PBMC CDC42 reveals the disease activity and treatment efficacy of TNF inhibitor in patients with ankylosing spondylitis.

OBJECTIVE: Cell division cycle 42 (CDC42) regulates the polarization of M2 macrophage and maintains the T cell homeostasis, to participate in multiple autoimmune diseases, while its clinical involvement in ankylosing spondylitis (AS) remains unclear. Hence, the current study aimed to investigate the correlation of CDC42 with clinical characteristics and treatment outcome in AS patients receiving tumor necrosis factor (TNF) inhibitor therapy. METHODS: Peripheral blood mononuclear cell (PBMC) CDC42 expression was detected at baseline, week (W) 4, W8, and W12 after TNF inhibitor treatment in 91 AS patients and in 50 HCs after enrollment. Furthermore, serum TNF-α, interferon-γ (IFN-γ), interleukin-10 (IL-10), and interleukin-17A (IL-17A) from AS patients were detected at baseline. RESULTS: Blood CDC42 was lower in AS patients compared with HCs (p < 0.001). Additionally, blood CDC42 was negatively linked with CRP (r = -0.349, p = 0.001), BASDAI score (r = -0.243, p = 0.020), and ASDASCRP score (r = -0.238, p = 0.023) in AS patients; however, blood CDC42 was not correlated with other clinical characteristics. Besides, CDC42 was negatively correlated with TNF-α (r = -0.237, p = 0.024) and IL-17A (r = -0.339, p = 0.001) but not with IFN-γ (p = 0.083) or IL-10 (p = 0.280). Moreover, blood CDC42 was elevated after TNF inhibitor treatment (p < 0.001). Meanwhile, blood CDC42 was not varied at baseline and W4 between response patients and non-response patients, while it was higher at W8 (p = 0.019) and W12 (p = 0.002) in response patients than in non-response patients after treatment. CONCLUSION: Blood CDC42 deficiency links with elevated pro-inflammatory cytokines, disease activity and unsatisfying response to TNF inhibitor in AS patients.

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.

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.

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.

Influence of passive smoking on the onset of Legg-Calvè-Perthes disease: a systematic review and meta-analysis.

The relationship between passive smoking and the onset of Legg-Calvè-Perthes disease is still controversial. Therefore, we conducted the study to systematically evaluate and analyze the relationship. A comprehensive search was conducted. Meta-analysis was performed with RevMan 5.3 software, with the odds ratio as the effect size. Eight English articles with a total of 1379 Legg-Calvè-Perthes disease patients were eventually included. Passive smoking type of family members smoking in indoor (odds ratio = 2.53), paternal smoking (odds ratio = 2.76), maternal smoking (odds ratio = 2.02), maternal smoking during pregnancy (odds ratio = 1.68), using stove indoor (odds ratio = 2.56) are statistically significant (P < 0.05). For the family members smoking indoor, region may be a confounding factor (European group I = 92%, odds ratio = 2.51; USA group I = 5%, odds ratio = 3.26; and Asian group I = 0%, odds ratio = 2.25). In addition, the type of maternal smoking (odds ratio = 0.80, for 1-10 per day; odds ratio = 2.73, for 10-20 per day; odds ratio = 2.78, for >20 per day) and the type of maternal smoking during pregnancy (odds ratio = 1.36, for 1-9 per day; odds ratio = 2.02, for ≥10 per day) may show a dose-effect relationship. Passive smoking is a risk factor for the onset of Legg-Calvè-Perthes disease, but the specific types of passive smoking (haze, etc.), dose, dose-effect relationship, regional confounding, pathological mechanisms, etc. also require clinicians and researchers to continue exploring.

[Ilizarov technique combined with flap instant expansion technique for the treatment of the tibia deformity with skin contracture at one stage].

OBJECTIVE: To discusses the necessity and methods of replantation for complete amputation of finger composite lateral tissue. METHODS: From March 2012 to April 2015, 62 cases of complete amputated finger lateral tissue for various causes were retrospectively analyzed, including 34 males and 28 females with an average age of 29.1 years old ranging from 17 to 52 years old, involved 27 cases of thumb, index finger in 15 cases, 13 cases of middle finger, ring finger in 8 cases, 2 cases of the little finger, 2 fingers were injured in 3 cases, 14 cases involving the distal interphalangeal joint. The time from injury to treatment was 30 min to 2 hour with an average of 1 hour. The appearance of the fingers, finger tip sensation and the recovery of the functional of the patients were followed up and observed. RESULTS: Of 62 cases, 58 cases survived, the survival time was 3 to 15 months with an average of 6.5 months. According to the Chinese medical association upper part of replantation function evaluation standard to assess efficacy trial, 52 cases were excellent, 3 cases were good, 3 cases were good, the excellent and good rate was 94.8%. CONCLUSIONS: The appearance and function is good after block from the broken replantation finger lateral organizations survive, as long as the patient general condition allows, away from the broken body is complete, there are available for blood vessels and nerves anastomosis, it should strive to reattach it.