The Effect of Ciprofol on Postoperative Delirium in Elderly Patients Undergoing Thoracoscopic Surgery for Lung Cancer: A Prospective, Randomized, Controlled Trial.

Purpose: This study was conducted to assess whether ciprofol vs propofol could affect the incidence of postoperative delirium (POD) in elderly patients with lung cancer after thoracoscopic surgery. Patients and Methods: In this study, a total of 84 elderly patients undergoing thoracoscopic surgery for lung cancer were recruited and randomized into two groups to receive anesthesia with either ciprofol or propofol. The primary outcome was the incidence of POD within three days after surgery. Secondary outcomes included the Confusion Assessment Method (CAM) score, intraoperative indicators related to mean arterial pressure (MAP), and cerebral tissue oxygen saturation (SctO2). Moreover, MAP- and SctO2-related indicators associated with POD were analyzed. Results: The incidence of POD was 7.1% and 16.7%, respectively, in the ciprofol group and the propofol group (risk ratio [RR], 0.37; 95% confidence interval [CI], 0.07 to 2.03; risk difference [RD], -9.6%; 95% CI, -23.3% to 4.1%; p = 0.178). Compared with those in the propofol group, patients in the ciprofol group had lower CAM scores three days after surgery (13 (12, 15) vs 15 (14, 17); 12 (11, 13) vs 14 (13, 16); 12 (11, 12) vs 13 (12, 14), p<0.05). Besides, patients in the ciprofol group exhibited higher mean and minimum MAP (88.63 ± 6.7 vs 85 ± 8.3; 69.81 ± 9.59 vs 64.9 ± 9.43, p<0.05) and SctO2 (77.26 ± 3.96 vs 75.3 ± 4.49, 71.69 ± 4.51 vs 68.77 ± 6.46, p<0.05) and percentage of time for blood pressure stabilization (0.6 ± 0.14 vs 0.45 ± 0.14, p<0.05) than those in the propofol group. Furthermore, MAP and SctO2-related indicators were validated to correlate with POD. Conclusion: Anesthesia with ciprofol did not increase the incidence of POD compared with propofol. The results demonstrated that ciprofol could improve intraoperative MAP and SctO2 levels and diminish postoperative CAM scores.

Dexmedetomidine alleviates hippocampal neuronal loss and cognitive decline in rats undergoing open surgery under sevoflurane anaesthesia by suppressing CCAAT/enhancer-binding protein beta.

Dexmedetomidine (Dex) may exert neuroprotective effects by attenuating inflammatory responses. However, whether Dex specifically improves postoperative cognitive dysfunction (POCD) by inhibiting microglial inflammation through what pathway remains unclear. In this study, the POCD model was constructed by performing open surgery after 3 h of continuous inhalation of 3% sevoflurane to rats, which were intraperitoneally injected with 25 µg/kg Dex .5 h before anaesthesia. The results displayed that Dex intervention decreased rat escape latency, maintained swimming speed and increased the number of times rats crossed the platform and the time spent in the target quadrant. Furthermore, the rat neuronal injury was restored, alleviated POCD modelling-induced rat hippocampal microglial activation and inhibited microglial M1 type polarization. Besides, we administered Dex injection and/or CCAAT/enhancer-binding protein beta (CEBPB) knockdown on the basis of sevoflurane exposure and open surgery and found that CEBPB was knocked down, resulting in the inability of Dex to function, which confirmed CEBPB as a target for Dex treatment. To sum up, Dex improved POCD by considering CEBPB as a drug target to activate the c-Jun N-terminal kinase (JNK)/p-38 signaling pathway, inhibiting microglial M1 polarization-mediated inflammation in the central nervous system.

Effects of Isoflurane on the Cell Pyroptosis in the Lung Cancer Through the HMGB1/RAGE Pathway.

There are many common malignant tumors in clinic. Among them, lung cancer is caused by the failure of suction system, which seriously threatens the life safety of patients. Recent studies have found that anesthetics have achieved certain efficacy in many cancers. Isoflurane, an inhaled anesthetic, is used in this study to explore whether it can prevent the lung cancer development. The A549 and H1299 were purchased. Cell viability was tested by CCK-8 experiment. Cell death and pyroptosis were analyzed by PI staining as well as flow cytometry. HMGB1 as well as RAGE protein levels were tested by Western blot. The same is true of pyroxin-related proteins. The HMGB1 as well as RAGE levels in the lung cancer tissues were determined by Western blot along with immunohistochemistry. Isoflurane treatment can reduce cell viability and promote cell pyroptosis. Additionally, the protein levels of cleaved caspase-1, IL-1ß, GSDMD-N, NLRP3, HMGB1, and RAGE were dramatically up-regulated in the lung cancer after isoflurane treatment. Down-regulated proteins in lung cancer tissues include HMGB1 and RAGE proteins. After HMGB1 knockdown or FPS-ZM1 treatment, the role of isoflurane in the lung cancer was neutralized. This study demonstrated that isoflurane induced the cell pyroptosis in the lung cancer through activating the HMGB1/RAGE pathway.

Identification and validation of ferroptosis-related biomarkers in steroid-induced osteonecrosis of the femoral head.

OBJECTIVES: Treatment of steroid-induced osteonecrosis of the femoral head (SIONFH) is challenging. Due to the limited understanding of its molecular mechanisms, investigating the potential mechanisms of ferroptosis will shed light on SIONFH and provide directions for treating this disease. METHODS: The GSE123568 dataset was utilized to apply various bioinformatics methodologies to identify ferroptosis-related hub genes (FRHGs). Subsequently, the importance of these genes and the reliability of the results were confirmed using protein data-independent acquisition (DIA) and cell experiments. Finally, we assessed the correlation between FRHG expression and immune cell infiltration. RESULTS: Thirty-one hub genes were identified and validated by constructing a protein-protein interaction network and subsequent screening using experimentally determined interactions. These 31 hub genes were enriched in immunity, the AMPK signaling pathway, and the Toll-like receptor signaling pathway. Next, we identified a diagnostic marker comprising two ferroptosis-related genes, NCF2 and SLC2A1. The differential expression of these two genes in healthy and necrotic regions was confirmed by protein DIA analysis. Cell experiments verified the link between FRHGs and ferroptosis and preliminarily explored the potential mechanism of the antioxidant vitexin in promoting osteogenic differentiation in cells. The diagnostic efficiency of these two markers was confirmed by receiver operating characteristic curve (ROC) curves, yielding an area under the curve of 1.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated enrichment of FRHGs in the superoxide anion and HIF-1 signaling pathways. A significant correlation was observed between FRHGs and various immune cell populations. CONCLUSION: NCF2 and SLC2A1 are promising ferroptosis-related diagnostic biomarkers of SIONFH. Concurrently, we embarked on a preliminary investigation to elucidate the potential mechanism underlying the promotion of osteogenic differentiation by the antioxidant vitexin. Moreover, these biomarkers are associated with distinct immune cell populations.

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.

Correction to "Febuxostat Prevents the Cytotoxicity of Propofol in Brain Endothelial Cells".

[This corrects the article DOI: 10.1021/acsomega.0c05708.].

Bupivacaine modulates the apoptosis and ferroptosis in bladder cancer via phosphatidylinositol 3-kinase (PI3K)/AKT pathway.

The study aimed to explore the effects of local anesthetic bupivacaine on bladder cancer cells in vivo and in vitro. The cytotoxicity was detected by MTT assay. Apoptosis was measured by Hoechst 33342 staining and TUNEL. The contents of Fe2+, Malondialdehyde (MDA), Glutathione (GSH) and reactive oxygen species (ROS) were evaluated by the corresponding kit. Mitochondrial membrane potential was assessed by JC-1 kit. HE staining, TUNEL and immunohistochemistry were used to detect the xenografted tumors. Protein expression was estimated by Western blot. Bupivacaine significantly inhibited the activity of T24 cells and 5637 cells at 0.25-16 mM. Bupivacaine promoted cell apoptosis with increased concentration. bupivacaine inhibited the expression of Bcl-2 and increased the expression of Bax and cytochrome C. Moreover, bupivacaine amplified the level of Fe2+ and ROS, and restrained the expression of cystine/glutamic acid reverse transporter (xCT) and glutathione peroxidase 4 (GPX4). Further results showed that bupivacaine decreased mitochondrial membrane potential, reduced GSH, and increased MDA levels. Besides, bupivacaine attenuated the phosphorylation of PI3K, Akt, and mTOR. In addition, bupivacaine suppressed the growth of xenografted tumors, induced apoptosis and ferroptosis, and inhibited the activity of PI3K/AKT signaling pathway in xenografted tumors. Bupivacaine could induce apoptosis and ferroptosis by inhibiting PI3K/Akt signaling pathway in bladder cancer cells.

Evaluation of Radiographic Outcomes after Core Decompression for Osteonecrosis of the Femoral Head: The Beijing University of Chinese Medicine X-ray Evaluation Method.

BACKGROUND: Joint-preserving treatments for osteonecrosis of the femoral head (ONFH) are an area of significant interest in orthopaedics as they may restore function and provide durable benefit to patients who would otherwise require early total hip arthroplasty. Studies reporting the outcomes for these procedures generally rely on a combination of radiographic and clinical outcomes. However, there is not currently a standardized radiographic scoring system that allows for objective reporting of radiographic outcomes following these procedures. This article introduces a novel scoring system (Beijing University of Chinese Medicine X-ray evaluation, BUCMXE) based on Anteroposterior (AP) hip radiographs to allow for objective evaluation and comparison of postoperative outcomes following joint-preserving treatments for ONFH. METHODS: The proposed scoring system utilizes AP radiographs of the hip and consists of a total score (0-10) derived from the sum of subscores in 3 domains: femoral head morphology, osteonecrotic lesion, and degree of osteoarthritis. Each radiographic parameter is scored from 0 (normal) to 3 or 4 (advanced disease). The scoring model was retrospectively applied to a cohort of patients who had undergone core decompression and cancellous bone grafting procedures by the principal investigator. RESULTS: The BUCMXE provided a clear and reproducible means of quantifying and communicating radiographic changes over the course of follow-up in our study cohort. Statistical analysis demonstrated that the BUCMXE was sensitive to detect the radiographic changes associated with the index procedure. The median total score was reduced from 3 preoperatively to 2 at the initial (3-month) follow-up for this cohort. This change was attributable to the obvious improvement of osteonecrotic lesion in patients who had more advanced disease at the time of their procedure. CONCLUSION: The BUCMXE system allowed for objective quantification of radiographic changes following joint-preserving hip surgery in our cohort. Statistical analysis of BUCMXE scores demonstrated that the scoring system was sensitive to detect subtle radiographic changes associated with disease progression in the follow-up period. LEVEL OF EVIDENCE: Therapeutic Level III.

General recommendation for assessment and management on the risk of glucocorticoid-induced osteonecrosis in patients with COVID-19.

BACKGROUND/OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a disaster in human medical history and glucocorticoids remain the most promising therapy. Osteonecrosis is a disease caused by reduced intraosseous blood flow to bones in the joints, which will rapidly induce joint destruction. Approximately one-third patients with severe acute respiratory syndrome (SARS) who received high cumulative doses and long treatment durations of glucocorticoids occurred osteonecrosis. Considering the similarity of SARS and COVID-19 on their pathogen, clinical characteristics, and therapeutic strategies, it is particularly desirable to investigate whether osteonecrosis will become a common sequela among convalescent COVID-19 patients. METHODS: This multi-strategy study was designed by integrating different research methods, such as meta-analysis, systematic review, and cross-sectional investigations to address above study objectives. At first, two meta-analyses were performed on the osteonecrosis incidence among SARS patients and the clinical data of glucocorticoid exposure among COVID-19 patients. Then, a systematic review of low-dosage glucocorticoid associated osteonecrosis and a cross-sectional investigation of glucocorticoid exposure of COVID-19 patients in Wuhan city of China were also conducted. Moreover, the pathogenesis, diagnosis, prevention, and treatment options for osteonecrosis patients with COVID-19 infection were further presented and discussed. RESULTS: Our meta-analysis showed that 32% of SARS patients had developed osteonecrosis after receiving glucocorticoid treatment with high dose, and our system review supported that low level glucocorticoid exposure might also lead to the occurrence of osteonecrosis. Similarly, 40% of COVID-19 patients had undergone glucocorticoid treatment according to our meta-analysis. The cross-sectional investigation in Wuhan city of China found that the average of cumulative glucocorticoid exposure level was 504 â€‹mg calculated by the dosage of methylprednisolone. Notably, a confirmed osteonecrosis case was identified from 1406 patients with COVID-19 during our cross-sectional investigation, implying that preventive management of osteonecrosis should be better started with regular clinical follow-up observation. CONCLUSION: Growing evidence of the glucocorticoid therapy for COVID-19 patients prompts us to establish risk-classification-based early screening and to introduce early prevention protocol of its associated osteonecrosis that will be of clinical significance in favor of improved prognosis of this disease. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: To establish risk-classification-based early screening and to introduce early prevention protocol of glucocorticoid-induced osteonecrosis will be of clinical significance in favor of improved prognosis of COVID-19.

Isoflurane Suppresses Proliferation, Migration, and Invasion and Facilitates Apoptosis in Colorectal Cancer Cells Through Targeting miR-216.

Objective: Surgery is the first line treatment of colorectal cancer (CRC). Anesthetic isoflurane may improve outcomes of cancer surgery. Herein, we investigated the effects of isoflurane on malignant behaviors of CRC cells and its underlying therapeutic target. Methods: SW620 and HCT116 CRC cells were exposed to a series of concentrations of isoflurane. CCK-8 assay was utilized for determination of the optimal concentration of isoflurane. Under treatment with isoflurane, proliferation, migration, and invasion were separately assessed via clone formation and transwell assays. Apoptotic levels were observed via flow cytometry and expression of Bax, Bcl-2, and Caspase3 proteins was quantified through western blot. MiR-216 expression was detected in isoflurane-induced SW620 and HCT116 cells by RT-qPCR. Following transfection with miR-216 mimic, malignant biological behaviors were examined in isoflurane-treated SW620 and HCT116 cells. Results: 40 µM isoflurane distinctly restrained proliferative, migrated, and invasive capacities and elevated apoptotic levels in SW620 and HCT116 cells. Up-regulation of miR-216 was found in CRC cells. Its expression was suppressed by isoflurane. MiR-216 mimic ameliorated the reduction in proliferation, migration, and invasion and the increase in apoptosis for 40 µM isoflurane-induced SW620 and HCT116 cells. Conclusion: Isoflurane, a promising drug of CRC, may suppress malignant biological behaviors of tumor cells. Furthermore, miR-216 is an underlying target of isoflurane. Thus, isoflurane could be adopted for CRC treatment.

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.

Febuxostat Prevents the Cytotoxicity of Propofol in Brain Endothelial Cells.

Background and purpose: A high risk of brain injury has been reported with the usage of general anesthetics such as propofol in infants. Experimental data indicated that oxidative stress and inflammation are involved in the neurotoxicity induced by propofol. Febuxostat is a novel anti-gout agent recently reported to exert an anti-inflammatory effect. The present study aims to investigate the protective property of febuxostat against the cytotoxicity of propofol in brain endothelial cells as well as the underlying preliminary mechanism. Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to screen the optimized incubation concentration of febuxostat. bEnd.3 brain endothelial cells were stimulated with 2% propofol in the presence or absence of febuxostat (10, 20 µM) for 24 h. The lactate dehydrogenase (LDH) release assay was conducted to detect cytotoxicity. The reactive oxygen species (ROS) levels were evaluated using dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining, and the concentration of reduced glutathione (GSH) was determined using a commercial kit. The expressions of TNF-α, IL-6, IL-12, CXCL-1, PDPN, CXCL8, VCAM-1, and E-selectin were determined using a quantitative real-time polymerase chain reaction (qRT-PCR) and an enzyme-linked immunosorbent assay (ELISA). Western blot and qRT-PCR were utilized to determine the expressions of COX-2 and KLF6. The production of PGE2 was evaluated by ELISA. Results: First, increased LDH release induced by propofol was significantly suppressed by febuxostat. The oxidative stress (elevated ROS levels and decreased GSH level) induced by propofol was alleviated by febuxostat. Second, the upregulated inflammatory factors (TNF-α, IL-6, and IL-12), pro-inflammatory chemokines (CXCL-1, PDPN, and CXCL8), adhesion molecules (VCAM-1 and E-selectin), and inflammatory mediators (COX-2 and PGE2) induced by propofol were greatly downregulated by febuxostat. Lastly, the expression of KLF6 was significantly suppressed by propofol but greatly elevated by febuxostat. Conclusion: Febuxostat prevented the cytotoxicity of propofol in brain endothelial cells by alleviating oxidative stress and inflammatory response through KLF6.

Epidemiological Study Based on China Osteonecrosis of the Femoral Head Database.

OBJECTIVE: The aim of the present study was to reveal the case characteristics of osteonecrosis of the femoral head (ONFH) in Mainland China. METHODS: This cross-sectional epidemiological study derived data for ONFH patients from July 2016 to December 2018 from the China Osteonecrosis of the Femoral Head Database (CONFHD). The derived data included gender, age, body mass index (BMI), height, occupation, region, and etiology of femoral head necrosis. A descriptive analysis was performed to summarize the epidemiological characteristics of the case data in the CONFHD. RESULTS: A total of 1844 ONFH patients (2945 hips) were included in this study, comprising 1302 men and 542 women. The age of patients ranged from 18 to 95 years, with a median of 50 years, and the male to female ratio was 2.4. Male patients are younger than female patients (48.26 ± 12.56 years old and 55.56 ± 14.94 years old, respectively). Among the 1844 patients (2945 hips), there were 528 (17.92%) hips at ARCO stage I, 941 (31.99%) hips at ARCO stage II, 873 (29.63%) hips at ARCO stage III, and 603 (20.46%) hips at ARCO stage IV. In the subclassification of ARCO stages I and II, the majority of cases were type C; type A comprised the majority in the subclassification of ARCO stage III. According to the Kellgren-Lawrence classification system, among the 603 ARCO stage IV hips, there were 178 (29.52%) grade 1 hips, 201 (33.34%) grade 2 hips, 176 (29.18%) grade 3 hips, and 48 (7.96%) grade 4 hips. Most were from three provinces: Henan (27.3%), Shanxi (13.9%), and Shandong (11.9%). Regarding BMI, 982 patients (53.25%) were overweight or obese. Among all patients, the largest proportion of patients engaged in level IV manual work. Of all the patients, there were 495 (26.84%) with steroid-induced ONFH, 685 (37.15%) were alcoholics, and 290 (15.73%) had traumatic ONFH. The 495 patients with steroid-induced ONFH included 278 men (56.16%) and 217 women (43.84 %), had a complete history of hormone use. Among the primary diseases, there were 195 cases (39.39%) of immune system diseases, followed by dermatological diseases, respiratory diseases, nephropathy, and other diseases. There were a total of 685 patients with alcoholic ONFH, 589 of these patients (85.99%) were men. A total of 188 (27.45%) patients had drunk alcohol for 6-10 years (comprising the highest proportion), and 280 patients (40.88%) consumed 3001-3500 mL of alcohol each week (the highest proportion). CONCLUSION: Osteonecrosis of the femoral head most commonly occurs after the age of 40. Male patients have an earlier onset than female patients, and the number of male patients is approximately twice that of female patients. The BMI of patients was mainly in the overweight and obese range, and half of these patients engaged in level IV manual work. From the imaging findings, the numbers of hips at ARCO stages II and III were greatest, and the number at stage I was relatively small. Among all the causes of disease, alcohol, steroid use and trauma were the three most common reasons for ONFH.

Dynamic evolution of osseous structure in osteonecrosis of the femoral head and dynamic collapse risks: a preliminary CT image study.

BACKGROUND: Collapse risk of osteonecrosis of the femoral head (ONFH) is estimated mainly based on static indicators, including lesion size and lesion location, but bone repairing is a dynamic process that lasts for years. The present study attempted to analyze the dynamic evolution of the osseous structure and its correlation with radiographic progression. METHODS: This retrospective study included 50 hips with ONFH from 50 patients. Participants were divided into the non-collapse group (n = 25) and the collapse group (n = 25). Original files of the initial computed tomography (CT) images were imported into imaging processing software for morphology analysis. The volume of sclerotic bone, the volume of soft tissue, and bone mineral density (BMD) were calculated. The linear correlations between the aforementioned indicators and the disease duration were estimated. The logistic regression analysis was conducted to evaluate the correlation of these indicators with the radiographic progression. Receiver operating characteristic (ROC) analysis was used to evaluate these indicators' prediction performance. RESULTS: The volume of sclerotic bone and the BMD grew with disease duration, but the volume of soft tissue decrease. The logistic regression analysis found that the volume of sclerotic bone and the BMD were statistically associated with radiographic progression. The ROC analysis found that the regression model, which integrated the volume of sclerotic bone and the BMD, had satisfactory performance in predicting radiographic progression. CONCLUSION: The present study suggested a dynamic evolution of the osseous structure and a dynamic variation trend of the collapse risk in ONFH. The volume of sclerotic bone and the BMD might serve as further prognostic indicators when estimating the collapse risk.

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.

Mechanisms and Molecular Targets of the Tao-Hong-Si-Wu-Tang Formula for Treatment of Osteonecrosis of Femoral Head: A Network Pharmacology Study.

The Tao-Hong-Si-Wu-Tang (THSWT) formula, a classic prescription of traditional Chinese medicine, has long been used for the treatment of osteonecrosis of femoral head (ONFH). However, its mechanisms of action and molecular targets are not comprehensively clear. In the present study, the Traditional Chinese Medicine System Pharmacology (TCMSP) database was employed to retrieve the active compounds of each herb included in the THSWT formula. After identifying the drug targets of active compounds and disease targets of ONFH, intersection analysis was conducted to screen out the shared targets. The protein-protein network of the shared targets was built for further topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were then carried out. A gene pathway network was constructed to screen the core target genes. We identified 61 active compounds, 155 drug targets, and 5443 disease targets. However, intersection analysis only screened out 37 shared targets. Kaempferol, luteolin, and baicalein regulated the greatest number of targets associated with ONFH. The THSWT formula may regulate osteocyte function through specific biological processes, including responses to toxic substances and oxidative stress. The regulated pathways included the relaxin, focal adhesion, nuclear factor-κB, toll-like receptor, and AGE/RAGE signaling pathways. RELA, VEGFA, and STAT1 were the important target genes in the gene network associated with the THSWT formula for the treatment of ONFH. Therefore, the present study suggested that the THSWT formula has an action mechanism involving multiple compounds and network targets for the treatment of ONFH.

Chinese herbal Huo-Gu formula for the treatment of steroid-associated osteonecrosis of femoral head: A 14-year follow-up of convalescent SARS patients.

PURPOSE: The coronavirus disease 2019 (COVID-19) reminds us of the severe acute respiratory syndrome (SARS) outbreak in 2003, and up to date, corticosteroid is commonly administrated to severe patients with COVID-19. Osteonecrosis of the femoral head (ONFH) is a common disabling complication among convalescent SARS patients who received corticosteroid therapy. In China, a considerable number of convalescent SARS patients with steroid-associated ONFH had undergone conservative treatment by traditional Chinese medicine, and this study aims to evaluate the long-term results of a spleen-invigorating Huo-Gu formula (HGF) therapy in these patients. PARTICIPANTS AND METHODS: A total of 33 convalescent SARS patients (9 males and 24 females) with bilateral steroid-associated ONFH (66 hips) were enrolled in this study. All patients received oral HGF therapy for 6 months when they were confirmed the diagnosis of steroid-associated ONFH. They had been regularly followed up at an interval of 1 year. Harris hip score and medical imaging modalities, including plain radiography, computed tomography and magnetic resonance imaging, were performed to evaluate the outcomes. RESULTS: Based on average 14 years of follow-up of HGF therapy (ranging from 6 to 16 years), 38 hips (57%) among the 66 hips developed definite osteoarthritis, and 14 hips (26%) in 53 precollapse hips (Association Research Circulation Osseous [ARCO] Stage I or II) progressed to femoral head collapse (ARCO Stage III or IV). Only five patients (also 5 hips) underwent total hip arthroplasty, and the mean hip survival time was over 15 years by the Kaplan-Meier analysis. We observed a mean Harris hip score of 63 points, which represented the reserve of 55% in pain score and 70% in physical function score. The severity of groin pain was not correlated to the severity of osteoarthritis. CONCLUSION: Chinese herbal HGF therapy demonstrates beneficial effects on preventing femoral head collapse, delaying total hip arthroplasty, and maintaining physical function in the treatment of steroid-associated ONFH. HGF therapy might be therefore a good alternative for the treatment of steroid-associated ONFH secondary to rheumatologic and infection diseases. TRANSLATIONAL POTENTIAL OF THE ARTICLE: HGF therapy might be a good alternative for the treatment of steroid-associated ONFH secondary to rheumatologic and infectious diseases.

Effect of dexmedetomidine on analgesia and sedation of sufentanil during anesthesia induction period of gynecological surgery.

To observe and analyze the effect of dexmedetomidine on analgesia and sedation of sufentanil during anesthesia induction period of gynecological surgery. A total of 160 patients demanding gynecologic surgery were enrolled in the study and randomly divided into study group and control group, each containing 80 patients. The control group was treated with sufentanil and normal saline, while the study group was treated with sufentanil and dexmedetomidine. Then, the therapeutic effect of the two groups was compared. NTI of the two groups was observed at A2, which was significantly lower in the study group than that in the control group. Moreover, NTI value of the two groups was significantly lower at A2 and A4 than at A1. When the NTI value was reduced to a minimum, the application time was significantly shorter in the study group than that in the control group. PTO and PPT of the two groups were higher at A4 than those at A1. At A1 and A4, The difference between PTO and PPT was significantly higher in the study group than that in the control group, p<0.05. The rate of adverse reactions was significantly lower in the study group than that in the control group, p<0.05. Dexmedetomidine has good effect on analgesia and sedation of sufentanil during anesthesia induction period of gynecological surgery, which should be popularized in clinical application.