The fission yeast kinetochore complex Mhf1-Mhf2 regulates the spindle assembly checkpoint and faithful chromosome segregation.

The outer kinetochore serves as a platform for the initiation of the spindle assembly checkpoint (SAC) and for mediating kinetochore-microtubule attachments. How the inner kinetochore subcomplex CENP-S-CENP-X is involved in regulating the SAC and kinetochore-microtubule attachments has not been well characterized. Using live-cell microscopy and yeast genetics, we found that Mhf1-Mhf2, the CENP-S-CENP-X counterpart in the fission yeast Schizosaccharomyces pombe, plays crucial roles in promoting the SAC and regulating chromosome segregation. The absence of Mhf2 attenuates the SAC, impairs the kinetochore localization of most of the components in the constitutive centromere-associated network (CCAN), and alters the localization of the kinase Ark1 (yeast homolog of Aurora B) to the kinetochore. Hence, our findings constitute a model in which Mhf1-Mhf2 ensures faithful chromosome segregation by regulating the accurate organization of the CCAN complex, which is required for promoting SAC signaling and for regulating kinetochore-microtubule attachments. This article has an associated First Person interview with the first author of the paper.

Mad2 promotes Cyclin B2 recruitment to the kinetochore for guiding accurate mitotic checkpoint.

Accurate mitotic progression relies on the dynamic phosphorylation of multiple substrates by key mitotic kinases. Cyclin-dependent kinase 1 is a master kinase that coordinates mitotic progression and requires its regulatory subunit Cyclin B to ensure full kinase activity and substrate specificity. The function of Cyclin B2, which is a closely related family member of Cyclin B1, remains largely elusive. Here, we show that Mad2 promotes the kinetochore localization of Cyclin B2 and that their interaction at the kinetochores guides accurate chromosome segregation. Our biochemical analyses have characterized the Mad2-Cyclin B2 interaction and delineated a novel Mad2-interacting motif (MIM) on Cyclin B2. The functional importance of the Cyclin B2-Mad2 interaction was demonstrated by real-time imaging in which MIM-deficient mutant Cyclin B2 failed to rescue the chromosomal segregation defects. Taken together, we have delineated a previously undefined function of Cyclin B2 at the kinetochore and have established, in human cells, a mechanism of action by which Mad2 contributes to the spindle checkpoint.

A new joint reconstruction technique in the treatment of giant cell tumors around the knee: Structural allograft and unicompartmental arthroplasty.

OBJECTIVE: The long-term prognosis of patients who underwent unicompartmental knee arthroplasty (UKA) with a structural allograft or hemiarticular allograft transplantation to treat giant cell tumors (GCTs) around the knee and the prosthesis survival rate were analyzed. METHODS: We retrospectively reviewed 73 patients who were diagnosed with GCTs around the knee and underwent surgery to restore joint function from 2000 to 2015. Patients were divided into two groups according to the surgical procedure used for functional knee reconstruction: hemiarticular allograft transplantation or structural allograft and UKA. The Knee Society Score (KSS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to analyze postoperative knee function between the two groups. The Kellgren-Lawrence (K-L) classification system was used to evaluate the progression of osteoarthritis. The incidence of complications and the prosthesis survival rate were also investigated. RESULTS: Patients who underwent UKA to treat GCT demonstrated significantly improved knee function. The rate of an excellent or good KSS was significantly different between the two groups (p = 0.041 at the 1-year follow-up, p = 0.033 at the last follow-up). The proportion of severe cases according to WOMAC in the two groups was also different (p = 0.030 at the 1-year follow-up, p = 0.021 at the last follow-up). According to the K-L grade of unaffected compartments, UKA better prevented the progression of osteoarthritis (p = 0.034). CONCLUSIONS: Patients with GCTs around the knee could benefit from UKA. In addition to providing better knee function and range of motion, UKA could also slow the progression of osteoarthritis in the knee joint. This new surgical method could meet the needs of patients wishing to preserve joint integrity and favorable joint function.

Catalyst-controlled regiodivergent Friedel-Crafts reactions of 1-naphthols with 2,3-dioxopyrrolidines: synthesis of polycyclic 2-pyrrolidinones.

In this study, we developed an organocatalyst-controlled site-selectivity switchable Friedel-Crafts reaction of 1-naphthols and 2,3-dioxopyrrolidines. The o-selective Friedel-Crafts reaction was achieved with chiral tertiary amines, while the p-selective Friedel-Crafts reaction was accomplished with Brønsted acids or Lewis acids. With this protocol, a range of functionalized polycyclic 2-pyrrolidinone derivatives were prepared. Moreover, theoretical mechanistic investigations provided insights into the site-selectivity reaction pathway and the origin of chiral induction for the o-selective Friedel-Crafts reaction.

Effectiveness of Needle Aspiration versus Surgical Excision for Symptomatic Synovial Cysts of the Hip: A Single-Center, Retrospective Study.

BACKGROUND This study was performed to evaluate the clinical effectiveness of needle aspiration vs surgical excision for symptomatic synovial cysts of the hip. MATERIAL AND METHODS This retrospective study analyzed the clinical data of patients diagnosed with synovial cysts of the hip and treated in a single-center hospital from January 2012 to April 2022. Patients receiving needle aspiration were assigned to group A and those treated with surgery were assigned to group B. Demographic characteristics, etiology, symptoms, cyst location, postoperative complications and recurrence, Harris Hip Score (HHS) and Visual Analog Scale of Pain (VAS) scores before treatment and at 3, 6, and 12 months after treatment were recorded to assess hip function in both groups. RESULTS This study recruited 44 patients, with 18 patients in group A and 26 in group B, and the 2 arms were well-balanced in terms of baseline patient profiles. Needle aspiration resulted in significantly better pain mitigation for patients at 24 h, 48 h, and 72 h after treatment vs surgical interventions (P<0.05). Needle joint aspiration resulted in significantly better function restoration of the hip joint than surgery at 3 months after treatment, as evidenced by the lower HHS score of 85.31±13.16 in group A vs 78.51±11.66 in group B (P=0.002). Surgery was associated with a significantly lower incidence of disease relapse (0.00%) vs needle aspiration (27.7%) (P=0.004). CONCLUSIONS Needle aspiration in the treatment of symptomatic synovial cysts of the hip causes less damage to the soft tissue and leads to faster recovery in the short term than surgical resection. Surgical resection has a lower recurrence rate and better long-term efficacy.

Efficacy of Direct Anterior Approach Versus Posterior Lateral Approach for Total Hip Replacement in Patients with Parkinson's Disease.

BACKGROUND The present study was performed to evaluate the efficacy of direct anterior approach (DAA) versus posterolateral approach (PLA) for total hip arthroplasty (THA) in patients with Parkinson's disease (PD). The aim of the study was to compare the speed of recovery of hip function and postoperative complications between the 2 approaches. MATERIAL AND METHODS The study included 285 Parkinson's patients who underwent THA; 209 eligible patients were recruited for analysis as per the inclusion criteria and assigned into DAA group (n=90) and PLA group (n=119) according to the surgical approach. Postoperative Harris Hip Score (HHS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and Forgotten joint score (FJS) were collected to assess hip function. RESULTS The DAA had a statistically lower incidence of postoperative complications than the PLA, particularly the rate of postoperative dislocation. Perioperative outcomes showed a longer operative time in the DAA than in the PLA group and more intraoperative blood loss in the DAA than in the PLA group. At 3 months postoperatively, the HHS and WOMAC scores in the DAA group showed significantly higher scores compared to the PLA group versus the DAA group. However, these differences disappeared at 6 months postoperatively and the FJS in the DAA group had a statistically higher score compared to the PLA group. CONCLUSIONS In patients with Parkinson's disease complicated with hip disease, the DAA approach exhibited a lower rate of dislocation than the PLA approach and had faster recovery of hip function.

Retrospective Study from a Single Center to Identify Risk Factors Associated with Reinfection in Patients Undergoing 2-Stage Revision Surgery for Periprosthetic Joint Infection.

BACKGROUND This study identified risk factors associated with reinfection and created a scoring system designed for patients with periprosthetic joint infection (PJI) who have undergone prosthetic resection and spacer implantation. MATERIAL AND METHODS Patients who underwent 2-stage revision for PJI from January 2010 to December 2017 were retrospectively analyzed in this study. Patients were divided into 2 groups: infection recurrence and infection cure. Demographic and clinical information, laboratory test results, and radiological images that were potentially associated with infection were obtained and analyzed. RESULTS Seven independent risk (protective) factors for infection recurrence in patients with PJI who underwent 2-stage hip revision surgery were identified: C-reactive protein level, type of bacterial infection, age, immunosuppression, albumin/globulin ratio, glucose level, and magnetic resonance imaging findings. Finally, a weighted scoring system of 100-mark system was established and the area under the curve was 0.965 (95% confidential interval=0.947-0.983). The predictive scores for low risk (≤30%), moderate risk (31-69%), and high risk (≥70%) of infection recurrence were ≤45, 46-77, and ≥78, respectively. CONCLUSIONS For patients with PJI who had already undergone joint resection and spacer implantation, this newly established scoring system might help determine the accurate risk of infection recurrence after a definitive new prosthesis implantation. Patients with scores greater than 78 points would be considered very likely to have an infection recurrence. Therefore, the second-stage revision surgery should be changed to an additional anti-infection treatment or a debridement surgery instead of a definitive prosthesis implantation surgery.

Clinical and radiologic outcomes in patients undergoing primary total hip arthroplasty with Collum Femoris Preserving stems: a comparison between the direct anterior approach and the posterior approach.

BACKGROUND: The direct anterior approach (DAA) and posterior approach (PA) are two of the most common surgical approaches used for total hip arthroplasty (THA) worldwide. The curved anatomical collum femoris-preserving (CFP) stem was designed to preserve the bone of the femoral neck and allow physiologic load transfer along the trabecular systems, which may better restore hip biomechanics, improve triplanar stem stability and improve the long-term survival rate. We believe this study will demonstrate whether the DAA is suitable for THA with CFP stems. METHODS: The data of patients who underwent primary THA with CFP stems from January 2010 to December 2015 were retrospectively analysed. These patients were divided into two groups (group A, DAA; group B, PA). The approach was selected by the surgeon. The demographic characteristics, preoperative diagnoses, preoperative Harris hip score, preoperative range of motion, postoperative complications, and radiologic measurements (neck-shaft angle, coronal alignment, sagittal alignment, stress shielding, anteversion, neck-preserving ratio, acetabular anteversion, acetabular inclination angle, acetabular depth, anterior-posterior offset, lateral offset, difference in leg length) were recorded for all patients. RESULTS: In this study, a total of 248 patients (185 male and 63 female) were included. No significant differences were found between group A and group B in terms of general patient information and radiologic measurements. However, the rate of nerve injury in group A (7/5.5%) was significantly higher than that in group B (1/0.8%) (p = 0.037). At 1 month after surgery, we found a significant difference between the two groups in the Harris hip score (HHS) (71.03 ± 8.04 in group A, 68.39 ± 8.37 in group B, P = 0.014) and forgotten joint score (FJS-12) (50.78 ± 7.57 in group A, 47.68 ± 7.34 in group B, P = 0.001). At 1 year after surgery, the mean FJS-12 score in group A (68.78 ± 7.54) was higher than that in group B (58.84 ± 8.91) (P < 0.001). At 5 years after surgery, the mean FJS-12 score in group A (73.38 ± 7.21) was higher than that in group B (67.16 ± 9.12) (P < 0.001). Post hoc analysis of the 1-month, 1-year, and 5-year postoperative FJS-12 scores using multiple linear regression analysis revealed that an excellent HHS led to good patient satisfaction at each time point. CONCLUSION: In summary, unlike a "standard" femoral stem, whose alignment might be affected by the surgical approach, alignment of the CFP stem is independent from the surgical approach. Even though the DAA had a higher nerve injury rate, nerve injury from the DAA did not typically cause severe dysfunction of the lower extremity. Therefore, decisions regarding the surgical approach for patients undergoing THA with CFP stems can be made primarily based on the preference of the surgeon.

Short uncemented femoral component for hip revision: prognosis and risk factors associated with failure.

BACKGROUND: The application of short femoral stems is partially restricted in revision surgery. This study will demonstrate the therapeutic effect and unsuitable situation for short stem revision. METHODS: Demographic characteristics of all patients were recorded in detail (Table 1). Anteroposterior view radiographic examinations of proximal femur are necessary before and after the operation for patients. The primary outcome of interest was the survival rate of the femoral stem at the final follow-up. Risk factors for failure were also investigated. The secondary outcomes of interest included the Harris hip score, excellent to good rate and incidence of complications. The Mann-Whitney U test was performed for comparisons between continuous variables. The chi-square test was performed for comparisons between categorical variables. Cox regression analysis was used to assess the association between potential risk factors and the failure of revision surgery. RESULTS: A total of 381 patients with short stems were retrospectively reviewed. There were 188 males and 193 females. The average age and body mass index before revision surgery were 58.85 ± 13.46 years and 23.72 ± 3.40 kg/m2, respectively. The mid-term survival rate of the short femoral component was 94.23%. The prognosis and complications of patients between the two groups were compared. There was no significant difference between the two groups in the Harris score, complication incidence or survival rate of the femoral component. The strongest risk factor in this study was intraoperative periprosthetic femoral fracture during revision surgery (HR = 5.477, 95% CI = 2.156-13.913). CONCLUSION: Three risk factors for failure were identified: ageing, osteoporosis and intraoperative periprosthetic femoral fracture during revision surgery. Therefore, a short femoral stem should be implanted in patients with these risk factors with additional caution.

Comparison of Bone Remodeling Between Collum Femoris-Preserving Stems and Ribbed Stems in 1-Stage Bilateral Total Hip Arthroplasty.

BACKGROUND This study examined a cohort of patients who underwent bilateral THAs. CFP prostheses and ribbed prostheses were each used on both sides. We assessed the midterm clinical, radiological, and bone remodeling outcomes around prosthesis of these patients. MATERIAL AND METHODS From January 2009 to January 2013, 53 patients were enrolled in our study. We clinically evaluated all patients by recording Harris hip and Oxford hip scores. Some radiological indicators of the femoral prosthesis position were measured. Periprosthetic bone remodeling was assessed via bone mineral density (BMD) measurements. RESULTS The mean preoperative HHS of the CFP group and ribbed group were no significantly different (P=0.570). The neck-shaft angle in the ribbed group was significantly greater than in the CFP group (P<0.001). The CFP group had a greater offset (P<0.001). There was no significant difference in leg-length discrepancy (P=0.727) or Engh score between the 2 groups at the last follow-up (P=0.858). The preoperative BMD was increased at the last follow-up in Gruen zones 3 and 5 (P<0.05) and decreased in Gruen zones 1 and 7 (P<0.05) on the CFP side. BMD was increased in Gruen zone 4 (P=0.007) on the ribbed side. Pearson correlations and rate of complications were not significantly different. CONCLUSIONS Both the CFP and ribbed stem significantly improved the preoperative HHSs and OHSs. The bone remodeling of the CFP stem was more concentrated in the middle and distal regions of the prosthesis, while that of the ribbed stem was more concentrated in the proximal portion of the prosthesis.

Comparison of Clinical Outcomes, Radiological Outcomes and Bone Remodeling Outcomes Between Proximal Coated Single-Wedge New Stem and Full Coated Dual-Wedge Classic Stem in 1-Stage Bilateral Total Hip Arthroplasty.

BACKGROUND This retrospective study investigated the clinical outcomes, radiological outcomes, and bone remodeling patterns associated with a Medial/Lateral Taper (M/L Taper) stem and Link Classic Uncemented (LCU) stem in 1-stage bilateral total hip arthroplasty (THA). MATERIAL AND METHODS The results of 52 patients who underwent 1-stage bilateral THA with a M/L Taper stem on one side and an LCU stem on the other between January 2012 and February 2015 were retrospectively compared. Patients were clinically assessed by the Harris hip score (HHS), visual analogue score (VAS) and incidence of complications. Radiological indicators were measured. Periprosthetic bone remodeling was assessed via bone mineral density (BMD) measurements. RESULTS The mean follow-up time was 5.2 years. At each follow-up, there was no difference in the HHS and VAS between the 2 groups. The neck-shaft angle, offset, vertical height of the rotational center and limb lengthening were lower in the M/L Taper group than in the LCU group (P<0.001). The Engh total score was lower in the LCU group (P=0.039). Significantly higher (P<0.001) BMDs were observed in the M/L Taper group in Gruen zones 1, 2, and 6. significantly lower (P<0.001) BMDs were observed in the M/L Taper group in Gruen zones 3 and 5. CONCLUSIONS Due to the increased postoperative neck-shaft angle, the full coated dual-wedge classic stem was prone to cause lower limb lengthening. The proximal coated single-wedge new stem patients were more likely to have an insufficient postoperative neck length. The new stem achieved load transfer and proximal fixation, leading to better proximal femoral bone preservation is more in line with human biomechanical characteristics.

Diagnosis, preoperative evaluation, classification and total hip arthroplasty in patients with long-term unreduced hip joint dislocation, secondary osteoarthritis and pseudoarthrosis.

BACKGROUND: Neglected long-term unreduced hip joint dislocation with secondary osteoarthritis and pseudoarthrosis poses a great challenge to hip surgeons. However, as this is an uncommon injury, few studies have systematically investigated these patients. METHODS: We retrospectively reviewed 16 patients from 2010 to 2017. The diagnostic values of three different types of common radiological examinations were evaluated. We evaluated the bone conditions of the original acetabulum and classified the patients into three types (four subtypes). The surgical procedures and prognosis of the patients were also investigated. RESULTS: With the combined application of X-ray, CT scans and 3D reconstruction, 93.8% of these patients (sensitivity = 93.8%, Youden's index = 0.93, intraclass correlation coefficient = 0.95) could be diagnosed correctly. There were 6/16 (37.5%) type A patients, 4/16 (25.0%) type B1 patients, 5/16 (31.3%) type B2 patients and 1/16 (6.3%) type C patient. For patients with type A injury, the surgical procedures for total hip arthroplasty were similar to "standard" total hip arthroplasty. For patients with type B injury, due to atrophy or partial bone deficiency of the original acetabulum, the surgical procedure for total hip arthroplasty was probably similar to those for patients with developmental dysplasia of the hip. For patients with type C injury, the situation was similar to that of revision surgery. The average Harris hip score postoperatively was 89.94 ± 5.78 points (range: 79-98 points). CONCLUSIONS: The new classification system could help surgeons estimate potential difficulties during total hip arthroplasty. The prognosis of most patients after total hip arthroplasty is expected to be excellent or good.

Does the limb lengthening reduce the incidence of hip dislocation in patients with neurological disorders and insufficient muscle tension who undergoing hip arthroplasty?

Background: The soft-tissue tension is closely associated with postoperative hip dislocation in patients undergoing total hip arthroplasty (THA), especially for those patients with neurological disorders and insufficient muscle tension. The aim of this study is to explore the effect of limb lengthening on the incidence of complications following THA in patients with neurological disorders and insufficient muscle tension. Methods: This retrospective analysis examines individuals with neurological disorders, such as ischemic stroke and poliomyelitis, who underwent primary total hip arthroplasty (THA) at our medical center between January 2015 and April 2021. Demographic and baseline characteristics (such as age, gender, muscle strength) were obtained from medical records. The limb length, offset and the positional parameters of both acetabular and femoral component were measured on pre- and postoperative plain radiograph. The primary outcome was the occurrence of hip dislocation. The secondary outcome included the incidence of other complications and the hip function (determined by Harris score). The correlation between the occurrence of hip dislocation and limb lengthening was analyzed. Results: A total of 258 patients were finally analyzed. The hip dislocations were identified in 35 patients (overall incidence = 13.57%). The incidence of early dislocation was lower in patients whose limb-length discrepancy (LLD) was over 20 mm (incidence = 4.1% for LLD >20 mm, 12.2% for LLD 10 mm-20 mm and 17% for LLD <10 mm). The odds ratio (OR) was 0.206 and 95% confidence interval (CI) was 0.058-0.737 (compared between LLD <10 mm and LLD >20 mm). But the no difference was identified regarding on the incidence of late dislocation among patients with different LLD. Moreover, the overall incidence of other complications was elevated in patients with LLD >20 mm (incidence = 17.58% for LLD >20 mm, 11.11% for LLD 10 mm-20 mm and 3.19% for LLD <10 mm; OR = 6.464, 95% CI = 1.768-23.640). And the Harris scores, which reflected the hip function, was gradually decreased with the increasing in LLD. In terms of the relationship between the offset and dislocation rate, it was found that increased offset discrepancy was associated with decreased dislocation incidence (incidence = 4.71% for offset discrepancy >10 mm, 12.5% for offset discrepancy 5 mm-10 mm and 17.20% for offset discrepancy <5 mm; OR = 0.238, 95% CI = 0.076-0.742). Furthermore, increased offset discrepancy also bring a reduction in late dislocation. The incidences of late dislocation were 0%, 2.5% and 10.8% for offset discrepancy >10 mm, offset discrepancy 5 mm-10 mm and 17.20% for offset discrepancy respectively. Different from that of LDD, the incidences of other complications were similar among patients with different offset discrepancy. Besides, no influence of offset discrepancy on the hip function was identified in this study. Conclusion: Unfortunately, although increasing in limb length could partially reduce early dislocation postoperatively, it could not affect the incidence of late dislocation in those patients with neurological disorders and insufficient muscle tension. Moreover, over limb lengthening was associated with other postoperative complications and worse hip function. Instead, additional offset could reduce the probability of postoperative dislocation, without increasing the incidence of other complications. Therefore, femoral stem with lower cervico-diaphyseal angle (higher offset) should be recommended to patients with neurological disorders who were in high risk of postoperative dislocation. Isolated increasing in limb length should be avoided.

Prickle1-driven basement membrane deposition of the iPSC-derived embryoid bodies is separable from the establishment of apicobasal polarity.

Basement membrane (BM) component deposition is closely linked to the establishment of cell polarity. Previously, we showed that Prickle1 is crucial for BM deposition and cell polarity events in tear duct elongation. To gain a deeper understanding of the intimate relationship between BM formation and cell polarity, we generated induced pluripotent stem cells (iPSCs)-derived embryoid bodies (EBs) with a basement membrane separating the visceral endoderm (VE) and inner EB cell mass. We found that Prickle1 was highly expressed in VE of the normal EBs, and the Prickle1 mutant EBs displayed severely impaired BM. Notably, the formation of the basement membrane appeared to rely on the proper microtubule network of the VE cells, which was disrupted in the Prickle1 mutant EBs. Moreover, disruption of vesicle trafficking in the VE hindered BM secretion. Furthermore, reintroducing Prickle1 in the mutant EBs completely rescued BM formation but not the apicobasal cell polarity of the VE. Our data, in conjunction with studies by others, highlight the conserved role of Prickle1 in directing the secretion of BM components of the VE cells during embryonic germ layer differentiation, even in the absence of established general polarity machinery. Our study introduces a novel system based on iPSCs-derived EBs for investigating cellular and molecular events associated with cell polarity.

Denosumab Can Prevent Collapse in Patients with Early-Stage Steroid-Induced Osteonecrosis of the Femoral Head by Inhibiting Osteoclasts and Autophagy.

OBJECTIVE: The osteoclastic bone resorption inhibitors might have positive effect in preventing femoral head collapse in patients with osteonecrosis of the femoral head (ONFH). However, as a novel osteoclastic inhibitor, whether denosumab can prevent collapse in steroid-induced ONFH remains unknown. This study aims to evaluate the treatment effect of denosumab and the potential protective mechanism. METHODS: This was a retrospective study. A total of 161 patients with steroid-induced ONFH who underwent denosumab treatment were reviewed, and 209 untreated patients were selected as controls. Their clinical characteristics and radiological exam results were obtained. Patients were treated with 60 mg denosumab every 6 months for 2 years. The primary outcome was the incidence of femoral head collapse at 2 years after the initial diagnosis of ONFH. Secondary outcomes included the Harris hip score, progression of osteosclerosis, increase in necrotic area, bone marrow oedema relief, and bone mineral density increase in the femoral head. The Mann-Whitney U test and chi-square tests were performed to identify the differences between the continuous and categorical variables, respectively. A multivariate logistic regression model was built to identify the factors associated with the treatment effect of denosumab. RESULTS: The incidence of femoral head collapse was 42.24% (68/161) in the denosumab group and 54.07% (113/209) in the control group (χ2  = 5.094, p = 0.024; relative risk = 0.787, 95% CI = 0.627-0.973). The excellent-good rates of the Harris hip score were 63.98% (103/161) in the denosumab group and 44.98% (94/209) in the control group (χ2  = 13.186, p < 0.001). The incidence of osteosclerosis progression in the denosumab group was 55.28% (89/161), which was significantly higher than that in the control group (43.54%, 91/209, χ2  = 5.016, p = 0.025). Meanwhile, a significant increase in bone mineral density was identified in 29.19% (47/161) and 7.18% (15/209) of patients in the denosumab and control groups, respectively (χ2  = 31.600, p < 0.001). The osteoclastic cytoplasm expression of LC3-II was more positive in the control group than in the denosumab group (immunohistochemistry scoring: 3.58 ± 2.27 vs 6.33 ± 2.64, Z = -2.684, p = 0.007). A total of three independent factors were considered to be associated with the positive treatment effect of denosumab, the time of first denosumab administration (OR = 2.010, 95% CI = 1.272-3.177), osteosclerosis (OR = 1.583, 95% CI = 1.024-2.445), and the necrotic area before denosumab administration (medium necrotic area: OR = 2.084, 95% CI = 1.245-3.487; large necrotic area: OR = 2.211, 95% CI = 1.255-3.893). CONCLUSIONS: The current study demonstrated that denosumab had a positive effect on preventing femoral head collapse in patients with steroid ONFH. This effect might be closely associated with the inhibition of osteoclasts and their autophagy.

Risk factors affecting the incidence of postoperative periprosthetic femoral fracture in primary hip arthroplasty patients: a retrospective study.

The purpose of this study was to identify the characteristics and risk factors for postoperative periprosthetic femoral fracture (PFF). This was a retrospective cohort study of 108 patients with and 432 control patients without postoperative PFF. Demographic characteristics, surgery-related information (primary hip disease diagnosed, fixation, femoral stem, method of operation, and bone resorption of the proximal femur), and postoperative patient outcomes (hip function, treatment history, and patients' lifestyle behaviors) were recorded and compared between the groups. PFF characteristics, such as the classification, time, and cause, were also documented, and a Cox regression model was built to identify the independent risk factors for postoperative PFF in these patients. Six independent risk factors for postoperative PFF were identified, namely, advanced age (hazard ratio (HR) = 1.026, 95% confidence interval (CI) = 1.007-1.045), femoral neck fracture as the primary disease (HR = 4.536, 95% CI = 2.955-6.961), osteoporosis (HR = 2.043, 95% CI = 1.234-3.383), hemiarthroplasty (or HA, HR = 2.173, 95% CI = 1.327-3.558), bone resorption of the proximal femur (HR = 1.627, 95% CI = 1.090-2.430), and a standard- or long-stem femoral prosthesis (HR = 2.996, 95% CI = 1.480-6.067). The predictive values for a low risk (estimated incidence ≤ 50%), moderate risk (estimated incidence 51%-89%), and high risk (estimated incidence ≥ 90%) of PFF were ≤ 3.0 points, 3.0-10.0 points, and ≥ 10.0 points, respectively. Most patients with postoperative PFF had Vancouver type B fractures. Six independent risk factors for postoperative PFF were identified: advanced age, hip fracture as the primary disease, osteoporosis, HA, bone resorption of the proximal femur, and a long femoral stem.

Femoral neck fracture patients with ischaemic stroke choose hemiarthroplasty or constrained liner total hip arthroplasty? A retrospective comparative study of 199 cases.

Background: The objective of this study was to assess the long-term survival rate, complications, as well as the clinical and radiological outcomes of hemiarthroplasty and total hip arthroplasty using constrained polyethylene liners in patients with ischemic stroke. Methods: This study was a retrospective cohort study that included patients with ischemic stroke who underwent hip arthroplasty from March 2010 to September 2017. In the Constrained Acetabular Liners (CAL) group, patients received an uncemented acetabular shell with a constrained polyethylene liner. The Dual Mobility (DM) group underwent hemiarthroplasty (HA). Additionally, hip function, range of motion, quality of life, the incidence of clinical complications, and prosthesis stability were investigated. Results: 96 patients with unilateral femoral neck fractures who underwent hip replacement with CAL were included in the CAL group, while 103 patients who underwent hip replacement with a dual mobility head were included in the DM group. VAS, and SF-36 data were available for both CAL and DM groups. At the 1-year postoperative follow-up, the HHS in the CAL group was significantly lower than that in the DM group (80.83 ± 3.91 vs. 83.17 ± 4.15, P < 0.05). The VAS score in the CAL group peaked at the 1-year follow-up (2.07 ± 0.91 vs. 1.49 ± 0.85, P < 0.05). However, there were no significant differences between the two groups in terms of HSS, VAS, and SF-36 at the last follow-up after surgery. Operative time and the amount of bleeding in the DM group were significantly lower than those in the CAL group (105.30 ± 29.68 vs. 94.85 ± 31.07; 355.11 ± 123.95 vs. 302.22 ± 107.68, P < 0.05). Additionally, there was no significant difference in the mean leg length discrepancy between the two groups. Conclusion: The clinical, imaging, and postoperative complications of the CAL and DM groups were analyzed. The prognosis for DM appears to be more beneficial for early patient recovery, but a higher likelihood of recurrent dislocation is observed. CAL offers excellent stability for primary THA in high-risk patients; however, attention should be given to preventing aseptic loosening.

Bone Remodelling of the Proximal Femur After Hip Revision with a Metaphyseal-Fixation Femoral Stem Component.

Background: Whether hip revision with a metaphyseal-fixation femoral stem component can restore the bone mass of the proximal femur remains unclear. The aims of this study were to identify whether the bone mineral density (BMD) of the proximal femur increases following hip revision with a metaphyseal-fixation femoral stem and to identify the factors associated with BMD recovery. Methods: This was a retrospective study involving 36 patients who underwent hip arthroplasty with a metaphyseal-diaphyseal fixation stem (standard length stem) and had indications for hip revision, which was performed with a proximal press-fit short-stem prosthesis for each patient. Dual-energy X-ray absorptiometry (DEXA) was used to obtain, evaluate, and compare the BMD at baseline and one year and two years postoperatively. The proximal femur was divided into several independent areas according to the Gruen zone (Gruen 1 to Gruen 7 from the greater trochanter counterclockwise to the lesser trochanter). Logistic regression analyses were used to assess potential factors significantly associated with an increase in BMD. Results: An increased BMD was obviously identified in the proximal femur. Two years after the surgery, the BMD of the Gruen 1, Gruen 2, Gruen 6, and Gruen 7 areas had increased by 22.6%, 12.6%, 16.2% and 24.2%, respectively, relative to baseline. Three independent risk factors associated with bone mineral density recovery were identified: age (OR=1.100, 95% CI=1.005-1.203, P=0.038), osteoporosis (OR=14.921, 95% CI=1.223-182.101, P=0.034) and fair to poor hip function (OR=13.142, 95% CI=1.024-168.582, P=0.048). Conclusion: This study confirms that metaphyseal-fixation stem hip revision can indeed help restore bone mass in the proximal femur, especially in the Gruen 1, Gruen 2, Gruen 6 and Gruen 7 zones. It was also found that advanced age, osteoporosis, and fair to poor hip joint function were three important risk factors affecting the recovery of proximal femur bone mass after surgery. Trial Registration: Retrospectively registered.

The diagnostic value of blood metagenomic next-generation sequencing in patients with acute hematogenous osteomyelitis.

Aims: This study aims to evaluate the diagnostic value of blood metagenomic next-generation sequencing (mNGS) in detecting pathogens from patients clinically diagnosed as acute hematogenous osteomyelitis (AHO). Methods: This retrospective study enrolled 66 patients with AHO. The test results of mNGS and bacterial culture on different samples, including blood and puncture fluid samples, from patients with AHO were compared to explore the diagnostic value of blood mNGS. Besides, this study also explored the efficacy of blood mNGS in decision making for antibiotic administration and analyzed the factors associated with the positive result of blood mNGS. Results: The most common causative pathogens were Staphylococcus and Streptococcus. The sensitivity of blood mNGS (77.3%) was higher than that of blood culture (42.4%) (P<0.001), while the turnaround time of blood mNGS (2.1 ± 0.4 d) is much less than that of blood culture (6.0 ± 2.1 d) (P<0.001). Besides, the sensitivity of blood mNGS tests (77.3%) was slightly lower than that of puncture fluid mNGS (89.4%). Furthermore, detection comparison at pathogen level unravels that blood mNGS might be suitable for diagnosing AHO caused by common pathogens, while puncture fluid mNGS could be considered as preferred examination in diagnosing AHO caused by uncommon pathogens. Finally, three independent factors associated with the true positive result of blood mNGS in patients with AHO were identified, including Gram-positive pathogens (OR=24.4, 95% CI = 1.4-421.0 for Staphylococcus; OR=14.9, 95%CI= 1.6-136.1 for other Gram-positive bacteria), body temperature at sampling time (OR=8.2, 95% CI = 0.6-107.3 for body temperature of >38.5°C; OR=17.2, 95% CI = 2.0-149.1 for patients who were chilling), and no use of antibiotics before sampling (OR=8.9, 95% CI =1.4-59.0). Conclusion: This is the first report on evaluating and emphasizing the importance of blood mNGS in diagnosing AHO. Blood sample might be an alternative sample for puncture fluid for mNGS, and its extensive application in diagnosing AHO could be expected.

Legume-specific SnRK1 promotes malate supply to bacteroids for symbiotic nitrogen fixation.

Nodulation is an energy-expensive behavior driven by legumes by providing carbon sources to bacteroids and obtaining nitrogen sources in return. The energy sensor sucrose nonfermenting 1-related protein kinase 1 (SnRK1) is the hub of energy regulation in eukaryotes. However, the molecular mechanism by which SnRK1 coordinates the allocation of energy and substances during symbiotic nitrogen fixation (SNF) remains unknown. In this study, we identified the novel legume-specific SnRK1α4, a member of the SnRK1 family that positively regulates SNF. Phenotypic analysis showed that nodule size and nitrogenase activity increased in SnRK1α4-overexpressing plants and decreased significantly in snrk1α4 mutants. We demonstrated that a key upstream kinase involved in nodulation, Does Not Make Infection 2 (DMI2), can phosphorylate SnRK1α4 at Thr175 to cause its activation. Further evidence clarified that SnRK1α4 phosphorylates the malate dehydrogenases MDH1/2 to promote malate production in the cytoplasm, supplying carbon sources to bacteroids. Therefore, our findings reveal an essential role of the DMI2-SnRK1α4-MDH pathway in supplying carbon sources to bacteroids for SNF and provide a new module for constructing cereal crops with SNF.