Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective: To examine the safety and feasibility of three-dimensional (3D) surgical planning system for guiding robot-assisted selective artery clamping partial nephrectomy (RASPN) in completely endophytic renal tumor. Methods: Clinical data of 32 patients who suffered from completely endophytic renal tumor and underwent RASPN associated with 3D surgical planning system in Department of Urology, Sun Yat-Sen University Cancer Center from November 2018 to August 2021 were analyzed retrospectively. There were 21 males and 11 females, with the age (M (IQR)] of 45.0 (17.5) years (range: 30 to 68 years). Fifteen tumors were located on the left and 17 on the right. Maximum tumor diameter, R.E.N.A.L. Score and preoperative estimated glomerular filtration rate (eGFR) were 27.5 (13.0) mm (range: 14 to 50 mm), 10.0 (1.8) (range: 7 to 11), and 105.5 (15.7) ml·min^-1·(1.73 m²)^-1 (range: 71.1 to 124.8 ml·min^-1·(1.73 m²)^-1), respectively. The 3D reconstruction before RASPN was performed in all patients to formulate surgical planning, mainly including stereo localization of renal mass, confirmation of tumor feeding artery, and injury prediction of collecting system or vessel via "2 mm distance method" defined as probable damage of renal pelvis/calyx and artery/vein when these tissues were less than 2 mm away from tumor. Results: Totally 32 patients successfully underwent RASPN guided by 3D surgical planning system, without conversion to open operation or radical nephrectomy. Rapid location of tumor and selective clamping of artery were achieved in all cases and no one encountered global ischemia, with branch occlusion time of 24.5 (15.4) min (range: 12 to 60 min) and coincidence rate of 95.0% (57/60) between planned and actual clamping vessels. The sensitivity and specificity of 2 mm distance method for predicting the injury of collecting system were 13/15 and 17/17, respectively. The operating time of 185 (48) minuetes (range: 76 to 295 minutes) and estimated blood loss of 200 (350) ml (range: 20 to 800 ml) were observed, without intraoperative transfusion case. There was one patient performed with renal vein repair. Clavien-Dindo postoperative grade Ⅱ and Ⅲa bleeding complications occurred in 2 cases, and no postoperative urinary fistula was found. The length of hospitalization was 3 (0) days (range: 2 to 10 days). The pathological diagnosis demonstrated 4 chromophobe cell carcinomas and 2 angiomyolipomas, besides 26 clear cell carcinomas including one positive surgical margin. The postoperative latest eGFR was 103.9(18.5) ml·min^-1·(1.73 m²)^-1 (range: 75.8 to 122.3 ml·min^-1·(1.73 m²)^-1) and no tumor recurrence or metastasis was detected during the follow-up time of 15.4 (13.9) months (range: 3 to 35 months). Conclusion: For RASPN in completely endophytic renal tumor, 3D surgical planning system is contributed to determining mass position, defining tumor feeding artery, and predicting collecting system/vessel injury, which benefited precise tumor resection, postoperative renal function preservation, and perioperative urinary fistula and bleeding complication decrease.
Male ; Female ; Humans ; Constriction ; Retrospective Studies ; Robotics ; Nephrectomy/methods* ; Kidney Neoplasms/surgery* ; Robotic Surgical Procedures/methods* ; Laparoscopy ; Arteries ; Urinary Fistula/surgery* ; Carcinoma/surgery* ; Treatment Outcome

Objective: To compare the short-term outcomes between off-pump and on-pump coronary artery bypass graft (CABG) by experienced surgeons with similar surgical team in a single large-volume cardiac surgery center. Methods: A total of 31 075 patients with multivessel coronary disease who underwent isolated off-pump or on-pump CABG between January 1, 2009 and December 31, 2019 by experienced surgeons in Fuwai hospital were enrolled in this retrospective study. Patients was divided into on-pump CABG group and on-pump CABG group on an intention-to treat basis. Short term safety endpoints, including 30 days mortality, composite endpoint of major morbidity or mortality, prolonged postoperative length of stay (PLOS), and prolonged ICU length of stay (PICULOS), and distal anastomosis were compared between the two groups. Mortality was evaluated on 30 days post operation, other endpoints were collected before discharge. After 1∶1 propensity-score matching of baseline characteristics for on-pump and off-pump CABG, postoperative endpoints were compared with use of McNemar's test and further adjusted with the use of a logistic regression model. Results: After propensity-score matching, 10 243 matched pairs of patients were included in the final analysis, there were 4 605(22.5%) females and mean age was (60.7±8.6) years. The standardized differences were less than 5% for all baseline variables in matched cohort. Univariate analysis indicated lower risk of 30 days mortality (0.2% vs. 0.7%, P<0.001), major morbidity or mortality (5.7% vs. 8.8%, P<0.001), PLOS (3.2% vs. 4.9%, P<0.001), PICULOS (9.4% vs. 12.2, P<0.001), and lower number of distal anastomosis ((3.3±0.8) vs. (3.6±0.8), P<0.001) in off-pump CABG group than in on-pump CABG group. After adjustment of cofounders, multivariate analysis showed that off-pump CABG was still associated with a lower risk of 30 days mortality (OR=0.29, 95%CI: 0.09-0.87, P=0.027), composite endpoint of major morbidity or mortality (OR=0.60, 95%CI: 0.53-0.68, P<0.001), PLOS (OR=0.64, 95%CI 0.54-0.75, P<0.001), PICULOS (OR=0.76, 95%CI: 0.69-0.84, P<0.001). Conclusions: Off-pump CABG is related with superior short-term safety outcomes than on-pump CABG by experienced surgeons in our center.
Aged ; Coronary Artery Bypass ; Coronary Artery Bypass, Off-Pump ; Coronary Artery Disease/surgery* ; Female ; Humans ; Middle Aged ; Postoperative Complications/epidemiology* ; Retrospective Studies ; Surgeons ; Treatment Outcome

BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.
Adult ; Aged ; Betacoronavirus ; genetics ; Clinical Laboratory Techniques ; Coronavirus Infections ; diagnosis ; genetics ; rehabilitation ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; genetics ; rehabilitation ; RNA, Viral ; genetics ; Real-Time Polymerase Chain Reaction ; Retrospective Studies

Background: A patient’s infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. Methods: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients’ oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. Results: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0–62.0) years were analyzed. After in-hospital treatment, patients’ inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0–11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients’ stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0–16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0–4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients’ urine specimens after throat swabs were negative. Using a multiple linear regression model (F=2.669, P=0.044, and adjusted R²=0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients’ stools (t=-2.699, P=0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs 8.0 days, respectively; t=2.550, P=0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs 11 days, respectively; t=4.631, P <0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P >0.05). Conclusions In brief, as the clearance of viral RNA in patients’ stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.

OBJECTIVETo investigate the hematopoietic reconstitution in immunodeficiency NPG(TM) mice after transplantation of G-CSF-mobilized peripheral blood CD34(+) hemopoietic stem cells.

METHODSCD34(+) cells were isolated from peripheral blood stem cells (PBSC) by magnetic activated cell sorting (MACS), and then were transplanted into NPG(TM) mice irradiated with sublethal dose of X ray by marrow cavity transplantation. The hemogram of mice after transplantation for 2, 4 weeks was observed; human cell populations (CD45(+), CD19(+)) in the peripheral blood of mice were dynamically analyzed by flow cytometry (FCM) at 4, 6, 8, 10 and 12 weeks after transplantation. Until the planned harvest at the 12 week after transplantation, the CD45(+), CD19(+) level in bone marrow, liver, spleen from each mouse were detected by flow cytometry; the expression of human Alu gene in the bone marrow cell of mouse was detected by PCR.

RESULTSThe purity of CD34(+) cells accounted for 96.3%; after irradiation, the nucleated cells and megalokaryocytes in the marrow cavity of NPG mice were reduced significantly or were lost, and reached the myeloablative effect. At week 4 after transplantation, components of blood cells in peripheral blood of transplanted mice were recovered to the level before irradiation; all the mice survived, human CD45(+), CD19(+) cells were found by FCM in the peripheral blood of all the surviving mice in transplantation group at week 4, 6, 8, 10, 12 after the transplantation; at the 12th week, the human Alu gene could be detected in the bone marrow of all the mice in transplantation group.

CONCLUSIONThe human-mouse chimeric model is successfully established in irradiation-induced NPG mouse by transplantation of CD34(+) HSC from G-CSF-mobilized peripheral blood via marrow cavity.

Animals ; Bone Marrow ; Bone Marrow Cells ; Bone Marrow Transplantation ; Cord Blood Stem Cell Transplantation ; Disease Models, Animal ; Granulocyte Colony-Stimulating Factor ; Hematopoietic Stem Cells ; Humans ; Mice ; Spleen

Osteonecrosis of the femoral head is frequently observed in patients treated with excessive corticosteroids. However, the pathogenesis of corticosteroid-induced osteonecrosis remains unclear. The purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) signaling pathway in steroid-induced femoral head osteonecrosis in rats. Male Sprague-Dawley rats were injected intramuscularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, twice per week. The animals were sacrificed at 2, 4 and 8 weeks after the last MP injection, respectively, and then allocated to the 2-, 4- and 8-week model groups (n=24 each). Rats in the control group (n=12) were not given any treatment. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in plasma was determined. The activation of osteoclasts in the femoral head was assessed by TRAP staining. The expression of TLR4, MyD88, TRAF6 and NF-κB p65 that are involved in TLR4 signaling, and MCP-1 production were detected by using real-time PCR (RT-PCR) and Western blotting. The results showed that the osteonecrosis in the femoral head was clearly observed and the concentration of TRAP in the plasma was increased in the model rats. The femoral head tissues in MP-treated rats were positive for TRAP and the intensity of TRAP staining was greater in MP-treated rats than in control rats. As compared with the control group, the mRNA expression of TLR4 signaling-related factors was enhanced significantly at 4 and 8 weeks, and the protein levels of these factors increased significantly with time. It was concluded that MP could induce the femoral head osteonecrosis in rats, which was associated with osteoclast activation via the TLR4 signaling pathway. These findings suggest that TLR4 signaling pathway plays a pivotal role in the pathogenesis of steroid-induced osteonecrosis.
Acid Phosphatase ; metabolism ; Animals ; Blotting, Western ; Chemokine CCL2 ; genetics ; metabolism ; Femur Head ; metabolism ; pathology ; Gene Expression ; Immunohistochemistry ; Isoenzymes ; metabolism ; Male ; Methylprednisolone ; Myeloid Differentiation Factor 88 ; genetics ; metabolism ; Osteonecrosis ; chemically induced ; genetics ; metabolism ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; TNF Receptor-Associated Factor 6 ; genetics ; metabolism ; Tartrate-Resistant Acid Phosphatase ; Time Factors ; Toll-Like Receptor 4 ; genetics ; metabolism ; Transcription Factor RelA ; genetics ; metabolism

Objective To observe the effects of acupuncture therapy with finger on back-shu point on acid reflux and lower esophageal sphincter pressure (LESP) of the patients with gastroesophageal reflux disease (GERD). Methods Totally 120 patients of GERD were randomly divided into treatment group and control group through random number table method, 60 cases in each group. Patients in the treatment group were treated with the acupuncture therapy with finger on back-shu point, and patients in control group were treated with lansoprazole tablets and dispersible mosapride citrate for two weeks. Total percentage of acid reflux time, the long time acid reflux episodes, and the longest acid reflux time of two groups were observed six months after the treatment. At the same time, the LESP variation of two groups was followed up six months after the treatment. Results The total percentage of acid reflux time, the long time acid reflux episodes, and the longest acid reflux time decreased significantly in all patients after treatment (P<0.01), while the comparison between groups showed no significant difference (P>0.05). After treatment, LESP of two groups was significantly improved (P<0.05) than before treatment. After stopping treatment half a year, the treatment group had obvious difference (P<0.05) compared with before treatment, while the control group had no significant difference (P>0.05). Conclusion The acupuncture therapy with finger on back-shu point can reduce acid reflux, and achieve the goal of treatment of GERD by improving the lower esophageal sphincter pressure. The duration of improving LESP is longer.

Osteonecrosis of the femoral head is frequently observed in patients treated with excessive corticosteroids. However, the pathogenesis of corticosteroid-induced osteonecrosis remains unclear. The purpose of this study was to investigate the role of Toll-like receptor 4 (TLR4) signaling pathway in steroid-induced femoral head osteonecrosis in rats. Male Sprague-Dawley rats were injected intramuscularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, twice per week. The animals were sacrificed at 2, 4 and 8 weeks after the last MP injection, respectively, and then allocated to the 2-, 4- and 8-week model groups (n=24 each). Rats in the control group (n=12) were not given any treatment. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in plasma was determined. The activation of osteoclasts in the femoral head was assessed by TRAP staining. The expression of TLR4, MyD88, TRAF6 and NF-κB p65 that are involved in TLR4 signaling, and MCP-1 production were detected by using real-time PCR (RT-PCR) and Western blotting. The results showed that the osteonecrosis in the femoral head was clearly observed and the concentration of TRAP in the plasma was increased in the model rats. The femoral head tissues in MP-treated rats were positive for TRAP and the intensity of TRAP staining was greater in MP-treated rats than in control rats. As compared with the control group, the mRNA expression of TLR4 signaling-related factors was enhanced significantly at 4 and 8 weeks, and the protein levels of these factors increased significantly with time. It was concluded that MP could induce the femoral head osteonecrosis in rats, which was associated with osteoclast activation via the TLR4 signaling pathway. These findings suggest that TLR4 signaling pathway plays a pivotal role in the pathogenesis of steroid-induced osteonecrosis.