Prognostic utility of sTREM-1 in predicting early neurological deterioration in patients with acute ischemic stroke treated without reperfusion therapy.

OBJECTIVE: Serum triggering receptor expressed on myeloid cells type 1 (sTREM-1) is a new type of immunoglobulin superfamily receptor related to inflammation that aggravates brain injury. This study aimed to assess the clinical value of sTREM-1 in predicting early neurological deterioration in patients with acute ischemic stroke (AIS) treated without reperfusion therapy. METHODS: This prospective cohort study enrolled 315 patients with acute ischemic stroke admitted to the Affiliated Taizhou People's Hospital of Nanjing Medical University between October 2020 and October 2022. The study excluded patients treated with reperfusion therapy. sTREM-1 levels were evaluated within 24 h of the acute ischemic stroke. Early neurological deterioration (END) was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points within three days after admission. Multivariable analyses were used to investigate the relationship between sTREM-1 levels and END. RESULTS: A total of 81 (25.7 %) patients had early neurological deterioration. Patients in the END group had a higher NIHSS score at admission (P =0.007), CRP levels (P =0.011), white blood cell count (P =0.002), fasting blood glucose levels (P =0.028), and sTREM-1 levels (P <0.001). After adjusting for confounders, higher sTREM-1 levels were significantly associated with an increased risk of early neurological deterioration (OR, 1.98; 95 % CI, 1.17-3.38, P=0.012). Moreover, sTREM-1 levels efficiently differentiated END (area under the curve: 0.779; 95 % CI: 0.731-0.822). Furthermore, the results showed significant differences between the high sTREM-1 group and the low sTREM-1 group in NIHSS scores (P=0.019), C-reactive protein (P=0.018), white blood cell count (P=0.013), and the incidence of early neurological deterioration (P<0.001). According to the multivariate logistic regression model, we discovered that the high sTREM-1 group was a significant independent predictor of early neurological deterioration incidence (OR, 4.19; 95 % CI, 1.46-9.84; P= 0.003). CONCLUSION: sTREM-1 could be a potential biomarker for predicting early neurological deterioration in AIS patients not treated with reperfusion therapy.

RUNX1 Ameliorates Rheumatoid Arthritis Progression through Epigenetic Inhibition of LRRC15.

Leucine-rich repeat containing 15 (LRRC15) has been identified as a contributing factor for cartilage damage in osteoarthritis; however, its involvement in rheumatoid arthritis (RA) and the underlying mechanisms have not been well characterized. The purpose of this study was to explore the function of LRRC15 in RA-associated fibroblast-like synoviocytes (RA-FLS) and in mice with collagen-induced arthritis (CIA) and to dissect the epigenetic mechanisms involved. LRRC15 was overexpressed in the synovial tissues of patients with RA, and LRRC15 overexpression was associated with increased proliferative, migratory, invasive, and angiogenic capacities of RA-FLS and accelerated release of pro-inflammatory cytokines. LRRC15 knockdown significantly inhibited synovial proliferation and reduced bone invasion and destruction in CIA mice. Runt-related transcription factor 1 (RUNX1) transcriptionally represses LRRC15 by binding to core-binding factor subunit beta (CBF-ß). Overexpression of RUNX1 significantly inhibited the invasive phenotype of RA-FLS and suppressed the expression of proinflammatory cytokines. Conversely, the effects of RUNX1 were significantly reversed after overexpression of LRRC15 or inhibition of RUNX1-CBF-ß interactions. Therefore, we demonstrated that RUNX1-mediated transcriptional repression of LRRC15 inhibited the development of RA, which may have therapeutic effects for RA patients.

Transcription factor Krüppel-like factor 5-regulated N-myc downstream-regulated gene 2 reduces IL-1ß-induced chondrocyte inflammatory injury and extracellular matrix degradation.

Previous research has identified N-myc downstream-regulated gene 2 (NDRG2) as one of the differentially expressed genes common to rat models of osteoarthritis (OA) and human OA. The purpose of this study was to investigate the role of NDRG2 in OA. In this study, an in vitro OA model was constructed by challenging ATDC5 chondrocytes with 10 ng/ml IL-1ß. After transfection of pcDNA3.1(+)/NDRG2, qPCR and western blot were performed to assay NDRG2 expression. The analyses of cell viability, apoptosis and inflammatory molecule expression were employed respectively by CCK-8, TUNEL and ELISA. The protein expression related to apoptosis, inflammation or extracellular matrix (ECM) degradation was detected by western blot. The binding of Krüppel-like factor 5 (KLF5) to NDRG2 promoter was verified by means of dual-luciferase reporter assay. After overexpression of both NDRG2 and KLF5 in IL-1ß-stimulated ATDC5 chondrocytes, corresponding assays were performed to examine cell viability, apoptosis, inflammatory response and ECM degradation. In ATDC5 chondrocytes challenged with IL-1ß, NDRG2 expression was much lower than that in the control group, whereas it's overexpression helped restored cell viability and reduce cell apoptosis, inflammatory response and ECM degradation. It was also observed that KLF5 expression was decreased in IL-1ß-stimulated ATDC5 chondrocytes, and that KLF5 bound to the NDRG2 promoter. Importantly, overexpressing KLF5 could reverse the protective effect of NDRG2 overexpression on IL-1ß-stimulated ATDC5. Overall, NDRG2 could be transcriptionally regulated by transcription factor KLF5 and may play a protective role against chondrocyte the inflammatory response and ECM degradation in OA.

Anthropometric measurements of patellar ridge using computed tomography-based three-dimensional computer models.

BACKGROUND: The objectives of this study were to investigate the anatomic morphology of patellar ridge using computed tomography-based three-dimensional (3D) computer models and to assess the center of the patellar ridge after virtual resections. METHODS: We selected 80 patients, 40 males (age, 33.2±6.8 years) and 40 females (age, 30.6±7.2 years), who were slightly symptomatic with soft tissue injury of the knee joint. The right or left knees were scanned by computed tomography (CT). The CT data of 160 knees was used to construct 3D computer models by image analysis software (Mimics). Variables such as the angle between the patellar ridge and patellar long axis, the distance between the center of the patellar ridge and the center of patellar cut after virtual resections were measured. We detect differences between the sides and genders with the 3D computer models by Student's t test. Simple linear regression and correlation test was used to correlate the patellar ridge center to the center of the patellar cut. RESULTS: According to the available data, there were significant gender differences in the length and width of patellar cut after virtual resections even with strict control for the height and weight of the patients. The angle between the patellar ridge and the patellar long axis was 11.24° ± 3.62°. The angle in male patients was 10.17° ± 4.82°, and it was 12.28°± 3.78° in female patients. The morphological difference was statistically significant (P < 0.05). After using the subchondral method to virtually resect the patellae, with reference to the center of the patellar cut, the center of the patellar ridge lies superiorly and medially in 88.75%, inferiorly and medially in 8.75%, laterally and superiorly in 2.5%, and in no case laterally and inferiorly. The intra-observer reliability regarding the dimensional measurements was excellent in this study. CONCLUSIONS: Advances in 3D computer models had resulted in the availability of preoperative measurement and virtual planning. The anthropometric dimensions of this study could provide general information for guiding surgical management of the patella in total knee arthroplasty (TKA) and were useful in designing patellar implants. CLINICAL RELEVANCE: The placement of the patellar component during TKA differs from one patella to another. The anatomic morphology information of the patellar ridge is helpful for surgeons to perform patellar resurfacing in TKA.

Protective Effect of Hydrogen Gas on Mouse Hind Limb Ischemia-Reperfusion Injury.

BACKGROUND: The aim of this study was to investigate the mechanism of hydrogen gas on hind limb IR injury. METHODS: Male C57BL/6 mice were randomly divided into three groups: sham group (Sham), ischemia-reperfusion group (IR), IR plus H2 inhalation group (IR + H2). IR was induced by interrupting hind limb blood flow for 3h, followed by 4h of reperfusion, and H2 was administered by inhalation throughout the reperfusion process. Our data show that H2 inhalation could significantly decrease the infarct-affected tissue volume (P < 0.05), attenuate the degree of morphological injury (P < 0.05), and suppress the level of oxidative stress damage (P < 0.05), compared with the IR group. In exploring the underlying mechanisms, we found that hydrogen could markedly mitigate the degree of IR-induced ER stress and apoptosis (P < 0.05). Additionally, hydrogen could markedly inhibit the IR injury by modulating the phosphorylated c-Jun N-terminal kinase (JNK) signaling pathway (P < 0.05). CONCLUSIONS: Taken together, these results revealed the protective effect of hydrogen gas on hind limb ischemia reperfusion injury on mice by attenuating oxidative stress, impairing ER stress and apoptosis, and its ability to modulate JNK signaling pathway.

[Two different kinds of total hip arthroplasty for unilateral Crowe IV developmental dysplasia of the hip in adults].

OBJECTIVE: To compare the clinical effects of total hip arthroplasty(THA) with non-osteotomy and subtrochanteric osteotomy in the treatment of Crowe type IV hip dysplasia (DDH) in adults. METHODS: Data of 35 Crowe type IV DDH patients who underwent THA were analyzed retrospectively, the patients were divided into two groups:15 cases of non-osteotomy and 20 cases of subtrochanteric osteotomy. There was no significant difference in age, gender, body mass index between two groups (P>0.05). The operative time, bleeding volume, hospitalization duration, Harris hip score and the limb length discrepancy (LLD) were evaluated. RESULTS: All of the patients were followed up for 12 to 48 months, no prosthesis loosening or infection occurred by the end of follow-up. In non-osteotomy group, 1 case had occurred by sciatic nerve injury and 1 case developed cutaneous branch injury of the femoral nerve, both of which were spontaneously recovered completely without treatment after 3 months. One case of dislocation occurred in subtrochanteric osteotomy group, after closed reduction, dislocation did not recur; three cases had proximal femoral crack fractures and received steel plate fixation; no reoperation was needed. There was significant difference in operation duration, bleeding volume, and hospitalization days between two groups(P<0.05). The Harris score at last follow-up was significantly increased compared with preoperative score in two groups(P<0.05), but there was no significant difference between two groups(P>0.05). The postoperative discrepancy of bilateral lower limbs had significant difference(P<0.05). CONCLUSIONS: THA with no femoral shortening osteotomy can achieve good clinical results in patients with unilateral Crowe IV developmental dysplasia of hip. Comparing with subtrochanteric osteotomy, the procedure of no femoral shortening osteotomy is easier technically. For unilateral high dislocation DDH patients with limb lengthening <=4 cm and good tissue conditions, THA without femoral osteotomy may be considered.

lncRNA­NR024118 overexpression reverses LPS­induced inflammatory injury and apoptosis via NF­κB/Nrf2 signaling in ATDC5 chondrocytes.

Osteoarthritis (OA) is one of the most prevalent types of chronic joint diseases. Chondrocytes survival is closely associated with the destruction of joints in patients with OA. Long noncoding RNAs (lncRNAs) serve a critical role in OA. However, to the best of our knowledge, the role of lncRNAs NR024118 in OA has not been examined. In the present study, the expression levels of NR024118 in lipopolysaccharide (LPS)­induced chondrocytes was measured using reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and the apoptosis levels of cells was determined using flow cytometry. The levels of scavenged reactive oxygen species and expression levels of the antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and heme oxygenase­1 (HO­1) were measured using specialized detection kits. The expression of interleukin (IL)­1ß, IL­6 and IL­18 were measured using ELISA. Expression of the cell apoptosis markers Bcl­2, Bax, Bcl­2­like protein 11, NF­κB, phosphorylated (p)­NF­κB inhibitor ß (IκBß), IκBß, p­transcription factor p65 (p65) and p65, and nuclear factor erythroid­2 related factor 2 (Nrf2) signaling pathways­associated proteins, Nrf2, HO­1 and quinone oxidoreductase­1 were detected by western blot analysis and RT­qPCR. The results indicated that in ATDC5 cells, apoptosis, oxidative stress and inflammation were significantly increased and the expression level of NR024118 was significantly decreased by LPS­mediated induction. NR024118 overexpression significantly reversed the effects of LPS treatment in the ATDC5 cell line. In addition, the overexpression of NR024118 decreased NF­κB expression levels and activated the Nrf2 signaling pathways in LPS­induced ATDC5 cells. The present study demonstrated that NR024118 attenuated the effects of LPS­induction on ATDC5 cells. These results suggest that NR024118 may be a potential target for diagnosis and treatment of OA.

Plasminogen activator inhibitor-1: a risk factor for deep vein thrombosis after total hip arthroplasty.

BACKGROUND: The onset of deep vein thrombosis (DVT) in patients after total hip arthroplasty (THA) may expand or enlarge and subsequently lead to significant mortality. The objective of this study was to investigate potential risk factors for DVT in patients after THA. METHODS: Eligible patients with hip joint diseases who were scheduled for unilateral primary THA at our hospital were prospectively included into this study. The demographic and clinical features, preoperative plasma biomarkers were detailed, recorded, and compared. The multiple logistic regression analysis was used to evaluate potential risk factors for DVT. RESULTS: A total of 214 subjects were enrolled into our study cohort for the final analysis, and 23 of them have suffered DVT with an incidence of 9.5%. The performance of logistic regression analysis showed that preoperative expression of plasminogen activator inhibitor-1 (PAI-1) was an independent risk factor for the onset of DVT in patients after THA (OR 1.18, 95% CI 1.04-1.29; p = 0.011). CONCLUSIONS: Our study indicated preoperative plasma PAI-1 expression as an independent risk factor for DVT in patients who underwent THA.

Double-layer versus single-layer bone-patellar tendon-bone anterior cruciate ligament reconstruction: a prospective randomized study with 3-year follow-up.

PURPOSE: To evaluate the clinical results of a randomized controlled trial of single-layer versus double-layer bone-patellar tendon-bone (BPTB) anterior cruciate ligament (ACL) reconstruction. METHODS: Fifty-eight subjects who underwent primary ACL reconstruction with a BPTB allograft were prospectively randomized into two groups: single-layer reconstruction (n = 31) and double-layer reconstruction (n = 27). The following evaluation methods were used: clinical examination, KT-1000 arthrometer measurement, muscle strength, Tegner activity score, Lysholm score, subjective rating scale regarding patient satisfaction and sports performance level, graft retear, contralateral ACL tear, and additional meniscus surgery. RESULTS: Forty-eight subjects (24 in single-layer group and 24 in double-layer group) who were followed up for 3 years were evaluated. Preoperatively, there were no differences between the groups. At 3-year follow-up, the Lachman and pivot-shift test results were better in the double-layer group (P = 0.019 and P < 0.0001, respectively). KT measurements were better in the double-layer group (mean 2.9 versus 1.5 mm; P = 0.0025). The Tegner score was also better in the double-layer group (P = 0.024). There were no significant differences in range of motion, muscle strength, Lysholm score, subjective rating scale, graft retear, and secondary meniscal tear. CONCLUSIONS: In ACL reconstruction, double-layer BPTB reconstruction was significantly better than single-layer reconstruction regarding anterior and rotational stability at 3-year follow-up. The results of KT measurements and the Lachman and pivot-shift tests were significantly better in the double-layer group, whereas there was no difference in the anterior drawer test results. The Tegner score was also better in the double-layer group; however, there were no differences in the other subjective findings.

Development and application of novel clonazepam molecularly imprinted coatings for stir bar sorptive extraction.

The molecularly imprinted magnetic stir bar coatings were created based on graft-functional Fe3O4 nanoparticles with magnetic field-induced self-assembly. The magnetic complex including clonazepam as template, the graft-functional Fe3O4 nanoparticles and methacrylic acid as monomers was pre-assembled through π-π interaction and hydrogen bonding, then was directionally adsorbed on the surface of magnetic stir bar under the magnetic induction. The molecularly imprinted coating with well-ordered structure was generated by one-step copolymerization based on the cross linking of ethylene glycol dimethacrylate. The molecularly imprinted coating with multiple recognition sites could be manufactured and applied in polar solvents, and showed superior selectivity and fast binding kinetics for benzodiazepines. The analytes in herbal health foods, treated by stir bar sorptive extraction, were determined by HPLC-UV. Good linearity was observed in the range of 0.01-2 µg mL(-1). The content of clonazepam in the herbal health foods was found to be 44 ng g(-1), and the average recoveries were 89.8-103.3% with a relative standard deviation (RSD) <6.5%, demonstrating the successful application in real sample analysis.

Mini-midvastus versus mini-medial parapatellar approach in simultaneous bilateral total knee arthroplasty with 24-month follow-up.

OBJECTIVE: Comparisons of mini-midvastus (mMV) with mini-medial parapatellar (mMPP) approach in total knee arthroplasty (TKA) have been performed in the past but were often compromised by variables such as disease, pain tolerance, bone quality, and surgeon. The aim of this study was to minimize the influence of these factors in order to more accurately evaluate these 2 approaches. METHODS: Forty-five patients who had bilateral arthritis of the knee with similar deformity and preoperative range of motion (ROM) on both sides agreed to have 1 knee replaced via mMV approach (Group I) and the other via mMPP approach (Group II) were evaluated. Postoperative clinical outcomes, postoperative complications, perioperative parameters, and knee component positioning were analyzed. RESULTS: No significant differences were found between the mMV and mMPP groups with regards to functional assessment, patient satisfaction, postoperative complication, quadricep strength, pain at the point of incision, degree of soft tissue release, as well as ROM. Nor were significant differences found between the 2 groups in terms of perioperative parameters and radiographic component positioning. CONCLUSION: The present study did not detect any substantive difference between the mMV and mMPP approaches for TKA. The decision between the 2 surgical approaches should be based on surgeon experience and preference.

[Clinical significance and expression of the inflammatory cytokines (IL-1, IL-2, IL-6 and IL-10) in blood serum of the patients after total hip replacement].

OBJECTIVE: To evaluate the changes in the expressions of the inflammatory cytokines (IL-1, IL-2, IL-6 and IL-10) in blood serum of the patients after total hip replacement (THR). METHODS: From February 2010 to June 2010, thirty patients undergone primary total hip arthroplasty in one side including 18 male and 12 female with the mean age of (58.4 +/- 6.6) years (ranged from 52 to 70 years). Twenty patients were Ficat II type,and 10 patients were Ficat III type. The contents of IL-1, IL-2, IL-6 and IL-10 in blood serum were detected on the day before operation and 1 to 3 days after operation respectively by ELISA. At the same time, the content of C reactive protein was also detected, and the results were statistically analyzed. RESULTS: The contents of IL-1, IL-6 and IL-10 in the serum of patients at the first day after THR were significantly higher than those before operation (t = 2.62, 3.51, 2.21, P < 0.05), and reached the peak at 1 to 3 days after operations, then subsequently decreased. However, the content of IL-2 in the serum of patients after operation was obvious lower (t = 2.16, P < 0.05),and recovered to normal level gradually. CONCLUSION: It is the key time of treatment at 1 to 3 days after THR. Monitoring IL-1, IL-2, IL-6 and IL-10 after operation in time, and monitoring life sign at the same time could sensitively observe the effect of treatment and forecast the trend of diseases in patients.

[Controlled clinical trials on effective means of drainage after total hip arthroplasty].

OBJECTIVE: To explore effective means of drainage after total hip arthroplasty (THA). METHODS: From March 2009 to September 2009, fifty patients who underwent primary total hip arthroplasty in one side were randomly divided into two groups. In the natural drainage group, there were 12 males and 13 females with a mean age of (58.0 +/- 15.2) years (from 23 to 79 years) and in the routine negative pressure drainage group there were 10 males and 15 females with a mean age of (55.0 +/- 17.8) years (from 30 to 75 years). The drainage volume, wound infection, abnormal exudation, the change of hemoglobin and the blood transfusion volume after operation were all observed and compared. RESULTS: The wound of all patients in two groups got primary healing without infections. There were no differences in the changes of hemoglobin between the two groups (t = 0.532, P > 0.05). However, in the natural drainage group the drainage volume was much less than that in the routine negative pressure drainage group; moreover, less patients in this group needed blood transfusion. There were obvious differences in the two groups (t = 4.405, 2.496, P < 0.05). CONCLUSION: After THA, the natural drainage can decrease the volume of blood loss and incidence of transfusion, and can not increase the infection rate, making it an ideal and deserved popularized drainage method.