Identification of a combined hypoxia and lactate metabolism prognostic signature in lung adenocarcinoma : Author.

BACKGROUND: In the tumor microenvironment (TME), a bidirectional relationship exists between hypoxia and lactate metabolism, with each component exerting a reciprocal influence on the other, forming an inextricable link. The aim of the present investigation was to develop a prognostic model by amalgamating genes associated with hypoxia and lactate metabolism. This model is intended to serve as a tool for predicting patient outcomes, including survival rates, the status of the immune microenvironment, and responsiveness to therapy in patients with lung adenocarcinoma (LUAD). METHODS: Transcriptomic sequencing data and patient clinical information specific to LUAD were obtained from comprehensive repositories of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A compendium of genes implicated in hypoxia and lactate metabolism was assembled from an array of accessible datasets. Univariate and multivariate Cox regression analyses were employed. Additional investigative procedures, including tumor mutational load (TMB), microsatellite instability (MSI), functional enrichment assessments and the ESTIMATE, CIBERSORT, and TIDE algorithms, were used to evaluate drug sensitivity and predict the efficacy of immune-based therapies. RESULTS: A novel prognostic signature comprising five lactate and hypoxia-related genes (LHRGs), PKFP, SLC2A1, BCAN, CDKN3, and ANLN, was established. This model demonstrated that LUAD patients with elevated LHRG-related risk scores exhibited significantly reduced survival rates. Both univariate and multivariate Cox analyses confirmed that the risk score was a robust prognostic indicator of overall survival. Immunophenotyping revealed increased infiltration of memory CD4 + T cells, dendritic cells and NK cells in patients classified within the high-risk category compared to their low-risk counterparts. Higher probability of mutations in lung adenocarcinoma driver genes in high-risk groups, and the MSI was associated with the risk-score. Functional enrichment analyses indicated a predominance of cell cycle-related pathways in the high-risk group, whereas metabolic pathways were more prevalent in the low-risk group. Moreover, drug sensitivity analyses revealed increased sensitivity to a variety of drugs in the high-risk group, especially inhibitors of the PI3K-AKT, EGFR, and ELK pathways. CONCLUSIONS: This prognostic model integrates lactate metabolism and hypoxia parameters, offering predictive insights regarding survival, immune cell infiltration and functionality, as well as therapeutic responsiveness in LUAD patients. This model may facilitate personalized treatment strategies, tailoring interventions to the unique molecular profile of each patient's disease.

A New Hope for the Treatment of Atrial Fibrillation: Application of Pulsed-Field Ablation Technology.

In recent years, the prevalence of and mortality associated with cardiovascular diseases have been rising in most countries and regions. AF is the most common arrhythmic condition, and there are several treatment options for AF. Pulmonary vein isolation is an effective treatment for AF and is the cornerstone of current ablation techniques, which have one major limitation: even when diagnosed and treated at a facility that specializes in ablation, patients have a greater chance of recurrence. Therefore, there is a need to develop better ablation techniques for the treatment of AF. This article first compares the current cryoablation (CBA) and radiofrequency ablation (RFA) techniques for the treatment of AF and discusses the utility and advantages of the development of pulsed-field ablation (PFA) technology. The current research on PFA is summarized from three perspectives, namely, simulation experiments, animal experiments, and clinical studies. The results of different stages of experiments are summarized, especially during animal studies, where pulmonary vein isolation was carried out effectively without causing injury to the phrenic nerve, esophagus, and pulmonary veins, with higher safety and shorter incision times. This paper focuses on a review of various a priori and clinical studies of this new technique for the treatment of AF.

A novel A2a adenosine receptor inhibitor effectively mitigates hepatic fibrosis in a metabolic dysfunction-associated steatohepatitis mouse model.

Hepatic fibrosis exacerbates mortality and complications in progressive metabolic dysfunction-associated steatohepatitis (MASH). The role of the adenosine 2A receptor (A2aAR) in hepatic fibrosis within the context of MASH remains uncertain. This study aims to elucidate the involvement of the A2aAR signaling pathway and the efficacy of a novel potent A2aAR antagonist in treating hepatic fibrosis in MASH-induced mice fed a chlorine-deficient, L-amino acid-defined, high fat diet (CDAHFD). A2aAR overexpression in LX-2 cells increased fibrosis markers, whereas the known A2aAR antagonist, ZM241385, decreased these markers. A novel A2aAR antagonist, RAD11, not only attenuated fibrosis progression but also exhibited greater inhibition of the A2aAR signaling pathway compared to ZM241385 in mice with MASH, activated primary hepatocytes, and LX-2 cells. RAD11 exhibited a dual antifibrotic mechanism by targeting both activated HSCs and hepatocytes. Its superior antifibrotic efficacy over ZM241385 in the MASH condition stems from its ability to suppress A2aAR-mediated signaling, inhibit HSC activation, reduce hepatic lipogenesis in hepatocytes, and mitigate lipid accumulation-induced oxidative stress-mediated liver damage. This study has shed light on the relationship between A2aAR signaling and hepatic fibrosis, presenting RAD11 as a potent therapeutic agent for managing MASH and hepatic fibrosis.

Identification and validation of a disulfidptosis-related genes prognostic signature in lung adenocarcinoma.

Disulfidptosis, a newly revealed form of cell death, regulated by numerous genes that has been recently identified. The exact role of disulfidptosis in lung adenocarcinoma (LUAD) still uncertain. Objective of this study was to explore potential prognostic markers among disulfidptosis genes in LUAD. By combining transcriptomic information from Gene Expression Omnibus databases and The Cancer Genome Atlas, we identified differentially expressed and prognostic disulfidptosis genes. By conducting least absolute shrinkage and selection operator with multivariate Cox regression, four disulfidptosis genes were selected to create the prognostic signature. The implementation of the signature separated the training and validation cohorts into groups with high- and low-risk. Subsequently, the model was verified by conducting an independent analysis of receiver operating characteristic (ROC) curves. Further comparisons were made between the two risk-divided groups with regards the tumor microenvironment, immune cell infiltration, immunotherapy response, and drug sensitivity. The signature was constructed using four disulfidptosis-related genes: SLC7A11, SLC3A2, NCKAP1, and GYS1. According to ROC curves, the signature was effective for predicting LUAD prognosis. In addition, the prognostic signature correlated with sensitivity to chemotherapeutic agents and the efficacy of immunotherapy in LUAD. Finally, through external validation, we showed that NCKAP1 are correlated with tumor migration, proliferation, and invasion of LUAD cells. GYS1 affects immune cell, especially M2 macrophage infiltration in the tumor microenvironment. The disulfidptosis four-gene model can reliably predict the prognosis of patients diagnosed with LUAD, thereby providing valuable information for clinical applications and immunotherapy.

Identification and Characterization of Klebsiella pneumoniae from Farmed American Bullfrogs (Rana catesbeiana).

Klebsiella pneumoniae is a major cause of nosocomial infection and is considered a clinically important bacterium with antibiotic-resistant strains. There are few reports of K. pneumoniae infections in cultured aquatic animals, and no natural infection has been reported in amphibians. From September to October 2021, a high-mortality disease outbreak occurred in a pond-raised American bullfrog farm in Guangzhou, China. The infected bullfrogs were characterized by multiple organ congestive enlargement and inflammation. A pathogenic bacterium was isolated from the viscera of infected bullfrogs and confirmed to be K. pneumoniae by morphological, biochemical, and phylogenetic analyses. Infection experiments confirmed the virulence of the pathogenic strain against bullfrogs and tadpoles. A histopathological examination showed that the strain was harmful to multiple organs. Antibiotic resistance experiments indicated the isolate was a carbapenemase-producing multidrug-resistant K. pneumoniae (MDR-KP) strain. This study is the first report of K. pneumoniae infected American bullfrogs (Rana catesbeiana) and amphibians. These results will shed light on the pathogenicity of K. pneumoniae and help prevent and control K. pneumoniae infections in bullfrogs. IMPORTANCE Klebsiella pneumoniae is recognized as the most common multidrug-resistant bacterial pathogen in humans, and little is known about its pathogenicity in aquatic animals. Recently, K. pneumoniae was found to cause substantial mortality and morbidity in American farm frogs. This was the first report of K. pneumoniae infecting amphibians. In this study, we analyzed the biochemical, growth, and phylogenetic characteristics of the K. pneumoniae strain and described the symptoms and pathological features of infected bullfrogs and tadpoles; this will provide useful data for the prevention and control of infectious diseases, which has been suggested to decrease economic losses in bullfrog farming and reduce the potential threat to public health posed by K. pneumoniae.

Early patellar tendon rupture after total knee arthroplasty: A direct repair method.

BACKGROUND: Patellar tendon rupture after total knee arthroplasty (TKA) is a catastrophic complication. Although the occurrence of this injury is rare, it can lead to significant dysfunction for the patient and is very tricky to deal with. There has been no standard treatment for early patella tendon rupture after TKA, and long-term follow-up data are lacking. AIM: To introduce a direct repair method for early patella tendon rupture following TKA and determine the clinical outcomes and complications of this method. METHODS: During the period of 2008 to 2021, 3265 consecutive TKAs were retrospectively reviewed. Twelve patients developed early patellar tendon rupture postoperatively and were treated by a direct repair method. Mean follow-up was 5.7 years. Demographic, operative, and clinical data were collected. The clinical outcomes were assessed using the Western Ontario and McMaster Universities (WOMAC) score, the Hospital for Special Surgery (HSS) score, knee range of motion, extensor lag, and surgical complications. Descriptive statistics and paired t test were employed to analyze the data. RESULTS: For all 12 patients who underwent direct repair for early patellar tendon rupture, 3 patients failed: One (8.3%) for infection and two (17.6%) for re-fracture. The two patients with re-fracture both underwent reoperation to reconstruct the extensor mechanism and the patient with infection underwent revision surgery. The range of motion was 109.2° ± 10.6° preoperatively to 87.9° ± 11° postoperatively, mean extensor lag was 21° at follow-up, and mean WOMAC and HSS scores were 65.8 ± 30.9 and 60.3 ± 21.7 points, respectively. CONCLUSION: This direct repair method of early patellar tendon rupture is not an ideal therapy. It is actually ineffective for the recovery of knee joint function in patients, and is still associated with severe knee extension lag and high complication rates. Compared with the outcomes of other repair methods mentioned in the literature, this direct repair method shows poor clinical outcomes.

Comparison of Preoperative Computed Tomography and Intraoperative Estimation in Predicting the Version of a Single-Wedge Femoral Stem.

OBJECTIVE: Early prediction of stem version aids in optimization of combined version during total hip arthroplasty (THA). This study aimed to analyze the discrepancy between stem version and native femoral version measured by different methods, and to explore which method can better predict the stem version. METHODS: We retrospectively reviewed 26 patients (39 hips) treated with robot-assisted THA in our hospital between September 2019 and December 2019. A straight, single-wedge, cementless stem (Accolade II) was used in all cases. Preoperative femoral version was measured at three levels on computerized tomography (CT) scan from the top to the middle level of femoral neck (Level 1 to Level 3). During THA, the version on cutting surface was measured prior to femoral broaching based on two reference lines: mid-cortical line and T line (trochanteric fossa to the middle of medial cortex). After femoral broaching, stem version was measured based on the femoral neck trial using Mako system (Stryker). In the statistical analysis, the difference and absolute discrepancy between stem version and femoral version measured with various methods were examined using paired t-test, and the relationship between stem version and various femoral versions were examined using correlation analysis. RESULTS: Mean femoral neck version (Level 1) was 9.5° ± 2.6° (range, -16.8°-42.5°), while mean stem version measured by Mako system was 19.9° ± 2.0° (range, -8.0°-49.0°). Femoral version measured with each method showed a moderate correlation with stem version (p < 0.05). There was a significant difference between stem version and femoral version except at Level 3, with a mean difference of 0.8° ± 13.6° (p = 0.729). With regard to the intraoperative estimation, stem version significantly increased compared to the value based on mid-cortical line, with a mean difference of 8.4° ± 13.1° (p < 0.001). However, the mean value of stem version was a little smaller than that of femoral version measured by reference to T line, but without statistical significance (p = 0.156). No postoperative dislocations occurred during the study period. No revision was required for any component. CONCLUSIONS: The middle level of femoral neck on CT scan and T line on cutting surface are better references to measure femoral version for predicting postoperative stem version. However, the relationship between stem version and predictive value was flexible. Therefore, further three-dimensional studies of postoperative CT are needed to validate the press-fit fixation and rotational freedom of the single-wedge stem.

Different squatting positions after total knee arthroplasty: A retrospective study.

BACKGROUND: Total knee arthroplasty (TKA) has been shown to improve quality of life and reduce pain. High-flexion activities such as squatting, kneeling, and floor transfers are mainly listed as demanding tasks. Among them, squatting is an important position. AIM: To provide a new squat position classification and evaluate the different squatting positions of a series of patients after primary TKA. METHODS: From May 2018 to October 2019, we retrospectively reviewed 154 video recordings of the squatting-related motions of patients after TKA. Among the included patients, 119 were women and 35 were men. Their mean age at the index surgery was 61.4 years (range, 30 to 77). RESULTS: The median follow-up was 12 mo (range, 6 to 156 mo). We classified those squatting-related motions into three major variations according to squatting depth: Half squat, parallel squat, and deep squat. The angles of hip flexion, knee flexion, and ankle dorsiflexion were measured in the screenshots captured from the videos at the moment of squatting nadir. A total of 26 patients were classified as half squats, 75 as parallel squats, and 53 as deep squats. The angles of hip flexion, knee flexion, and ankle dorsiflexion all differed significantly among the three squatting positions (P < 0.001). In the parallel squat group, the mean knee flexion angle (°) was 116.5 (SD, 8.1; range, 97 to 137). In the deep squat group, the mean knee flexion angle (°) was 132.5 (SD, 9.3; range, 116 to 158). CONCLUSION: Among the three squatting positions, deep squat showed the highest hip, knee, and ankle flexion angles, followed by the parallel squat. With the improvement of squatting ability, the patient's postoperative satisfaction rate was also significantly enhanced. However, the different squatting abilities of the patients cannot be effectively distinguished from the scoring results (P > 0.05). Our squatting position classification offers a pragmatic approach to evaluating patients' squatting ability after TKA.

Isoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3ß/ß-cat signaling pathway.

Tubulointerstitial fibrosis (TIF) is a prominent pathological manifestation for the progression of almost all chronic kidney diseases (CKDs) to end-stage renal failure. However, there exist few efficient therapies to cure TIF. Our recent results showed that (8R, 12S)-isoandrographolide (ISA), a diterpenoid lactone ingredient of traditional Chinese herbal Andrographis paniculata (Burm.f.) Nees, exhibited anti-pulmonary fibrosis in silica-induced mice. Herein, we investigated the therapeutic effect of ISA on TIF, using mice subjected to unilateral ureteral obstruction (UUO) and human kidney proximal tubular epithelial (HK-2) cells treated with transforming growth factor-ß1 (TGF-ß1) or tumor necrosis factor-α (TNF-α). The pathological changes and collagen deposition results displayed that ISA administration significantly attenuated inflammatory response, ameliorated TIF, and protected the kidney injury. Interestingly, ISA revealed much lower cytotoxicity on HK-2 cells, but exhibited stronger inhibitory effect on tubular epithelial mesenchymal transformation (EMT) and inflammation, as compared to andrographolide (AD), the major ingredient of A. paniculata extract that has been reported to ameliorate TIF in diabetic nephropathy mice. It was further clarified that the amelioration of TIF by ISA was associated with suppressing the aberrant activation of AKT/GSK-3ß/ß-catenin pathway through network pharmacology analysis and experimental validation. Taken together, these findings indicate that ISA is a promising lead compound for development of anti-TIF, and even broad-spectrum anti-fibrotic drugs.

Change of Pelvic Sagittal Tilt after Total Hip Arthroplasty in Patients with Bilateral Crowe Type IV Developmental Dysplasia of the Hip.

OBJECTIVE: To explore and analyze the change of pelvic sagittal tilt (PST) after total hip arthroplasty (THA) in patients with bilateral Crowe type IV developmental dysplasia of the hip (DDH). METHODS: The study retrospectively evaluated 43 patients with bilateral Crowe type IV DDH undergoing THA from January 2008 to June 2019 who were followed up for 12 months postoperatively. Four parameters, including the ratio between the height and width of the obturator foramina(H/W ratio), the vertical distance between the upper edge of the symphysis and the middle of the sacrococcygeal joint (SSc distance), the vertical distance between the upper edge of the symphysis and the line connecting bilateral hip centers (SC distance) and the vertical distance between the upper edge of the symphysis and the line connecting the bilateral lower ends of the sacroiliac joints (SSi distance), which could indirectly reflect the change of PST, were observed and measured by radiographs. The change of each parameter before operation, immediately after operation, and in 3, 6 and 12 months postoperatively was compared and analyzed. RESULTS: Compared with the value before operation, the H/W ratio immediately after operation and in 3, 6 and 12 months postoperatively were 0.61 ± 0.12 (t = 0.893, P = 0.377), 0.61 ± 0.11 (t = 1.622, P = 0.112), 0.67 ± 0.10 (t = 5.995, P < 0.001) and 0.76 ± 0.12 (t = -9.313, P < 0.001), respectively, and the SSc, SC and SSi distance in 6 months postoperatively were 30.12 ± 7.06 mm (t = 3.506, P = 0.002), 42.8 ± 7.7 mm (t = 5.843, P < 0.001), 129.3 ± 12.6 mm (t = 5.888, P < 0.001), respectively, and in 12 months postoperatively were 27.24 ± 7.68 mm (t = 6.510, P < 0.001), 36.1 ± 9.1 mm (t = 9.230, P < 0.001), 118.9 ± 14.9 mm (t = 8.940, P < 0.001), respectively. The radiographs obtained in 6 and 12 months postoperatively demonstrated a significantly increased H/W ratio and decreased SSc, SC and SSi distance. At the last follow-up, the clinical evaluations significantly improved in all patients and there were no revisions. CONCLUSION: The significant change of pelvic sagittal posterior tilt in patients with bilateral Crowe type IV DDH might be a significant phenomenon after THA, which could occur in 6 months postoperatively.

Factors Affecting Squatting Ability in Total Knee Arthroplasty Using High Flexion Prosthesis.

PURPOSE: Total knee arthroplasty (TKA) is widely used as a treatment for knee osteoarthritis. Few studies have analysed the factors affecting the squatting ability of patients after TKA. The purpose of this study was to comprehensively analyse the factors affecting squatting ability after TKA and to determine which ones are important. PATIENTS AND METHODS: Three hundred primary TKA cases with a minimum 3-year follow-up were retrospectively analysed. All patients received a conventional posterior-stabilized TKA implant and underwent a standard perioperative care pathway. The patients were divided into two groups according to the squatting position and knee flexion angle while weight-bearing (Group I - inability to squat group, Group II - ability to squat group). Demographic, operative, and clinical data were collected. Radiographic assessment included joint line elevation, patellar position, posterior condylar offset (PCO), etc. Statistical analysis of the effect of all the above factors on squatting ability was performed. RESULTS: The preoperative range of motion and joint line of Group I were 82.9±12.6 and 3.24±1.07, respectively, and those of Group II were 107±9.6 and 1.83±0.89 respectively. The univariate analysis showed that age, prosthesis size, preoperative ROM and joint line position were correlated with squatting ability. But in the final multivariate analysis, joint line position and preoperative ROM were independent influencing factors that affected squatting ability after TKA (p value < 0.01). CONCLUSION: Preoperative ROM and joint line position were independent influencing factors affecting squatting ability after TKA. Patients should be counseled accordingly and be made to understand these factors. To ensure that patients can squat postoperatively, we should improve surgical techniques to control joint line elevation.

[Application of individualized setting of femoral opening point and valgus angle in artificial total knee arthroplasty for patients with external femoral arch].

OBJECTIVE: To investigate whether shifting the femoral opening point and setting a personalized femoral valgus angle can improve the lower limb force line of total knee arthroplasty (TKA) patients with external femoral arch. METHODS: From March 2016 to October 2018, 50 patients (55 knees) with osteoarthritis with genu varus deformity combined with external femoral arch for TKA were selected. There were 10 males and 40 females. The age ranged from 63.1 to 80.5 years old, with an average of (67.8±5.8) years old. Forty-five cases were unilateral and 5 cases were bilateral. The osteoarthritis stages of 55 knees were Kellgren-Lawrence grade Ⅲ to Ⅳ; and the course of disease ranged from 2 to 10 years. PreoperativeSpecial Surgery (Hospital for Special Surgery) scores:pain was 15.20±3.52; function was 8.30±2.96;mobility was 10.15±2.85;muscle strength was 4.20±1.95;flexion deformity was 5.50±3.05;stability was 6.15±2.20; total score was 47.93±3.39. The external femoral arch angle ranged from 6.4° to 16.7°, with a mean of (10.63±2.29) °. The tibiofemoral angle ranged from 7.4° to 12.6°, with a mean of (12.04±3.59)°. The anatomical distal femoral angle ranged from 83.10° to 91.20°, with a mean of (84.55± 1.66)°. And the distance from the center of the knee joint to the lower limb line of force ranged from 2.01 to 6.00 cm, with a mean of (3.57±1.12) cm. During the replacement surgery, the femoral opening point and the valgus angle were individually set to obtain a good line of force of the lower limbs. RESULTS: Before the operation, the distance of femoral opening point ranged from 0.24 to 0.74 cm, with a mean of (0.54±0.10) cm. The distance between the internal and external condyles of the femur ranged from 6.86 to 8.12 cm, with a mean of (7.27±0.27) cm. The preoperative valgus correction angle (VCA) ranged from 7.20° to 13.80°, with a mean of (9.38±1.38) °. The post-correction valgus correction angle' (VCA') ranged from 6.10° to 9.50°, with a mean of (7.36±0.82) °. All patients were followed up, and the duration ranged from 3 to 36 months, with an average of (13.5±5.8) months. All patients obtained good knee function after operation. Three months after operation, HSS scores included pain of 25.30±3.05, function of 18.25±2.05, mobility of 16.05±0.75, muscle strength of 6.20±2.10, flexion deformity of 8.80±1.85, stability of 8.20±1.75; and the total score ranged from 90.00 to 93.00, with an average of 91.82±0.98. The total score was higher than that before operation (t=1.728, P=0.038). Postoperative X-ray examination showed that there were no signs of loosening, sinking, or osteolysis of the prosthesis. The tibiofemoral angle on the weight-bearing X-ray on the second day after surgery ranged from 1.30° to 4.90°, with a mean of (2.53±0.83) °;the angle ranged from 87.50° to 91.30°, with a mean of (88.73±0.86) °;and the distance from the center of the knee joint to the lower limb line of force ranged from 0.02 cm to 1.20 cm, with a mean of (0.23±0.05) cm; which were improved compared with those before operation (t=2.415, P=0.019;t=1.496, P=0.041;t=1.912, P=0.033). CONCLUSION: In TKA combined with external femoral arch, good lower limb force line and knee joint function can be obtained by externally shifting the femoral opening point and setting a personalized femoral valgus angle.

Treatment of Osteoarthritis Secondary to Severe Coxa Vara with Modular Total Hip Arthroplasty.

OBJECTIVE: We aimed to demonstrate the methods of treatment for coxa vara with modular total hip arthroplasty (THA) and evaluate clinical and radiographic outcomes, and further survivorship at the midterm follow-up. METHODS: We retrospectively reviewed 33 patients (42 hips) who underwent modular THA for coxa vara deformity from May 2008 to December 2019. The clinical and radiographic results, including Harris Hip Score (HHS), leg length discrepancy (LLD), greater trochanteric height, femoral offset, abductor lever arm, stem alignment and limp, and complications, were evaluated. RESULTS: The follow-up time was mean 69.9±43.7 months. Clinically, the HHS improved significantly (p<0.001) on average from 42.90±14.44 points to 89.54±4.75 points. The mean LLD decreased from 33.3±19.4 mm to 5.0±5.8 mm (p<0.001), and 27 patients (82%) thought that total equality of the lower limbs was obtained. Patients demonstrated diminished or no limping in 88% (29/33) of hips and a significant improvement of biomechanics. At the final follow-up, all stems of hips were in clinical neutral alignment and the prostheses survivorship rates for all-causes revisions was 97.6%. CONCLUSION: Modular THA is a valuable alternative to render favorable outcomes for treatment of osteoarthritis secondary to severe coxa vara.

Factors influencing knee valgus alignment in Crowe type IV hip dysplasia after total hip arthroplasty.

BACKGROUND: Valgus deformity of the knee remains a complaint after total hip arthroplasty (THA) among some patients with Crowe type IV hip dysplasia. We aimed to identify the knee alignment in these patients before and after surgery, and to explore the factors contributing to postoperative knee valgus alignment. MATERIALS AND METHODS: We retrospectively reviewed a series of Crowe type IV patients who received THA between February 2010 and May 2019 in our hospital. The patients' medical data were collected from the hospital information system. On both preoperative and postoperative full limb length standing radiographs, the following parameters were measured: hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle, anatomical tibiofemoral angle, anatomical lateral distal femoral angle, femoral neck-shaft angle, pelvic obliquity, limb length, height and lateral distance of hip center, and femoral offset. Univariate and multivariate binary logistic regression were used to identify the factors influencing postoperative knee valgus alignment. RESULTS: A total of 64 Crowe type IV patients (87 hips) were included in the study. Overall, HKA improved from 176.54 ± 3.52° preoperatively to 179.45 ± 4.31° at the last follow-up. Those hips were subdivided into non-valgus group (≥ 177.0°, n = 65) and valgus group (< 177.0°, n = 22) according to postoperative HKA. Only postoperative mLDFA was a significant factor in the multivariate regression model. CONCLUSIONS: The postoperative mLDFA is a major factor related to knee valgus alignment after THA, which combines the preoperative anatomy and surgical reconstruction. Other factors previously published were found to have no significance. LEVEL OF EVIDENCE: III.

Sox11 Modified Tendon-Derived Stem Cells Promote the Repair of Osteonecrosis of Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a leading cause of mobility impairment which may lead to a total hip replacement. Recent studies have found tendon derived stem cells (TDSCs) might be an ideal cell source for musculoskeletal tissue regeneration. And our previous study has shown Sox11 could promote osteogenesis of bone marrow-derived MSCs. However, the effect of TDSCs or Sox11 over-expressing TDSCs (TDSCs-Sox11) on bone regeneration in ONFH has not been investigated. In the present study, TDSCs were infected with AAV carrying Sox11 or empty vector. We showed that Sox11 could promote the proliferation and osteogenic differentiation of TDSCs, as well as angiogenesis in vitro. The western blot analysis showed that Sox11 could activate the PI3K/Akt signaling pathway to promote osteogenesis of TDSCs. Finally, using a rabbit model of hormone-induced ONFH, our result demonstrated that local administration of TDSCs or TDSCs overexpressing Sox11 could accelerate bone regeneration in necrotic femoral heads, and TDSCs overexpressing Sox11 showed better effects. TDSCs over-expressing Sox11 might be a promising cell source for stem cell therapy to promote bone regeneration, such as ONFH, fracture, bone defect, and so on.

The Influence of Femoral Proximal Medullary Morphology on Subtrochanteric Osteotomy in Total Hip Arthroplasty for Unilateral High Dislocated Hips.

OBJECTIVE: To evaluate the predictive values of femoral proximal medullary morphology for the use of subtrochanteric osteotomy (STO) in unilateral Crowe IV developmental dysplasia of the hip (DDH). METHODS: Ninety four patients with unilateral Crowe type IV DDH (59 hips in STO group and 35 hips in the non-STO group) between April 2008 and June 2019 were enrolled. All patients underwent THA using the Pinnacle acetabular shell, ceramic liner and femoral head, the S-ROM stem with proximal sleeve. Three parameters on the standard anteroposterior hip radiographs were measured: the widths of medullary canals at 20 mm above the center of lesser trochanter (CLT)，20 mm below the CLT and the isthmus. Canal flare index (CFI), metaphyseal canal flare index (MCFI), diaphyseal canal flare index (DCFI) were calculated. A S-ROM femoral stem was used in all patients during total hip arthroplasty (THA). RESULTS: The CFI and DCFI in the STO group were lower than those in the non-STO group. However, there was no statistical difference in MCFI between the two groups. The receiver operating characteristic (ROC) curves shown that DCFI had the highest area under the curve (AUC), at 0.885. This was followed by the CFI, which had an AUC of 0.847. The AUC of MCFI was 0.579. The optimal threshold for DCFI was 1.44, which lead to a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 0.771, 0.898, 0.869, and 0.818, respectively. For CFI, the optimal threshold was 3.28, resulting in a sensitivity, specificity, PPV, and NPV of 0.829, 0.729, 0.878, and 0.644, respectively. CONCLUSIONS: The DCFI and CFI may be potent indicators in predicting the use of STO in unilateral Crowe IV DDH. The optimal threshold for CFI and DCFI were 3.28 and 1.44 and had good sensitivity and specificity for predicting the use of STO during THA.

False acetabulum is preoperative guidance for Crowe type IV hips on hip reduction without femoral shortening during total hip arthroplasty.

BACKGROUND: We aimed to analyze if the false acetabulum is a good indicator for determining femoral shortening. METHODS: We retrospectively included 102 patients with unilateral Crowe type IV developmental dysplasia who underwent primary total hip arthroplasty from April 2008 to May 2019. Based on the presence of false acetabulum, the 102 hips were further classified Crowe IVA group and Crowe IVB group. Radiographic measurement included the height of greater trochanter (HGT) preoperatively and postoperatively, which reflected the distalisation of greater trochanter (DGT). Harris hip score (HHS), limb length discrepancy (LLD), and complications were collected as clinical evaluation. RESULTS: Sixty hips were classified into Crowe IVA group, and 42 hips were classified into Crowe IVB group. Within Crowe IVA group, the proportion of hips treated with subtrochanteric osteotomy was significantly higher than that in Crowe IVB group (97% vs. 12%) (P < 0.001). The DGT in Crowe IVA group was also greater (67 vs. 32 mm) (P < 0.001). At last follow-up, both two groups obtained excellent clinical scores. There was no significant difference in postoperative LLD between the two groups (P = 0.001). Six dislocations occurred and three patients developed femoral nerve palsy, while all recovered in a year. CONCLUSION: The false acetabulum is a promising and good indicator for determining femoral shortening.

Jumbo cup in hip joint renovation may cause the center of rotation to increase.

BACKGROUND: Utilizing the large jumbo cup in revision total hip arthroplasty is an effective approach to cure many lacunar and segmental peripheral bone defects. However, with the use of the jumbo cup, the center of the hip joint may become elevated relative to the primary acetabulum, and the diameter of the large cup is greater. AIM: To study the height and the significance of the elevation of the hip joint center. METHODS: Eighty-eight patients matched the criteria for this condition and were included in the study. The center height of the hip joint was measured relative to the opposite normal hip joint. The diameter of the jumbo cup was measured and checked according to operation notes, and the diameter of the jumbo cup was measured with a prosthesis label. Then, the horizontal and vertical centers of rotation were measured on the surgical side and opposite side. The average center height of the hip joint on the renovated side and the opposite side and the position of the hip cup relative to the teardrop were compared using a paired t-test. RESULTS: Radiometric analysis showed that the average hip joint center was elevated by 7.6 mm. The rotational center height delta of the renovated hip was 7.6 ± 5.6 mm, and there was an obvious difference between the two groups (P = 0.00). The difference in horizontal distance was 0.5 ± 5.1 mm (-11.5 -14.0 mm), and there was no obvious difference between the two groups (P = 0.38). According to the foreign standard, the rotational center height delta of the renovated hip was 7.5 ± 6.2 mm, and there was a significant difference between the two groups (P = 0.00). There was no obvious difference between the domestic and foreign standards (P > 0.05) between the two groups. CONCLUSION: The application of the jumbo cup elevates the rotational center of the hip joint, but it is feasible and effective to use the jumbo cup.

The Three-Dimensional Morphology of Femoral Medullary Cavity in the Developmental Dysplasia of the Hip.

OBJECTIVE: This study aimed to assess the morphology of the femoral medullary canal in subjects with developmental dysplasia of the hip (DDH) with the intent of improving the design of femoral stems in total hip arthroplasty. METHODS: Computed tomography images of 56 DDH hips, which were classified into Crowe I to Crowe IV, and 30 normal hips were collected and used to reconstruct three-dimensional morphology of the femoral medullary cavity. Images of twenty-one cross sections were taken from 20 mm above the apex of the lesser trochanter to the isthmus. The morphology of femoral cavity was evaluated on each cross section for the longest canal diameter, the femoral medullary torsion angle (FMTA), and the femoral medullary roundness index (FMRI). RESULTS: The Crowe IV group displayed the narrowest medullary canal in the region superior to the end of the lesser trochanter, but then gradually aligned with the medullary diameter of the other groups down to the isthmus. The FMTA along the femoral cavity increased with the severity of DDH, but the rate of variation of FMTA along the femoral canal was consistent in the DDH groups. The DDH hips generally showed a larger FMRI than the normal hips, indicating more elliptical shapes. CONCLUSION: A femoral stem with a cone shape in the proximal femur and a cylindrical shape for the remainder down to the isthmus may benefit the subjects with severe DDH. This design could protect bone, recover excessive femoral anteversion and facilitate the implantation in the narrow medullary canal.