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.

Femoral Tunnel Malposition, Increased Lateral Tibial Slope, and Decreased Notch Width Index Are Risk Factors for Non-Traumatic Anterior Cruciate Ligament Reconstruction Failure.

PURPOSE: To identify risk factors for patients who sustain nontraumatic anterior cruciate ligament reconstruction (ACLR) failure. METHODS: A retrospective analysis was performed on patients undergoing primary or revision ACLR in our institution between 2010 and 2018. Patients sustaining insidious-onset knee instability without history of trauma were identified as nontraumatic ACLR failure and assigned to the study group. The control group of subjects who showed no evidence of ACLR failure with minimum 48-month follow-up were matched in a 1:1 ratio based on age, sex, and body mass index. Anatomic parameters including tibial slope (lateral [LTS], medial [MTS]); tibial plateau subluxation (lateral [LTPsublx], medial [MTPsublx]); notch width index (NWI); and lateral femoral condyle ratio were measured with magnetic resonance imaging or radiography. Graft tunnel position was assessed using 3-dimensional computed tomography and reported in 4 dimensions: deep-shallow ratio (DS ratio) and high-low ratio for femoral tunnel, anterior-posterior ratio and medial-lateral ratio for tibial tunnel. Interobserver and intraobserver reliability were evaluated by the intraclass correlation coefficient (ICC). Patients' demographic data, surgical factors, anatomic parameters, and tunnel placements were compared between the groups. Multivariate logistic regression and receiver operating characteristic curve analysis was used to discriminate and assess the identified risk factors. RESULTS: A total of 52 patients who sustained nontraumatic ACLR failure were included and matched with 52 control subjects. Compared to patients with intact ACLR, those who sustained nontraumatic ACLR failure showed significantly increased LTS, LTPsublx, MTS, and deceased NWI (all P < .001). Moreover, the average tunnel position in the study group was significantly more anterior (P < .001) and superior (P = .014) at the femoral side and more lateral (P = .002) at the tibial side. Multivariate regression analysis identified LTS (odds ratio [OR] = 1.313; P = .028), DS ratio (OR = 1.091; P = .002), and NWI (OR = 0.813; P = .040) as independent predictors of nontraumatic ACLR failure. LTS appeared to be the best independent predictive factor (area under the curve [AUC] = 0.804; 95% confidence interval [CI], 0.721-0.887), followed by DS ratio (AUC = 0.803; 95% CI, 0.717-0.890), and NWI (AUC = 0.756; 95% CI, 0.664-0.847). The optimal cutoff values were 6.7° for increased LTS (sensitivity = 0.615, specificity = 0.923); 37.4% for increased DS ratio (sensitivity = 0.673, specificity = 0.885); and 26.4% for decreased NWI (sensitivity = 0.827, specificity = 0.596). Intraobserver and interobserver reliability was good to excellent, with ICCs ranging from 0.754 to 0.938 for all radiographical measurements. CONCLUSIONS: Increased LTS, decreased NWI, and femoral tunnel malposition are predictive risk factors for nontraumatic ACLR failure. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Increased Lateral Femoral Condyle Ratio Measured by Magnetic Resonance Imaging Is Associated With Anterior Cruciate Ligament Rerupture.

PURPOSE: To investigate the association between lateral femoral condyle ratio (LFCR) measured by magnetic resonance imaging (MRI) and anterior cruciate ligament (ACL) rerupture after anatomic ACL reconstruction (ACLR) and to compare the diagnostic accuracy between MRI and radiograph measurements. METHODS: A retrospective review was conducted on patients who underwent anatomic ACLR in our institution between 2015 and 2018. Patients who experienced rerupture after ACLR were identified and matched 1:1 with control patients who showed no evidence of graft failure during a minimum 48-month follow-up. The matching criteria included age, sex, and body mass index. LFCR was measured on MRI scans and radiographs of the affected limb. Patients' characteristics, surgical features, and anatomic measurements were compared between groups. Conditional logistic regression was performed to investigate whether MRI-measured LFCR is a risk factor for ACL rerupture. The optimal cutoff value was determined by receiver operating characteristic curves (ROC). Delong's test was performed to compare the diagnostic accuracy between MRI and radiograph measurements. RESULTS: A total of 72 patients who sustained ACL rerupture were included and matched with 72 control subjects. Compared to patients with intact ACLR, those who sustained ACL rerupture showed a significant increase in LFCR on MRI scans (63.38% ± 2.26% [95% CI, 62.84%-63.91%] vs 61.10% ± 2.19% [95% CI, 60.59%-61.61%], P < .001). An MRI-measured LFCR >62.18% was set as the cutoff point to discern patients at a higher risk of graft failure after anatomic ACLR, with sensitivity and specificity of 75.0% and 70.8%, respectively. MRI-measured LFCR demonstrated superior diagnostic accuracy during ROC curve analysis, achieving a higher area under the curve compared to radiograph-measured LFCR (0.783 ± 0.051 vs 0.668 ± 0.060, P = .041). CONCLUSIONS: The study found that MRI-measured LFCR was associated with ACL rerupture. A cutoff value of 62.18% was determined, which can help identify patients at a higher risk of rerupture. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

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.

Arthroscopic Anatomical Double-Bundle Medial Patellofemoral Complex Reconstruction Improves Clinical Outcomes in Treating Recurrent Patellar Dislocation Despite Trochlear Dysplasia, Elevated Tibial Tubercle-Trochlear Groove Distance, and Patellar Alta.

PURPOSE: To evaluate the clinical outcomes of arthroscopically assisted double-bundle medial patellofemoral complex reconstruction (MPFC-R). METHODS: A retrospective review was carried out among adult patients who experienced at least 2 patellar dislocations and underwent primary arthroscopically assisted MPFC-R between January 2014 and November 2019. Dejour classification, tibial tubercle-trochlear groove (TT-TG) distance, and patellar height (with Insall-Salvati index) were measured. Pre- and postoperative patellar tilt were compared. Information on outcome scores, ability to return to sports, postoperative recurrent dislocations, and complications was recorded. RESULTS: A total of 42 MPFC-Rs in 39 patients were included. Mean age at surgery was 22.2 ± 7.6 years; 69.2% of patients were female. Mean follow-up was 47.3 ± 20.2 months. Seventy-four percent of cases had Dejour B (19.0%), C (33.3%), and D (21.4%) trochlear dysplasia; mean TT-TG distance was 19.6 ± 3.5 mm, and mean Insall-Salvati index was 1.21 ± 0.17. Mean patellar tilt decreased from 27.6 ± 11.6° to 9.4 ± 6.5° (P < .001). All patients had statistically significant (P < .001) improvement in mean International Knee Documentation Committee (IKDC) (44.9 ± 18.2 to 87.5 ± 6.9), Lysholm (61.4 ± 16.6 to 94.1 ± 6.4), Kujala (56.0 ± 16.8 to 92.9 ± 5.3), and Tegner score (2.7 ± 1.3 to 4.6 ± 1.4). The majority of patients (96.9%) returned to sports, with 90.3% returning to the same or greater level of activity. No postoperative dislocations or subluxations were reported. CONCLUSIONS: Arthroscopically assisted double-bundle MPFC-R is a promising procedure to treat recurrent patellar instability at 2- to 7-year mid-term follow-up, despite the presence of trochlear dysplasia, elevated TT-TG distance and patellar alta. The improvement of IKDC score exceeded the minimal clinically important difference in 95.2% patients, and 66.7% surpassed the patient acceptable symptomatic state based on postoperative IKDC score with no redislocations being reported at latest follow-up. LEVEL OF EVIDENCE: Level IV, case series, retrospective.

Effect of Xuefu Zhuyu Capsule () on Angiogenesis in Hindlimb Ischemic Rats.

OBJECTIVE: To investigate the effect and mechanism of Xuefu Zhuyu Capsule (, XZC) on pro-angiogenesis in the hindlimb ischemic model rats. METHODS: A total of 100 Sprague Dawley rats were randomly divided into a model group, a regular-dose XZC group (0.48 g•kg-1•d-1) and a high-dose XZC group (0.96 g•kg-1•d-1) using random number table method. The model of hindlimb ischemic rats were made through femoral artery embolization with Bletilla microsphere agent. XZC were given on the first day after embolization surgery and lasted 5 days. Finally 72 models were obtained with 12 in each group for each time point. The lower ischemic limb was amputated on the third day after embolization surgery. Histopathological characters and the number of blood vessels of granulation tissues were observed at 36 and 48 h after amputation, respectively. The main genes were obtained from microarray analysis and were validated using real-time quantitative polymerase chain reaction. RESULTS: The vascular number of granulation tissues at both 36 and 48 h were characterized by new and fresh vessels. The number of angiogenesis in the high-dose XZC group at 36 and 48 h was greater compared with that in the regular-dose XZC and model groups (P<0.01), and high-dose XZC at 36 h increased more vessels than that at 48 h (P<0.01). Consequently, granulation tissues from the high-dose XZC group at 36 h were chosen for microarray analysis. In all, 2,085 differentially expressed genes (DEGs) were detected and 25 DEGs were determined to be directly related to angiogenesis. Four biological process terms were found including angiogenesis, regulation of angiogenesis, positive regulation of angiogenesis, and positive regulation of vascular endothelial growth factor receptor signaling pathway (P<0.05). Microarray analysis also showed 49 pathways including 11 pathways related to angiogenesis. CONCLUSION: XZC promoted angiogenesis moderately and the mechanism involved multiple DEGs and multiple pathways.

Combination of Ligusticum Chuanxiong and Radix Paeonia Promotes Angiogenesis in Ischemic Myocardium through Notch Signalling and Mobilization of Stem Cells.

OBJECTIVE: To study the cardioprotective mechanism by which the combination of Chuanxiong (CX) and Chishao (CS) promotes angiogenesis. METHODS: Myocardial infarction (MI) mouse models were induced by ligation of the left anterior descending coronary artery. The effects on cardiac function were evaluated in the perindopril tert-butylamine group (PB group) (3 mg/kg/d), CX group (55 mg/kg/d), CS group (55 mg/kg/d), and CX and CS combination (CX-CS) group (27.5 mg/kg/d CX plus 27.5 mg/kg/d CS). RO4929097, an inhibitor of Notch γ secretase, was used (10 mg/kg/d) to explore the role of Notch signalling in the CX-CS-induced promotion of angiogenesis in the myocardial infarcted border zone (IBZ). The left ventricular ejection fraction (LVEF) and percentage of MI area were evaluated with animal ultrasound and Masson staining. The average optical densities (AODs) of CD31 and vWF in the myocardial IBZ were detected by immunofluorescence. Angiogenesis-related proteins including hypoxia-inducible factor 1-alpha (HIF-1α), fibroblast growth factor receptor 1 (FGFR-1), Notch1 and Notch intracellular domain (NICD), and stem cell mobilization-related proteins including stromal cell-derived factor 1 (SDF-1), C-X-C chemokine receptor type 4 (CXCR-4), and cardiotrophin1 were detected by western blot analysis. RESULTS: Compared with the model group, the CX-CS and PB groups both showed markedly improved LVEF and decreased percentage of MI area after 21 days of treatment. Although the CX group and CS group showed increased LVEF and decreased MI areas compared with the model group, the difference was not significant. The AOD of CD31 in the IBZ in both the model and the CX-CS-I group was markedly reduced compared with that in the sham group. CX-CS significantly increased the CD31 AOD in the IBZ and decreased the AODs of CD31 and vWF in the infarct zone compared with those in the model group. The expression of HIF-1α in both the model group and the CX-CS group was higher than that in the sham group. Compared with the model group, the expression of FGFR-1, SDF-1, cardiotrophin1, Notch1, and NICD was increased in the CX-CS group. Notch1 and NICD expression in the CX-CS-I group was reduced compared with that in the CX-CS group. CONCLUSIONS: The combination of CX and CS protected cardiomyocytes in the IBZ better than CX or CS alone. The mechanism by which CX-CS protects ischemic myocardium may be related to the proangiogenesis effect of CX-CS exerted through Notch signalling and the mobilization of stem cells to the IBZ.

[Effect of Ginkgo biloba extract (EGb50) on mitochondrial function in SH-SY5Y cells after hypoxia/reoxygenation injury].

Ischemic cerebrovascular disease and cerebral ischemia/reperfusion injury threaten the health of human being. We studied the protective effect of Ginkgo biloba extract 50 (EGb50) on the mitochondrial function in SH-SY5Y cells after hypoxia/reoxygenation (H/R) injury and explored its mechanisms, so as to provide new ideas for studies on the treatment for ischemic cerebrovascular disease. We established the H/R injury model in SH-SY5Y cells after administrating EGb50. Subsequently, the mitochondrial membrane potential and the concentration of intracellular Ca²âº were measured by flow cytometer. The levels of optic atrophy1 (Opa1) and dynamin-like protein 1 (Drp1) were evaluated by immunofluorescence and western blot. The results showed that the mitochondrial membrane potential was decreased and the level of intracellular Ca²âº was increased after H/R injury. Moreover, the expression of mitochondrial fusion protein Opa1 was decreased, while the expression of mitochondrial fission protein Drp1 was increased. However, EGb50 significantly increased the mitochondrial membrane potential and suppressed the level of intracellular Ca²âº. In addition, EGb50 increased the expression of Opa1 and decreased the expression of Drp1. The results demonstrated that EGb50 has a neuroprotective effect on SH-SY5Y cells after H/R injury, and could improve the energy metabolism and mitochondrial function. The underlying mechanisms may be associated with the regulation of mitochondrial fusion and fission, which provided data support for the treatment of ischemic cerebrovascular disease with EGb50.

Holistic Regulation of Angiogenesis with Chinese Herbal Medicines as a New Option for Coronary Artery Disease.

Effectively improving myocardial blood flow and controlling atherosclerotic plaque have always been key and difficult points in the prevention and treatment of coronary artery disease (CAD). Although "therapeutic angiogenesis" is regarded as a promising approach for ischemic heart disease by improving blood flow, angiogenesis itself can induce the destabilization of atherosclerotic plaque, which reflects the double-edged role of angiogenesis. Modulating the balance of angiogenesis can be an important target for CAD treatment. Traditional Chinese medicine (TCM) emphasizes the holistic view and dynamic balance of the body. Furthermore, the principle of activating blood circulation and removing blood stasis (ABCRS) is closely connected with angiogenesis and CAD. Recent research suggests that Chinese herbal medicines for ABCRS are effective in balancing the regulation of angiogenesis. This review presents the progress of recent research on the angiogenesis regulation with Chinese herbal medicines for ABCRS in CAD. Moreover, this review demonstrates that Chinese herbal medicines for ABCRS can not only promote angiogenesis in the ischemic area to improve myocardial blood flow but also alleviate angiogenesis to stabilize plaque in atherosclerosis, which reflects the holistic regulatory role in CAD treatment.

Detection of fetal epigenetic biomarkers through genome-wide DNA methylation study for non-invasive prenatal diagnosis.

The discovery of cell-free DNA fetal (cff DNA) in maternal plasma during pregnancy provides a novel perspective for the development of non­invasive prenatal diagnosis (NIPD). Against the background of maternal DNA, the use of the relatively low concentration of cff DNA is limited in NIPD. Therefore, in order to overcome the complication of the background of maternal DNA and expand the scope of cff DNA application in clinical practice, it is necessary to identify novel universal fetal­specific DNA markers. The GeneChip Human Promoter 1.0R Array set was used in the present study to analyze the methylation status of 12 placental tissue and maternal peripheral blood whole­genome DNA samples. In total, 5 fetus differential hypermethylation regions and 6 fetus differential hypomethylation regions were identified. In order to verify the 11 selected methylation regions and detect the differential CpG sites in these regions, a bisulfate direct sequencing strategy was used. In total, 87 fetal differential methylation CpG sites were identified from 123 CpG sites. The detection of fetal differential methylation DNA regions and CpG sites may be instrumental in the development of efficient NIPD and in the expansion of its application in other disorders.

Integrated miRNA and mRNA expression profiling in fetal hippocampus with Down syndrome.

BACKGROUNDS: Down syndrome (DS), caused by triplication of human chromosome 21, is the most common aneuploidies. The main characteristic of DS patients is intellectual disability. MicroRNAs (miRNAs) play important regulatory roles in various biological processes, such as embryonic development, cell differentiation, proliferation and apoptosis. Several miRNAs have shown association with DS. However, the role of miRNAs in DS patients has not been well elaborated. METHODS: In this research, total RNA extracted from fetal hippocampal tissues was used to analyze miRNA and mRNA expression via Affymetrix miRNA 4.0 and PrimeView Human Gene Expression Array, respectively. Then miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their predicted target mRNAs. Microarray data were further validated by real-time PCR. Regulation of zeste homolog 2 (EZH2) expression by hsa-miR-138 was determined by luciferase reporter assay. RESULTS: We analyzed microRNA expression profile in hippocampal tissues from DS fetal using miRNA microarray. Further with the use of mRNA microarray data, we integrate miRNA expression and mRNA expression in hippocampus of trisomy 21 fetus to elucidate the mechanism that underlying DS abnormalities. We characterized the repertoire of specific miRNAs involved in hippocampus in trisomy 21 patients, highlighting hsa-miR-138 and hsa-miR-409, in particular the importance of hsa-miR-138, especially the -5p strand. Furthermore, the expression level of predicted target genes of hsa-miR-138-5p in trisomy 21 fetus, including zeste homolog 2 (EZH2) were further confirmed. In addition, luciferase assay indicated that EZH2 was a direct target of hsa-miR-138 in HEK293T cells. CONCLUSION: The function of hsa-miR-138-5p and its target EZH2 was involved in hippocampus in DS patients. Our findings provide a clue to study the underlying molecular mechanisms in DS patients, and its potential contribution in improving understanding of intellectual disability development in DS patients.

[Role of SP3111 protein in fertilization and early embryo development in mice].

OBJECTIVE: To study the function of the SP3111 protein in fertilization and early embryo development through in vitro fertilization (IVF) experiments following anti-SP111 antibody (Ab2438) blocking. METHODS: Sperm samples collected from male mice were divided into an experimental, a blank control and a negative control group before IVF. The sperm of the experimental group was incubated with Ab2438 for 1 h followed by IVF and observed for the rates of fertilization and embryo fragmentation at 2, 4, 6, 8 and 22 h. Then the fertilized eggs were incubated with Ab2438, and the rates of fertilization embryo fragmentation were observed at 22 h. RESULTS: After the sperm was incubated with Ab2438, the incidences of embryo fragmentation were 5.26, 8.77, 23.25, 43.42 and 59.21% at 2, 4, 6, 8 and 22 h, respectively, with significant differences from the control groups (P < 0.01). After 22 h Ab2438 incubation of the fertilized eggs, the rates of normal and fragmented embryos of the experimental group were 23.64 and 63.64%, respectively, significantly different from those of the control groups (P < 0.01). CONCLUSION: Anti-SP3111 antibodies remarkably affected fertilization and early embryo development in mice. The SP3111 protein may be a signal molecule and plays a role in fertilization and early embryo development together with other proteins. Further studies on the function of the SP3111 protein in reproduction may offer a new insight into the molecular mechanism of infertility.