Current Status and Influencing Factors of Secondary Traumatic Stress in Emergency and Intensive Care nurses:A Cross-Sectional Analysis.

Objective: Secondary traumatic stress (STS) is stress caused by helping or wanting to help someone who has suffered a traumatic event. STS has adverse effects on nurses and their work, such as reduced career achievement, an increased staff turnover rate, inability to complete work, avoidance of contact with patients, mental exhaustion, negative emotions which seriously affect the quality of their work and life. The study to investigate secondary traumatic stress in emergency and intensive care nurses and analyze factors that influence it. Material and Methods: The study was a cross-sectional survey. Convenience sampling was used to select hospital emergency and intensive care department nurses (n=434) who met the inclusion and exclusion criteria from August to October 2021 to participate in this study. They provided demographic data and completed measures of secondary traumatic stress, emotional intelligence, anxiety and depression. Data analysis included independent samples t-tests, one-way analysis of variance, Pearson correlation analysis and multiple linear regression analysis. Results: Almost one-third (30.7%) of participants were at moderate risk for Secondary Traumatic Stress Scale or above, with high average scores on measures of anxiety (GAD-7 average = 6.05 ± 4.13), and depression (PHQ-9 average = 6.35 ± 4.85). The results of multiple linear regression analysis showed that the average daily amount of sleep in the past week, the number of night shifts in the past month, emotional intelligence, anxiety, and depression influenced secondary traumatic stress, explaining 70.8% of the variance. Conclusion: The STS of emergency and intensive care nurses in Changzhou is at a high level. Sleep time, number of night shifts and emotional intelligence are related to secondary traumatic stress and anxiety and depression significantly predicted the degree of secondary traumatic stress. Nurses need to master effective treatment methods for secondary traumatic stress, to improve their work efficiency and nursing quality and ensure nursing safety.

Gossypol Acetic Acid alleviates the Ferroptosis of Chondrocytes in Osteoarthritis by Inhibiting GPX4 Methylation.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease, usually accompanied by degeneration of the articular cartilage, fibrosis, bone hyperplasia around the joint, and damage to the entire articular surface. Gossypol is a natural phenolic compound isolated from the seed of cotton plants, and gossypol acetic acid (GAA) is a medicinal form of Gossypol. Recently, various biological activities of GAA, including anti-inflammatory and anti-tumor effects, have been widely reported. However, its effect on chondrocytes in OA has yet to be determined. METHODS: In this study, we investigated the effect of GAA on ferroptosis in OA chondrocytes. The effect of GAA on the cell viability and cytotoxicity of chondrocytes in rat cells was investigated using CCK8. Western blotting, Reverse-transcription PCR (RT-PCR), and immunofluorescence staining were used to elucidate the molecular mechanisms and signaling pathways of GAA inhibition of ferroptosis in OA chondrocytes. The effect of GAA on reactive oxygen species (ROS) production and lipid peroxidation levels in chondrocytes was examined using dihydroethidium (DHE) staining and fluorescent dye BODIPY581/591 C11. in vivo, micro-CT imaging, hematoxylin and eosin staining, Safranin O-Fast staining, and immunohistochemistry were performed to evaluate the effects of GAA on OA cartilage. RESULTS: The results showed that GAA treatment regulated the expression of chondrocyte extracellular matrix (ECM) related factors, including ADAMTS5, MMP13, SOX9, Aggrecan, and COL1A2 and reduced the ROS and lipid peroxidation levels. Besides, Erastin could reverse the effects of GAA on chondrocytes. Similar to GAA, 5-AZA caused the reduction of ROS and lipid peroxidation levels and reversed the effect of IL-1ß on the expression of ECM-related factors in OA chondrocytes. The above results clarified that GAA alleviated the ferroptosis of chondrocytes in OA by inhibiting GPX4 methylation. CONCLUSION: Our findings revealed that GAA might be developed as a drug for treating OA clinically.

Calcipotriol suppresses GPX4-mediated ferroptosis in OA chondrocytes by blocking the TGF-ß1 pathway.

Globally, tens of millions of individuals experience osteoarthritis (OA), a degenerative joint condition for which a definitive cure is currently lacking. This condition is characterized by joint inflammation and the progressive deterioration of articular cartilage. In this study, western blotting, quantitative reverse-transcription polymerase chain reaction, and immunofluorescence analysis were performed to elucidate the molecular mechanisms by which calcipotriol alleviates chondrocyte ferroptosis. The effect of calcipotriol on reactive oxygen species and lipid peroxidation levels in chondrocytes was assessed using dihydroethidium staining and the fluorescent dye BODIPY. To replicate OA, the destabilized medial meniscus model was employed, followed by the injection of calcipotriol into the knee articular cavity. Morphological analysis was conducted through hematoxylin and eosin staining, safranin O-Fast green staining, and micro-computed tomography analysis. Immunohistochemical analysis was performed to validate the effect of calcipotriol in vivo. Our results demonstrate that the expression of SOX9, col2a1, and Aggrecan, as well as MMP13 and ADAMTS5 protein expression levels, decrease upon treatment with calcipotriol in interleukin-1ß stimulated chondrocytes. Despite these promising outcomes, the exact mechanism underlying calcipotriol's therapeutic effect on OA remains uncertain. We discovered that calcipotriol inhibits chondrocyte GPX4-mediated ferroptosis by suppressing the expression of transforming growth factor-ß1. Furthermore, our study established an in vivo model of OA using rats with medial meniscus instability. Our experiments on rats with OA revealed that intra-articular calcipotriol injection significantly reduces cartilage degradation caused by the disease. Our findings suggest that calcipotriol can mitigate OA by impeding GPX4-mediated ferroptosis of chondrocytes, achieved through the suppression of the TGF-ß1 pathway.

CK1ε drives osteogenic differentiation of bone marrow mesenchymal stem cells via activating Wnt/ß-catenin pathway.

The treatment of bone defects is a difficult problem in orthopedics. At present, the treatment mainly relies on autologous or allogeneic bone transplantation, which may lead to some complications such as foreign body rejection, local infection, pain, or numbness at the bone donor site. Local injection of conservative therapy to treat bone defects is one of the research hotspots at present. Bone marrow mesenchymal stem cells (BMSCs) can self-renew, significantly proliferate, and differentiate into various types of cells. Although it has been reported that CK1ε could mediate the Wnt/ß-catenin pathway, leading to the development of the diseases, whether CK1ε plays a role in bone regeneration through the Wnt/ß-catenin pathway has rarely been reported. The purpose of this study was to investigate whether CK1ε was involved in the osteogenic differentiation (OD) of BMSCs through the Wnt/ß-catenin pathway and explore the mechanism. We used quantitative reverse transcription-polymerase chain reaction (qRT-qPCR), Western blots, immunofluorescence, alkaline phosphatase, and alizarin red staining to detect the effect of CK1ε on the OD of BMSCs and the Wnt/ß-catenin signaling pathway. CK1ε was highly expressed in BMSCs with OD, and our study further demonstrated that CK1ε might promote the OD of BMSCs by activating DLV2 phosphorylation, initiating Wnt signaling downstream, and activating ß-catenin nuclear transfer. In addition, by locally injecting a CK1ε-carrying adeno-associated virus (AAV5- CK1ε) into a femoral condyle defect rat model, the overexpression of CK1ε significantly promoted bone repair. Our data show that CK1ε was involved in the regulation of OD by mediating Wnt/ß-catenin. This may provide a new strategy for the treatment of bone defects.

Adipokines regulate mesenchymal stem cell osteogenic differentiation.

Mesenchymal stem cells (MSCs) can differentiate into various tissue cell types including bone, adipose, cartilage, and muscle. Among those, osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies. Moreover, the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing. Recently, with the gradual recognition of adipokines, the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism, inflammation, immune regulation, energy disorders, and bone homeostasis. At the same time, the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely. Therefore, this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs, emphasizing bone formation and bone regeneration.

Resistin targets TAZ to promote osteogenic differentiation through PI3K/AKT/mTOR pathway.

Osteogenic differentiation (OD) of bone marrow mesenchymal stem cells (BMSCs) contributes significantly to the regeneration of bone defects. Resistin, an adipose tissue-specific secretory factor, has been shown to involve many different functions, including metabolism, inflammation, cancer, and bone remodeling. However, the effects and mechanisms of resistin on OD of BMSCs remain unclear. Herein, we demonstrated that resistin was highly expressed in BMSCs with OD. Upregulation of resistin contributed to the progression of OD of BMSCs by activating PI3K/AKT/mTOR signaling pathway. In addition, resistin facilitated OD by targeting transcriptional co-activator with PDZ-binding motif (TAZ). In a rat femoral condyle bone defect model, local injection of resistin significantly promoted bone repair and improved bone formation. This work contributes to better understanding the mechanism of resistin directly involved in the OD and might provide a new therapeutic strategy for bone defect regeneration.

Functionalized acellular periosteum guides stem cell homing to promote bone defect repair.

The periosteum plays a key role in bone tissue regeneration, especially in the promotion and protection of new bones. However, among the bone repair materials, many biomimetic artificial periosteum lack the natural periosteal structure, stem cells, and immunoregulation required for bone regeneration. In this study, we used natural periosteum to produce acellular periosteum. To retain the appropriate cell survival structure and immunomodulatory proteins, we grafted the functional polypeptide SKP on the surface collagen of the periosteum via an amide bond, providing the acellular periosteum with the ability to recruit mesenchymal stem cells. Thus, we developed a biomimetic periosteum (DP-SKP) with the ability to promote stem cell homing and immunoregulation in vivo. Compared to the blank and simple decellularized periosteum groups, DP-SKP was more conducive to stem cell adhesion, growth, and osteogenic differentiation in vitro. Additionally, compared with the other two groups, DP-SKP significantly promoted mesenchymal stem cell homing to the periosteal transplantation site, improved the bone immune microenvironment, and accelerated new lamellar bone formation in the critical size defect of rabbit skulls in vivo. Therefore, this acellular periosteum with a mesenchymal stem cell homing effect is expected to be used as an extracellular artificial periosteum in clinical practice.

Isorhynchophylline alleviates cartilage degeneration in osteoarthritis by activating autophagy of chondrocytes.

CONTEXT: Osteoarthritis is a common degenerative disease, the cause of it is still unknown, and the treatment mainly focuses on improving symptoms. Studies have found that Isorhynchophylline (Isorhy) has antioxidant, anti-inflammatory, antiproliferative and neuroprotective effects. OBJECTIVE: This study investigates the role and mechanism of Isorhy in OA. METHODS: The destabilized medial meniscus model was used to mimic OA. Fifteen male Sprague Dawley rats were partitioned into three portions: Normal group, OA group (surgery; normal saline treatment) and OA + Isorhy group (surgery; 50 µM Isorhy treatment) were performed on the first day of every week from the 5th to the 8th week after surgery. After 4 weeks of drug treatment, the rats have been processed without debridement of the knee specimens and fixed using 4% paraformaldehyde for two days. The morphological analysis was performed by H&E, Safranin O-Fast green staining and micro-CT analysis. The specimens were researched employing Micro-CT. In the part of the aggregate methods that were evaluated by qRT-PCR and western blot of the following proteins LC3II/LC3I, Beclin-1, ATG5, ATG7, MMP3 andMMP13. Akt/PI3K signaling related proteins (p-AKT, AKT, p-PI3K, PI3K, p-mTOR, mTOR) were detected by Western blot. BECLIN1 and MMP3 were detected by Immunofluorescence assay. RESULTS: In this present research, it was proved that autophagy-related and cartilage matrix-related proteins in osteoarthritis could be regulated by Isorhynchophylline treatment. The transcriptome sequencing results suggested the regulation was closely associated with PI3K/AKT/mTOR pathway, thereby alleviating osteoarticular inflammation. In-depth study showed that Isorhy could also affect OA in rat OA models, that was indicated by H&E, Safranin O-Fast green staining, and also micro-CT analysis. CONCLUSION: Our findings indicated that Isorhy could be regarded as a prospective candidate for OA treatment.

Effect of pharmacist intervention on antibiotic prophylaxis in orthopedic internal fixation: A retrospective study.

BACKGROUND: Despite the availability of guidelines and official policies, antibiotic prophylaxis in clean surgery remains suboptimal. OBJECTIVE: The aim of this study was to evaluate the clinical effects and cost-effectiveness of pharmacist-led intervention in the perioperative anti-infection prophylaxis of patients undergoing orthopedic internal fixation. METHODS: We performed a retrospective analysis based on the medical records of internal fixation surgery in a tertiary hospital from July 2019 to June 2020. Data were divided into two groups based on whether a full-time pharmacist participated in the treatment. The research parameters included use of antibiotics, rationality of medication, postoperative complications, and related cost. To deal with selection bias, propensity score matching method was employed at a ratio of 1:1. Meanwhile, a cost-effectiveness analysis was used to evaluate the impact of pharmacist intervention on antibiotic prevention in internal fixation surgery. RESULTS: A total of 537 participants were included in this study. After matching, 236 patients were comparable in each group. During the pharmacist intervention period, less pharmacologic prophylaxis (96.6% vs 100.0%, p = 0.007) and shorter prophylaxis duration (1.60 vs 2.28 days, p < 0.001) were observed. The reasonable rate increased dramatically in usage and dosage (96.6% vs 83.9%, p < 0.001), timing of administration (94.5% vs 78.4%, p < 0.001) and medication duration (64.4% vs 37.7%, p < 0.001). In addition, pharmacist intervention yielded net economic benefits. A remarkable reduction was observed in average length of stay (10.43 vs 11.14 days, p = 0.012), drug cost ($610.57 vs $706.60, p = 0.001) and defined daily doses (2.31 vs 3.27, p < 0.001). The cost-effectiveness ratios, divided drug cost savings by cost of pharmacist time, were 28:1 for drug and 2:1 for antibiotics, respectively. CONCLUSION: Pharmacist-driven antibiotic stewardship for orthopedic internal fixation patients improved compliance with peri-procedure antibiotic prophylaxis, and reduced the cost and utilization of antibiotics. This helped to bring significant clinical and economic benefits.

Bridged combined fixation system versus locking plate in the treatment of patients with implant periprosthetic refracture following proximal femoral fracture surgery: A retrospective observational study.

Locking plate (LP) re-fixation is mainly used to treat postoperative implant periprosthetic refractures; however, the extensive trauma and the fixation form of LP make the operation difficult. The bridge combined fixation system (BCFS) is a new clip-rod internal fixation system, and its clinical application is in its infancy. To compare the clinical effect of BCFS and LP in the treatment of geriatric postoperative implant periprosthetic refracture following proximal femoral fracture surgery. Thirty-two patients (14 with BCFS and 18 with LP) with postoperative implant periprosthetic refracture following proximal femoral fracture surgery, who underwent surgery in our hospital, were analyzed retrospectively. The incision length, operation time, intraoperative bleeding volume, postoperative drainage volume, postoperative hospital stay, fracture healing time and complications of each patient were recorded. Regular radiographs were taken after the operation to evaluate the fracture reduction and fixation. All the patients were followed for 12 months to evaluate their limb function by Johner-Wruhs scoring criteria. The patients were followed for an average of 24.1 months, and all achieved bony union, with no complications such as infection, nonunion, and internal fixation instrument falling off and loosening after the operation. Delayed healing occurred in two cases in the LP group. The average value of surgical incision length, operation time, postoperative hospitalization time and fracture healing time in the BCFS group were significantly smaller than those in the LP group, accompanied by a decrease in intraoperative bleeding and postoperative drainage volumes (P < .05). The rate of limb function in the BCFS group (85.7%) was higher than that in the LP group (83.3%), with no significance (P > .05). The BCFS in the refracture around the implant of the proximal femoral fracture exhibited many advantages such as simple operation, strong plasticity, effective reduction of surgical trauma, promotion of fracture healing and early functional rehabilitation, etc, making it an advantageous clinical application.

Artemisinin relieves osteoarthritis by activating mitochondrial autophagy through reducing TNFSF11 expression and inhibiting PI3K/AKT/mTOR signaling in cartilage.

Osteoarthritis (OA) is a widespread chronic degenerative joint disease characterized by the degeneration of articular cartilage or inflamed joints. Our findings indicated that treatment with artemisinin (AT) downregulates the protein levels of MMP3, MMP13, and ADAMTS5, which are cartilage degradation-related proteins in OA, and inhibits the expression of inflammatory factors in interleukin-1ß (IL-1ß)-stimulated chondrocytes. However, the mechanism of the role of AT in OA remains unclear. Here, we performed gene sequencing and bioinformatics analysis in control, OA, and OA + AT groups to demonstrate that several mRNA candidates were enriched in the PI3K/AKT/mTOR signaling pathway, and TNFSF11 was significantly downregulated after AT treatment. TNFSF11 was downregulated in the OA + AT group, whereas it was upregulated in rat OA tissues and OA chondrocytes. Therefore, we confirmed that TNFSF11 was the target gene of AT. In addition, our study revealed that AT relieved cartilage degradation and defection by activating mitochondrial autophagy via inhibiting the PI3K/AKT/mTOR signaling pathway in IL-1ß-induced chondrocytes. Furthermore, an OA model was established in rats with medial meniscus destabilization. Injecting AT into the knee joints of OA rat alleviated surgical resection-induced cartilage destruction. Thus, these findings revealed that AT relieves OA by activating mitochondrial autophagy by reducing TNFSF11 expression and inhibiting PI3K/AKT/mTOR signaling.

SEMA6D, Negatively Regulated by miR-7, Contributes to C28/I2 chondrocyte's Catabolic and Anabolic Activities via p38 Signaling Pathway.

MiR-7 has been recognized as an osteoarthritis (OA-)-promoting factor, but the specific downstream pathway of miR-7 still remains unknown. Further investigation of the molecular regulatory mechanism of miR-7 might help develop a novel therapeutic method for OA. In this study, we revealed that Semaphorin 6D (SEMA6D) was a direct target gene of miR-7 and presented a negative regulatory relation with SEMA6D in vitro and in vivo. SEMA6D could improve OA in rat OA models, as indicated by H&E and Safranin O-Fast green staining, and also µCT analysis. Further evaluation of SEMA6D suggested that SEMA6D promotes the anabolism and reduces the catabolism of C28/I2 chondrocytes via inhibiting the activation of the p38 pathway. The present research illustrated that SEMA6D is a negatively regulatory factor of miR-7 and a pivotal mediator of catabolism and anabolism in C28/I2 chondrocytes. SEMA6D exerts its function via inhibiting the activation of the p38 pathway.

Comparison of the Effectiveness of Simple Plate Fixation and Plate Combined with Local Fixation of Broken Ends in the Treatment of Oblique Fracture of Midshaft Clavicle.

OBJECTIVE: To compare the clinical efficacy of performing simple plate fixation with that using a plate combined with fracture end fixation to investigate the necessity of fracture end fixation outside the plate in cases of oblique fracture of the middle clavicle. METHODS: This was a retrospective follow-up study of patients with middle clavicle oblique fractures (Robinson types 2A1 and 2A2) between 2015 and 2020. Patients were divided into two groups according to their treatment options: the simple plate fixation (SPF) group (n = 79; 43 men and 36 women; average age, 46.37 ± 14.54 years) and the plate combined with fracture local fixation (PLFP) group (n = 81; 36 men and 45 women; average age, 48.42 ± 12.55 years). Intraoperative blood loss, operation time, postoperative fracture healing time, postoperative shoulder function score (Constant-Murley and disabilities of the arm, shoulder, and hand [DASH] scores), clinical complications, and postoperative subjective satisfaction were compared between the two groups. RESULTS: One hundred sixty patients with a sufficient follow-up period were included in the final analysis: 79 in the SPF group (follow-up time: 16.24 ± 3.94 months) and 81 in the PLFP group (follow-up time: 16.15 ± 3.43 months). Age, sex, body mass index, follow-up duration, fracture classification, and cause of injury were not significantly different between the two groups. There was no significant difference in blood loss, Constant-Murley and DASH scores, follow-up period, and postoperative subjective satisfaction between the two groups (P > 0.05). The fracture healing time was shorter in the PLFP group than in the SPF group (4.41 ± 0.99 vs. 4.87 ± 1.60 months, P < 0.05), but the operation duration was longer in the PLFP group than in the SPF group (65.48 ± 16.48 min, P < 0.05). There were seven (complication rate, 8.86%) and five (complication rate, 6.17%) cases that had complications in the SPF and PLFP groups, respectively. There was no significant difference in the complication rates between the two groups (P > 0.05). CONCLUSION: Although the healing time was shorter in the PLFP group than in the SPF group, the clinical efficiency of the two methods in the treatment of oblique fracture of the middle clavicle was similar.

The effects of Peptide Mel4-coated titanium plates on infection rabbits after internal fixation of open fractures.

INTRODUCTION: Infection after internal fixation surgery is an orthopedic serious complication which affect the fracture healing. The primary objective of this study was to verify the effects of a Peptide Mel4-coated titanium plate applied in the treatment of infection after internal fixation of open fracture. MATERIALS AND METHODS: Eighty-eight rabbits were intravenously inoculated with Staphylococcus aureus or Pseudomonas aeruginosa suspensions. Bacterial cultures were obtained from titanium plates at 1st, 3rd, 5th, 7th and 9th days. Blood samples were collected at 1st, 3rd, 5th, 7th and 9th days after the infection. RESULTS: Mel4-coated titanium plates have significant inhibitory effects on Staphylococcus aureus and Pseudomonas aeruginosa (P < 0.05), and there are significant differences in serum IL-1 and TNF-α levels (P < 0.05). CONCLUSION: We suggest that the use of Mel4-coated titanium plates may be a promising way to control postoperative infection of open fracture in vivo.

KLF4, negatively regulated by miR-7, suppresses osteoarthritis development via activating TGF-ß1 signaling.

Osteoarthritis (OA) is a chronic degenerative disease which seriously affects the patients' daily activities and quality of life. In our previous findings, we demonstrated that overexpression of miR-7 was found in OA and promoted OA development. Its exact mechanism remains unclear. Herein, we confirmed that KLF4 was the target gene of miR-7 and KLF4 was down-regulated in human OA tissues and OA chondrocyte. KLF4 was negatively modulated by miR-7 via dual luciferase reporter assay. Cartilage-specific genes (SOX9, COL2A1, RUNX2, MMP13) are crucial regulators in cartilage degeneration. Through qRT-PCR and western blot, we observed that KLF4 overexpression could increase the expression of SOX9 and COL2A1, decrease RUNX2 and MMP13. In the meanwhile, miR-7 was proven to regulate the expression of the above cartilage-specific genes by targeting KLF4, which demonstrated KLF4 could prevent OA development. Subsequently, KLF4 also activated TGF-ß1 signaling pathway, thereby affecting OA progression. Excessive KLF4 could up-regulate TGF-ß1 and p-Smad2/3 level, and Smad4 level was prevented in OA chondrocytes, while adding TGF-ß1 inhibitor SB525334 could rescue this impact, along with reduced TGF-ß1 and p-Smad2/3 level, enriched Smad4 level. KLF4 could also reverse the effect of miR-7 on TGF-ß1 signaling. Besides, it was confirmed that KLF4 could improve OA in rat OA models by HE and Safranin O-Fast green staining, and immunohistochemistry. Collectively, our findings will give more detailed evidence about miR-7 and KLF4 in OA diagnosis and treatment.

miR-7/EGFR/MEGF9 axis regulates cartilage degradation in osteoarthritis via PI3K/AKT/mTOR signaling pathway.

Osteoarthritis (OA) is a common degenerative disease in middle-aged and elderly people. Our previous study has proved that microRNA-7 (miR-7) exacerbated the OA process. This study was aimed to explore the downstream genes and mechanism regulated by miR-7 to affect OA. Multiple EGF-like-domains 9 (MEGF9) was the predicted target of miR-7 by databases. Luciferase report experiment results confirmed that MEGF9 could bind to miR-7. Among the 10 collected pairs of OA and healthy samples, the expression levels of miR-7 and MEGF9 were both up-regulated when compared with healthy subjects by qRT-PCR and immunohistochemistry (IHC). The increased MEGF9 levels were due to the interaction with epidermal growth factor receptor (EGFR) by co-immunoprecipitation. Evaluations found that upregulation of miR-7 or MEGF9 can increase the expression of EGFR, matrix metalloproteinase-13 (MMP-13) and a disintegrin like and metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS-5), so as to aggravate cartilage degradation. In addition, this effect induced by miR-7/EGFR/MEGF9 axis was by activation of PI3K/AKT signaling. The IHC and western blot assay results on OA model mice also demonstrated that miR-7/EGFR/MEGF9 axis regulated cartilage degradation in vivo. In summary, miR-7/EGFR/MEGF9 axis may perform a crucial function in the regulation of OA, providing potential for OA treatment.

IDUA Gene Variants and Response to Zoledronic Acid Treatment in Chinese Women with Postmenopausal Osteoporosis.

PURPOSE: Alpha-L-iduronidase (IDUA) rs3755955 and rs6831280 polymorphisms have been demonstrated to be associated with bone mineral density (BMD). However, no study has investigated the association of these two polymorphisms with osteoporosis (OP) susceptibility in Chinese postmenopausal women. PATIENTS AND METHODS: IDUA gene polymorphisms were genotyped in 278 women with OP and 303 healthy controls via polymerase chain reaction and Sanger sequencing. RESULTS: Our data indicated that IDUA rs3755955 and rs6831280 polymorphisms increased the risk of OP in homozygous, dominant, and allelic models. We observed lower lumbar spine BMD in younger women with the AA genotype of rs3755955 polymorphism. Finally, mutant genotypes with rs6831280 polymorphism were more sensitive to zoledronic acid treatment, and the treatment effect was significant in terms of BMD levels. CONCLUSION: In conclusion, IDUA rs3755955 and rs6831280 polymorphisms demonstrated susceptibility to OP in Chinese postmenopausal women. IDUA rs6831280 polymorphism caused differences in response to zoledronic acid treatment.

The elevated expression of IL-38 serves as an anti-inflammatory factor in osteoarthritis and its protective effect in osteoarthritic chondrocytes.

The objective of this study is to investigate the role of IL-38 in osteoarthritis (OA). IL-38 levels in serum and synovial fluid (SF) of patients with OA were examined to identify the correlation between IL-38 expression and OA activity and to determine its anti-inflammatory effects in IL-1ß-induced chondrocytes. A total of 75 patients with OA who underwent joint replacement surgery and 25 age- and sex-matched healthy volunteers were recruited. The levels of IL-38 in serum and SF are shown to be significant elevated in OA patients compared with that of healthy controls. Serum and SF IL-38 levels of OA patients are positively correlated with Kellgren-Lawrence (K-L) grades 2 to 3, as well as with pro-inflammatory cytokines IL-6, IL-23, and TNF-α, but are negatively correlated with the anti-inflammatory cytokine IL-10 in K-L grades 3 to 4. Furthermore, overexpression of IL-38 in vitro is shown to attenuate the expression of pro-inflammatory cytokines such as COX-2, IL-6, IL-8, IL-36Ra, IL-36α/ß/γ, iNOS, and TNF-α, as well as matrix degrading enzymes such as MMP3, MMP13, and ADAMTS5, and apoptosis-related indicators Bax/Bcl-2, cleaved caspase 3/pro-caspase 3, and cleaved caspase 9/pro-caspase 9. IL-38 overexpression also reduces expression of the signaling proteins p-p38, p-p65, p-JNK, and RhoA significantly. Taken together, our results show that expression of IL-38 is increased in OA tissues and OA rat chondrocytes, and is positively correlated with early disease activity. This increased IL-38 expression lead to the inactivation of MAPK, NF-κB, JNK, and RhoA signaling pathways, which might have impletion on OA chondrocytes apoptosis, degradation and inflammatory effect. Thus, IL-38 probably serves as a novel therapeutic target for the treatment of OA.

The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis.

Background: Rheumatoid arthritis (RA) is related to several pivotal susceptibility genes, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecule (CD80/CD86) genes. Although the connection between polymorphisms of CTLA-4 and CD86 genes in different populations of RA have been studied extensively, the results are controversial. Objective: To clarify the correlation in the Chinese Han population between CTLA-4, CD80/86, and CD28 gene polymorphisms, and RA susceptibility. Methods: A case-control study (574 RA patients and 804 controls) was conducted to determine the correlation between CTLA-4 rs231775 and rs16840252 gene polymorphisms, CD86 rs17281995 gene polymorphisms, and the risk of RA for the Chinese Han population. Furthermore, an additional meta-analysis, including three single nucleotide polymorphisms (SNPs) (CTLA-4 rs231775, CTLA-4 rs3087243, and CTLA-4 rs5742909) from 32 citations, including 43 studies, 24,703 cases and 23,825 controls was performed to elucidate the relationship between known SNPs in the CTLA-4 genes and RA for more robust conclusions. Results: The results showed that CTLA-4 rs231775 gene polymorphism decreased the RA risk (GA vs. AA, OR = 0.77, P = 0.025), whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA susceptibility. Stratification analyses by RF, ACPA, CRP, ESR, DAS28, and functional class identified significant associations for CTLA-4 rs231775 and rs16840252 gene polymorphisms in the RF-positive and RF-negative groups. A meta-analysis of the literature on CTLA-4 gene polymorphisms and RA risk revealed that the risk of RA was decreased by CTLA-4 rs231775 gene polymorphisms. Conclusions: The CTLA-4 rs231775 gene polymorphism decreased the risk of RA, whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA risk. A meta-analysis indicated that CTLA-4 rs231775 and rs3087243 gene polymorphisms decreased the risk of RA. To support these analytical results, additional clinical cases should be investigated in further studies.

Down-regulated ciRS-7/up-regulated miR-7 axis aggravated cartilage degradation and autophagy defection by PI3K/AKT/mTOR activation mediated by IL-17A in osteoarthritis.

Osteoarthritis (OA) is one of the most painful and widespread chronic degenerative joint diseases and is characterized by destructed articular cartilage and inflamed joints. Previously, our findings indicated that circular RNA ciRS-7 (ciRS-7)/microRNA 7 (miR-7) axis is abnormally expressed in OA, and regulates proliferation, inflammatory responses, and apoptosis of interleukin-1ß (IL-1ß)-stimulated chondrocytes. However, its underlying role in OA remains unknown. In this study, we first validated cartilage degradation and defection of autophagy in samples of OA patients. IL-1ß initially stimulated autophagy of chondrocytes, and ultimately significantly suppressed autophagy. Upregulated ciRS-7/down-regulated miR-7 aggravated IL-1ß-induced cartilage degradation, and restrained autophagy in vitro. Gene sequencing and bioinformatics analysis performed on a control group, IL-1ß group, and IL-1ß+miR-7-mimics group demonstrated that seven of the most significant mRNA candidates were enriched in the interleukin-17 (IL-17) signaling pathway. Increased IL-17A levels were also observed by qRT-PCR and ELISA. In addition, it was revealed that the ciRS-7/miR-7 axis ameliorated cartilage degradation and defection of autophagy by PI3K/AKT/mTOR activation in IL-1ß-induced chondrocytes. Furthermore, an OA model was established in rats with medial meniscus destabilization. miR-7-siRNA-expressing lentiviruses alleviated surgical resection-induced cartilage destruction of OA mice, whereas miR-7 mimics worsened the effects. Thus, these findings revealed that the mechanism of the ciRS-7/miR-7 axis involved regulating OA progression and provided valuable directions for OA treatment.