperm maturation in rats and that the GGCX SNP mutation rs699664 was associated with asthenozoospermia (AZS) in humans. Here, we investigated the expression patterns of GGCX and MGP in the mouse epididymis and generated GgcxK325Q knock-in (KI) mice. We also tested the effects of this mutation on epididymal calcium homeostasis, sperm function, and male fertility in GgcxK325Q-/- mice. The results showed that both GGCX and MGP were enriched in all regions of the mouse epididymis, especially in the initial segment of the epididymis. Double immunofluorescence staining revealed that GGCX colocalized with MGP in the epithelial cells of the initial segment and caput regions as well as in the lumen of the corpus and cauda regions of the mouse epididymis. However, the GgcxK325Q-/- mice were fertile with normal epididymal morphology, sperm functions, and epididymal calcium concentration. Overall, our findings revealed that the GgcxK325Q mutation does not exert any discernible effect on male fertility in mice.

6.
J Orthop Surg Res ; 19(1): 315, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807173

ABSTRACT

BACKGROUND: The impact of anatomical factors, such as the lateral tibial slope (LTS), on outcomes following anterior cruciate ligament (ACL) reconstruction is an area of growing interest. This study was led by the observation that patients with a higher LTS may have different recovery trajectories. HYPOTHESIS/PURPOSE: The purpose of this study was to investigate the correlation between a higher LTS and long term subjective outcomes following single-bundle ACL reconstruction. STUDY DESIGN: This study was designed as a retrospective cohort study. METHODS: The study comprised 138 patients who underwent single-bundle ACL reconstruction. The LTS was measured on preoperative radiographs. Patient-reported outcome measures (PROMs) were collected, which included the Lysholm Knee Score, UCLA Activity Score, IKDC Score, and Tegner Activity Score, over a mean follow-up duration of 137 months. RESULTS: A significant negative correlation was found between LTS and all measured PROMs (p < 0.001). The established cut-off value of LTS distinguishing between "Good" and "Fair" Lysholm scores was 8.35 degrees. Female patients have statistically significant higher LTS and lower PROMs scores than male. Patients with LTS greater than or equal to 8.35 had significantly lower PROMs, indicative of poorer functional and subjective outcomes. CONCLUSION: Our findings suggest that a higher LTS is associated with inferior subjective outcomes following single-bundle ACL reconstruction in long term. The LTS cut-off value of 8.35 degrees could potentially be used as a reference in preoperative planning and patient counseling. CLINICAL RELEVANCE: Understanding the relationship between LTS and ACL reconstruction outcomes could inform surgical planning and postoperative management. These findings highlight the need to consider anatomical variances, such as LTS, when assessing patient-specific risks and recovery expectations, contributing to the advancement of personalized care in sports medicine.


Subject(s)
Anterior Cruciate Ligament Reconstruction , Patient Reported Outcome Measures , Tibia , Humans , Anterior Cruciate Ligament Reconstruction/methods , Male , Female , Retrospective Studies , Adult , Tibia/surgery , Tibia/diagnostic imaging , Young Adult , Treatment Outcome , Adolescent , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Injuries/diagnostic imaging , Middle Aged , Cohort Studies , Follow-Up Studies , Time Factors
7.
Article in English | MEDLINE | ID: mdl-38796728

ABSTRACT

PURPOSE: Multifaceted factors contribute to inferior outcomes following anterior cruciate ligament (ACL) reconstruction surgery. A particular focus is placed on the posterior tibial slope (PTS). This study introduces the integration of machine learning and artificial intelligence (AI) for efficient measurements of tibial slopes on magnetic resonance imaging images as a promising solution. This advancement aims to enhance risk stratification, diagnostic insights, intervention prognosis and surgical planning for ACL injuries. METHODS: Images and demographic information from 120 patients who underwent ACL reconstruction surgery were used for this study. An AI-driven model was developed to measure the posterior lateral tibial slope using the YOLOv8 algorithm. The accuracy of the lateral tibial slope, medial tibial slope and tibial longitudinal axis measurements was assessed, and the results reached high levels of reliability. This study employed machine learning and AI techniques to provide objective, consistent and efficient measurements of tibial slopes on MR images. RESULTS: Three distinct models were developed to derive AI-based measurements. The study results revealed a substantial correlation between the measurements obtained from the AI models and those obtained by the orthopaedic surgeon across three parameters: lateral tibial slope, medial tibial slope and tibial longitudinal axis. Specifically, the Pearson correlation coefficients were 0.673, 0.850 and 0.839, respectively. The Spearman rank correlation coefficients were 0.736, 0.861 and 0.738, respectively. Additionally, the interclass correlation coefficients were 0.63, 0.84 and 0.84, respectively. CONCLUSION: This study establishes that the deep learning-based method for measuring posterior tibial slopes strongly correlates with the evaluations of expert orthopaedic surgeons. The time efficiency and consistency of this technique suggest its utility in clinical practice, promising to enhance workflow, risk assessment and the customization of patient treatment plans. LEVEL OF EVIDENCE: Level III, cross-sectional diagnostic study.

8.
Biochem Biophys Res Commun ; 710: 149874, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38581950

ABSTRACT

Synaptic plasticity is crucial as it dynamically molds the strength and connectivity of neural circuits, influencing learning, memory, and the development of neurological disorders. Metformin, a widely prescribed anti-diabetic medication, has been shown to readily cross the blood-brain barrier (BBB) and the placenta. However, its prolonged impact on neuronal morphology and functions remains underexplored. In this study, we investigated the influence of metformin on dendrite development and synaptic plasticity in embryonic brains and primary rat cortical neurons. Our findings reveal a negative modulation of dendrite development by metformin, as evidenced by altered dendritic arborization, impaired dendritic spine morphology and disruptions in synaptic plasticity, suggesting a potential link between metformin exposure and aberrations in neuronal connectivity. In addition, we extend our insights to the impact of maternal metformin exposure on embryonic brains, revealing a significant inhibition of dendrite development in E18.5 rat brains. In conclusion, this study adds to the expanding knowledge base on the non-metabolic effects of metformin, emphasizing the significance of assessing its potential influence on both neuronal structure and function. There is an urgent need for further investigations into the enduring impact of prolonged metformin administration on the structural and functional aspects of neurons.


Subject(s)
Neuronal Plasticity , Neurons , Pregnancy , Female , Rats , Animals , Neuronal Plasticity/physiology , Learning , Blood-Brain Barrier , Dendrites
9.
Medicina (Kaunas) ; 60(4)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38674191

ABSTRACT

There is currently no consensus on the optimal placement of the tibial tunnel for double-bundle posterior cruciate ligament (PCL) reconstruction. The purpose of this study was to compare the clinical and radiologic outcomes of double-bundle PCL reconstruction utilizing anatomic versus low tibial tunnels. We conducted a retrospective cohort study involving patients who underwent double-bundle PCL reconstruction between Jan 2019 and Jan 2022, with a minimum follow-up of 2 years (n = 36). Based on the tibial tunnel position on postoperative computed tomography, patients were categorized into two groups: anatomic placement (group A; n = 18) and low tunnel placement (group L; n = 18). We compared the range of motion, stability test, complications, and side-to-side differences in tibial posterior translation using kneeling stress radiography between the two groups. There were no significant differences between the groups regarding clinical outcomes or complication rates. No significant differences in the posterior drawer test and side-to-side difference on kneeling stress radiography (2.5 ± 1.2 mm in group A vs. 3.7 ± 2.0 mm in group L; p = 0.346). In conclusion, the main findings of this study indicate that both anatomic tunnel and low tibial tunnel placements in double-bundle PCL reconstruction demonstrated comparable and satisfactory clinical and radiologic outcomes, with similar overall complication rates at the 2-year follow-up.


Subject(s)
Posterior Cruciate Ligament Reconstruction , Tibia , Humans , Male , Female , Retrospective Studies , Adult , Tibia/surgery , Tibia/diagnostic imaging , Follow-Up Studies , Posterior Cruciate Ligament Reconstruction/methods , Range of Motion, Articular , Middle Aged , Treatment Outcome , Posterior Cruciate Ligament/surgery , Posterior Cruciate Ligament/injuries , Tomography, X-Ray Computed/methods , Cohort Studies , Radiography/methods
10.
Am J Physiol Cell Physiol ; 326(6): C1648-C1658, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38682237

ABSTRACT

The authors' previous research has shown the pivotal roles of cyclin-dependent kinase 5 (CDK5) and its regulatory protein p35 in nerve growth factor (NGF)-induced differentiation of sympathetic neurons in PC12 cells. During the process of differentiation, neurons are susceptible to environmental influences, including the effects of drugs. Metformin is commonly used in the treatment of diabetes and its associated symptoms, particularly in diabetic neuropathy, which is characterized by dysregulation of the sympathetic neurons. However, the impacts of metformin on sympathetic neuronal differentiation remain unknown. In this study, we investigated the impact of metformin on NGF-induced sympathetic neuronal differentiation using rat pheochromocytoma PC12 cells as a model. We examined the regulation of TrkA-p35/CDK5 signaling in NGF-induced PC12 differentiation. Our results demonstrate that metformin reduces NGF-induced PC12 differentiation by inactivating the TrkA receptor, subsequently inhibiting ERK and EGR1. Inhibition of this cascade ultimately leads to the downregulation of p35/CDK5 in PC12 cells. Furthermore, metformin inhibits the activation of the presynaptic protein Synapsin-I, a substrate of CDK5, in PC12 differentiation. In addition, metformin alters axonal and synaptic bouton formation by inhibiting p35 at both the axons and axon terminals in fully differentiated PC12 cells. In summary, our study elucidates that metformin inhibits sympathetic neuronal differentiation in PC12 cells by disrupting TrkA/ERK/EGR1 and p35/CDK5 signaling. This research contributes to uncovering a novel signaling mechanism in drug response during sympathetic neuronal differentiation, enhancing our understanding of the intricate molecular processes governing this critical aspect of neurodevelopment.NEW & NOTEWORTHY This study unveils a novel mechanism influenced by metformin during sympathetic neuronal differentiation. By elucidating its inhibitory effects from the nerve growth factor (NGF) receptor, TrkA, to the p35/CDK5 signaling pathways, we advance our understanding of metformin's mechanisms of action and emphasize its potential significance in the context of drug responses during sympathetic neuronal differentiation.


Subject(s)
Cell Differentiation , Cyclin-Dependent Kinase 5 , Metformin , Nerve Growth Factor , Neurons , Receptor, trkA , Animals , Metformin/pharmacology , Rats , PC12 Cells , Cyclin-Dependent Kinase 5/metabolism , Cyclin-Dependent Kinase 5/antagonists & inhibitors , Nerve Growth Factor/metabolism , Nerve Growth Factor/pharmacology , Receptor, trkA/metabolism , Receptor, trkA/antagonists & inhibitors , Neurons/drug effects , Neurons/metabolism , Cell Differentiation/drug effects , Signal Transduction/drug effects , Neurogenesis/drug effects , Early Growth Response Protein 1/metabolism , Early Growth Response Protein 1/genetics , Nerve Tissue Proteins/metabolism , Nerve Tissue Proteins/genetics , Phosphotransferases
11.
Chemosphere ; 358: 142124, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677614

ABSTRACT

Metformin, the most commonly prescribed drug for the treatment of diabetes, is increasingly used during pregnancy to address various disorders such as diabetes, obesity, preeclampsia, and metabolic diseases. However, its impact on neocortex development remains unclear. Here, we investigated the direct effects of metformin on neocortex development, focusing on ERK and p35/CDK5 regulation. Using a pregnant rat model, we found that metformin treatment during pregnancy induces small for gestational age (SGA) and reduces relative cortical thickness in embryos and neonates. Additionally, we discovered that metformin inhibits neural progenitor cell proliferation in the sub-ventricular zone (SVZ)/ventricular zone (VZ) of the developing neocortex, a process possibly mediated by ERK inactivation. Furthermore, metformin induces neuronal apoptosis in the SVZ/VZ area of the developing neocortex. Moreover, metformin retards neuronal migration, cortical lamination, and differentiation, potentially through p35/CDK5 inhibition in the developing neocortex. Remarkably, compensating for p35 through in utero electroporation partially rescues metformin-impaired neuronal migration and development. In summary, our study reveals that metformin disrupts neocortex development by inhibiting neuronal progenitor proliferation, neuronal migration, cortical layering, and cortical neuron maturation, likely via ERK and p35/CDK5 inhibition. Consequently, our findings advocate for caution in metformin usage during pregnancy, given its potential adverse effects on fetal brain development.


Subject(s)
Cell Proliferation , Cyclin-Dependent Kinase 5 , Metformin , Neocortex , Metformin/pharmacology , Animals , Female , Pregnancy , Neocortex/drug effects , Cyclin-Dependent Kinase 5/metabolism , Rats , Cell Proliferation/drug effects , Neural Stem Cells/drug effects , Neural Stem Cells/metabolism , MAP Kinase Signaling System/drug effects , Neurons/drug effects , Rats, Sprague-Dawley , Cell Differentiation/drug effects , Neurogenesis/drug effects , Cell Movement/drug effects , Apoptosis/drug effects , Signal Transduction/drug effects
12.
Andrology ; 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38436139

ABSTRACT

BACKGROUND: As a component of the nucleosome remodeling and deacetylating (NuRD) complex, metastasis-associated protein 1 (MTA1) has been reported to be abundant in male reproductive system and might participate in spermatogenesis and sperm maturation, whereas the precise functional role of MTA1 in these processes is still undetermined. OBJECTIVE: To investigate the effect and potential function of MTA1 in male fertility. MATERIALS AND METHODS: Mta1 knockout mice (Mta1-/- ) were employed to detect their reproductive phenotype. The pH value of Mta1-/- epididymal luminal fluid was measured, and the potential mechanism of MTA1 involved in regulating luminal acidification was detected in vivo and in vitro. A vasectomy model with abnormal pH of epididymal lumen was established to further detect the effect of MTA1 on epididymal luminal microenvironment. RESULTS: Mta1-/- mice were fertile without any detectable defects in spermatogenesis or sperm motility while the deficiency of MTA1 could acidify the initial segment of epididymis to a certain extent. MTA1 could interact with estrogen receptor alpha (ERα) and inhibit the transcription of ERα target gene, hydrogen exchanger 3 (NHE3), and ultimately affect the epididymal luminal milieu. After vasectomy, the Mta1-/- mice presented a more acidic epididymal lumen which was closer to the normal state compared to the wild-type model. DISCUSSION AND CONCLUSION: MTA1 is dispensable for male fertility in mice, but plays a potentially important function in regulating luminal acidification of the epididymis.

13.
Arthroscopy ; 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38447626

ABSTRACT

PURPOSE: To prospectively compare pain intensity and patient-reported outcomes (PROs) after arthroscopic rotator cuff repair (ARCR) between patients who received ultrasound-guided suprascapular nerve block (SSNB) and axillary nerve block (ANB) as well as preincisional parecoxib and patients who received preincisional parecoxib only. METHODS: Sixty-one patients receiving ARCR between March 2020 and March 2021 were prospectively enrolled. They were randomly assigned to the peripheral nerve block group (group N, n = 30) or control group (group C, n = 31). Two patients in group C were excluded because of miscommunication. All patients were administered 40 mg of parecoxib intravenously prior to induction of anesthesia. SSNB and ANB were performed after general anesthesia in group N, whereas no nerve block was performed in group C. Pain intensity was compared before surgery, as well as immediately, 24 hours, and 2 weeks after surgery. PROs, including the Oxford Shoulder Score, University of California-Los Angeles shoulder score, and Single Assessment Numeric Evaluation score, were compared before and 6 months after surgery. RESULTS: The numerical rating scale (NRS) score for resting pain was significantly lower in group N (4.9 ± 3.1 vs 7.6 ± 2.5, P < .001) immediately after surgery, but no difference was noted 24 hours after surgery. The resting pain NRS score 2 weeks after surgery was significantly lower in group N (1.4 ± 1.6 vs 2.7 ± 2.7, P = .03), but the scores for movement-evoked pain and night pain were similar. All PROs significantly improved 6 months after surgery in both groups, but there was no difference between the 2 groups. CONCLUSIONS: The addition of preoperative ultrasound-guided SSNB and ANB to parecoxib offered better resting pain control immediately and 2 weeks after ARCR, but there was no benefit for PROs 6 months after surgery. LEVEL OF EVIDENCE: Level II, prospective randomized controlled trial.

14.
BMC Sports Sci Med Rehabil ; 16(1): 44, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38347601

ABSTRACT

BACKGROUND: Ultrasonographic structural abnormalities are regarded as one of the risk factors of elbow injuries. Elbow injuries are commonly associated with decreased shoulder/elbow range of motion (ROM). The purpose of this study is to determine the relationship between shoulder/elbow ROM and elbow ultrasonographic structural abnormalities in Taiwan high school baseball players. METHODS: A total of 533 Taiwan high school baseball players were enrolled. Physical examinations including measurements on shoulder/elbow ROM and elbow sonographic examinations were performed and recorded by professional physicians. The analyses were conducted in three subgroups according to their defensive position because the training programs were different. All players pooled, pitchers-only, and fielders-only, due to several demographic differences among these subgroups. In all the subgroups, univariate analyses were conducted separately for participants with and those without elbow ultrasonographic structural abnormalities, and then multivariate analyses were conducted to identify factors significantly related. The odds ratios (ORs) were used to estimate the risk of elbow ultrasonographic structural abnormalities. RESULTS: Demographic data showed that pitchers had taller body height (P < 0.001) and greater elbow flexion/extension ROM (P < 0.001). When all players were pooled, significant risk factors included started playing baseball at an younger age (OR = 1.202; 95% CI = 1.064-1.357; P = 0.003), longer experience of official baseball (OR = 1.154; 95% CI = 1.038-1.283; P = 0.008), lower total shoulder rotation angle (OR = 1.007; 95% CI = 1.000-1.014; P = 0.050), and less total elbow arm angle (OR = 1.052; 95% CI = 1.017-1.088; P = 0.003) For pitchers, significant risk factors included longer experience of official baseball (OR = 1.342; 95% CI = 1.098-1.640; P = 0.004), lower total shoulder rotation angle (OR = 1.016; 95% CI = 1.004-1.027; P = 0.006), and lower total elbow arm angle (OR = 1.075; 95% CI = 1.024-1.129; P = 0.004) (Table 5). There were no significant risk factors for elbow structural abnormalities in fielders. CONCLUSION: For Taiwan high school pitchers, longer official baseball experience, decreased shoulder total rotational angle, and decreased elbow total flexion/extension angle, were related to ultrasonographic structural abnormalities in elbows.

15.
Arch Orthop Trauma Surg ; 144(2): 619-626, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37962635

ABSTRACT

PURPOSE: To determine if there is a correlation between lateral tibial slope and long-term clinical results in patients who underwent double-bundle ACL reconstruction. METHODS: We retrospectively reviewed patients that received double-bundle ACL reconstruction at a single institution by a single surgeon from January 2011 to December 2014. All the magnetic resonance imaging were reviewed and lateral tibial slopes (LTS) were recorded by an experienced surgeon and rechecked by the other two authors of this study that specialized in orthopedic knee surgery. The relationship between PROMs measurement and lateral tibial slope were analyzed. The patients were then separated into two groups (LTS > 7.4° and < 7.4°) according to the previous study. RESULTS: A total of 119 patients were enrolled in this study. All enrolled patients were followed for at least 8 years. The PROMS result were negatively correlated with the lateral tibial slope (p values all < 0.001). The patients with high lateral tibial slope had significantly lower PROMS values (Lysholm 94.26 ± 5.61 vs 80.15 ± 8.28, p = 0.013; IKDC 82.99 ± 4.55 vs 70.09 ± 7.15, p = 0.003; Tegner 9.32 ± 0.95 vs 6.85 ± 1.99, p < 0.001). Finally, the LTS cutoff value between patients with "Good" and "Fair" Lysholm score in our study was 7.55 degrees. CONCLUSIONS: Patients with high lateral tibial slope may result in inferior long-term subjective outcomes. The using of double-bundle ACL reconstruction along cannot overcome the negative impact caused by steep lateral tibial slope. A lateral tibial slope of 7.55° may be used as a cut-off for a good clinical outcome. LEVEL OF EVIDENCE: III retrospective comparative prognostic trial.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Humans , Retrospective Studies , Anterior Cruciate Ligament Injuries/surgery , Anterior Cruciate Ligament Reconstruction/methods , Knee Joint/surgery , Tibia/surgery
16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1029076

ABSTRACT

The clinical data of 160 elderly patients with upper urinary tract stones who underwent flexible ureteroscopic lithotripsy (FURL) in Beijing Hospital from May 2021 to November 2022 were retrospectively analyzed, including 80 patients with ambulatory surgery (study group) and 80 patients with the traditional surgery (control group). The efficacy and safety were compared between two groups. There were no significant differences in the rate of complete stone removal (91.3% (73/80) vs. 90.0% (72/80), P>0.05), operation time (60.0 (41.0, 90.0)min vs.61.0(50.0, 96.5)min, P>0.05), and incidence of postoperative systemic inflammatory response syndrome (SIRS) (8.8% (7/80) vs.12.5% (10/80), P>0.05) between two groups, while the postoperative length of hospital stay (5.0 (5.0, 6.0)h vs. 18.0 (16.2, 30.0)h, P<0.05) was shorter and the medical expenses ((20 696.7±4 645.5)Yuan vs. (31 030.8±6 275.1)Yuan, P<0.05) was less in the study group than those in the control group. The study indicates that the day surgery mode of flexible ureteroscopic lithotripsy has advantages of faster recovery and less cost over the traditional surgery mode for elderly patients.

17.
Toxicol In Vitro ; 96: 105768, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38135130

ABSTRACT

Although immature differentiation and uncontrolled proliferation of hematopoietic stem cells are thought to be the primary mechanisms of acute myeloid leukemia (AML), the pathophysiology in most cases remains unclear. Dinaciclib, a selective small molecule targeting multiple cyclin-dependent kinases (CDKs), is currently being evaluated in oncological clinical trials. Despite the proven anticancer potential of dinaciclib, the differential molecular mechanisms by which it inhibits the growth of different AML cell lines remain unclear. In the current study, we treated HL-60 and KG-1 AML cell lines with dinaciclib and investigated the potential mechanisms of dinaciclib-induced AML cell growth inhibition using flow cytometry and western blotting assays. Data from HL-60 and KG-1 AML cells were validated using human primary AML cells. The results showed that the growth inhibitory effect of dinaciclib was more sensitive in HL-60 cells (IC50: 8.46 nM) than in KG-1 cells (IC50: 14.37 nM). The protein decline in Cyclin A/B and CDK1 and cell cycle arrest in the G2/M phase were more profound in HL-60 cells, corresponding to its growth inhibition. Although the growth inhibition of KG-1 cells by dinaciclib was still pronounced, the cell cycle-associated proteins were relatively insensitive. In addition to cell cycle regulation, the activation/expression of ERK1/STAT3/MYC signaling was significantly reduced by dinaciclib in KG-1 cells compared with that in HL-60 cells. Regarding the results of primary AML cells, we observed ERK1/STAT3/MYC inhibition and cell cycle regulation in different patients. These findings suggest that the cell cycle-associated and ERK1/STAT3/MYC signaling pathways might be two distinct mechanisms by which dinaciclib inhibits AML cells, which could facilitate the development of combination therapy for AML in the future.


Subject(s)
Cyclic N-Oxides , Indolizines , Leukemia, Myeloid, Acute , Proto-Oncogene Proteins c-myc , Pyridinium Compounds , Humans , Signal Transduction , Cell Division , Cell Cycle , Cell Cycle Proteins , Leukemia, Myeloid, Acute/drug therapy , STAT3 Transcription Factor
18.
Medicina (Kaunas) ; 59(10)2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37893536

ABSTRACT

Introduction: Concomitant nerve injuries with musculoskeletal injuries present a challenging problem. The goals of nerve reconstruction for the shoulder include shoulder abduction and external rotation. When patients fail to achieve acceptable shoulder external rotation and shoulder abduction, tendon transfers such as trapezius transfer offer a reliable option in the subsequent stage. Case Presentation: A 32-year-old male presented with weak external rotation in his left shoulder, after previous axillary nerve reconstruction. He received the ipsilateral lower trapezius transfer with the aim of improving the external rotation. Discussion: The lower trapezius restores a better joint reaction force in both the compressive-distractive and anterior-posterior balancing and provides a centering force through the restoration of the anterior-posterior force couple. Conclusion: We believe that the ipsilateral lower trapezius transfer to the infraspinatus is a good outcome and is effective in improving overall shoulder stability and the shoulder external rotation moment arm or at least maintaining in neutral position with the arm fully adducted in patients with post axillary nerve injuries post unsatisfactory nerve reconstruction to increase the quality of life and activities of daily living.


Subject(s)
Rotator Cuff Injuries , Superficial Back Muscles , Male , Humans , Adult , Rotator Cuff Injuries/complications , Rotator Cuff Injuries/surgery , Superficial Back Muscles/surgery , Tendon Transfer , Activities of Daily Living , Quality of Life , Range of Motion, Articular/physiology , Treatment Outcome
19.
Sci Rep ; 13(1): 16760, 2023 10 05.
Article in English | MEDLINE | ID: mdl-37798330

ABSTRACT

Conventionally, efficiency is indirectly estimated through a respiratory gas analyser (oxygen, carbon dioxide), which is a complex and rather costly calculation method that is difficult to perform in many situations. Therefore, the present study proposed a modified definition of efficiency, called the efficiency factor (EF) (i.e., the ratio of work to the corresponding exercise intensity), and evaluated the relation between the EF and maximal oxygen uptake ([Formula: see text]), as well as compared the prediction models established based on the EF. The heart rate (maximal heart rate: 186 ± 6 beats min-1), rating of perceived exertion (19 ± 1), and [Formula: see text] (39.0 ± 7.1 mL kg-1 min-1) of 150 healthy men (age: 20 ± 2 years; height: 175.0 ± 6.0 cm; weight: 73.6 ± 10.7 kg; body mass index [BMI]: 24.0 ± 3.0 kg m-2; percent body fat [PBF]: 17.0 ± 5.7%) were measured during the cardiopulmonary exercise test (CPET). Through multiple linear regression analysis, we established the BMI model using age and BMI as parameters. Additionally, we created the PBF modelHRR utilizing weight, PBF, and heart rate reserve (HRR) and developed PBF modelEF6 and PBF modelEF7 by incorporating EF6 from the exercise stage 6 and EF7 from the exercise stage 7 during the CPET, respectively. EF6 (r = 0.32, p = 0.001) and EF7 (r = 0.31, p = 0.002) were significantly related to [Formula: see text]. Among the models, the PBF modelEF6 showed the highest accuracy, which could explain 62.6% of the variance in the [Formula: see text] at with a standard error of estimate (SEE) of 4.39 mL kg-1 min-1 (%SEE = 11.25%, p < 0.001). These results indicated that the EF is a significant predictor of [Formula: see text], and compared to the other models, the PBF modelEF6 is the best model for estimating [Formula: see text].


Subject(s)
Exercise , Oxygen Consumption , Male , Humans , Adolescent , Young Adult , Adult , Feasibility Studies , Oxygen Consumption/physiology , Exercise/physiology , Exercise Test/methods , Oxygen
20.
CPT Pharmacometrics Syst Pharmacol ; 12(12): 1988-2000, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37723849

ABSTRACT

Erenumab is a fully human anti-canonical calcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. The Migraine-Specific Quality-of-Life Questionnaire (MSQ) is a 14-item patient-reported outcome instrument that measures the impact of migraine on health-related quality of life. Erenumab data from four phase II/III clinical trials were used to develop an item response theory (IRT) model within a nonlinear mixed effects framework, (i) evaluate the MSQ item information with respect to patient disability, (ii) characterize the longitudinal progression of the MSQ, and (iii) quantify the effect of erenumab on the MSQ in patients with migraine. The majority (80%) of information was found to be contained in 9 out of 14 items, extending the current knowledge on the reliability of the MSQ as a psychometric tool. Simulations across three MSQ domains show significant improvement from baseline, exceeding minimally important differences. Overall, the IRT model platform developed herein allows for systematic quantification of the effect of erenumab on the MSQ in patients with migraine.


Subject(s)
Migraine Disorders , Quality of Life , Humans , Reproducibility of Results , Migraine Disorders/drug therapy , Migraine Disorders/prevention & control , Surveys and Questionnaires
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