This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

Objective:To investigate the clinical application effect of absorbable plates in the treatment of children with craniosynostosis.Methods:Retrospective analysis was performed on the clinical data of patients with congenital craniosynostosis who were treated in the Department of Burns and Plastic Surgery, Children’s Hospital of Nanjing Medical University from January 2019 to October 2022. Preoperatively, three dimensional CT scan of the skull was performed in order to make a frontal and orbital model. All patients underwent traditional fronto-orbital reconstruction with skull flaps. With the assistance of the frontal and orbital model, the skull flap were rotated and shaped, and then absorbable plates and screws were used for internal fixation under direct vision. Postoperative follow-up observations were conducted on the complications such as infection, incision dehiscence, foreign body reactions of absorbable plates, and the stability of the skull flap.Results:A total of 12 patients were enrolled, 9 males and 3 females, aged 3-17 months, with an average of 11.3 months. There were 7 cases of unilateral coronal craniosynostosis, 3 cases of unilateral coronal craniosynostosis, and 2 cases of Apert syndrome. All cases underwent operation uneventfully, the operation time was 2.8-4.5 hours with an average of 3.6 hours. Follow-up ranged from 13 to 32 months (average, 24.5 months). One patient experienced incision dehiscence 45 days after surgery, which healed after conservative management. The remaining patients had no infections, hematomas, or other complications. All patients had visible and palpable raised masses at the site of absorbable plate implantation in 3-5 months after surgery, which gradually resolved in 10-15 months after surgery.The head shape of patients with craniosynostosis had been significantly improved after surgery, and follow-up CT scans of the skull revealed no displacement of the skull flaps and good osteogenesis.Conclusion:The use of absorbable plates for internal fixation in children with craniosynostosis can achieve stable fixation effects with few complications, and is worthy of clinical promotion and application.

Objective:To investigate the clinical application effect of absorbable plates in the treatment of children with craniosynostosis.Methods:Retrospective analysis was performed on the clinical data of patients with congenital craniosynostosis who were treated in the Department of Burns and Plastic Surgery, Children’s Hospital of Nanjing Medical University from January 2019 to October 2022. Preoperatively, three dimensional CT scan of the skull was performed in order to make a frontal and orbital model. All patients underwent traditional fronto-orbital reconstruction with skull flaps. With the assistance of the frontal and orbital model, the skull flap were rotated and shaped, and then absorbable plates and screws were used for internal fixation under direct vision. Postoperative follow-up observations were conducted on the complications such as infection, incision dehiscence, foreign body reactions of absorbable plates, and the stability of the skull flap.Results:A total of 12 patients were enrolled, 9 males and 3 females, aged 3-17 months, with an average of 11.3 months. There were 7 cases of unilateral coronal craniosynostosis, 3 cases of unilateral coronal craniosynostosis, and 2 cases of Apert syndrome. All cases underwent operation uneventfully, the operation time was 2.8-4.5 hours with an average of 3.6 hours. Follow-up ranged from 13 to 32 months (average, 24.5 months). One patient experienced incision dehiscence 45 days after surgery, which healed after conservative management. The remaining patients had no infections, hematomas, or other complications. All patients had visible and palpable raised masses at the site of absorbable plate implantation in 3-5 months after surgery, which gradually resolved in 10-15 months after surgery.The head shape of patients with craniosynostosis had been significantly improved after surgery, and follow-up CT scans of the skull revealed no displacement of the skull flaps and good osteogenesis.Conclusion:The use of absorbable plates for internal fixation in children with craniosynostosis can achieve stable fixation effects with few complications, and is worthy of clinical promotion and application.

Objective:To establish a classification system for the repair band in the subchondral bone origination point in MRI for traumatic osteonecrosis of the femoral head (ONFH) and preliminarily explore the correlation between this classification and the progression of femoral head collapse.Methods:A retrospective analysis was conducted on 73 cases of traumatic ON-FH treated at the Quanzhou Orthopedic-traumatological hospital from January 2000 to December 2019. Among them, there were 46 males and 27 females with an average age of 34.9±8.3 years (range 19-55 years). Clinical and radiological data such as age, gender, side, fracture classification, reduction quality, JIC classification, and bone repair band (BRB) classification were recorded. The progression of traumatic ONFH was assessed using the ARCO staging system, with stages IIIA and IIIB defined as mild collapse and progressive collapse, respectively. The BRB classification was established based on MRI findings, and the inter- and intra-observer consistency of the BRB classification was analyzed using Kappa test. The correlation between the BRB classification and progressive femoral head collapse was analyzed using the Kaplan-Meier survival curve and binary variable Cox regression analysis.Results:According to the BRB classification, 73 cases were divided into type 1 with superficial lesion in 38.4%, type 2 with uncertain lesion in 21.9%, and type 3 with extensive lesion in 39.7%. The inter-observer consistency Kappa value for the BRB classification was 0.798, and the intra-observer consistency Kappa value was 0.896, indicating a high level of consistency. A follow-up of 73 cases (54.8±34.9 months, range 24-165 months) showed a significant correlation between the BRB classification and ARCO staging at the last follow-up (χ 2=37.556, P<0.001), with progression to stages IIIA and IIIB as follows: type 1 had 3 and 1 cases, type 2 had 4 and 1 cases, and type 3 had 14 and 12 cases, respectively. Using the occurrence of progressive collapse (stage IIIB) as the endpoint, the risk of progression to stage IIIB for type 2 was not statistically different from type 1 [ HR=1.766, 95% CI (0.465, 6.702), P=0.403]; the risk of progression to stage IIIB for type 3 was significantly higher than for type 1 [ HR=15.126, 95% CI (4.708, 48.592), P<0.001]. Conclusion:The BRB classification is closely related to the progression of traumatic ONFH and is an independent risk factor for predicting the occurrence of progressive collapse; this classification is helpful for early diagnosis and predicting the progression of collapse and treatment plan decision-making.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective: Understanding mental health status of students with learning disabilities in Beijing to provide a basis for mental health promotion of students with learning disabilities. Methods: By means of random cluster sampling, 5 787 enrolled students in grade one and grade two of 11 public junior middle schools in Beijing were selected as the survey subjects. A self designed questionnaire was used to investigate the students’ learning disabilities and mental health status through anonymous self filling. Results: About 11.6% students self reported learning disabilities. The proportions of students with learning difficulty in mathematical reasoning and calculation were higher, 44.1% and 40.7% respectively. The reported rate of mental health problems was 38.3%. The top four of the 10 symptoms were obsessive compulsive symptoms, learning pressure, emotional instability and anxiety(2.19±0.77)(2.17±0.99)(2.09±0.90)(2.07±1.08). Compared with students without learning disabilities, students with self reported learning disabilities had poorer mental health status(OR=1.47), and learning disabilities were related to most factors of mental health. Different types of learning disabilities were associated with different mental health factors. Conclusion Mental health problems of students with learning disabilities are higher than that of students without learning disabilities. It is necessary to strengthen the mental health support for students with learning disabilities and improve their mental health.

Objective:To investigate the efficacy and safety of oral sirolimus in the treatment of refractory vascular anomalies.Methods:From February 2017 to February 2018, 20 cases of vascular deformity with no obvious improvements after multiple therapies in our hospital were included. Among them, 5 have Kaposiform hemangioendothelioma (KHE) with Kasabach-Merritt phenomenon (KMP), 10 have lymphatic malformation, 3 have venous malformation and 2 have lymphatic venous malformation. A single course of oral sirolimus lasted for 3 months. Initial dose was 0.8 mg/m 2 once, oral administration twice per day, and subsequent dose was adjusted to maintain the concentration of blood drug at 10-15 ng/ml. Before and after taking sirolimus, the general information, tumor changes and the adverse reactions were gathered. Efficacy was evaluated at the end of the treatment course. Effective: tumor volume reduced by more than 50% and or platelets stabilized in the normal range. Partly effective: tumor volume reduced by 25%-50%. No effect: tumor volume reduced by less than 25% or no significant change. Results:All the patients were treated with sirolimus orally for 1-3 courses, among which 11 were effective, 6 were partially effective, and 3 were ineffective. They were followed up for more than 3 months after the end of the whole course and no tumor enlargement was observed. All the 5 cases with KHE and KMP had significantly reduced tumor size and the platelets were stable in the normal range, but 2 of them suffered from severe pneumonia, one of them eventually perished. Two of the remaining children had elevated liver enzymes and high fever. The lesions of 10 patients with lymphatic malformations were reduced, and 4 of them had mild liver dysfunction. Two with lymphatic venous malformations had shrunk in different degree, and 3 with venous malformations had no effect. Three of them showed significant relief of pain symptoms, and their pain score was significantly lower than that before oral administration (8.7±1.2 vs 1.3±1.2, P=0.001). Except for 1 case with venous malformation had oral ulcer. No obvious adverse reaction were observed in the remaining 11 patients. Conclusions:Oral sirolimus may be effective and safe in the treatment of refractory vascular anomalies, but it should be treated with caution in little infants.

Objective:To investigate the safety and efficacy of sirolimus through the change in platelet counts during the sirolimus therapy on Kasaback-Merritt phenomenon(KMP).Methods:Four patients were treated in Nanjing Children Hospital between Jaunary 2017 and June 2019 were enrolled in the study, including two males and two females. Their age was ranged from two days to three months. They all presented with huge mass located in neck or retroperitoneal and thrombocytopenia, hypofibrinogenemia. Their coagulation could not be improved by surgery or palate transfusion or steroids. They were all diagnosed as Kaposiform hemangioendothelioma(KHE) with KMP according to the biopsy, coagulation index and CT. Sirolimus were administered with 0.1 mg -1·kg -1·d -1 or 0.8 mg/m 2, twice daily. Subsequent dose was adjusted to maintain the trough level between 10-15 ng/ml.Steroids were weaned gradually. Blood accounts were measured following the sirolimus administration. Results:All the four patients got improvement in platelet counts. Three patients went through a significant decreasing of palate counts after adding sirolimus for about 1-4 days. Two lesions prompted improvement with smaller size, lighter color and softer texture without complete regression. Two patients had elevated liver enzymes and/or interstitial pneumonia. One recovered while the other died of severe pneumonia with dyspnea. All the palate counts of survived patients remained in normal level in the following one year.Conclusions:Sirolimus is an effective method in treating KMP and stabilizing platelet counts. However, it can not cure hemangioendothelioma.

Objective:To investigate the efficacy and safety of oral sirolimus in the treatment of refractory vascular anomalies.Methods:From February 2017 to February 2018, 20 cases of vascular deformity with no obvious improvements after multiple therapies in our hospital were included. Among them, 5 have Kaposiform hemangioendothelioma (KHE) with Kasabach-Merritt phenomenon (KMP), 10 have lymphatic malformation, 3 have venous malformation and 2 have lymphatic venous malformation. A single course of oral sirolimus lasted for 3 months. Initial dose was 0.8 mg/m 2 once, oral administration twice per day, and subsequent dose was adjusted to maintain the concentration of blood drug at 10-15 ng/ml. Before and after taking sirolimus, the general information, tumor changes and the adverse reactions were gathered. Efficacy was evaluated at the end of the treatment course. Effective: tumor volume reduced by more than 50% and or platelets stabilized in the normal range. Partly effective: tumor volume reduced by 25%-50%. No effect: tumor volume reduced by less than 25% or no significant change. Results:All the patients were treated with sirolimus orally for 1-3 courses, among which 11 were effective, 6 were partially effective, and 3 were ineffective. They were followed up for more than 3 months after the end of the whole course and no tumor enlargement was observed. All the 5 cases with KHE and KMP had significantly reduced tumor size and the platelets were stable in the normal range, but 2 of them suffered from severe pneumonia, one of them eventually perished. Two of the remaining children had elevated liver enzymes and high fever. The lesions of 10 patients with lymphatic malformations were reduced, and 4 of them had mild liver dysfunction. Two with lymphatic venous malformations had shrunk in different degree, and 3 with venous malformations had no effect. Three of them showed significant relief of pain symptoms, and their pain score was significantly lower than that before oral administration (8.7±1.2 vs 1.3±1.2, P=0.001). Except for 1 case with venous malformation had oral ulcer. No obvious adverse reaction were observed in the remaining 11 patients. Conclusions:Oral sirolimus may be effective and safe in the treatment of refractory vascular anomalies, but it should be treated with caution in little infants.

Objective:To investigate the safety and efficacy of sirolimus through the change in platelet counts during the sirolimus therapy on Kasaback-Merritt phenomenon(KMP).Methods:Four patients were treated in Nanjing Children Hospital between Jaunary 2017 and June 2019 were enrolled in the study, including two males and two females. Their age was ranged from two days to three months. They all presented with huge mass located in neck or retroperitoneal and thrombocytopenia, hypofibrinogenemia. Their coagulation could not be improved by surgery or palate transfusion or steroids. They were all diagnosed as Kaposiform hemangioendothelioma(KHE) with KMP according to the biopsy, coagulation index and CT. Sirolimus were administered with 0.1 mg -1·kg -1·d -1 or 0.8 mg/m 2, twice daily. Subsequent dose was adjusted to maintain the trough level between 10-15 ng/ml.Steroids were weaned gradually. Blood accounts were measured following the sirolimus administration. Results:All the four patients got improvement in platelet counts. Three patients went through a significant decreasing of palate counts after adding sirolimus for about 1-4 days. Two lesions prompted improvement with smaller size, lighter color and softer texture without complete regression. Two patients had elevated liver enzymes and/or interstitial pneumonia. One recovered while the other died of severe pneumonia with dyspnea. All the palate counts of survived patients remained in normal level in the following one year.Conclusions:Sirolimus is an effective method in treating KMP and stabilizing platelet counts. However, it can not cure hemangioendothelioma.