HIF-1α Induced by Hypoxia Promotes Peripheral Nerve Injury Recovery Through Regulating Ferroptosis in DRG Neuron.

Peripheral nerve injury (PNI) usually has a poor effect on functional recovery and severely declines the patient's quality of life. Our prior findings indicated that hypoxia remarkably promoted nerve regeneration of rats with sciatic nerve transection. However, the underlying molecular mechanisms of hypoxia in functional recovery of PNI still remain elusive. In this research, we tried to explain the functional roles and mechanisms of hypoxia and the hypoxia-inducible factor-1α (HIF-1α) in PNI. Our results indicated that hypoxia promoted proliferation and migration of dorsal root ganglia (DRG) and increased the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Mechanistically, hypoxia suppressed ferroptosis through activating HIF-1α in DRG neurons. Gain and loss of function studies were performed to evaluate the regulatory roles of HIF-1α in ferroptosis and neuron recovery. The results revealed that up-regulation of HIF-1α enhanced the expression of solute carrier family membrane 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) and increased the contents of cysteine and glutathione, while inhibiting the accumulation of reactive oxygen species (ROS). Our findings provided novel light on the mechanism of ferroptosis involved in PNI and manifest hypoxia as a potential therapeutic strategy for PNI recovery.

HIF-1α-induced upregulation of m6A reader IGF2BP1 facilitates peripheral nerve injury recovery by enhancing SLC7A11 mRNA stabilization.

The recovery of peripheral nerve injury (PNI) is not ideal in clinic. Our previous study revealed that hypoxia treatment promoted PNI repair by inhibiting ferroptosis. The aim of this study was to investigate the underlying molecular mechanism of HIF-1α in hypoxia-PNI recovery. M6A dot blot was used to determine the total level of m6A modification. Besides, HIF-1α small interfering RNA (siRNA) or IGF2BP1 overexpression vector was transfected into dorsal root ganglion (DRG) neurons to alter the expression of HIF-1α and IGF2BP1. Subsequently, MeRIP-PCR analysis was applied to validate the m6A methylation level of SLC7A11. We demonstrated the hypoxia stimulated HIF-1α-dependent expression of IGF2BP1 and promoted the overall m6A methylation levels of DRG neurons. Overexpression of HIF-1α increased the expressions of neurotrophic factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor (GDNF), which could be effectively reversed by siRNA knockdown of IGF2BP1. Moreover, upregulation of HIF-1α contributed to the m6A methylation level and mRNA stabilization of SLC7A11. This study revealed that the HIF-1α/IGF2BP1/SLC7A11 regulatory axis facilitated the recovery of injured DRG neurons. Our findings suggest a novel insight for the m6A methylation modification in PNI recovery.

BRAFV600E genetic testing should be recommended for Bethesda III or V thyroid nodules based on fine-needle aspiration.

The preoperative diagnosis of thyroid nodules now routinely includes BRAFV600E genetic testing in most provincial and municipal hospitals in China. This study identified the most suitable patients of thyroid nodule for BRAFV600E genetic testing. We retrospectively collected data of patients from the Hospital Information System that had undergone fine needle aspiration biopsy (FNAB) from May 2019 to December 2021. Data of FNAB, BRAFV600E genetic testing, and post-surgical pathological diagnosis were collected. A total of 12,392 patients were included in this study. Among them, 7,010 patients underwent solely FNAB, while 5,382 patients had both FNAB and BRAFV600E genetic testing. In the FNAB group, 2,065 thyroid nodules were surgically removed, with a 93.12% malignancy rate. In the FNAB + BRAF group, 2,005 nodules were dissected, and the malignancy rate was 98.20%. However, it was evident that in the subgroups, the combination of FNAB and BRAFV600E genetic testing only benefited Bethesda III (p < 0.001) and V (p = 0.001) nodules. Overall, the combination of FNAB with BRAFV600E genetic testing significantly improved the malignancy rate of surgical thyroid nodes at our hospital when compared to FNAB alone. The subgroup analysis showed that BRAFV600E genetic testing only benefited Bethesda III and V nodules. These findings provide a clinical reference for rationally selecting the most suitable population for BRAFV600E genetic testing.

Assessing lateral femoral condyle cartilage prior to medial UKA: MRI vs. Valgus stress radiograph.

BACKGROUND: The cartilage quality of the lateral compartment needs to be clarified prior to medial unicompartmental knee arthroplasty (UKA). Valgus stress radiograph has been recommended as the preferred tool. Some studies also show that magnetic resonance imaging (MRI) has a higher diagnostic value. So, we conducted this study to compare whether valgus stress radiographic lateral joint space width (LJSW) and MRI grading can accurately reflect cartilage quality and its screening value for UKA-suitable patients. METHODS: One hundred and thirty eight knees proposed for UKA were enrolled prospectively. Valgus stress radiograph was taken to measure LJSW. LJSW > 4 mm was considered normal and suitable for UKA. For weight-bearing area cartilage of lateral femoral condyle, Recht grade was assessed by MRI preoperatively. Recht grades ≤ 2 were treated as non-high-grade injuries while Recht grades > 2 were treated as high-grade injuries. Outerbridge grade was the gold standard and was assessed intraoperatively. Patients with Outerbridge grades 0-2 (non-high-grade injuries) underwent UKA, and patients with Outerbridge grades 3-4 (high-grade injuries) underwent total knee arthroplasty (TKA). The diagnostic parameters of valgus stress radiograph and MRI for the selection of UKA candidates were calculated, and receiver operating characteristic curves were drawn. P < 0.05 was considered significant. RESULTS: Of 138 knees, 120 underwent UKAs, and 18 underwent TKAs. In terms of selecting UKA candidates, the sensitivity was close between MRI (95.0%) and valgus stress radiograph (96.7%), and the specificity, accuracy, positive predictive value and negative predictive value of MRI (94.4%, 94.9%, 99.1%, 73.9%, respectively) were higher than that of valgus stress radiograph (5.9%, 85.5%, 88.0%, 20.0%, respectively). The difference in area under the curve (AUC) between MRI (0.950) and LJSW (0.602) was significant (P = 0.001). CONCLUSION: Compared with valgus stress radiograph, MRI has excellent evaluation value in diagnosing lateral weight-bearing cartilage injuries and can be used as a reliable tool for selecting suitable UKA patients.

Valgus Stress Radiograph Can Predict Alignment Change of Medial Mobile-Bearing Unicompartmental Knee Arthroplasty.

OBJECTIVE: Finding reliable tools to predict alignment change after medial mobile-bearing unicompartmental knee arthroplasty (UKA) can help surgeons avoid under- or over-correction. This prospective study aimed to investigate whether the parameters related to medial collateral ligament tension on valgus stress radiograph can predict the alignment change of medial mobile-bearing UKA and establish a prediction model. METHODS: This study prospectively included the patients undergoing medial mobile-bearing UKA for knee osteoarthritis from November 2018 and April 2021. Patients took valgus stress radiograph and MRI preoperatively and took full-length weight-bearing anterior-posterior radiograph of the lower extremity preoperatively and postoperatively. The medial joint space width (MJSW) on valgus stress radiograph, area of femoral and tibial osteophyte on MRI, medial extrusion distance (MED) of the meniscus on MRI, and the change in hip-knee-ankle angle (∆HKAA) were measured. Factors influencing ∆HKAA were analyzed by correlation analysis. Univariable and multivariable linear regression analysis was performed to establish a prediction model of ∆HKAA. RESULTS: One hundred and seven knees were included. On average, the preoperative HKAA was 170.84° ± 3.73°, and UKA corrected the alignment to 175.16° ± 3.21° postoperatively (p < 0.001), with ∆HKAA of 4.33° ± 1.93°. Correlation analysis showed that ∆HKAA correlated with MJSW (r = 0.628, p < 0.001), MED (r = 0.262, p < 0.001), and tibial osteophyte area (r = 0.235, p < 0.001). The prediction model for ∆HKAA was obtained by multivariable linear regression: ∆HKAA = -2.003 + 0.947 × MJSW(mm) + 1.838 × total osteophyte area(cm2 ). CONCLUSION: Valgus stress radiographic MJSW and osteophyte area are correlated to the alignment change of medial mobile-bearing UKA. The prediction model for HKAA change is: ∆HKAA = -2.003 + 0.947 × MJSW(mm) + 1.838 × total osteophyte area(cm2 ).

How much the leg length has changed after the MOUKA through measurement of the full length radiographs? Beware of splicing error.

BACKGROUND: Leg length change after knee arthroplasty is one of the most concerned problems for patients and doctors. However, as there was only one literture focused on the leg length change after unicompartmental knee arthroplasty, we aimed to clarify the leg length change after medial mobile-bearing unicompartmental knee arthroplasty (MOUKA) using a novel double calibration method. METHODS: We enrolled patients who underwent MOUKA and had taken full-length radiographs in a standing position prior to and at 3 months after the operation. We eliminated the magnification by a calibrator and corrected the longitudinal splicing error by measuring the femur and tibia lengths before and after operation. Perceived leg length change was collected 3 months after operation. Bearing thickness, preoperative joint line convergence angle, preoperative and postoperative varus angles, flexion contracture and Oxford knee score (OKS) were also collected. RESULTS: From June 2021 to February 2022, 87 patients were enrolled.76 (87.4%) of them showed an increase with an average of 0.32 cm (range from -0.30 cm to 1.05 cm) in leg length change. The lengthening was strongly correlated with the degree of varus deformity and its correction value (r = 0.81&0.92, P < 0.01). Only 4 (4.6%) patients perceived leg length lengthening after operation. There was no difference in OKS between the patients who had an increase in leg length and those who had a decrease (P = 0.99). CONCLUSIONS: Majority of patients only experienced a slight increase in leg length after MOUKA, and such an increase did not affect patients' perception and short-term function.

In Vitro Application of a Wireless Sensor in Flexion-Extension Gap Balance of Unicompartmental Knee Arthroplasty.

Unicompartmental knee arthroplasty (UKA) is an effective treatment for end-stage anteromedial osteoarthritis (AMOA). The key to UKA is the flexion-extension gap balance, which is closely related to postoperative complications such as bearing dislocation, bearing wear, and arthritis progression. The traditional gap balance assessment is performed by indirectly sensing the tension of the medial collateral ligament by a gap gauge. It relies on the surgeon's feel and experience, which is imprecise and difficult for beginners. To accurately assess the flexion-extension gap balance of UKA, we developed a wireless sensor combination consisting of a metal base, a pressure sensor, and a cushion block. After osteotomy, the insertion of a wireless sensor combination allows the real-time measurement of intra-articular pressure. It accurately quantifies the flexion-extension gap balance parameters to guide further femur grinding and tibia osteotomy, to improve the accuracy of gap balance. We conducted an in vitro experiment with the wireless sensor combination. the results showed that there was a difference of 11.3 N after applying the traditional method of flexion-extension gap balance performed by an experienced expert.

Induction of lncRNA MALAT1 by hypoxia promotes bone formation by regulating the miR-22-3p/CEBPD axis.

Adaptation to hypoxia promotes fracture healing. However, the underlying molecular mechanism remains unknown. Increasing evidence has indicated that long non-coding RNAs (lncRNAs) play crucial roles in several diseases, including fracture healing. In the present study, lncRNA microarray analysis was performed to assess the expression levels of different lncRNAs in MC3T3-E1 cells cultured under hypoxic conditions. A total of 42 lncRNAs exhibited significant differences in their expression, including metastasis associated lung adenocarcinoma transcript 1 (MALAT1), maternally expressed 3, AK046686, AK033442, small nucleolar RNA host gene 2 and distal-less homeobox 1 splice variant 2. Furthermore, overexpression of MALAT1 promoted osteoblast differentiation, alkaline phosphatase (ALP) activity and matrix mineralization of MC3T3-E1 cells, whereas its knockdown diminished hypoxia-induced cell differentiation, ALP activity and matrix mineralization in these cells. Moreover, functional analysis indicated that MALAT1 regulated the mRNA and protein expression levels of CCAAT/enhancer binding protein δ by competitively binding to microRNA-22-3p. Adenoviral-mediated MALAT1 knockdown inhibited fracture healing in a mouse model. Taken together, the results indicated that MALAT1 may serve a role in hypoxia-mediated osteogenesis and bone formation.

Resting-state functional connectivity alteration in elderly patients with knee osteoarthritis and declined cognition: An observational study.

Objective: This study is designed to investigate the brain function changed regions in elderly patients with knee osteoarthritis (KOA) and to explore the relationship between neuropsychological tests and resting-state functional magnetic resonance imaging (rs-fMRI) network to clarify the possible mechanism underlying cognitive changes in KOA patients. Materials and methods: Fifty-two patients aged ≥ 65 with KOA and twenty-two healthy-matched controls were recruited in this study. All participants were given rs-fMRI check. We used graph theory analysis to characterize functional connectivity (FC) and topological organization of the brain structural network. The relationship between FC values, topological properties, and the neuropsychological test scores was analyzed. Results: Compared with the controls, fourteen edges with lower functional connectivity were noted in the KOA group. Local efficiency and small-worldness of KOA patients decreased compared to the healthy controls. No significant alterations of nodal topological properties were found between the two groups. There was a significant positive correlation between the AVLT-H (L) and the internetwork of default mode network (DMN) (left/right orbitofrontal Superior cortex) and limbic/cortical areas (left/right caudate, right amygdala). AVLT-H(L) was positively correlated with small-worldness and local efficiency. Conclusion: The results indicated that for elderly KOA patients with declined cognition, topological properties, FC between DMN and subcortical limbic network related regions are significantly decreased compared to healthy controls. These alterations demonstrated a significant correlation with the neuropsychological test scores.

The effects of acrylamide-mediated dorsal root ganglion neurons injury on ferroptosis.

Acrylamide (ACR) is a water-soluble chemical applied in industrial and laboratory processes. The neurotoxicity induced by acrylamide involves both peripheral and central nervous system. Hence, there is a growing urgency to investigate the mechanisms of acrylamide-induced neurotoxicity and search novel therapeutic target for the nerve repair. The effects of ACR on the proliferation, reactive oxygen species (ROS) and iron production of dorsal root ganglia (DRG) neurons and Schwann cells were determined. 5-Ethynyl-2'-deoxyuridine (EDU) staining and transwell assay were applied to detect the proliferation and migration capacity of DRG cells. Ferrostatin-1 (Fer-1) was used to suppress ferroptosis induced by ACR. RT-PCR analysis was performed to examine the expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and glial cell line-derived neurotrophic factor (GDNF). Moreover, Iron, ROS, malondialdehyde (MDA) and glutathione (GSH) contents were measured to reveal the regulation of ferroptosis in ACR-related nerve injury. ACR inhibited the proliferation and migration of DRG neurons and the supplementation of Fer-1 reversed the effects induced by ACR. Besides, the treatment of Fer-1 effectively increased the expression of NGF, BDNF, VEGF and GDNF. Furthermore, ACR increased the iron level, MDA and ROS contents while inhibited the level of GSH. It was unveiled that ACR attenuated the proliferation, migration and neuron repair of DRG neurons through regulating ferroptosis. The modulation of ferroptosis might be a promising therapeutic strategy and provide references for future treatment of acrylamide-induced nerve damage.

A Low Free T3 to Free T4 Ratio Is Associated with Sarcopenia in Euthyroid Patients with Type 2 Diabetes Mellitus.

Background: This research evaluated the link between normal thyroid hormone levels and sarcopenia in patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional study enrolled 312 euthyroid patients with T2DM from Qilu Hospital of the Shandong University, China. Body composition, grip strength, and physical performance were assessed as per the 2019 consensus guidelines of the Asian Working Group for Sarcopenia. Binary logistic regression was used to examine the correlation between thyroid hormone levels and sarcopenia and its components. Results: The prevalence of sarcopenia was 26.9%. Following adjustments for potential confounders, a high-normal serum free triiodothyronine (FT3) level (odds ratio (OR) = 0.522, 95% confidence interval (CI): 0.304-0.895, P = 0.018), a low-normal serum free thyroxine (FT4) level (OR = 1.126, 95% CI: 1.009-1.258, P = 0.034), and a heightened FT3/FT4 ratio (OR = 0.923, 95% CI: 0.879-0.969, P = 0.001) were linked to a low prevalence of sarcopenia. Considering the components of sarcopenia, FT3 concentration was positively associated with muscle strength (OR = 0.525, 95% CI: 0.305-0.902, P = 0.020) and physical performance (OR = 0.443, 95% CI: 0.259-0.758, P = 0.003), while FT4 concentration was negatively linked to muscle mass (OR = 1.114, 95% CI: 1.009-1.232, P = 0.036). The FT3/FT4 ratio was positively linked to muscle mass (OR = 0.943, 95% CI: 0.905-0.981, P = 0.006), muscle strength (OR = 0.945, 95% CI: 0.901-0.992, P = 0.021), and physical performance (OR = 0.934, 95% CI: 0.894-0.975, P = 0.002). Nevertheless, thyroid-stimulating hormone concentration was not associated with sarcopenia. Conclusion: A high FT3/FT4 ratio was significantly linked to a lowered risk of sarcopenia in euthyroid patients with T2DM.

Orthopedic Surgery Causes Gut Microbiome Dysbiosis and Intestinal Barrier Dysfunction in Prodromal Alzheimer Disease Patients: A Prospective Observational Cohort Study.

OBJECTIVE: To investigate gut microbiota and intestinal barrier function changes after orthopedic surgery in elderly patients with either normal cognition (NC) or a prodromal Alzheimer disease phenotype (pAD) comprising either subjective cognitive decline (SCD) or amnestic mild cognitive impairment (aMCI). BACKGROUND: Homeostatic disturbances induced by surgical trauma and/or stress can potentially alter the gut microbiota and intestinal barrier function in elderly patients before and after orthopedic surgery. METHODS: In this prospective cohort study, 135 patients were subject to preoperative neuropsychological assessment and then classified into: NC (n=40), SCD (n=58), or aMCI (n=37). Their gut microbiota, bacterial endotoxin (lipopolysaccharide), tight junction (TJ) protein, and inflammatory cytokines in blood were measured before surgery and on postsurgical day 1, 3, and 7 (or before discharge). RESULTS: The short-chain fatty acid (SCFA)-producing bacteria were lower while the gram-negative bacteria, lipopolysaccharide and TJ were higher preoperatively in both the SCD and aMCI (pAD) groups compared with the NC group. After surgery, a decrease in SCFA-producing bacteria, and an increase in both gram-negative bacteria and plasma claudin were significant in the pAD groups relative to the NC group. SCFA-producing bacteria were negatively correlated with TJ and cytokines in pAD patients on postsurgical day 7. Furthermore, surgery-induced perioperative metabolic stress and inflammatory responses were associated with gut microbiota alterations. CONCLUSIONS: Surgery exacerbates both preexisting microbiota dysbiosis and intestinal barrier dysfunction in pAD patients, all of which may be associated with systemic inflammation and, in turn, may lead to further cognitive deterioration.

Does diabetes mellitus increase the incidence of early thrombosis in deep vein following unicompartmental knee arthroplasty: a retrospective cohort study.

BACKGROUND: Many patients following unicompartmental knee arthroplasty (UKA) also suffer from diabetes mellitus, which may lead to an increased likelihood of postoperative deep venous thrombosis (DVT). Therefore, we evaluated whether DVT incidence would increase 3 days following UKA in diabetic patients. METHODS: Patients who underwent UKA from August 2018 to September 2021 in our hospital were retrospectively included. Age, gender, body mass index, hypertension, mode of anesthesia, surgery time, intraoperative blood loss, tourniquet pressure and time, and glycosylated hemoglobin concentration were recorded as confounders. We compared the incidence and type of DVT between non-diabetic and diabetic patients and evaluated the effect of glycosylated hemoglobin levels on DVT. RESULTS: Of all the 224 patients, 96 had diabetes and 128 did not. Within 3 days after surgery, DVT occurred in 25 cases in the diabetic group and 17 cases in the non-diabetic group (p < 0.05), and the difference mainly exists in the lower limbs on the surgical side. Logistic regression analysis demonstrated that the risk of DVT in the diabetic group was 4.50 times higher compared with the non-diabetic group. For every 1 unit increase of glycosylated hemoglobin, the incidence of DVT increased 2.35 times. Differences in age, gender, body mass index, hypertension, mode of anesthesia, surgery time, intraoperative blood loss, tourniquet pressure, and time between the two groups were not significant. CONCLUSIONS: The incidence of DVT in diabetic patients within 3 days after UKA was significantly higher than that in non-diabetic patients and was proportional to the concentration of glycosylated hemoglobin.

Slight cartilage damage in weight-bearing area of lateral femoral condyle do not compromise short-term outcomes of medial unicompartmental knee arthroplasty.

INTRODUCTION: Medial unicompartmental knee arthroplasty (mUKA) requires full-thickness cartilage in the lateral compartment, but slight damage of the cartilage surface can be ignored. However, as this statement lacks literature support, we investigated whether slight cartilage damages in the weight-bearing area of the lateral femoral condyle would affect the outcome of mUKAs. MATERIALS AND METHODS: Outerbridge grading was performed on the cartilage in the weight-bearing area of the lateral femoral condyle intraoperatively. The patients, grouped as normal or as having lateral condyle cartilage of Outerbridge grade 1-2 (slight cartilage damage), underwent mUKA. Full-length lower extremity radiographs were taken and hip-knee-ankle angles (HKAAs) were measured both preoperatively and postoperatively. Using magnetic resonance imaging, the lateral meniscal extrusion distance was also measured. In addition, the Oxford Knee Score (OKS) was assessed preoperatively and at the last follow-up, in addition to the patient satisfaction assessment. RESULTS: We enrolled 152 knees of 142 patients proposed for mUKAs. The mean age of participants was 69.5 years (51-89 years) and they were followed up for a mean of 25.4 months (15-44 months). There was no significant difference in preoperative (p = 0.746) and postoperative (p = 0.202) mean OKS between the normal, Outerbridge grade 1 and Outerbridge grade 2 groups. While the normal group had a higher change in OKS than the group with cartilage damage, this difference was not significant (p = 0.910). The UKA corrected the patients' mean HKAA from 171.1° (preoperatively) to 176.1° (postoperatively). From all patients, only four had slight lateral meniscus extrusion with MEDs of ≤ 0.25 mm. With the exception of one patient with a poor outcome in normal group, the rest were satisfied with the outcome of mUKA. No patients had prosthesis-related complications or revision surgery. CONCLUSIONS: Cartilage damage of Outerbridge grade 1 and grade 2 in the weight-bearing area of the lateral femoral condyle will not compromise the short-term outcome of medial mobile-bearing UKA.

Staged open reduction and internal fixation with double-locking plates to treat bilateral distal femur periprosthetic fractures after total knee arthroplasty: A case report.

Background: The incidence of periprosthetic fractures after total knee arthroplasty (TKA) increases in parallel with the number of procedures. Comminuted fractures along the primary fracture line extending to the edge of the prosthesis are challenging, and bilateral fractures are rarely reported, especially with open injuries. Case presentation: A 65-year-old female had undergone bilateral TKA in our hospital 5 years before admission. She was admitted with a traumatic bilateral Rorabeck type II B distal femur periprosthetic fracture (closed right, open left, Gustilo II) and was treated with bilateral staged open reduction and internal fixation (ORIF) with double-locking plates. The patient experienced a prolonged delayed fracture union and finally healed around 21 months postoperatively. The function was satisfactory after 4 years of follow-up. Conclusion: ORIF with double-locking plates can be used to treat Rorabeck II B periprosthetic fracture where the primary fracture line extends beyond the edge of the prosthesis; however, there may be delayed healing or nonunion. Patients need to undergo long-term rehabilitation and endure long disability times and require good rehabilitation nursing care. Once they achieve bone healing, the treatment achieves bone preservation and substantial prosthesis survival.

Hybrid Oxford unicompartmental knee arthroplasty has lower residual cement extrusion than cemented arthroplasty in treating end-stage unicompartmental knee osteoarthritis.

BACKGROUND: Hybrid Oxford unicompartmental knee arthroplasty (OUKA) consists of cementless femoral prostheses and cemented tibial prostheses. Although a hybrid OUKA has been used in clinical practice, the clinical outcome has not been reported. The purpose of this study was to compare the short-term clinical outcomes and rate of residual bone cement extrusion between hybrid and cemented prostheses and analyse the possible reasons for differences between outcomes. METHODS: A total of 128 knees (118 patients) with end-stage osteoarthritis were included in this study, of which underwent consecutive operations using unicondylar Oxford phase 3 implants from July 2017 and September 2019 in our centre. Follow-up was performed at 6 weeks, 3 and 6 months, 1 year and every year after operation, and complications and changes in the Oxford knee score (OKS) were recorded. The OKS of the two groups was analysed by the generalized estimating equation approach. Prosthesis-based standard fluoroscopy was performed in a timely manner after each operation, and the rate of residual cement extrusion of the two groups was estimated using T-tests and a multivariate regression analysis. RESULTS: Excluding the cases that lost follow-up, a total of 120 knees (65 in hybrid group and 55 in cemented group) were included in the analysis. There was no statistically significant difference in patient characteristics between the two groups (p > 0.05). The average follow-up time was 23.4 months (and ranged from 12 to 38 months). As of the last follow-up, there were no complications, such as dislocation, fracture, prosthesis loosening and subsidence, but one patient in the cemented group experienced symptoms caused by residual loose cement. Postoperative OKS in both groups improved significantly (p < 0.001). There was no significant difference in the OKS at any point during the follow-up or in the improvement of the OKS between the two groups (p > 0.05). Residual cement was mainly extruded behind the tibial prosthesis. The rate of hybrid periprosthetic residual cement extrusion was significantly lower in the hybrid group than in the cemented group, and the difference was statistically significant (OR = 3.38; p = 0.014). CONCLUSIONS: Hybrid OUKA is as effective as cemented OUKA in the short term after operation and can significantly reduce the residual cement extrusion rate around the tibial prosthesis.

Haplotype-resolved genome assembly and allele-specific gene expression in cultivated ginger.

Ginger (Zingiber officinale) is one of the most valued spice plants worldwide; it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance. Here, we present a haplotype-resolved, chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb. Remarkable structural variation was identified between haplotypes, and two inversions larger than 15 Mb on chromosome 4 may be associated with ginger infertility. We performed a comprehensive, spatiotemporal, genome-wide analysis of allelic expression patterns, revealing that most alleles are coordinately expressed. The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements, greater coding sequence divergence, more relaxed selection pressure, and more transcription factor binding site differences. We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis. Our allele-aware assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in ginger.

Elevated serum granzyme B levels are associated with disease activity and joint damage in patients with rheumatoid arthritis.

OBJECTIVES: Little is known about the roles of granzyme B in rheumatoid arthritis (RA). We aimed to evaluate the serum level of granzyme B in patients with RA and determine relationships with clinical features and joint destruction of RA. METHODS: We enrolled 100 patients with RA, 50 patients with osteoarthritis (OA), and 50 healthy controls (HC). Granzyme B serum concentrations were measured by ELISA; we then analyzed associations between granzyme B levels, clinical features, and joint destruction by calculating Sharp scores and disease activity as measured by Disease Activity Score-28 based on erythrocyte sedimentation rate (DAS28-ESR) in patients with RA. RESULTS: Compared with HC and patients with OA, serum granzyme B levels in patients with RA were remarkably elevated. Serum granzyme B levels did not differ between patients with OA and HC. Granzyme B levels correlated with ESR, rheumatoid factor, swollen joint counts, joint erosion scores, total Sharp scores, and DAS28-ESR. Moreover, patients with RA with high disease activity had higher granzyme B levels. CONCLUSIONS: Serum granzyme B levels were elevated significantly in patients with RA and correlated positively with disease activity and joint destruction. Serum granzyme B may have potential applications in laboratory evaluation of patients with RA.

An elderly female with adult-onset Still's disease initially misdiagnosed as prosthetic joint infection after total knee arthroplasty: lessons in differential diagnosis and treatment.

BACKGROUND: High fever, knee swelling and pain after knee arthroplasty are often considered as symptoms of acute prosthetic joint infection. However, similar symptoms can also present as primary manifestations of adult-onset Still's disease, which creates some interference in differential diagnosis. To our knowledge, this is the first published case of misdiagnosis of adult Still's disease after total knee arthroplasty, who was initially misdiagnosed as an prosthetic joint infection due to the above-mentioned symptoms. The symptoms of the knee infection was not relieve after several revisions and continous antibiotic treatment. Finally, after several consultations and repeated evaluation it was diagnosed as adult-onset Still's disease. CASE PRESENTATION: A 77-year-old female who underwent bilateral total knee arthroplasty 6 years ago was admitted to our hospital with high fever, right knee effusion and painful knee. Based on the results of joint fluid aspiration and culture, we treated the right knee as acute hematogenous prosthetic joint infection. After three debridement and revision surgeries, the patient's symptoms continued to persist. Subsequent manifestations of other symptoms such as typical rash and sore throat and laboratory examination suggested the possibility of adult-onset Still's disease. So she underwent diagnostic steroid hormone therapy at the recommendation of a rheumatologist, and a final revision was performed after symptom was controlled. At the one-year follow-up, the patient's symptoms completely resolved and the knee revision was functioning well. CONCLUSIONS: When joint swelling and pain occurs after knee arthroplasty, the possibility of joint infection should not only be considered, but rheumatic autoimmune diseases should also be differentiated. Because the manifestations of joint infection and rheumatic immune disease sometimes overlap highly, when reasonable treatment over a period of time fails to relieve symptoms and signs, we should notice subtle differences in symptoms and laborotary tests and look for other diagnostic possibilities in time.

Altered Intrinsic Brain Activity and Functional Connectivity Before and After Knee Arthroplasty in the Elderly: A Resting-State fMRI Study.

Objective: This study aimed to investigate the brain functional alterations with resting-state functional magnetic resonance imaging (rs-fMRI) in older patients with knee osteoarthritis (KOA) before and after total knee arthroplasty (TKA) and to assess the causal relationship of the brain function and neuropsychological changes. Methods: We performed rs-fMRI to investigate brain function of 23 patients aged ≥65 with KOA and 23 healthy matched controls. Of the KOA patients, 15 completed postoperative rs-fMRI examinations. Analyzes of the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) were used to estimate differences in brain functional parameters between KOA patients, postoperative patients, and the controls. The relationship between changes of pre- and post-surgical status in ALFF and neuropsychological test results was analyzed. Results: Compared with the controls, all patients with KOA exhibited decreased ALFF in the default mode network (bilateral angular gyrus, precuneus gyrus, medial superior frontal gyrus) and increased ALFF in the bilateral amygdala and cerebellum posterior lobe before surgery (P < 0.001). Altered ALFF persisted in the same brain regions 1 week postoperatively. The decreased ALFF in the left precuneus gyrus and middle temporal gyrus was found after surgery when compared with preoperative data (P < 0.01). Preoperatively, the KOA patients exhibited increased FC between the left precuneus gyrus and the right supplementary motor area compared to the controls (P < 0.001), but this connectivity became no significant difference after TKA. The left Cerebelum_9 was found to have decreased FC with the right precuneus gyrus postoperatively (P < 0.001) although this was not significantly different before surgery. The significantly altered ALFF values were not correlated with changes in cognitive assessment scores. Conclusion: In older patients with end-stage KOA, functional alterations in important brain regions were detected with the persistence and further changes observed at an early stage after knee replacement. Our data further our understanding of brain functional abnormalities and cognitive impairment in older patients following knee replacement, which may provide therapeutic targets for preventive/treatment strategy to be developed. Trial registration: Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, ChiCTR1800016437; Registered June 1, 2018.