Determining Maximal Outcome Improvement Thresholds for Patient-Reported Outcome Measures After Primary ACL Reconstruction: A Mid-Term Follow-up Study Using the Anchor Method.

BACKGROUND: The clinical interpretation of patient-reported outcome measures (PROMs) after anterior cruciate ligament (ACL) reconstruction (ACLR) can be challenging. This study aimed to establish the clinical relevance of PROMs by determining maximal outcome improvement (MOI) thresholds at mid-term follow-up after primary ACLR. METHODS: A total of 343 patients who underwent primary single-bundle ACLR using hamstring tendon autograft at our institute were included. Patients were queried with a 2-option anchor question regarding satisfaction with their current knee symptom state. The MOI of a PROM was calculated for each patient as the percentage of improvement normalized by the maximal possible improvement. The MOI threshold for each PROM was determined as the optimal cutoff value for predicting patient satisfaction based on receiver operating characteristic curve analysis. Multivariable logistic regression analyses were performed to identify predictors of achieving these thresholds. Subgroup analyses that stratified the time from injury to surgery within the cohort were performed, and MOI thresholds were recalculated within each of these subgroups. The PROMs evaluated in this study were the modified Lysholm Knee Score and the International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC) score. RESULTS: The calculated MOI threshold was 35.1% for the Lysholm score and 46.7% for the IKDC score. A longer time from injury to surgery reduced the odds of achieving the MOI threshold for the Lysholm score (odds ratio [OR] per time bracket = 0.7114, p < 0.0001) and IKDC score (OR = 0.8038, p = 0.0003). Male sex was associated with higher odds of achieving the MOI threshold for the IKDC score (OR = 1.9645, p = 0.0143). For patients with chronicity of ≤6 months, the MOI threshold was 35.1% for the Lysholm score and 57.9% for the IKDC score, and for patients with chronicity of >6 months, the thresholds were 24.5% and 27.1%, respectively. CONCLUSIONS: The calculated MOI thresholds for the Lysholm and IKDC scores at mid-term follow-up after primary ACLR were 35.1% and 46.7%, respectively. Greater chronicity of the ACL injury was associated with lower odds of achieving the MOI thresholds for the PROMs at mid-term follow-up. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

CD276 is a promising biomarker for the prognosis of clear cell renal cell carcinoma.

This study aimed to investigate the role of cluster of differentiation 276 (CD276) in evaluating the prognosis of clear cell renal carcinoma (ccRCC) and to build a nomogram for predicting ccRCC progression post-surgery. Using data downloaded from The Cancer Genome Atlas (TCGA) database, we constructed a Kaplan-Meier (KM) curve depicting the relationship between CD276 expression levels and the progression-free interval (PFI) in 539 ccRCC cases. We further validated this by plotting a KM curve of the relationship between CD276 expression levels and PFI in 116 ccRCC patients from our hospital. Using clinical data collected from 116 patients, we identified independent risk factors affecting postoperative PFI in patients with ccRCC through univariate and multivariate COX analyses and created a nomogram for visual representation. Both TCGA and clinical data revealed a negative correlation between the expression levels of CD276 and PFI (p < 0.05). Univariate COX analysis revealed that the prognostic nutritional index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory index, World Health Organization grading, tumor diameter, CD276 expression levels, T stage, and N stage were related to PFI (p < 0.05). Furthermore, multivariate COX analysis indicated that tumor diameter and CD276 expression levels were independent risk factors for postoperative PFI in patients with ccRCC (p < 0.05). The calibration curve of the established nomogram exhibited a slope close to 1, with a Hosmer-Lemeshow goodness-of-fit test result of 2.335 and a p-value of 0.311. In patients with ccRCC, a negative correlation was noted between tumor CD276 expression and PFI. The larger the tumor diameter and the higher the tumor CD276 expression level, the shorter is the PFI.

Hybrid nanostructures for neurodegenerative disease theranostics: the art in the combination of biomembrane and non-biomembrane nanostructures.

The diagnosis of neurodegenerative diseases (NDDs) remains challenging, and existing therapeutic approaches demonstrate little efficacy. NDD drug delivery can be achieved through the utilization of nanostructures, hence enabling multimodal NDD theranostics. Nevertheless, both biomembrane and non-biomembrane nanostructures possess intrinsic shortcomings that must be addressed by hybridization to create novel nanostructures with versatile applications in NDD theranostics. Hybrid nanostructures display improved biocompatibility, inherent targeting capabilities, intelligent responsiveness, and controlled drug release. This paper provides a concise overview of the latest developments in hybrid nanostructures for NDD theranostics and emphasizes various engineering methodologies for the integration of diverse nanostructures, including liposomes, exosomes, cell membranes, and non-biomembrane nanostructures such as polymers, metals, and hydrogels. The use of a combination technique can significantly augment the precision, intelligence, and efficacy of hybrid nanostructures, therefore functioning as a more robust theranostic approach for NDDs. This paper also addresses the issues that arise in the therapeutic translation of hybrid nanostructures and explores potential future prospects in this field.

Black holes regulate cool gas accretion in massive galaxies.

The nucleus of almost all massive galaxies contains a supermassive black hole (BH)1. The feedback from the accretion of these BHs is often considered to have crucial roles in establishing the quiescence of massive galaxies2-14, although some recent studies show that even galaxies hosting the most active BHs do not exhibit a reduction in their molecular gas reservoirs or star formation rates15-17. Therefore, the influence of BHs on galaxy star formation remains highly debated and lacks direct evidence. Here, based on a large sample of nearby galaxies with measurements of masses of both BHs and atomic hydrogen (HI), the main component of the interstellar medium18, we show that the HI gas mass to stellar masses ratio (µHI = MHI/M⋆) is more strongly correlated with BH masses (MBH) than with any other galaxy parameters, including stellar mass, stellar mass surface density and bulge masses. Moreover, once the µHI-MBH correlation is considered, µHI loses dependence on other galactic parameters, demonstrating that MBH serves as the primary driver of µHI. These findings provide important evidence for how the accumulated energy from BH accretion regulates the cool gas content in galaxies, by ejecting interstellar medium gas and/or suppressing gas cooling from the circumgalactic medium.

A new isocoumarin derivative from endophytic fungus Pezicula neosporulosa VDB39 from Vaccinium dunalianum.

Four isocoumarin derivatives (1-4) and five phenols (5-9) were obtained from the endophytic fungus Pezicula neosporulosa VDB39, which was isolated from the branches of Vaccinium dunalianum Wight (Ericaceae). Compound 1 is a new derivative of isocoumarin. The structures were elucidated by spectroscopic methods. Single X-ray crystallography confirmed the absolute configuration of compound 1. Additionally, the antiphytopathogenic fungi activity of isocoumarin derivatives (1-4) was evaluated.

Survival disparities among racial groups with hepatic malignant tumors.

BACKGROUND: Investigating the impact of race on the clinicopathologic characteristics and prognosis of hepatic malignant tumors represents a complex and significant area of research. Notably, distinct differences exist among various racial groups in terms of the clinical manifestations, pathologic features, and prognosis of hepatic malignant tumors. AIM: To explore the effect of race on clinicopathologic features and prognosis of hepatic malignancies. METHODS: Data from patients with hepatic malignancies diagnosed between 2000 and 2019 were collected from the Surveillance, Epidemiology, and End Results database and statistically analyzed. RESULTS: This study included 123558 patients with hepatic malignant tumors, among whom 21078 (17.06%) were Asian, 14810 (11.99%) were Black, and 87670 (70.95%) were white. The median survival times for patients with hepatic malignant tumors of different races were 12.56, 7.70, and 9.35 months for Asian patients, Black patients, and white patients, respectively. The 3-year survival rates for Asian, Black, and white patients were 29%, 19%, and 21%, respectively, and the 5-year survival rates were 22%, 13%, and 15%, respectively. The Kruskal-Wallis test indicated a significant difference in the survival time of patients with hepatic malignant tumors between different races (P < 0.001). Univariate analysis revealed gender disparities in the prognosis among different ethnic groups (Asian: P > 0.05; Black: P < 0.001; White: P < 0.05). Among Black patients, the prognosis was less affected by the degree of hepatic fibrosis than among Asian patients and white patients (Black patients: P < 0.05; Asian patients: P < 0.001; White patients: P < 0.001). Significant differences were observed in the median survival time among patients with hepatic neuroendocrine tumors and hepatoblastomas during pathologic staging between races. Tumor number was inversely related to the prognosis. Cox regression analyses revealed that T stage, M stage, surgery, chemotherapy, alpha-fetoprotein, and tumor size independently influenced prognosis. Age was a specific independent prognostic factor for white patients. Among the tumor stages, N stage is a self-reliant prognostic element specific to white patients. Conversely, radiotherapy and liver fibrosis were not self-reliant prognostic factors for Black patients. Income alone did not independently influence the prognosis of Asian patients. CONCLUSION: The prognosis of hepatic malignant tumors is better among Asian patients than among Black patients. The prognosis of hepatic malignant tumors among white patients is affected by multiple factors, including age and N stage.

CD276 enhances sunitinib resistance in clear cell renal cell carcinoma by promoting DNA damage repair and activation of FAK-MAPK signaling pathway.

OBJECTIVE: This study aimed to explore the effect of CD276 expression on the sunitinib sensitivity of clear cell renal cell carcinoma (ccRCC) cell and animal models and the potential mechanisms involved. METHODS: CD276 expression levels of ccRCC and normal samples were analyzed via online databases and real-time quantitative PCR (RT-qPCR). CD276 was knocked down in ccRCC cell models (sunitinib-resistant 786-O/R cells and sunitinib-sensitive 786-O cells) using shRNA transfection, and the cells were exposed to a sunitinib (2 µM) environment. Cells proliferation was then analyzed using MTT assay and colony formation experiment. Alkaline comet assay, immunofluorescent staining, and western blot experiments were conducted to assess the DNA damage repair ability of the cells. Western blot was also used to observe the activation of FAK-MAPK pathway within the cells. Finally, a nude mouse xenograft model was established and the nude mice were orally administered sunitinib (40 mg/kg/d) to evaluate the in vivo effects of CD276 knockdown on the therapeutic efficacy of sunitinib against ccRCC. RESULTS: CD276 was significantly upregulated in both ccRCC clinical tissue samples and cell models. In vitro experiments showed that knocking down CD276 reduced the survival rate, IC50 value, and colony-forming ability of ccRCC cells. Knocking down CD276 increased the comet tail moment (TM) values and γH2AX foci number, and reduced BRCA1 and RAD51 protein levels. Knocking down CD276 also decreased the levels of p-FAK, p-MEK, and p-ERK proteins. CONCLUSION: Knocking down CD276 effectively improved the sensitivity of ccRCC cell and animal models to sunitinib treatment.

Pro-cancer role of CD276 as a novel biomarker for clear cell renal cell carcinoma.

OBJECTIVE: Renal cell carcinoma (RCC) is a common malignant tumor with a high incidence in males and the elderly, and clear cell RCC (ccRCC) is the most common RCC subtype. ccRCC is highly metastatic with a poor prognosis. Therefore, it is crucial to obtain a detailed understanding of the molecular mechanism of ccRCC and to identify suitable biomarkers to realize early diagnosis and improve prognosis. METHODS: We analyzed data from the Cancer Genome Atlas, investigated the overall differential expression of CD276 in ccRCC, and evaluated the influence of CD276 on patient survival and prognosis. We also performed gene set enrichment analysis (GSEA) and pathway enrichment analysis and investigated cell infiltration and drug responsiveness to further assess the regulatory effect of CD276 on ccRCC. Furthermore, we verified CD276 expression in RCC cell lines and control cell lines. RESULTS: The CD276 expression level in ccRCC samples was higher than that in corresponding samples adjacent to the tumors. Moreover, high CD276 expression levels were positively correlated with poor prognosis in patients with RCC. GSEA revealed that CD276 was significantly involved in immune-related pathways, and the level of CD276 expression was confirmed as associated with immune cell infiltration to some extent. Notably, some drugs were predicted to act on CD276, and this was confirmed by molecular docking. Furthermore, high levels of CD276 expression in RCC cell lines were verified. CONCLUSION: CD276 expression was significantly increased in ccRCC tissues and cells and positively correlated with patient prognosis. CD276 is a potential prognostic biomarker of ccRCC. Overall, this study provides a potential therapeutic strategy for ccRCC.

Association of Concomitant MRI-Determined Anterolateral Complex Injury With Quantitative Measurements of Altered Rotational Tibiofemoral Position on MRI in Patients With ACL Injury.

Background: Reduced graft failure rates have been reported after anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex (ALC) augmentation. However, the preoperative diagnosis of concomitant ALC injury remains a clinical challenge. Purpose: To identify the altered rotational tibiofemoral position on magnetic resonance imaging (MRI) in ACL-injured patients with concomitant ALC injury. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Based on the evaluation of ALC abnormalities on MRI scans by experienced surgeons, 123 patients with nonchronic (<3 months) ACL injury confirmed by arthroscopy were included. The patients were divided into 2 groups-an ALC-injured group (n = 57) and an ALC-intact group (n = 66). The altered rotational tibiofemoral position was evaluated and compared by quantitatively measuring internal rotational tibial subluxation (IRTS) and axial internal tibial rotation (ITRa) on MRI. Multivariate logistic regression and receiver operating characteristic (ROC) analyses were performed to identify the factors associated with concomitant MRI-determined ALC injury. Results: The ALC-injured group showed significantly increased IRTS (P < .001), ITRa (P < .001), lateral anterior tibial subluxation (ATS) (P < .001), and global ATS (GATS) (P = .002) compared with the ALC-intact group, while no significant difference in medial ATS (P = .810) was observed. A strong positive correlation was identified between IRTS and ITRa (rP = 0.809; P < .001). Multivariate analyses revealed that IRTS (P < .001) and GATS (P = .016) were associated factors for the presence of concomitant MRI-determined ALC injury. IRTS (area under the curve [AUC] = 0.734) was more strongly associated with the outcome than GATS (AUC = 0.658) in ROC analyses, suggesting a more significant internal rotational subluxation than anterior subluxation of the tibia. An IRTS threshold of 3.1 mm demonstrated a specificity of 84.2% for indicating the presence of concomitant MRI-determined ALC injury. Conclusion: The presence of concomitant MRI-determined ALC injury in ACL-injured patients was associated with a significant increase in IRTS and ITRa compared with those with intact ALC, indicating that these MRI measurements of the altered rotational tibiofemoral position could serve as potential quantifiable indicators for identifying concomitant ALC injury in clinical practice.

Marker Ki-67 is a potential biomarker for the diagnosis and prognosis of prostate cancer based on two cohorts.

BACKGROUND: Prostate cancer (PCa) is a widespread malignancy, predominantly affecting elderly males, and current methods for diagnosis and treatment of this disease continue to fall short. The marker Ki-67 (MKI67) has been previously demonstrated to correlate with the proliferation and metastasis of various cancer cells, including those of PCa. Hence, verifying the association between MKI67 and the diagnosis and prognosis of PCa, using bioinformatics databases and clinical data analysis, carries significant clinical implications. AIM: To explore the diagnostic and prognostic efficacy of antigens identified by MKI67 expression in PCa. METHODS: For cohort 1, the efficacy of MKI67 diagnosis was evaluated using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. For cohort 2, the diagnostic and prognostic power of MKI67 expression was further validated using data from 271 patients with clinical PCa. RESULTS: In cohort 1, MKI67 expression was correlated with prostate-specific antigen (PSA), Gleason Score, T stage, and N stage. The receiver operating characteristic (ROC) curve showed a strong diagnostic ability, and the Kaplan-Meier method demonstrated that MKI67 expression was negatively associated with the progression-free interval (PFI). The time-ROC curve displayed a weak prognostic capability for MKI67 expression in PCa. In cohort 2, MKI67 expression was significantly related to the Gleason Score, T stage, and N stage; however, it was negatively associated with the PFI. The time-ROC curve revealed the stronger prognostic capability of MKI67 in patients with PCa. Multivariate COX regression analysis was performed to select risk factors, including PSA level, N stage, and MKI67 expression. A nomogram was established to predict the 3-year PFI. CONCLUSION: MKI67 expression was positively associated with the Gleason Score, T stage, and N stage and showed a strong diagnostic and prognostic ability in PCa.

[Preparation of sulfonic acid functionalized covalent organic framework solid phase microextraction fibers and their application in the analysis of neurotransmitters in the mouse brain].

Neurotransmitters (NTs) are essential for intercellular communication and primarily include monoamine, amino acid, and cholinergic NTs. These molecules play important roles in the body's stress response, motor coordination, neuronal communication, and homeostatic functions. Previous studies have shown that abnormal changes in NT levels are associated with various neurological disorders. Therefore, the development of accurate analytical methods for NT detection will enhance the current understanding on complex neuropathophysiology by providing functional knowledge and techniques for early diagnosis, thereby facilitating the development of new therapeutic options for the related diseases. The solid phase microextraction (SPME) technique combines sample preparation, separation, and enrichment in a single step and is minimally invasive, low cost, solvent free, and high throughput. SPME has been successfully applied to the in vivo analysis of target analytes in animal, human, and plant tissues. The coating material plays a significant role in the development of in vivo SPME methods and must meet various analytical requirements, including a suitable geometry for the SPME device, high extraction capacity, excellent selectivity, and wide extraction coverage for the target analytes. Covalent organic frameworks (COFs) are porous crystalline polymers constructed from organic framework units through strong covalent bonds; these materials are characterized with a low density, large specific surface area, permanent porosity, excellent chemical/thermal stability, and easy functionalization.In this study, a sulfonic acid-functionalized COF material (COF-SO3H) with good crystallinity, excellent chemical/thermal stability, strong hydrophobicity, a uniform mesoporous structure, and narrow pore size distribution was prepared using 2,4,6-triformylphloroglucinol and 1,4-diamino-2-nitrobenzene as monomers. Then, the COF-SO3H was coated onto the surface of stainless-steel fibers and used for in vivo enrichment of NTs. The structural properties of COF-SO3H were characterized using various techniques, such as scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FT-IR), and X-ray diffraction (XRD), all of which showed that COF-SO3H had a good crystalline structure and uniform mesopore distribution with a specific surface area of 46.17 m2/g. Compared with the SPME fibers of HLB, C18, MCX, amino, and PXC columns, the prepared COF-SO3H fibers showed better extraction efficiency for the target NTs. Next, the factors affecting SPME efficiency were optimized. The optimal desorption solvent was formic acid-methanol-water (0.5∶49.5∶50, v/v/v), and the optimal extraction and desorption times were 15 min. A method for the in vivo analysis of NTs in the brains of mice was established by combining the COF-SO3H fibers with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) under optimal conditions. The NTs were separated on an Acquity UPLC BEH-C18 analytical column (100 mm×2.1 mm, 1.7 µm) with 0.1% formic acid aqueous solution (A) and acetonitrile (B) as the mobile phases. The flow rate was set to 0.2 mL/min, and the gradient elution procedure was as follows: 0-4 min, 5%B-6%B; 4-7 min, 6%B-5%B; 7-11 min, 5%B. Under optimal conditions, the method showed good linearity (r2>0.99). The limits of quantification (S/N≥5) were in the range of 0.003-0.005 µg/mL and 3-5 µg/mL for monoamine and amino acid NTs, respectively, with RSDs of less than 20%. The method showed good precision (0.80%-9.70%) and accuracy (2.08%-17.72%), with absolute matrix effects in the range of 82.22%-117.92%. These values reflect the good purification and enrichment abilities of the proposed fibers for the target analytes. Finally, the established SPME method was combined with UPLC-MS/MS and successfully applied to quantify target NTs in the brains of mice. The proposed strategy provides a practical method for the in vivo detection and quantitative analysis of NTs and expands the applications of functionalized COF materials for the analysis of various targets.

Chronic ACL-injured patients show increased medial and global anterior tibial subluxation measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction.

BACKGROUND: The association between chronic anterior cruciate ligament (ACL) injury and inferior postoperative outcomes following ACL reconstruction (ACLR) has been highlighted in the literature. However, the inclusion of postoperative radiological assessments in previous studies has been limited. The aim of this study is to investigate whether chronic ACL injury is associated with an inferior tibiofemoral position measured on magnetic resonance (MR) images after primary ACLR. METHODS: A total of 62 patients that underwent primary ACLR were included in this study based on the time from injury to surgery, namely the acute ACL-injured group (within 6 weeks) and the chronic ACL-injured group (more than 1 year) and were matched 1:1 according to sex, age (± 2 years), and time from surgery to follow-up (± 3 months). Patient demographics, surgical records and follow-up data were retrieved and analyzed. The altered tibiofemoral position was measured quantitatively on preoperative and at least 1-year postoperative MR images and compared between the two groups, including the lateral, medial and global anterior tibial subluxation (LATS, MATS and GATS) and internal rotational tibial subluxation (IRTS). RESULTS: No significant differences in preoperative LATS, MATS, GATS or IRTS were identified between the acute and chronic ACL-injured groups. The chronic ACL-injured patients showed significantly increased postoperative MATS (p = 0.001) and GATS (p = 0.012), while no significant difference was identified in postoperative LATS or IRTS. Multivariate linear regression analyses showed that chronic ACL injury resulted in an estimated increase of 2.0 mm in postoperative MATS (p = 0.012) and 1.9 mm in postoperative GATS (p = 0.040). A significant improvement in postoperative LATS was observed in the acute ACL-injured group (p = 0.044) compared to preoperative LATS, while no improvements in these MRI measurements were observed in the chronic ACL-injured group. CONCLUSION: Chronic ACL-injured patients showed increased MATS and GATS measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction, while no difference was identified in rotational tibiofemoral position. The acute ACL-injured group demonstrated a significant improvement in postoperative LATS, whereas no improvements were observed in the chronic ACL-injured group. Level of evidence Level III.

Analysis and prediction of postoperative recurrence of unilateral upper ureteral calculi in 243 cases (nomogram).

Objective: This study aimed to identify the risk factors for postoperative recurrence of unilateral upper ureteral calculi and develop a predictive nomogram. Patients and Methods: A retrospective analysis was conducted on 243 patients diagnosed with unilateral upper ureteral calculi who were treated at our hospital between January 1, 2016 and December 31, 2018. Patients were divided into two groups: recurrence or non-recurrence cohort. Differences in age, gender, smoking and/or drinking habit, laterality, stone diameter, ureteral stricture, stone incarceration, urinary tract infection, surgical intervention, operation time, body mass index, and metabolic syndrome were analyzed. Discrete risk factors were screened, and a nomogram was developed to predict the probability of stone recurrence. Results: The study found that the recurrence of ureteral calculi was associated with factors including stone diameter, ureteral stricture, stone incarceration, surgical intervention, operation time, metabolic syndrome, body mass index, triglycerides, diabetes, and high blood pressure (p < 0.05). Ureteral stricture, surgical intervention, metabolic syndrome, and triglycerides were found to be discrete risk factors for stone recurrence (p < 0.05). In addition, the study revealed that the stone recurrence rate of metabolic syndrome patients was significantly elevated (p < 0.05), as demonstrated by the survival curve. Lastly, using the nomogram, with an area under the curve value of 0.929, the recurrence rate of ureteral calculi was predicted. Conclusions: The study identified that preoperative ureteral stricture, laparoscopic ureterolithotomy, metabolic syndrome, and triglycerides are closely related to postoperative recurrence of ureteral calculi. The nomogram developed in this study can be used as a predictive tool for the recurrence rate of ureteral calculi.

Comparisons of diagnostic performance and the reliability in identifying ACL injury between two measuring protocols of anterior tibial subluxation on MR images.

OBJECTIVES: To evaluate the diagnostic performance in identifying an anterior cruciate ligament (ACL) injury and the reliability between two measuring protocols of anterior tibial subluxation (ATS). MATERIALS AND METHODS: A total of 165 patients with ACL injury and 157 ACL-intact patients were included in this study. Two different measuring protocols of ATS were performed on sagittal MR images, including the modified protocol using the longitudinal tibial axis (axis protocol) and the established protocol using a line perpendicular to the tibial plateau (plateau protocol). Receiver-operating characteristic (ROC) curves were calculated to evaluate the diagnostic performance in identifying an ACL injury, and areas under the curves (AUCs) were compared between the two protocols. Intra- and interobserver reliability tests were performed to evaluate the reliability of the measurements. RESULTS: Lateral ATS (P < 0.001) and medial ATS (P < 0.001) were increased in patients with ACL injury under both protocols. To identify an ACL injury, ATS measured under the axis protocol showed higher AUC values than the plateau protocol, including lateral ATS (AUC 0.828 vs. 0.688, P < 0.001), medial ATS (AUC 0.829 vs. 0.789, P = 0.013), and the combined indicator of lateral and medial ATS (AUC 0.885 vs. 0.810, P < 0.001). Reliability tests showed that both protocols were reliable. CONCLUSIONS: ATS measured under the modified protocol using the longitudinal tibial axis showed superior diagnostic performance in identifying an ACL injury compared to the established protocol, indicating that the modified protocol may better reflect the characteristics of an ACL-deficient knee.

Hypermethylation of the Bmp4 promoter dampens binding of HIF-1α and impairs its cardiac protective effects from oxidative stress in prenatally GC-exposed offspring.

The exposure to an unhealthy environment in utero can lead to the occurrence of cardiovascular diseases in the offspring. Glucocorticoids (GC) are essential for normal development and maturation of fetal organs and is a first-line treatment for pregnant women affected by autoimmune diseases. However, excess prenatal GC exposure might program the development of fetal organs and cause a number of chronic diseases in later life. Our previous studies indicated that cardiac functions were significantly compromised in rat offspring prenatally exposed to the synthetic glucocorticoid dexamethasone (DEX), only after ischemia-reperfusion. In the present study, we further observed that DNA hypermethylation of bone morphogenetic protein 4 (Bmp4) promoter in cardiomyocytes caused by prenatal DEX exposure substantially dampened the binding activity of transcription factor HIF-1α induced by cardiac ischemia. Therefore, prenatal DEX exposure inhibits the induction of BMP4 upon I/R and attenuates the protective effects of BMP4 in cardiomyocytes, which eventually manifests as malfunction of the adult heart. Moreover, we employed two cardiac-specific Bmp4 knock-in mouse models and found that in vivo BMP4 overexpression could rescue the cardiac dysfunction caused by prenatal GC exposure. In depth mechanistic research revealed that BMP4 protects the cardiomyocytes from mitophagy and apoptosis by attenuating mitochondrial PGC-1α expression in a p-Smad and Parkin-dependent manner. These findings suggest that prenatal GC exposure increases the susceptibility of the offspring's heart to a "second strike" after birth, due to the failure of hypoxia-induced HIF-1α transactivation of the hypermethylated Bmp4 promoter in cardiomyocytes. Pretreatment with the DNA methylation inhibitor, 5-Aza-2'-deoxycytidine, could be a potential therapeutic method for this programming effect of GC exposure during pregnancy on neonatal cardiac dysfunction.

Stellar initial mass function varies with metallicity and time.

Most structural and evolutionary properties of galaxies strongly rely on the stellar initial mass function (IMF), namely the distribution of the stellar mass formed in each episode of star formation1-4. The IMF shapes the stellar population in all stellar systems, and so has become one of the most fundamental concepts of modern astronomy. Both constant and variable IMFs across different environments have been claimed despite a large number of theoretical5-7 and observational efforts8-15. However, the measurement of the IMF in Galactic stellar populations has been limited by the relatively small number of photometrically observed stars, leading to high uncertainties12-16. Here we report a star-counting result based on approximately 93,000 spectroscopically observed M-dwarf stars, an order of magnitude more than previous studies, in the 100-300 parsec solar neighbourhood. We find unambiguous evidence of a variable IMF that depends on both metallicity and stellar age. Specifically, the stellar population formed at early times contains fewer low-mass stars compared with the canonical IMF, independent of stellar metallicities. In more recent times, however, the proportion of low-mass stars increases with stellar metallicity. The variable abundance of low-mass stars in our Milky Way establishes a powerful benchmark for models of star formation and can heavily affect results in Galactic chemical-enrichment modelling, mass estimation of galaxies and planet-formation efficiency.

Intra-Articular Biomechanical Changes of the Meniscus and Ligaments During Stance Phase of Gait Circle after Different Anterior Cruciate Ligament Reconstruction Surgical Procedures: A Finite Element Analysis.

OBJECTIVE: The debate on the superiority of single- or double-bundle for anterior cruciate ligament reconstruction has not ceased. The comparative studies on intra-articular biomechanics after different surgical reconstructions are rare. This study is to evaluate the biomechanical stress distribution intra-knee after single- and double-bundle anterior cruciate ligament reconstruction by three-dimensional finite element analysis, and to observe the change of stress concentration under the condition of vertical gradient loads. METHODS: In this study, magnetic resonance imaging data were extracted from patients and healthy controls for biomechanical analysis. Patients included in the three models were matched in age and sex. The strength and distribution of induced stresses were analyzed in two frequently used procedures, anatomical single-bundle anterior cruciate ligament reconstruction and anatomical double-bundle anterior cruciate ligament reconstruction, using femoral-graft-tibial system under different loads, to mimic a post-operation mechanical motion. The three-dimensional finite-element models for normal ligament and two surgical methods were applied. A vertical force simulating daily walking was performed on the models to assess the interfacial stresses and displacements of intra-articular tissues and ligaments. The evaluation results mainly included the stress of each part of ligament and meniscus. The stress values of different parts of three models were extracted and compared. RESULTS: The stress of ligament/graft at femoral side of three finite-element models was significantly higher than at tibial side, while the highest level was observed in single-bundle reconstruction finite-element model. With the increase of force, the maximum stress in the medial (7.1-7.1 MPa) and lateral (4.9-7.4 MPa) meniscus of single-bundle reconstruction finite-element model shifted from the anterior horn to the central area (p = 0.0161, 0.0479, respectively). The stress was shown to be at a lower level at femoral side and posterior cruciate ligament of intra-knee in two reconstruction finite-element models than that in normal finite-element models, while presented higher level at the tibial side than normal knee (p = 0.3528). The displacement of the femoral side and intra-knee areas in reconstruction finite-element models was greater than that in normal finite-element model (p = 0.0855). CONCLUSION: Compared with the single-bundle technique, the graft of double-bundle anterior cruciate ligament reconstruction has better stress dissipation effect and can prevent postoperative meniscus tear more effectively.

Arthroscopic Treatment for Femoroacetabular Impingement Syndrome in Adolescents: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of this review was to analyze the effect of arthroscopic surgery for femoroacetabular impingement syndrome (FAI) in adolescents and factors that may influence the revision rate. DESIGN: Systematic review and meta-analysis. SETTING: PubMed, Scopus, Cochrane Library, EMBASE, and MEDLINE were searched from their earliest records to May 2021. PATIENTS: Adolescents who underwent primary arthroscopic treatment for FAI. INTERVENTIONS: Hip arthroscopic treatment. MAIN OUTCOME MEASURES: Patient-reported outcomes (PROs), alpha angle, revision rates, and the rate of complications. RESULTS: A total of 832 hips in 753 patients were included in this study. All PROs improved significantly. The modified Harris Hip Score pooled mean difference was 24.99 (95% CI, 22.88-27.10, P < 0.0001, I2 = 19.9%), Hip Outcome Score (HOS)-Sports-Specific Subscale was 35.88 (95% CI, 33.07-38.68, P < 0.0001, I2 = 0%), HOS-Activities of Daily Living was 23.53 (95% CI, 21.21-25.85, P < 0.0001, I2 = 0%), and the Nonarthritic Hip Score was 22.34 (95% CI, 18.40-26.28, P < 0.0001, I2 = 40.9%). The visual analog scale for pain decreased by 40.39 (44.39-36.40, P < 0.0001, I2 = 0%). The alpha angle decreased by 22.0 degrees from 62.9 degrees to 40.9 degrees after arthroscopic surgery. The rate of complication and revision surgery was 1.2% (10/832) and 3.4% (28/832), respectively, with high postoperative patient satisfaction. CONCLUSIONS: All PROs significantly improved after surgery, with a low rate of complications and reoperation. High postoperative patient satisfaction was also reported.

Anterior tibial subluxation measured under a modified protocol is positively correlated with posterior tibial slope: a comparative study of MRI measurement methods.

PURPOSE: Anatomic factors, such as posterior tibial slope (PTS) and anterior tibial subluxation (ATS) obtained by quantitative measurement, have been proposed as predictors for clinical outcomes of anterior cruciate ligament (ACL) reconstruction. However, the correlation between PTS and ATS is controversial, and the method for quantitative ATS measurement remains unsettled. This study aimed to identify the correlation between PTS and ATS in patients with injured and intact ACLs and compare the two ATS measuring protocols. METHODS: This study included 128 ACL-injured and 176 ACL-intact patients with no concomitant ligament injuries. PTS and ATS were measured on sagittal MRI. ATS was measured using two measuring protocols, including the modified protocol using the longitudinal tibial axis (axis protocol) and the established protocol using a line perpendicular to the tibial plateau (plateau protocol). Correlation analyses between PTS and ATS and between PTS and the difference in the ATS value measured under the two protocols (ATSdiff) were performed. The difference between the two ATS measuring protocols was further analyzed by trigonometric analysis. Intra- and interobserver reliability tests were performed for the axis protocol. RESULTS: Under the axis protocol, ATS was positively correlated with PTS in both the ACL-injured and ACL-intact groups (p < 0.001). Under the plateau protocol, no correlation was observed in the ACL-injured group. In the ACL-intact group, no correlation was observed for lateral ATS, and a negative correlation was observed for medial ATS (p = 0.001). ATSdiff was positively correlated with PTS (p < 0.001), indicating that the two protocols varied greatly in those with a steep PTS. Trigonometric analysis showed that a steep PTS influenced the measurement of ATS under the plateau protocol but not the axis protocol. Intra- and interobserver reliability tests showed good-to-excellent strength of reliability for the ATS measurement under the axis protocol. CONCLUSION: ATS measured under the axis protocol was positively correlated with PTS, indicating that a steep PTS was associated with a worse anatomic tibiofemoral relationship. The axis protocol for ATS measurement is a promising method for clinical use since it is not influenced by PTS and reflects the global position of the tibia. LEVEL OF EVIDENCE: III.

Removal of levofloxacin by an oleaginous microalgae Chromochloris zofingiensis in the heterotrophic mode of cultivation: Removal performance and mechanism.

Microalgae-based technology is an environmental-friendly and cost-effective method for treating antibiotics-contaminated wastewater. This work investigated the removal of levofloxacin (LEV) by an oleaginous microalgae Chromochloris zofingiensis under photoautotrophic and heterotrophic conditions. The results showed that the significantly higher biomass production, accumulation of extracellular polymeric substance and LEV removal efficiency were achieved in heterotrophic C. zofingiensis compared with the photoautotrophic ones. The removal efficiencies under the heterotrophic condition were 97%, 88% and 76% at 1, 10, and 100 mg/L LEV, respectively. HPLC-MS/MS and RNA-Seq analyses suggested that LEV could be bioaccumulated and biodegraded by heterotrophic C. zofingiensis through the reactions of defluorination, hydroxylation, demethylation, ring cleavage, oxidation, dehydrogenation, denitrification, and decarboxylation. The chemical composition of the algal biomass obtained after LEV treatment indicated the potential of this alga for removing LEV from wastewaters and simultaneously producing biodiesel, astaxanthin, and other products. Collectively, this research shows that the heterotrophic C. zofingiensis can be identified as a promising candidate for removing LEV in wastewater remediation.