Identification and validation of endoplasmic reticulum stress-related genes in patients with steroid-induced osteonecrosis of the femoral head.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a debilitating condition caused by long-term corticosteroid use, leading to impaired blood flow and bone cell death. The disruption of cellular processes and promotion of apoptosis by endoplasmic reticulum stress (ERS) is implicated in the pathogenesis of SONFH. We identified ERS-associated genes in SONFH and investigated their potential as therapeutic targets. We analysed the GSE123568 GEO dataset to identify differentially expressed genes (DEGs) related to ERS in SONFH. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, identified hub genes by protein-protein interaction (PPI) analyses, and evaluated their functions by gene set enrichment analysis (GSEA). We constructed mRNA-miRNA networks, identified potential therapeutics, and assessed immune cell infiltration. We performed cross-validation using the GEO dataset GSE74089, qRT-PCR on clinical samples from patients with SONFH and controls, and a receiver operating characteristic (ROC) curve analysis to assess the diagnostic performance of the hub genes. We identified 195 ERS-related genes in SONFH, which were primarily involved in oxidative stress, immune responses, and metabolic pathways. The PPI network suggested CXCL8, STAT3, IL1B, TLR4, PTGS2, TLR2, CASP1, CYBB, CAT, and HOMX1 to be key hub genes, which were shown by GSEA to be involved in biological pathways related to metabolism, immune modulation, and cellular integrity. We also identified 261 microRNAs (miRNAs) as well as drugs such as dibenziodolium and N-acetyl-L-cysteine that modulated inflammatory responses in SONFH. Twenty-two immune cell subtypes showed significant correlations, such as a positive correlation between activated mast cells and Tregs, and patients with SONFH had fewer dendritic cells than controls. The hub genes CYBB and TLR4 showed significant correlations with M1 macrophages and CD8 T cells, respectively. Cross-validation and qRT-PCR confirmed the upregulation of STAT3, IL1B, TLR2, and CASP1 in patients with SONFH, validating the bioinformatics findings. An ROC curve analysis confirmed the diagnostic potential of the hub genes. The top 10 hub genes show promise as ERS-related diagnostic biomarkers for SONFH. We discovered that 261 miRNAs, including hsa-miR-23, influence these genes and identified potential therapeutics such as dibenziodolium and simvastatin. Immune profiling indicated altered immune functions in SONFH, with significant correlations among immune cell types. Validation confirmed the upregulation of STAT3, IL1B, TLR2 and CASP1, which had diagnostic potential. The findings suggest potential diagnostic markers and therapeutic targets for SONFH.

Ceramic fragmentation after total hip arthroplasty: two case reports and literature review.

Background: Ceramic fragmentation is a rare but serious complication after total hip arthroplasty (THA). We reviewed the PubMed literature from 1990 to 2023 and found only 31 case reports of ceramic fragmentation after THA. Our case reports help to expand understanding of this rare complication. We shared our surgical experience and identified an ideal material for revision surgery, which can serve as a useful reference for other orthopedic surgeons to perform ceramic fragmentation revision surgery in the future. We also analyzed the possible causes, diagnosis, and treatment opinions of ceramic fragmentation. Case presentation: This study presents two cases of ceramic fragmentation after THA. One patient had ceramic head fragmentation 10 years after the primary THA, and one patient had ceramic liner fragmentation 5 years after the primary THA. Both patients presented with pain, and one patient also reported a clicking sound in the hip. The two patients described here had BMIs of 23.7 and 23.1, respectively. Both patients' ceramic fragmentation were due to aseptic loosening, not periprosthetic joint infections, as confirmed by negative microbiological cultures. Radiographic examinations of both patients revealed radio-opaque wear debris around the hip joint prostheses and we describe the surgical protocols and intraoperative findings in both cases in detail. Conclusion: Our cases and the literature suggest that ceramic fragmentation can occur at any time after THA. The most immediate symptoms are pain and noise, but some patients may be asymptomatic. Ceramic on polyethylene bearings is recommended for revision surgery whenever possible; metal bearings should be avoided.

A slow-releasing donor of hydrogen sulfide inhibits neuronal cell death via anti-PANoptosis in rats with spinal cord ischemia‒reperfusion injury.

BACKGROUND: Spinal cord ischemia‒reperfusion injury (SCIRI) can lead to paraplegia, which leads to permanent motor function loss. It is a disastrous complication of surgery and causes tremendous socioeconomic burden. However, effective treatments for SCIRI are still lacking. PANoptosis consists of three kinds of programmed cell death, pyroptosis, apoptosis, and necroptosis, and may contribute to ischemia‒reperfusion-induced neuron death. Previous studies have demonstrated that hydrogen sulfide (H2S) exerts a neuroprotective effect in many neurodegenerative diseases. However, whether H2S is anti-PANoptosis and neuroprotective in the progression of acute SCIRI remains unclear. Thus, in this study we aimed to explore the role of H2S in SCIRI and its underlying mechanisms. METHODS: Measurements of lower limb function, neuronal activity, microglia/macrophage function histopathological examinations, and biochemical levels were performed to examine the efficacy of H2S and to further demonstrate the mechanism and treatment of SCIRI. RESULTS: The results showed that GYY4137 (a slow-releasing H2S donor) treatment attenuated the loss of Nissl bodies after SCIRI and improved the BBB score. Additionally, the number of TUNEL-positive and cleaved caspase-3-positive cells was decreased, and the upregulation of expression of cleaved caspase-8, cleaved caspase-3, Bax, and Bad and downregulation of Bcl-2 expression were reversed after GYY4137 administration. Meanwhile, both the expression and activation of p-MLKL, p-RIP1, and p-RIP3, along with the number of PI-positive and RIP3-positive neurons, were decreased in GYY4137-treated rats. Furthermore, GYY4137 administration reduced the expression of NLRP3, cleaved caspase-1 and cleaved GSDMD, decreased the colocalization NeuN/NLRP3 and Iba1/interleukin-1ß-expressing cells, and inhibited proinflammatory factors and microglia/macrophage polarization. CONCLUSIONS: H2S ameliorated spinal cord neuron loss, prevented motor dysfunction after SCIRI, and exerted a neuroprotective effect via the inhibition of PANoptosis and overactivated microglia-mediated neuroinflammation in SCIRI.

Advancements in drug-loaded hydrogel systems for bone defect repair.

Bone defects are primarily the result of high-energy trauma, pathological fractures, bone tumor resection, or infection debridement. The treatment of bone defects remains a huge clinical challenge. The current treatment options for bone defects include bone traction, autologous/allogeneic bone transplantation, gene therapy, and bone tissue engineering amongst others. With recent developments in the field, composite scaffolds prepared using tissue engineering techniques to repair bone defects are used more often. Among the various composite scaffolds, hydrogel exhibits the advantages of good biocompatibility, high water content, and degradability. Its three-dimensional structure is similar to that of the extracellular matrix, and as such it is possible to load stem cells, growth factors, metal ions, and small molecule drugs upon these scaffolds. Therefore, the hydrogel-loaded drug system has great potential in bone defect repair. This review summarizes the various natural and synthetic materials used in the preparation of hydrogels, in addition to the latest research status of hydrogel-loaded drug systems.

Systematic analysis of hip-preserving treatment for early osteonecrosis of the femoral head from the perspective of bibliometrics (2010-2023).

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a serious condition that causes bone tissue death, femoral head collapse, and hip joint destruction. Early intervention through hip-preserving treatment is crucial to slow down disease progression, preserve hip joint function, and improve the quality of life of patients. We analyzed the knowledge map, research gaps, and future research directions in the field of hip-preserving treatment for early ONFH. METHODS: All publications related to hip-preserving treatment for early ONFH published between 2010 and 2023 were identified from the Web of Science Core Collection and analyzed using VOSviewer 1.6.19, CiteSpace 6.2.R2, and Scimago Graphica 1.0.35. RESULTS: In total, 234 articles were analyzed. The results showed an exponential growth trend in the number of publications related to hip-preserving treatment for early ONFH in the past decade. China and the USA were the main contributors. International Orthopaedics published the most papers in this field, whereas Bone and Joint Surgery-American Volume had the highest average citation count per article. Several stable research topics were noted in this field, including core decompression (CD), osteotomy, bone transplantation in hip-preserving surgery, and cell therapy, which have become research hotspots in hip-preserving treatment. CONCLUSIONS: Hip-preserving treatment for early ONFH has received increasing attention, and research in this field is expected to grow. Stable research topics include core decompression (CD), osteotomy, bone transplantation, and cell therapy. Future research is predicted to focus on cell therapy and combination therapy, resulting in an increasing number of publications on hip-preserving treatment for early ONFH.

Extracellular vesicle therapy for traumatic central nervous system disorders.

Traumatic central nervous system (CNS) disorders have catastrophic effects on patients, and, currently, there is no effective clinical treatment. Cell transplantation is a common treatment for traumatic CNS injury in animals. In recent years, an increasing number of studies have reported that the beneficial effect of transplanted cells for CNS repair is mediated primarily through the extracellular vesicles (EVs) secreted by the cells, in which microRNAs play a major role. Accordingly, numerous studies have evaluated the roles and applications of EVs secreted by different cell types in neurological diseases. Furthermore, due to their unique biological features, EVs are used as disease biomarkers and drug delivery systems for disease prevention and treatment. We discuss current knowledge related to EVs, focusing on the mechanism underlying their effects on traumatic CNS diseases, and summarize existing research on the potential clinical utility of EVs as disease biomarkers and drug delivery systems.

Medial pivot prosthesis has a better functional score and lower complication rate than posterior-stabilized prosthesis: a systematic review and meta-analysis.

PURPOSE: We aimed to compare the postoperative clinical efficacy and safety of medial pivot (MP) prosthesis and posterior-stabilized (PS) prosthesis in the treatment of knee osteoarthritis (KOA). METHODS: All studies involving MP and PS prosthesis in PubMed, EMBASE, Cochrane Library, and Web of Science were searched since the establishment of the database. The included outcomes were knee range of motion (ROM), functional score, radiographic results, complication rate, and revision rate. Studies were independently evaluated by the Newcastle-Ottawa Scale for case-control studies and the assessment tool of the Cochrane Collaboration for randomized controlled trials. I2 was used to test the heterogeneity, and fixed- or random-effects models were selected for meta-analysis according to the heterogeneity results. RESULTS: A total of 19 studies, consisting of 3592 patients and 3783 knees (MP: 1811 knees, PS: 1972 knees), were included in the meta-analysis. The WOMAC (MD = - 1.11, 95% CI - 1.98 to - 0.23; P = 0.01) and HSS (MD = - 4.32, 95% CI - 8.30 to - 0.34; P = 0.03) in the MP group were significantly lower compared with the PS group, and the complication rate (OR 0.53, 95% CI 0.33-0.87; P = 0.01) was also lower compared with the PS group. There was no significant difference in ROM, radiographic results, and revision rate between the two groups (P > 0.5). CONCLUSIONS: The existing literature provided evidence to support better clinical effect and lower complication rate of MP prosthesis compared to PS prosthesis. These results provide a reference for clinicians when choosing a suitable prosthesis.

The influence of posterior tibial slope on the mid-term clinical effect of medial-pivot knee prosthesis.

OBJECTIVE: To evaluate the effect of posterior tibial slope (PTS) on the mid-term clinical outcome following a medial-pivot (MP) prosthesis. METHOD: Two hundred thirty-three patients from The Affiliated Hospital of Qingdao University, who had undergone a total knee arthroplasty (TKA) with MP prosthesis between January 2015 and December 2015, were retrospectively included in this study. They were divided into 3 groups according to postoperative PTS: A ≤ 5°; B 5-7°; and C ≥ 7°. Multiple assessments were made on the patient postoperatively and recorded in the three groups, the measurements of this study included: the range of motion (ROM), knee scoring system (KSS), Western Ontario and McMaster universities osteoarthritis index (WOMAC), posterior condylar offset (PCO), joint line height, and postoperative complications. RESULTS: The average post-operative ROM for groups B and C were 108° and 110° respectively; this was significantly higher than that of group A (98°, P < 0.001). The WOMAC scores of patients in group C were significantly lower than those in groups A and B (P < 0.05). However, there were no significant differences in KSS, PCO, and joint line height among the 3 groups (P > 0.05). Only 2 cases of postoperative complications occurred in group C, these were ameliorated after operation. CONCLUSION: With an increase to PTS, the postoperative ROM can be significantly increased for the patient. However, the knee joint function will not be significantly improved, and the stability of knee joint will not be affected when within the limits of appropriate PTS.

Comparative study on mid- and long-term clinical effects of medial pivot prosthesis and posterior-stabilized prosthesis after total knee arthroplasty.

OBJECTIVE: The purpose of this study was to explore the mid-and long-term clinical effects of Chinese patients with medial pivot (MP) prosthesis and posterior-stabilized (PS) prosthesis after total knee arthroplasty (TKA), to provide a reference for the recommendation of clinical prostheses. METHODS: A retrospective analysis of 802 patients who received TKA was performed from June 2010 to December 2013. A total of 432 patients received a MP prosthesis (MP group) and 375 patients received a PS prosthesis (PS group). Postoperative range of motion (ROM), clinical scores including the knee scoring system (KSS), the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), the forgotten joint score (FJS), and postoperative complications were compared between the two groups. RESULTS: A total of 527 patients were followed up, including 290 in the MP group and 237 in the PS group. Both groups achieved satisfactory results in terms of KSS score, WOMAC score, and postoperative ROM, which were significantly improved compared with those before surgery, but the difference between the groups was not statistically significant (P > 0.05). The FJS scores of the MP group and the PS group were satisfactory and no significant difference was observed (P = 0.426). Postoperative complications occurred in 5 and 11 patients in the MP group and PS group, respectively. CONCLUSION: The clinical results of TKA with MP or PS in Chinese patients at mid- and long-term are encouraging, and no significant differences were observed between the two types of prostheses. Studies have also shown that both prostheses are safe for Chinese patients.

Date on identification of flavonoids in Plumula nelumbinis by UPLC-ESI-QTOF-MS and antioxidant activity from 13 habitats in China.

Plumula nelumbinis is a well-known health food and a traditional Chinese medicine, is used in many countries around the world. For its pharmacological properties are related to its chemical composition, a ultra-performance liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) method was used to identify the flavonoids in P. nelumbinis. The first set of data shows the MS-MS Spectrograms of 12 flavonoid standards and 38 flavonoids detected in the P. nelumbinis from Xiangtan, Hunan province. The second set of data shows the total flavonoids content and the antioxidant activity of total flavonoid in P. nelumbinis from 13 habitats. The antioxidant activity were accomplished with 1,1-diphenyl-2-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and ferric reducing ability of plasma (FRAP) assays.