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.

Metabolic analysis of early nonalcoholic fatty liver disease in humans using liquid chromatography-mass spectrometry.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disease that affects 20-30% of individuals worldwide. Liver puncture remains the gold standard for the diagnosis of liver diseases despite limitations regarding invasive nature and sample variability. It is of great clinical significance to find noninvasive biomarkers to detect and predict NAFLD. OBJECTIVE: The aims of this study were to identify potential serum markers in individuals with early-stage NAFLD and to advance the mechanistic understanding of this disease using a high-throughput mass spectrometry-based untargeted metabolomics approach. METHODS: One hundred and twelve patients with early-stage NAFLD aged 18-55 were recruited according to the guidelines. The control group included 112 healthy participants. The demographic, anthropometric, clinical and laboratory data of all participants were systematically collected. Serum samples were obtained after an overnight fast. The comprehensive serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. The resultant data was processed by Compound Discover and SIMCA-P software to validate the potential biomarkers. Significantly altered metabolites were evaluated by variable importance in projection value (VIP > 1) and ANOVA (p < 0.01). Pathway analysis was performed using MetaboAnalyst 4.0. RESULTS: The liver function test of early NAFLD patients showed no statistical differences to control group (p > 0.05). However, obvious differences in blood lipids were observed between subjects with NAFLD and controls (p < 0.001). In total, 55 metabolites showed significant changes in experimental group were identified. The area under curve (AUC) values deduced by receiver operating curve (ROC) analysis indicated that these newly identified biomarkers have high predictability and reliability. Of these, 15 metabolites with AUC greater than 0.9 were of great diagnostic value in early NAFLD patients. CONCLUSION: In this study, a total of 15 serum metabolites were found to strongly associate with early NAFLD. These biomarkers may have great clinical significance in the early diagnosis of NAFLD, as well as to follow response to therapeutic interventions.

Circ_0020093 ameliorates IL-1ß-induced apoptosis and extracellular matrix degradation of human chondrocytes by upregulating SPRY1 via targeting miR-23b.

Osteoarthritis (OA) is a chronic disease characterized by articular cartilage degeneration and uncontrolled chondrocyte apoptosis. At present, accumulating evidence introduces that circular RNA (circRNA) is involved in the development of OA. The aim of our study was to explore the role and the functional mechanism of circ_0020093 in OA cell model. Human chondrocytes were treated with interleukin-1 beta (IL-1ß) to construct OA model. The expression of circ_0020093, miR-23b, and Sprouty 1 (SPRY1) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis was assessed by flow cytometry assay. The expression of extracellular matrix (ECM)-associated markers and SPRY1 protein level was detected by qRT-PCR and Western blot. Bioinformatics analysis-predicted relationship between miR-23b and circ_0020093 or SPRY1 was further verified by dual-luciferase reporter assay and RNA pull-down assay. In this study, we found that the expression of circ_0020093 and SPRY1 was declined, while miR-23b expression was elevated in IL-1ß-treated chondrocytes. IL-1ß induced chondrocyte apoptosis and ECM degradation, while these negative effects were alleviated by circ_0020093 overexpression or miR-23b inhibition. MiR-23b was a target of circ_0020093, and SPRY1 was a downstream target of miR-23b. Rescue experiments showed that miR-23b enrichment reversed the role of circ_0020093 overexpression, and SPRY1 knockdown also reversed the effects of miR-23b inhibition. Importantly, circ_0020093 positively regulated SPRY1 expression by targeting miR-23b. In conclusion, circ_0020093 ameliorates IL-1ß-induced apoptosis and ECM degradation of human chondrocytes by regulating the miR-23b/SPRY1 axis.

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.

Patient outcomes in Anteromedial osteoarthritis patients over 80 years old undergoing Oxford Unicompartmental knee Arthroplasty in China.

BACKGROUND: The use of Oxford Unicompartmental Knee Arthroplasty (UKA) has increased rapidly in both Western and Asian populations, with excellent functional outcomes and high patient satisfaction. While previous evidence regarding clinical outcomes and survival rates after Oxford UKA was based on studies in Western populations, the results may be different in Asian patients. The relevance of age for postoperative function after Oxford UKA also remains unclear. Hence, the aim of our study was to clarify the effectiveness and safety of Oxford UKA in Asian patients aged over 80 years. METHODS: A retrospective review was performed and included 195 patients (209 knees) who underwent an Oxford UKA between June 2015 and July 2018. We divided the patients into three groups by age: Group 1, 60-69 years; Group 2, 70-79 years; and Group 3, over 80 years. We used the Hospital for Special Surgery (HSS) score and Western Ontario and McMaster (WOMAC) Universities Osteoarthritis Index score to evaluate the general condition of the patients' knees before surgery and at last follow-up. We also recorded perioperative and short-term complications. RESULT: Group 1 consisted of 60 patients (60 knees); Group 2, 70 patients (79 knees); and Group 3, 65 patients (70 knees). The mean follow-up was 21.34 ± 12.04, 22.08 ± 11.38, and 21.76 ± 10.20 months in groups 1, 2, and 3, respectively. At last follow-up, the patients in Group 3 showed lower function scores compared to groups 1 and 2 (P < 0.05), but the HSS scores and the WOMAC scores were significantly improved in all three groups. In terms of perioperative and other complications, the three age groups did not differ significantly. CONCLUSION: Oxford UKA is an effective and safe treatment for osteoarthritis, even in elderly patients in China. Elderly patients have lower knee function scores than younger patients. However, the knee joint pain of the elderly patients was relieved and function improved compared to the preoperative condition.

Administration of CoCl2 Improves Functional Recovery in a Rat Model of Sciatic Nerve Transection Injury.

Peripheral nerve injury is known to activate the hypoxia-inducible factor-1α (HIF-1α) pathway as one of pro-regenerative transcriptional programs, which could stimulate multiple injury-induced gene expression and contribute to axon regeneration and functional recovery. However, the role of HIF-1α in peripheral nerve regeneration remains to be fully elucidated. In this study, rats were divided into three groups and treated with sham surgery, surgery with cobalt chloride (CoCl2) and surgery with saline, respectively. Sciatic functional index, morphologic evaluations of muscle fibers, and never conduction velocity were performed to measure the functional recovery at 12 weeks postoperatively. In addition, the effects of CoCl2 on the expression of HIF-1α, glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were determined at mRNA levels; as well as HIF-1α, the dual leucine zipper kinase (DLK), the c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), BDNF and NGF were measured at protein level at 4 weeks postoperatively. Systemic administration of CoCl2 (15 mg/kg/day intraperitoneally) significantly promoted functional recovery of rats with sciatic nerve transection injury. This study demonstrated in rats treated with CoCl2, the expression of HIF-1α, GDNF, BDNF and NGF was significantly increased at mRNA level, while HIF-1α, DLK, p-JNK, BDNF and NGF was significantly increased at protein level.

Deposition of microparticles by neutrophils onto inflamed epithelium: a new mechanism to disrupt epithelial intercellular adhesions and promote transepithelial migration.

Neutrophil [polymorphonuclear leukocyte (PMN)] transepithelial migration (TEM) is a hallmark of inflammatory mucosal disorders. PMN TEM is associated with epithelial injury; however, mechanisms involved in this process are not well defined. The current work describes a new mechanism whereby deposition of PMN membrane-derived microparticles (PMN-MPs) onto intestinal epithelial cells (IECs) during TEM leads to loss of epithelial cadherins, thus promoting epithelial injury and increased PMN recruitment. PMN-MPs secreted by activated PMNs during TEM displayed a high level of enzymatically active matrix metalloproteinase 9 (MMP-9), and were capable of mediating potent effects on IEC integrity. Isolated PMN-MPs efficiently bound to IEC monolayers and induced cleavage of desmoglein-2 (DSG-2) but not E-cadherin, leading to disruption of IEC intercellular adhesions. Furthermore, PMN-MP binding to intestinal epithelium in vitro in transwell assays and in vivo in ligated intestinal loop preparations facilitated increases in PMN TEM. These effects were MMP-9 dependent and were reversed in the presence of specific pharmacological inhibitors. Finally, we demonstrated that IEC Dsg-2 serves as a barrier for migrating PMNs, and its removal by PMN-MP-associated MMP-9 facilitates PMN trafficking across epithelial layers. Our findings thus implicate PMN-MPs in PMN-mediated inflammation and epithelial damage, as observed in inflammatory disorders of mucosal surfaces.-Butin-Israeli, V., Houser, M. C., Feng, M., Thorp, E. B., Nusrat, A., Parkos, C. A, Sumagin, R. Deposition of microparticles by neutrophils onto inflamed epithelium: a new mechanism to disrupt epithelial intercellular adhesions and promote transepithelial migration.

Hypoxia-Induced MicroRNA-429 Promotes Differentiation of MC3T3-E1 Osteoblastic Cells by Mediating ZFPM2 Expression.

BACKGROUND/AIMS: Hypoxia has been reported to regulate osteoblastic differentiation of bone cells and cartilage development. However, information concerning the molecular mechanisms remains largely unknown. METHODS: The expression of miR-429 was evaluated by quantitative real-time PCR analysis. To test whether miR-429 directly regulate the expression level of ZFPM2 at transcription level, dual-luciferase reporter gene assay was performed. Western blotting was performed to detect osteogenesis related protein expression. The cell proliferation, apoptosis, alkaline phosphatase activity and matrix mineralization were performed to assess the functions of miR-429 in vitro and in vivo the effects of miR-429 on fracture healing. RESULTS: Expression of miR-429 was increased in MC3T3-E1 cells treated with 200 µM CoCl2 by qRT-PCR, and overexpression of miR-429 promoted cell differentiation, and enhanced alkaline phosphatase activity and matrix mineralization. Luciferase reporter assays suggested that miR-429 directly targets the 3'UTR of ZFPM2. In addition, knockdown of ZFPM2 could phenocopy the effects of miR-429 expression. Furthermore, overexpression of ZFPM2 in miR-429-expressing MC3T3-E1 cells suppressed cell differentiation. CONCLUSIONS: Our results provide valuable insight into the potential role of hypoxia in regulation of osteoblastic cell differentiation.

Galectin-3 regulates desmoglein-2 and intestinal epithelial intercellular adhesion.

The desmosomal cadherins, desmogleins, and desmocollins mediate strong intercellular adhesion. Human intestinal epithelial cells express the desmoglein-2 isoform. A proteomic screen for Dsg2-associated proteins in intestinal epithelial cells identified a lectin referred to as galectin-3 (Gal3). Gal3 bound to N-linked ß-galactosides in Dsg2 extracellular domain and co-sedimented with caveolin-1 in lipid rafts. Down-regulation of Gal3 protein or incubation with lactose, a galactose-containing disaccharide that competitively inhibits galectin binding to Dsg2, decreased intercellular adhesion in intestinal epithelial cells. In the absence of functional Gal3, Dsg2 protein was internalized from the plasma membrane and degraded in the proteasome. These results report a novel role of Gal3 in stabilizing a desmosomal cadherin and intercellular adhesion in intestinal epithelial cells.

Immediate reduction under general anesthesia and single-staged anteroposterior spinal reconstruction for fracture-dislocation of lower cervical spine.

Fracture-dislocation of the lower cervical spine is a severe traumatic lesion, most frequently resulting in tetraplegia. Treatment is usually painful and time consuming. This retrospective study evaluated the clinical curative effect of immediate reduction under general anesthesia and single-staged anteroposterior spinal reconstruction for fracture-dislocation of the lower cervical spine. Twelve cases of traumatic lower cervical spinal fracture-dislocation were retrospectively analyzed from January 2006 to December 2011. The injury level was C4/C5 in 4, C5/C6 in 5, and C6/C7 in 3 patients. The spinal cord function grades according to the American Spinal Injury Association impairment scale (2000 edition amended) before operation were as follows: grade A in 2 cases, grade B in 2 cases, grade C in 5 cases, grade D in 2 cases, and grade E in 1 case. On admission, all patients underwent immediate reduction under general anesthesia and single-staged anteroposterior spinal reconstruction by circumferential fixation/fusion. The spinal cord function grades according to American Spinal Injury Association after operation were as follows: grade A in 1 case, grade B in 1 case, grade C in 3 cases, grade D in 3 cases, and grade E in 4 cases. All 12 patients showed evidence of stability at the instrumented level on the final follow-up examination (mean follow-up, 3.7 y). Immediate reduction under general anesthesia followed by a single-stage combined anteroposterior spinal reconstruction is a safe and reliable way of treating patients with lower cervical spine fracture-dislocations.

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.

Meta-analysis of factors influencing anterior knee pain after total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is a mature procedure recommended for correcting knee osteoarthritis deformity, relieving pain, and restoring normal biomechanics. Although TKA is a successful and cost-effective procedure, patient dissatisfaction is as high as 50%. Knee pain after TKA is a significant cause of patient dissatisfaction; the most common location for residual pain is the anterior region. Between 4% and 40% of patients have anterior knee pain (AKP). AIM: To investigate the effect of various TKA procedures on postoperative AKP. METHODS: We searched PubMed, EMBASE, and Cochrane from January 2000 to September 2022. Randomized controlled trials with one intervention in the experimental group and no corresponding intervention (or other interventions) in the control group were collected. Two researchers independently read the title and abstract of the studies, preliminarily screened the articles, and read the full text in detail according to the selection criteria. Conflicts were resolved by consultation with a third researcher. And relevant data from the included studies were extracted and analyzed using Review Manager 5.4 software. RESULTS: There were 25 randomized controlled trials; 13 were comparative studies with or without patellar resurfacing. The meta-analysis showed no significant difference between the experimental and control groups (P = 0.61). Six studies were comparative studies of circumpatellar denervation vs non-denervation, divided into three subgroups for meta-analysis. The two-subgroup meta-analysis showed no significant difference between the experimental and the control groups (P = 0.31, P = 0.50). One subgroup meta-analysis showed a significant difference between the experimental and control groups (P = 0.001). Two studies compared fixed-bearing TKA and mobile-bearing TKA; the results meta-analysis showed no significant difference between the experimental and control groups (P = 0.630). Two studies compared lateral retinacular release vs non-release; the meta-analysis showed a significant difference between the experimental and control groups (P = 0.002); two other studies compared other factors. CONCLUSION: Patellar resurfacing, mobile-bearing TKA, and fixed-bearing TKA do not reduce the incidence of AKP. Lateral retinacular release can reduce AKP; however, whether circumpatellar denervation can reduce AKP is controversial.

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.

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.

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.

Preferentially expressed antigen in melanoma immunohistochemistry as an adjunct for differential diagnosis in acral lentiginous melanoma and acral nevi.

Preferentially expressed antigen in melanoma (PRAME) has shown promising utility in distinguishing benign melanocytic lesions from melanomas, but knowledge of its expression pattern in acral lentiginous melanoma (ALM) and acral nevi (ANs) is limited. Immunohistochemical expression of PRAME was examined in 75 ALMs and 34 ANs. The clinical and histopathologic characteristics of patients with ALM were collected. PRAME was immunoreactive in 89.3% (67/75) of ALMs, but entirely negative in 94.1% (32/34) of ANs. When staining at least 50% of lesional melanocytes was determined as positivity, the sensitivity and specificity of PRAME for distinguishing ALM from ANs were 69.3% and 100%, respectively. Seventy-one cases of ALMs had tumor cells in the epidermis; 71.8% (51/71) of them showed positive for PRAME. By contrast, 61 ALMs had tumor cells in the dermis; 65.6% (40/61) exhibited positive expression. Twenty-nine of 39 (74.4%) epithelioid cell ALMs were observed to be positive for PRAME. By comparison, 63.8% (23/36) of ALMs with spindle tumor cells were positive for PRAME. However, PRAME positive expression was not associated with any clinical and histopathologic characteristics of patients with ALM, including Breslow thickness, ulcer, cytomorphology, lymph node metastasis, or tumor-infiltrated lymphocytes (TILs). Nevertheless, we observed that 82.6% (19/23) of ALMs with lymph node involvement at diagnosis expressed PRAME, compared with 57.6% (20/35) of those without. In summary, PRAME immunohistochemistry can serve as a helpful adjunct in the differential diagnosis of ALMs and ANs with good sensitivity and high specificity. Additionally, PRAME tends to have a higher positive rate in epidermal melanocytes than in the dermis and is inclined to express in epithelioid cells than in spindle cells of ALMs.

Clinical outcome of femoral neck system versus cannulated compression screws for fixation of femoral neck fracture in younger patients.

BACKGROUND: The clinical outcome of a new fixation device (femoral neck system, FNS) for femoral neck fractures remains unclear. The main purpose of this study was to evaluate two different internal fixation methods for the treatment of femoral neck fractures in patients aged under 60 years. METHODS: We retrospectively studied patients who underwent internal fixation surgery in our hospital for femoral neck fractures between January 2017 and January 2020. Cannulated compression screws (CCS) and FNS groups were divided according to different internal fixation methods. General data (such as sex, age, body mass index, type of fracture) of all patienFemoral neck shorteningts were collected, and joint function was evaluated using the Harris Hip Score (HHS) before and 1 year after surgery. We recorded related surgical complications, including femoral head necrosis, nonunion, and femoral neck shortening. RESULTS: There were no significant differences in age, sex, or body mass index between the two groups. There was no statistical difference in HHSs between the two groups before surgery. Patients who underwent FNS treatment had longer surgery time (79.75 ± 26.35 min vs. 64.58 ± 18.56 min, p = 0.031) and more blood loss (69.45 ± 50.47 mL vs. 23.71 ± 28.13 mL, p < 0.001). The degree of femoral neck shortening in the FNS group was significantly lower than that in the CCS group (10.0% vs 37.5%, p = 0.036). Regarding postoperative complications, there was no statistical difference in the incidence of femoral head necrosis and fracture nonunion between the two groups. CONCLUSION: Patients younger than 60 with femoral neck fractures can obtain satisfactory clinical results with CCS or FNS treatment. FNS has excellent biomechanical properties and shows significantly higher overall construct stability.

Efficacy and mid/long-term survivorship of mobile-bearing unicompartmental knee arthroplasty for medial compartment knee osteoarthritis combined patellofemoral joint arthritis: a prospective cohort study protocol.

INTRODUCTION: Unicompartmental knee arthroplasty (UKA) is one of the most effective surgical procedures for treating isolated medial compartment knee osteoarthritis. However, previous studies have regarded patellofemoral osteoarthritis as a contraindication for UKA. In contrast, most current research shows that damage to the articular cartilage of the patellofemoral joint, even to the extent of full-thickness cartilage loss, has no influence on the outcome of UKA. METHODS AND ANALYSIS: Study settings: This study is a prospective cohort study that will compare the Forgotten Joint Score and Lonner patellofemoral joint score of patients who have undergone UKA; the patients will be divided into two groups (with and without patellofemoral joint osteoarthritis (PFJOA)). PRIMARY OBJECTIVE: Long-term follow-up will be used to evaluate the effect of the operation on the above-mentioned scores in both the groups. SECONDARY OBJECTIVE: We will divide the patients from the with PFJOA group into three subgroups according to the localisation of patellofemoral cartilage lesions (medial zone, lateral zone and central zone). We aim to compare knee joint scores among these groups and clarify the impact of different wear sites on clinical efficacy. We will use CT to explore the potential mechanism through which UKA affects patellofemoral joint-related parameters (lateral patellar tilt, lateral patellar shift and tibia tuberosity-trochlear groove distance). We will also record mid-term/long-term post-surgery complications. ETHICS AND DISSEMINATION: This study's protocol is in accordance with the Declaration of Helsinki. This study was approved by the Ethics Committee of Xuanwu Hospital. The results of this study will be disseminated in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000030310.