Short-Term but Not Long-Term Knee Symptoms and Functional Improvements of Tissue Engineering Strategy for Meniscus Defects: A Systematic Review of Clinical Studies.

PURPOSE: To investigate the up-to-date clinical outcomes of tissue-engineered meniscus implants for meniscus defects. METHODS: A search was performed by 3 independent reviewers on PubMed, MEDLINE, EMBASE, and Cochrane from 2016 to June 18, 2023, with the term "meniscus" with all the following terms: "scaffolds," "constructs," "implant," and "tissue engineering." Inclusion criteria included "Clinical trials" and "English language articles" that involved isolated meniscus tissue engineering strategies for meniscus injuries. Only Level I to IV clinical studies were considered. The modified Coleman Methodology score was used for quality analysis of included clinical trials. The Methodological Index for Non-Randomized Studies was employed for analysis of the risk of study bias and methodological quality. RESULTS: The search identified 2,280 articles, and finally 19 original clinical trials meeting the inclusion criteria were included. Three types of tissue-engineered meniscus implants (CMI-Menaflex, Actifit, and NUsurface) have been clinically evaluated for meniscus reconstruction. Lack of standardized outcome measures and imaging protocols limits comparison between studies. CONCLUSIONS: Tissue-engineered meniscus implants can provide short-term knee symptom and function improvements, but no implants have been shown to propose significant long-term benefits for meniscus defects. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV studies.

Efficacy and safety of Gutong Patch compared with NSAIDs for knee osteoarthritis: A real-world multicenter, prospective cohort study in China.

The Gutong Patch (GTP) is common in clinical practice for bone diseases. This study compared the efficacy and safety of GTP and nonsteroidal anti-inflammatory drugs (NSAIDs) for KOA patients from 35 medical centers assigned to GTP, selective COX-2 inhibitor (SCI), GTP + SCI, non-selective COX-2 inhibitor (NSCI), and GTP + NSCI groups. The visual analog scale (VAS) pain score, EuroQol-VAS, EuroQol 5D-3 L, time to articular pain relief / disappearance, and joint motion recovery were the efficacy assessments. Safety assessments included contact dermatitis, gastrointestinal disorders, etc. The p-value < 0.05 was considered statistically significant. After statistical analysis, the SCI and GTP + SCI groups showed better improvement of VAS than the GTP group; the time to articular pain relief in the NSCI group was shorter than that in GTP and SCI group; the time to joint motion recovery in the GTP + NSCI group was longer than that in the SCI group. Additionally, the improvement of the quality of life in all groups was significant after treatments. While the incidence of gastrointestinal adverse events in the NSAIDs group was higher than that in the GTP and GTP + NSAIDs groups. GTP and NSAIDs are effective for KOA patients, and GTP is more suitable for KOA patients with cardiovascular and gastrointestinal comorbidities. This study was approved by the Ethics Committee at Peking Union Medical College Hospital (HS-1766) and registered in the Chinese Clinical Trial Registry (ChiCTR2100046391).

Rice FLOURY ENDOSPERM22, encoding a pentatricopeptide repeat protein, is involved in both mitochondrial RNA splicing and editing and is crucial for endosperm development.

Most of the reported P-type pentatricopeptide repeat (PPR) proteins play roles in organelle RNA stabilization and splicing. However, P-type PPRs involved in both RNA splicing and editing have rarely been reported, and their underlying mechanism remains largely unknown. Here, we report a rice floury endosperm22 (flo22) mutant with delayed amyloplast development in endosperm cells. Map-based cloning and complementation tests demonstrated that FLO22 encodes a mitochondrion-localized P-type PPR protein. Mutation of FLO22 resulting in defective trans-splicing of mitochondrial nad1 intron 1 and perhaps causing instability of mature transcripts affected assembly and activity of complex Ⅰ, and mitochondrial morphology and function. RNA-seq analysis showed that expression levels of many genes involved in starch and sucrose metabolism were significantly down-regulated in the flo22 mutant compared with the wild type, whereas genes related to oxidative phosphorylation and the tricarboxylic acid cycle were significantly up-regulated. In addition to involvement in splicing as a P-type PPR protein, we found that FLO22 interacted with DYW3, a DYW-type PPR protein, and they may function synergistically in mitochondrial RNA editing. The present work indicated that FLO22 plays an important role in endosperm development and plant growth by participating in nad1 maturation and multi-site editing of mitochondrial messager RNA.

Glomus tumors around or in the knee: a case report and literature review.

BACKGROUND: Glomus tumors commonly affect the extremities, especially subungual. And glomus tumors rarely occur around knee, which are often misdiagnosed. A lack of experience with glomus tumors is likely the cause. CASE PRESENTATION: A 42-year-old female presented with continuous dull pain of right knee for the past 7 years. Severe pain was experienced after walking a few hundred meters or climbing up or down stairs. The patient had a slight limp, and the lateral superior aspect of her right knee was tender to palpation. The range of motion and skin around her right knee were normal. Magnetic resonance imaging revealed a well-defined abnormal lesion confluent with the periosteum on the femoral lateral supracondylar. She was finally diagnosed with glomus tumor according to pathological results. After surgery, the pain disappeared, and the patient was discharged three days postoperatively. At the 18-month follow-up visit, the patient reported sustained pain relief, and regular follow-ups were continued. Additionally, 30 published reports documenting 36 cases of glomus tumors around the knee were reviewed, which showed that 20% of all reported cases of glomus tumor around the knee had a history of trauma. The median age for male with glomus tumor was greater than that of female; however, the median duration of illness between the two groups was equivalent. The mean diameters of glomus tumors ranged from 4 to 65 mm, and locations around the knee included the knee joint cavity, soft tissue (e.g. popliteal fossa, patellar tendon, iliotibial band, and Hoffa's fat pad), distal femur, and proximal tibia. CONCLUSION: Literature review demonstrated that no significant differences were found between male and female with glomus tumor in regard to location (left or right side) and illness duration. It was noting that a history of trauma may be a cause of glomus tumor and approximate 94.4% of glomus tumors was benign. The most effective therapy accepted for glomus tumors is complete surgical excision, and recurrence was rare after complete surgical excision.

Three-hour post-ERCP amylase level: a useful indicator for early prediction of post-ERCP pancreatitis.

BACKGROUND: To evaluate the value of the 3-h post-ERCP serum amylase level for early prediction of post-ERCP pancreatitis (PEP). METHOD: A study of 206 patients performed ERCP (Encoscopic Retrograde Cholangio-Pancreatography) at a single centre was done from Jan. 2011 to Nov. 2016. The serum amylase or lipase level was measured at 3 h after ERCP. The patients with PEP were recorded. ROC curves were used to statistically analyze the data: The enrolled patients were divided into two groups according to gender, then we analyzed the data respectively. We comprehensively evaluated the predictive value of PEP by 3-h post-ERCP serum amylase level based on the results above. RESULTS: Two hundred six patients (92 males, 114 females) were enrolled. PEP occurred in 21 patients (10.19%) among them. The median time to discharge was 7 days (min = 1d, max = 13d) after the procedure. In the 206 patients, the 3-h post-ERCP pancreatic amylase level was used as the test variable, and the PEP occurrence as the state variable to plot the ROC curve. The area under the curve (AUC) was 0.816, and was statistically significant (P < 0.001). The standard error (SE) was 0.0507, the 95% confidence interval (CI) was 0.756-0.866, and the optimal cut-off value was 351 U/L (sensitivity 76.19%, specificity 83.24%, positive likelihood ratio 4.55, negative likelihood ratio 0.29, Youden index 59.43%). Of the 206 patients, there were 83 patients with both 3-h post-ERCP amylase level and lipase level detected, and the ROC curves were plotted for both serum amylase and lipase respectively. The ROC curve matched-pair testing was carried out: The areas under the ROC curves were statistically significant. (P < 0.001) The area under the ROC curve for the 3-h post-ERCP lipase was 0.778, the 95% confidence interval was 0.673-0.862, and optimal cut-off value was 1834 U/L. The area under the ROC curve for the 3-h post-ERCP serum amylase was 0.780, and the 95% confidence interval was 0.676-0.864. The optimal cut-off is 380 U/L, and there was no statistically significant difference between the two for diagnostic accuracy. According to gender, 206 patients were divided into 2 groups, and the ROC curves were drawn respectively. Based on statistical analysis, there was no statistically significant difference in the diagnostic accuracy of the two groups. In the male group, 436 U/L serum amylase provided the greatest diagnostic accuracy with sensitivity (SE) of 70.5%, specificity (SP) of 89.2%, positive predictive value (PPV) 87.5%, and negative predictive value (NPV) 78.1%. Whereas, in the female group, 357 U/L serum amylase provided the greatest diagnostic accuracy with sensitivity of 76.9%, specificity of 81.2%, positive predictive value of 80.4%, negative predictive value of 77.9%. CONCLUSIONS: 1. The 3-h post-ERCP serum amylase level is a useful measurement for predicting post-ERCP pancreatitis. 2. There was no significant difference between serum amylase and lipase 3-h post-ERCP for predicting PEP. 3. There was no statistically significant difference between male and female using the 3-h post-ERCP serum amylase level to predict PEP. For female, the optimal cut-off value was 357 U/L, whereas male 436 U/L .

Surgical treatment of a distal radius and ipsilateral metacarpal hemophilic pseudotumor without recurrence or functional deficit: a case report.

Background: Distal hemophilic pseudotumor (HP) occurring distal to the wrist appear to be secondary to intraosseous hemorrhage, which develops rapidly and should be treated primarily with long-term replacement therapy and cast immobilization. Surgical removal or even amputation is indicated when conservative management fails to prevent progression. Here, a practical strategy was described for those patients who cannot afford the cost of routine coagulation factor replacement therapy, namely immediate surgical curettage and bone grafting as well as continuous follow-up. Case description: A 7-year-old boy with a history of mild hemophilia A was admitted to our medical center because of a 2-year history of progressive swelling and pain around right forearm and hand. Coagulation factor VIII level was 11.1% of normal with no inhibitor. Radiographs revealed expansile swelling, bone destruction, and deformity of the distal right radius and the second metacarpal bone. He was diagnosed with distal HP. Surgical procedure of curettage and bone grafting was performed. The function and appearance of the right wrist were almost normal without discomfort at the 101-month follow-up. Significantly, the same patient was hospitalized again because of a year-long progressive swelling and pain around the left hand when he was 14 years old. X-ray showed multiple bone destruction of the left proximal phalanges of left thumb, middle finger and little finger with local pathological fractures. Surgical procedure of HPs including curettage and bone grafting was performed. Postoperative recovery was good, and the last clinical follow-up at 18 months after the operation displayed a satisfactory shape and functional outcomes. Conclusions: Curettage and bone grafting prove to be safe and feasible for patients with distal HP and continuous follow-up of patients with distal HP is very vital for timely finding and then treating successive HP in developing countries.

Advances in Mesenchymal Stem Cell Therapy for Osteoarthritis: From Preclinical and Clinical Perspectives.

The prevalence of osteoarthritis (OA), a degenerative disorder of joints, has substantially increased in recent years. Its key pathogenic hallmarks include articular cartilage destruction, synovium inflammation, and bone remodeling. However, treatment outcomes are unsatisfactory. Until recently, common therapy methods, such as analgesic and anti-inflammatory treatments, were aimed to treat symptoms that cannot be radically cured. Mesenchymal stem cells (MSCs), i.e., mesoderm non-hematopoietic cells separated from bone marrow, adipose tissue, umbilical cord blood, etc., have been intensively explored as an emerging technique for the treatment of OA over the last few decades. According to existing research, MSCs may limit cartilage degradation in OA by interfering with cellular immunity and secreting a number of active chemicals. This study aimed to examine the potential mechanism of MSCs in the treatment of OA and conduct a thorough review of both preclinical and clinical data.

Layered Double Hydroxides: A Novel Promising 2D Nanomaterial for Bone Diseases Treatment.

Bone diseases including bone defects, bone infections, osteoarthritis, and bone tumors seriously affect life quality of the patient and bring serious economic burdens to social health management, for which the current clinical treatments bear dissatisfactory therapeutic effects. Biomaterial-based strategies have been widely applied in the treatment of orthopedic diseases but are still plagued by deficient bioreactivity. With the development of nanotechnology, layered double hydroxides (LDHs) with adjustable metal ion composition and alterable interlayer structure possessing charming physicochemical characteristics, versatile bioactive properties, and excellent drug loading and delivery capabilities arise widespread attention and have achieved considerable achievements for bone disease treatment in the last decade. However, to the authors' best knowledge, no review has comprehensively summarized the advances of LDHs in treating bone disease so far. Herein, the advantages of LDHs for orthopedic disorders treatment are outlined and the corresponding state-of-the-art achievements are summarized for the first time. The potential of LDHs-based nanocomposites for extended therapeutics for bone diseases is highlighted and perspectives for LDHs-based scaffold design are proposed for facilitated clinical translation.

A MgFe-LDH Nanosheet-Incorporated Smart Thermo-Responsive Hydrogel with Controllable Growth Factor Releasing Capability for Bone Regeneration.

Although growth factor (GF)-loaded hydrogels have been explored as promising materials in repairing bone defects, it still remains challenging to construct smart hydrogels with excellent gelation/mechanical properties as well as controllable GF releasing capability. Herein, the incorporation of bone morphogenetic protein 2 (BMP-2)-functionalized MgFe-layered double hydroxide (LDH) nanosheets into chitosan/silk fibroin (CS) hydrogels loaded with platelet-derived growth factor-BB (PDGF-BB) to construct a smart injectable thermo-responsive hydrogel (denoted as CSP-LB), which can achieve a burst release of PDGF-BB and a sustained release of BMP-2, for highly efficient bone regeneration is reported. The incorporation of MgFe-LDH in CS hydrogel not only shortens the gelation time and decreases sol-gel transition temperature, but also enhances the mechanical property of the hydrogel. Because of the sequential release of dual-GFs and sustained release of bioactive Mg2+ /Fe3+ ions, the in vitro experiments prove that the CSP-LB hydrogel exhibits excellent angiogenic and osteogenic properties compared with the CS hydrogel. In vivo experiments further prove that the CSP-LB hydrogel can significantly enhance bone regeneration with higher bone volume and mineral density than that of the CS hydrogel. This smart thermo-sensitive CSP-LB hydrogel possesses excellent gelation capability and angiogenic and osteogenic properties, thus providing a promising minimally invasive solution for bone defect treatment.

Bone tissue engineering for treating osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a devastating and complicated disease with an unclear etiology. Femoral head-preserving surgeries have been devoted to delaying and hindering the collapse of the femoral head since their introduction in the last century. However, the isolated femoral head-preserving surgeries cannot prevent the natural progression of ONFH, and the combination of autogenous or allogeneic bone grafting often leads to many undesired complications. To tackle this dilemma, bone tissue engineering has been widely developed to compensate for the deficiencies of these surgeries. During the last decades, great progress has been made in ingenious bone tissue engineering for ONFH treatment. Herein, we comprehensively summarize the state-of-the-art progress made in bone tissue engineering for ONFH treatment. The definition, classification, etiology, diagnosis, and current treatments of ONFH are first described. Then, the recent progress in the development of various bone-repairing biomaterials, including bioceramics, natural polymers, synthetic polymers, and metals, for treating ONFH is presented. Thereafter, regenerative therapies for ONFH treatment are also discussed. Finally, we give some personal insights on the current challenges of these therapeutic strategies in the clinic and the future development of bone tissue engineering for ONFH treatment.

Bone Density May Be a Promising Predictor for Blood Loss during Total Hip Arthroplasty.

BACKGROUND: Total hip arthroplasty (THA), which is performed mostly in elderly individuals, can result in substantial blood loss and thereby imposes a significant physical burden and risk of blood transfusion. The femoral neck cut and reamed acetabulum are the main sites of intraoperative bleeding. Whether the bone density in that region can be used to predict the amount of blood loss in THA is unknown. METHODS: We retrospectively analyzed adult patients undergoing primary THA in the Department of Orthopedics, Peking Union Medical College Hospital, from January 2018 to January 2020. All these patients underwent primary unilateral THA. Patients had their bone mineral density (BMD) recorded within the week before surgery and were stratified and analyzed for perioperative blood loss. Multivariable regressions were utilized to adjust for differences in demographics and comorbidities among groups. RESULTS: A total of 176 patients were included in the study. Intraoperative blood loss was 280.1 ± 119.56 mL. Pearson correlation analysis showed a significant correlation between blood loss and preoperative bone density of both the femoral greater trochanter (R = 0.245, p = 0.001) and the Ward's triangle (R = 0.181, p = 0.016). Stepwise multiple linear regression showed that preoperative bone density of the greater trochanter (p = 0.015, 95% CI: 0.004-0.049) and sex (p = 0.002) were independent risk factors for THA bleeding. The area under the receiver operating characteristic curve (AUROC) of the greater trochanter and Ward's triangle was 0.593 (95% CI: 0.507-0.678, p = 0.035) and 0.603 (95% CI: 0.519-0.688, p = 0.018), respectively. The cutoff T value on the femoral greater trochanter for predicting higher bleeding was -1.75. CONCLUSIONS: In THA patients, preoperative bone density values of the femoral greater trochanter and sex could be promising independent predictors for bleeding during surgery. Osteoporosis and female patients might have lower blood loss in the THA operation.

Surface Functionalization of Hydroxyapatite Scaffolds with MgAlEu-LDH Nanosheets for High-Performance Bone Regeneration.

Although artificial bone repair scaffolds, such as titanium alloy, bioactive glass, and hydroxyapatite (HAp), have been widely used for treatment of large-size bone defects or serious bone destruction, they normally exhibit unsatisfied bone repair efficiency because of their weak osteogenic and angiogenesis performance as well as poor cell crawling and adhesion properties. Herein, the surface functionalization of MgAlEu-layered double hydroxide (MAE-LDH) nanosheets on porous HAp scaffolds is reported as a simple and effective strategy to prepare HAp/MAE-LDH scaffolds for enhanced bone regeneration. The surface functionalization of MAE-LDHs on the porous HAp scaffold can significantly improve its surface roughness, specific surface, and hydrophilicity, thus effectively boosting the cells adhesion and osteogenic differentiation. Importantly, the MAE-LDHs grown on HAp scaffolds enable the sustained release of Mg2+ and Eu3+ ions for efficient bone repair and vascular regeneration. In vitro experiments suggest that the HAp/MAE-LDH scaffold presents much enhanced osteogenesis and angiogenesis properties in comparison with the pristine HAp scaffold. In vivo assays further reveal that the new bone mass and mineral density of HAp/MAE-LDH scaffold increased by 3.18- and 2.21-fold, respectively, than that of pristine HAp scaffold. The transcriptome sequencing analysis reveals that the HAp/MAE-LDH scaffold can activate the Wnt/ß-catenin signaling pathway to promote the osteogenic and angiogenic abilities.

LncRNA THUMPD3-AS1 enhances the proliferation and inflammatory response of chondrocytes in osteoarthritis.

OBJECTIVE: Long noncoding RNAs (lncRNAs) regulate the occurrence and development of osteoarthritis (OA), whereas the biological roles and mechanisms of the lncRNA THUMPD3-AS1 (THUMPD3 antisense RNA 1) in OA remain still unclear. This study described the role and molecular mechanism of lncRNA THUMPD3-AS1 in regulating OA biology. METHOD: The knee normal and OA cartilage tissues from ten participants were sequenced to reveal the differentially expressed lncRNAs. The interleukin (IL)-1ß-stimulated C28/I2 cell served as OA cells. Flow cytometry assays, Western blot, enzyme-linked immunosorbent assays were used for our experiments. RESULTS: The results revealed that lncRNA THUMPD3-AS1 was downregulated in OA cartilage tissues and IL-1ß-stimulated chondrocyte cell line. Overexpression of lncRNA THUMPD3-AS1 alleviated cell apoptosis and facilitated inflammatory responses, whereas knockdown had opposite effects. LncRNA THUMPD3-AS1 markedly increased the cyclin E2, cyclin-dependent kinase 4, B-cell lymphoma 2, tumor necrosis factor-α, nitric oxide, and IL-6 levels, and decreased the caspase-3 level. Furthermore, the target proteins of phosphorylation were identified as nuclear factor-κB p65 and mitogen-activated protein kinase p38, which could be indirectly suppressed by lncRNA THUMPD3-AS1 knockdown. CONCLUSION: Our findings highlight the different effects of lncRNA THUMPD3-AS1 on cell apoptosis and inflammatory response, which extend the multiple functions of lncRNA epigenetics in OA biology.

Naringin protects against perfluorooctane sulfonate-induced liver injury by modulating NRF2 and NF-κB in mice.

Perfluorooctane sulfonate (PFOS), a persistent organic pollutant, has been demonstrated to cause multiple toxicities. In this study, we explored the role of naringin (Nar) in alleviating PFOS-caused mouse liver injury and its potential mechanisms. Male mice were intragastrically administered PFOS (10 mg/kg/day) alone or with Nar (100 mg/kg/day) for 3 weeks. Nar supplementation led to resumption of elevated serum hepatic enzyme activities and increased relative liver weight in PFOS-challenged mice. Moreover, Nar treatment increased hepatic expression of transcription factor NRF2 protein and its regulated antioxidative enzyme genes heme oxygenase­1, superoxide dismutase and catalase, with an inhibition of malondialdehyde and hydrogen peroxide production. Furthermore, simultaneous administration of Nar suppressed PFOS-induced elevation in NF-κB activity and generation of inflammatory cytokines TNF-α and IL-6 in the liver. In addition, Nar enhanced anti-apoptotic Bcl-2 expression, decreased pro-apoptotic Bax expression and inhibited caspase­3 activation in liver tissue in mice exposed to PFOS. Our results indicate that Nar protects against PFOS-induced hepatotoxicity in mice via modulating oxidative, inflammatory and apoptotic pathways.