The κ-Opioid Receptor Agonist U50488H Ameliorates Neuropathic Pain Through the Ca2+/CaMKII/CREB Pathway in Rats.

Objective: To observe the ameliorative effect of kappa opioid receptor (KOR) agonist on rats with neuropathic pain (NP) and investigate the mechanism of action of the calcium ion (Ca2+)/calcium/calmodulin-dependent protein kinase II (CaMKII)/cyclic AMP response element-binding protein (CREB) pathway. Methods: A total of 40 Sprague Dawley rats were randomly divided into four groups: sham-operation group (Sham group), NP model group (NP group), NP + KOR agonist U50488H group (NU group) and NP + specific CaMKII antagonist (KN93) + U50488H group (NKU group). The thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) of each group of rats were determined. ELISA was applied to examine the changes in inflammatory factors and oxidative stress factors, and the apoptotic rate in dorsal root ganglia was observed using TUNEL staining. Ca2+ concentration, content of oxidative stress index ROS and the release of calcitonin gene-related peptide (CGRP) and N-methyl-D-aspartate receptor (NMDAR) in the dorsal root ganglia were measured by the immunofluorescence assay. Finally, Western blotting was performed to detect expression changes in the Ca2+/CaMKII/CREB pathway. Results: The KOR agonist U50488H could improve the values of TWL and MWT of NP the rats, inhibit inflammatory responses and relieve oxidative stress injury. Its mechanisms of action were associated with U50488H repression of Ca2+ influx, reduction of CGRP and NMDAR releases in the dorsal root ganglia and decreases in CaMKII and CREB phosphorylations in NP rats. Conclusion: The KOR agonist ameliorates NP through suppressing the activity of the Ca2+/CaMKII/CREB pathway.

Does propofol ameliorate occurrence of postoperative cognitive dysfunction after general anaesthesia? A protocol of systematic review.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common condition after general anesthesia (GA). Previous studies have reported that propofol can ameliorate the occurrence of such disorder. However, its results are still inconsistent. Therefore, this systematic review will assess the efficacy and safety of propofol on POCD after GA. METHODS: Literature sources will be sought from inception to the present in Cochrane Library, MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure for randomized controlled trials (RCTs) assessing the administration of propofol on POCD after GA. All searches will be carried out without limitations to language and publication status. Outcomes comprise of cognitive impairments changes, impairments in short-term memory, concentration, language comprehension, social integration, quality of life, and adverse events. Cochrane risk of bias tool will be utilized to assess study quality. We will evaluate the quality of evidence for each outcome using Grading of Recommendations Assessment, Development and Evaluation approach. A narrative synthesis or a meta-analysis will be undertaken as appropriate. DISCUSSION: This study will systematically and comprehensively search literature and integrate evidence on the efficacy and safety of propofol on POCD after GA. Our findings will be of interest to clinicians and health-related policy makers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020164096.

Exploring the Risk Factors for the Misdiagnosis of Osteonecrosis of Femoral Head: A Case-Control Study.

OBJECTIVE: The purpose of the present study was to evaluate the present situation and risk factors for the misdiagnosis of osteonecrosis of femoral head (ONFH), providing the basis for accurate diagnosis of ONFH. METHODS: For this retrospective study, 1471 patients with ONFH were selected from the China Osteonecrosis of Femoral Head Database (CONFHD). These patients had been recruited between July 2016 and December 2018. According to whether or not they were misdiagnosed, the patients were divided into two groups, with 1168 cases (22-84 years old) included in the diagnosis group and 303 cases (21-80 years old) in the misdiagnosis group. Misdiagnosis was measured using the following criteria: (i) the patient had the same symptoms and signs, and the second diagnosis was not consistent with the initial diagnosis within 6 months; and (ii) the patient was admitted to a hospital participating in CONFHD and the previous diagnosis was inconsistent with the diagnosis given by the expert group. Comparisons of age, visual analogue scale for pain, and body mass index between the two groups were performed using a t-test. Gender, causes of ONFH, primary diseases requiring corticosteroids, methods of corticosteroid use, corticosteroid species, type of trauma, onset side of the disease, pain side, whether symptoms are hidden, and type of imaging examination at the initial visit were compared using the χ2 -test. Years of alcohol consumption, weekly alcohol consumption, and physician title at the initial visit were compared using a Mann-Whitney U-test. Furthermore, the statistically significant factors were evaluated using multiple regression analysis to investigate the risk factors of misdiagnosis. RESULTS: A total of 303 patients (20.6%) were misdiagnosed: 118 cases were misdiagnosed as lumbar disc herniation, 86 cases as hip synovitis, 48 cases as hip osteoarthritis, 32 cases as rheumatoid arthritis, 11 cases as piriformis syndrome, 5 cases as sciatica, and 3 cases as soft-tissue injury. Whether symptoms are hidden (P = 0.038, odds ratio [OR] = 1.546, 95% confidence interval [CI] = 1.025-2.332), physician title at the initial visit (P < 0.001, OR = 3.324, 95% CI = 1.850-5.972), X-ray examination (P < 0.001, OR = 4.742, 95% CI = 3.159-7.118), corticosteroids (P < 0.001, OR = 0.295, 95% CI = 0.163-0.534), alcohol (P < 0.001, OR = 0.305, 95% CI = 0.171-0.546), and magnetic resonance imaging (MRI) examination (P = 0.042, OR = 0.649, 95% CI = 0.427-0.985) were each found to be associated with misdiagnosis. CONCLUSION: Osteonecrosis of the femoral head is easily misdiagnosed as lumbar disc herniation, hip synovitis, hip osteoarthritis, and rheumatoid arthritis. Patient history of corticosteroid use or alcohol abuse and MRI examination at the initial diagnosis may be protective factors for misdiagnosis. Hidden symptoms, physician title at the initial visit (as attending doctor or resident doctor), and only X-ray examination at the initial diagnosis may be risk factors for misdiagnosis.

Current Treatment Modalities for Osteonecrosis of Femoral Head in Mainland China: A Cross-Sectional Study.

OBJECTIVE: To investigate the application of treatment modalities for patients with osteonecrosis of the femoral head (ONFH) in mainland China. METHODS: This cross-sectional study was based on the online application of China Osteonecrosis of the Femoral Head Database (CONFHD). Between July 2016 to December 2018, the CONFHD program planned to recruit ONFH patients from 12 administrative areas across mainland China. Real-world medical records of treatment regimens for these patients, including surgeries and prescriptions, were approved to upload to the CONFHD application for further analysis. The surgeries performed on these patients were classified into total hip arthroplasty and hip-preserving procedures, and the latter was further classified into core decompression, bone grafting, and tantalum rod implantation. Prescription medications were classified into chemical medicine and Chinese herbal medicine (CHM); chemical medicine was further classified according to their chemical compounds, and CHM was classified according to therapeutic functions based on traditional Chinese medicine theory. Descriptive analysis was performed to summarize the application of different treatment regimens on the overall sample. RESULTS: A total of 1491 patients (2381 hips) who fulfilled the protocol criteria were included. There were 1039 males and 452 females with a mean age of 47.29 ± 12.69 years. The causes of ONFH were alcoholism in 642 patients (43%), corticosteroid in 439 patients (29%), trauma in 239 patients (16%), and idiopathic ONFH in 171 patients (11%). Operative treatments (including total hip arthroplasty and hip-preserving procedures) were performed on 49% of patients (43% of hips), chemical medicine therapy (including bisphosphonate, statins, and prostacyclin) was given to 37% of patients (37% of hips), and CHM was administrated to 72% of patients (75% of hips). The aforementioned interventions were not always used alone, since 47% of patients (52% of hips) received combined regimens with multiple interventions. Among hips treated by surgery, all hips with ARCO stage IV ONFH received THA (305 hips), and THA was also performed on 63 hips with stage II ONFH. Over half of hips with stage I (81%), II (91%), and III (92%) ONFH had received pharmacological treatments. Prostacyclin and bisphosphonate were the top two most prescribed medicines used alone. CHM therapies with multiple CHM functions were more commonly prescribed. CONCLUSION: Current treatment modalities for ONFH patients in mainland China include operative treatment, chemical medicine, and CHM. Combined regimens with different treatment modalities are common in real-world clinical practices.

Prediction of Collapse Using Patient-Specific Finite Element Analysis of Osteonecrosis of the Femoral Head.

OBJECTIVE: To develop a prediction method for femoral head collapse by using patient-specific finite element analysis of osteonecrosis of the femoral head (ONFH). METHODS: The retrospective study recruited 40 patients with ARCO stage-II ONFH (40 pre-collapse hips). Patients were divided into two groups according to the 1-year follow-up outcomes: patient group without femoral head collapse (noncollapse group, n = 20) and patient group with collapse (collapse group, n = 20). CT scans of the hip were performed for all patients once they joined the study. Patient-specific finite element models were generated based on these original CT images following the same procedures: segmenting the necrotic lesion and viable proximal femur, meshing the computational models, assigning different material properties according to the Hounsfield unit distribution, simulating the stress loading of the slow walking gait, and measuring the distribution of the von Mises stress. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance of the maximum level of the von Mises stress. The optimal cut-off value was selected based on the Youden index and the corresponding predictive accuracy was reported as well. RESULTS: The mean level of the maximum von Mises stress in the collapse group was 2.955 ± 0.539 MPa, whereas the mean stress level in the noncollapse group was 1.923 ± 0.793 MPa (P < 0.01). ROC analysis of the maximum von Mises stress found that the area under the ROC curve was 0.842 (95% CI: 0.717-0.968, P < 0.01). The maximum Youden index was 0.60, which corresponded to two optimal cut-off values: 2.7801 MPa (sensitivity: 0.70; specificity: 0.90; predictive accuracy: 80.00%; LR+: 7), and 2.7027 MPa (sensitivity: 0.75; specificity: 0.85; predictive accuracy: 77.50%; LR+: 5). CONCLUSION: Finite element analysis is a potential method for femoral head collapse prediction among pre-collapse ONFH patients. The maximum level of the von Mises stress on the weight-bearing surface of the femoral head could be a good biomechanical marker to classify the collapse risk. The collapse prediction method based on patient-specific finite element analysis is, thus, suitable to apply to clinical practice, but further testing on a larger dataset is desirable.