BACKGROUND:The elastic modulus of bone-cartilage integration scaffolds differs significantly from that of natural bone-cartilage tissue,which can lead to a stress shield effect.As a result,the implants become loose and deformed,affecting the repair of osteochondral tissue.Cell gradient scaffolds made by axial direction three-period minimal surface have the same porosity and elasticity modulus as the human body,which provides a new idea for bone-cartilage scaffold design.OBJECTIVE:To study the effect of cell type and pore size on the mechanical properties of cell gradient scaffolds.METHODS:Three basic cells of Gyroid(G)type,Diamond(D)type,and Primitive(P)type were used.Through mathematical modeling of three-period minimal surface,different sizes and types of cells were used in the gradient region.A total of six kinds of cell gradient scaffolds(G-2P-4D,P-2D-4G,D-2P-4D,G-2D-4P,P-2G-4D,and D-2G-4P)were constructed and mechanical experiments and simulation experiments were conducted to evaluate the mechanical properties of the scaffolds.Flow performance parameters of the fluids in the scaffolds were obtained through computational fluid dynamics simulation.RESULTS AND CONCLUSION:Finite element mechanical simulation and compression experiment showed that P-2G-4D and P-2D-4G with the highest elastic modulus(148.67 MPa and 152.1 MPa),bearing a higher body load,improved the stability of the scaffold.The stress distribution in D-2P-4G was even and effectively reduced stress concentration,so that the connection function area could effectively transfer stress and reduce stress shielding.Flow rate was changing the least in G-2D-4P(0.10-0.48 mm/s).Permeability was higher than other scaffolds so that body fluids were able to flow though the gradient scaffold after implantation.This design method provides a new idea for the design of osteochondral scaffolds,and the simulation analysis results also provide a reference for the prediction of bone integration after implantation of scaffolds.

Objective To develop a core outcome set(COS)for clinical effectiveness trials of heart failure with preserved ejection fraction(HFpEF).Methods Outcome measures were collected through database literatures search,clinical experts questionnaire survey and semi-structured patients interview.Then,the outcome measures pool was constructed and domains were divided.Candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,a consensus meeting was held to determine COS and reach a consensus.Results A total of 317 outcome measures which could be divided into 6 domains were collected through literature research,questionnaire survey and semi-structured interview.15 candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,the consensus meeting reached consensus on a COS with 6 entries.Conclusion In this study,a COS for clinical effectiveness trials of HFpEF was developed,which is conducive to the standardization of efficacy evaluation.

BACKGROUND:The elastic modulus of bone-cartilage integration scaffolds differs significantly from that of natural bone-cartilage tissue,which can lead to a stress shield effect.As a result,the implants become loose and deformed,affecting the repair of osteochondral tissue.Cell gradient scaffolds made by axial direction three-period minimal surface have the same porosity and elasticity modulus as the human body,which provides a new idea for bone-cartilage scaffold design.OBJECTIVE:To study the effect of cell type and pore size on the mechanical properties of cell gradient scaffolds.METHODS:Three basic cells of Gyroid(G)type,Diamond(D)type,and Primitive(P)type were used.Through mathematical modeling of three-period minimal surface,different sizes and types of cells were used in the gradient region.A total of six kinds of cell gradient scaffolds(G-2P-4D,P-2D-4G,D-2P-4D,G-2D-4P,P-2G-4D,and D-2G-4P)were constructed and mechanical experiments and simulation experiments were conducted to evaluate the mechanical properties of the scaffolds.Flow performance parameters of the fluids in the scaffolds were obtained through computational fluid dynamics simulation.RESULTS AND CONCLUSION:Finite element mechanical simulation and compression experiment showed that P-2G-4D and P-2D-4G with the highest elastic modulus(148.67 MPa and 152.1 MPa),bearing a higher body load,improved the stability of the scaffold.The stress distribution in D-2P-4G was even and effectively reduced stress concentration,so that the connection function area could effectively transfer stress and reduce stress shielding.Flow rate was changing the least in G-2D-4P(0.10-0.48 mm/s).Permeability was higher than other scaffolds so that body fluids were able to flow though the gradient scaffold after implantation.This design method provides a new idea for the design of osteochondral scaffolds,and the simulation analysis results also provide a reference for the prediction of bone integration after implantation of scaffolds.

BACKGROUND:Osteonecrosis of the femoral head is a common complication in patients with systemic lupus erythematosus.The prediction and validation of the risk in advance will help to avoid or delay the progression of osteonecrosis of the femoral head.OBJECTIVE:To analyze risk factors for the occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients and to construct and validate a nomogram prediction model of systemic lupus erythematosus patients with osteonecrosis of the femoral head.METHODS:A retrospective study was conducted to analyze the medical records of 914 systemic lupus erythematosus patients who first visited First Affiliated Hospital of Henan University of Chinese Medicine between January 2013 and December 2022.All patients were divided into osteonecrosis of the femoral head(n=100)and non-osteonecrosis of the femoral head(n=814)groups according to whether they had suffered from osteonecrosis of the femoral head or not.Univariate,LASSO regression,and multifactorial logistic regression analyses were used to screen and identify the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head.The dataset was also randomly divided into training and test sets in a ratio of 7:3.A nomogram prediction model of the risk of systemic lupus erythematosus complicating osteonecrosis of the femoral head was constructed based on the results of the multifactorial logistic regression analysis.The performance of the nomogram was evaluated using the receiver operating characteristic curve,Hosmer-Lemeshow calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:(1)There were significant differences in disease duration of systemic lupus erythematosus,systemic lupus erythematosus disease activity,lupus nephritis,respiratory involvement,gastrointestinal involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,complement C3 decrease,cyclophosphamide,mycophenolate mofetil,biologics,maximum daily dose of glucocorticosteroids,and pulses of intravenous methylprednisolone between the osteonecrosis of the femoral head and non-osteonecrosis of the femoral head groups(P＜0.05).(2)Ten predictor variables related to the risk of osteonecrosis of the femoral head in patients with systemic lupus erythematosus were screened using LASSO regression analysis.Multivariate logistic regression analysis further confirmed disease duration of systemic lupus erythematosus,respiratory involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,cyclophosphamide,mycophenolate mofetil,biologics,and maximum daily dose of glucocorticosteroids were independent risk factors for osteonecrosis of the femoral head in systemic lupus erythematosus patients(P＜0.05).(3)The area under the receiver operating characteristic curve for predicting the risk of occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients was 0.802(95％CI=0.742-0.862)in the training set and 0.811(95％CI=0.745-0.876)in the testing set.The Hosmer-Lemeshow calibration curve fit was well(P=0.447 in raining set;P=0.870 in testing set).Decision curve analysis showed that it was beneficial in predicting the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients using the nomogram prediction model.(4)Menstrual abnormalities were one of the risk factors for osteonecrosis of the femoral head in female systemic lupus erythematosus patients.(5)The results suggest that the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head are multi-factorial,and a nomogram prediction model containing nine risk factors was also developed,which could be used to predict the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients.In addition,we reported for the first time that menstrual abnormalities were one of the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head in female.

Objective To develop a core outcome set(COS)for clinical effectiveness trials of heart failure with preserved ejection fraction(HFpEF).Methods Outcome measures were collected through database literatures search,clinical experts questionnaire survey and semi-structured patients interview.Then,the outcome measures pool was constructed and domains were divided.Candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,a consensus meeting was held to determine COS and reach a consensus.Results A total of 317 outcome measures which could be divided into 6 domains were collected through literature research,questionnaire survey and semi-structured interview.15 candidate outcome measures of COS were screened through two rounds of Delphi survey.Finally,the consensus meeting reached consensus on a COS with 6 entries.Conclusion In this study,a COS for clinical effectiveness trials of HFpEF was developed,which is conducive to the standardization of efficacy evaluation.

OBJECTIVE: To investigate the effectiveness of posterior minimally invasive approach in the treatment of posterior wall acetabular fractures. METHODS: The clinical data of 17 patients with posterior wall acetabular fractures treated with posterior minimally invasive approach between March 2019 and June 2023 were retrospectively analyzed. There were 14 males and 3 females with an average age of 41 years ranging from 28 to 57 years. The causes of injury were traffic accident in 12 cases and falling from height in 5 cases. There were 3 cases complicated with posterior hip dislocation and 2 cases complicated with sciatic nerve injury. According to AO/Orthopaedic Trauma Association (AO/OTA) classification, there were 11 cases of type A1.1 and 6 cases of type A1.2. The time from injury to operation was 5-8 days, with an average of 6.2 days. The incision length, intraoperative blood loss, and operation time were recorded. The quality of posterior wall fracture reduction were evaluated by Matta criteria, and hip function were evaluated by modified Merle d'Aubign-Postel score criteria at 6 months after operation and last follow-up. RESULTS: The operation was successfully completed in 17 cases. The length of incision ranged from 7 to 9 cm, with an average of 8.3 cm, and all incisions healed by first intention. The intraoperative blood loss ranged from 200 to 350 mL, with an average of 281 mL. The operation time ranged from 45 to 70 minutes, with an average of 57 minutes. Two patients had sciatic nerve injury before operation, and the sciatic nerve function recovered completely at 3 months after operation; the other 15 patients had no symptoms of sciatic nerve injury after operation. All the 17 patients were followed up 14-27 months, with an average of 19.5 months. At 1 week after operation, according to the Matta criteria, anatomical reduction was achieved in 12 cases and satisfactory reduction in 5 cases, with a satisfaction rate of 100%. According to the modified Merle d'Aubign-Postel scoring system, the hip function score was 13-18 (mean, 16.1) at 6 months after operation. Among them, 5 cases were excellent, 9 were good, and 3 were fair, with an excellent and good rate of 82.4%. At last follow-up, the hip function score was 7-18 (mean, 13.7), of which 3 cases were excellent, 9 were good, 3 were fair, and 2 were poor, with an excellent and good rate of 70.6%. During the follow-up, there was no infection, failure of internal fixation, and femoral head necrosis, and heterotopic ossification occurred in 2 cases. CONCLUSION The posterior minimally invasive approach has the advantages of less trauma, shorter operation time, less blood loss, without cutting off the external rotator muscle. Exposure through the gluteus medius-piriformis space and piriformis-supercilium space can provide sufficient safe exposure for the posterior wall acetabulum fracture, which is a reliable alternative approach for the posterior acetabular fracture.
Humans ; Acetabulum/surgery* ; Male ; Female ; Adult ; Middle Aged ; Minimally Invasive Surgical Procedures/methods* ; Retrospective Studies ; Fracture Fixation, Internal/instrumentation* ; Fractures, Bone/diagnostic imaging* ; Treatment Outcome ; Operative Time

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

Objective To construct intrauterine adhesion (IUA) mouse models induced by two different concentrations of ethanol injury, compare the phenotypes, and optimize a more stable IUA modeling method. Methods Twenty 8-week-old female C57BL/6N mice were randomly divided into two groups: the 95% ethanol injury group and the 50% ethanol injury group. Using a self-control method, the left uterine horn was infused with ethanol to establish the IUA model, while the right uterine horn was infused with saline as the sham operation. Five mice from each group were euthanized on day 7 and 15 after modeling, and uterine tissues were collected. Hematoxylin-eosin (HE) staining was used to observe the endometrial pathology, and Masson staining was used to assess the degree of endometrial fibrosis. Quantitative real-time PCR was employed to detect the expression levels of fibrosis markers and pro-inflammatory factors in the uterine tissues. Results Compared to the sham operation, these two ethanol injury led to a significant reduction in elasticity of the uterus, an increase in inflammatory infiltration, and a marked increase in the degree of fibrosis on day 7 after modeling (P<0.05). The 95% ethanol injury group showed a significant decrease in endometrial thickness (P<0.05), whereas no significant change was observed in the 50% ethanol injury group when compared to the sham operation (P>0.05). The expression levels of fibrotic marker molecules collagen type Ⅳ alpha 1 chain (Col4A1), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and pro-inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly elevated in the 50% ethanol injury group when compared to the sham operation (P<0.05), although there was an increasing trend of the same markers in the 95% ethanol injury group, the differences were not statistically significant (P>0.05). On day 15 after modeling, the histopathological changes in both ethanol injury groups were not significant when compared to the sham operation, the expression levels of Col4A1, TGF-β, TNF-α and IL-1β remained significantly higher in the 50% ethanol injury group (P<0.05), while only IL-1β was significantly elevated in the 95% ethanol injury group (P<0.05). Conclusion Uterine infusion with 95% ethanol results in more marked histopathological changes in the IUA mouse model compared to the 50% ethanol injury group. The 95% ethanol injury model is suitable for histopathological studies. However, the 50% ethanol injury group shows higher expression levels of fibrosis markers and pro-inflammatory factors compared to the 95% ethanol injury group, suggesting that the 50% ethanol injury model is more suitable for molecular pathological study.

BACKGROUND:Osteonecrosis of the femoral head is a common complication in patients with systemic lupus erythematosus.The prediction and validation of the risk in advance will help to avoid or delay the progression of osteonecrosis of the femoral head.OBJECTIVE:To analyze risk factors for the occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients and to construct and validate a nomogram prediction model of systemic lupus erythematosus patients with osteonecrosis of the femoral head.METHODS:A retrospective study was conducted to analyze the medical records of 914 systemic lupus erythematosus patients who first visited First Affiliated Hospital of Henan University of Chinese Medicine between January 2013 and December 2022.All patients were divided into osteonecrosis of the femoral head(n=100)and non-osteonecrosis of the femoral head(n=814)groups according to whether they had suffered from osteonecrosis of the femoral head or not.Univariate,LASSO regression,and multifactorial logistic regression analyses were used to screen and identify the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head.The dataset was also randomly divided into training and test sets in a ratio of 7:3.A nomogram prediction model of the risk of systemic lupus erythematosus complicating osteonecrosis of the femoral head was constructed based on the results of the multifactorial logistic regression analysis.The performance of the nomogram was evaluated using the receiver operating characteristic curve,Hosmer-Lemeshow calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:(1)There were significant differences in disease duration of systemic lupus erythematosus,systemic lupus erythematosus disease activity,lupus nephritis,respiratory involvement,gastrointestinal involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,complement C3 decrease,cyclophosphamide,mycophenolate mofetil,biologics,maximum daily dose of glucocorticosteroids,and pulses of intravenous methylprednisolone between the osteonecrosis of the femoral head and non-osteonecrosis of the femoral head groups(P＜0.05).(2)Ten predictor variables related to the risk of osteonecrosis of the femoral head in patients with systemic lupus erythematosus were screened using LASSO regression analysis.Multivariate logistic regression analysis further confirmed disease duration of systemic lupus erythematosus,respiratory involvement,Sj?gren's syndrome,osteoporosis,anti-ribonucleoprotein,cyclophosphamide,mycophenolate mofetil,biologics,and maximum daily dose of glucocorticosteroids were independent risk factors for osteonecrosis of the femoral head in systemic lupus erythematosus patients(P＜0.05).(3)The area under the receiver operating characteristic curve for predicting the risk of occurrence of osteonecrosis of the femoral head in systemic lupus erythematosus patients was 0.802(95％CI=0.742-0.862)in the training set and 0.811(95％CI=0.745-0.876)in the testing set.The Hosmer-Lemeshow calibration curve fit was well(P=0.447 in raining set;P=0.870 in testing set).Decision curve analysis showed that it was beneficial in predicting the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients using the nomogram prediction model.(4)Menstrual abnormalities were one of the risk factors for osteonecrosis of the femoral head in female systemic lupus erythematosus patients.(5)The results suggest that the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head are multi-factorial,and a nomogram prediction model containing nine risk factors was also developed,which could be used to predict the risk of osteonecrosis of the femoral head in systemic lupus erythematosus patients.In addition,we reported for the first time that menstrual abnormalities were one of the risk factors for systemic lupus erythematosus complicating osteonecrosis of the femoral head in female.

To summarize Professor WANG Xixing's clinical experience in treating advanced breast cancer with anxiety and depression from the perspective of shaoyang pivot. It is believed that the core pathogenesis of advanced breast cancer with anxiety and depression lies in the dysfunction of shaoyang pivot （referring to the imbalanced regulatory function of the shaoyang meridian system that governs the transportation and transformation of qi， blood， and body fluids）. This dysfunction can lead to abnormal circulation of qi， blood， and body fluids， as well as the intermingling of phlegm and blood stasis， which further promotes the spread and diffusion of cancer toxin. Meanwhile， it disturbs mental activity， resulting in a condition characterized by stagnation of cancer toxin and concurrent disorders of both the physical body and the spirit. Based on this pathogenesis， the basic therapeutic principles of harmonizing shaoyang， regulating the pivot to calm the spirit， and dissipating masses and resolving toxins are proposed. Clinically， the disease is classified into three syndromes for differentiation and treatment. For shaoyang pivot dysfunction syndrome， treatment should use self-prescribed Chaiqin Hengshu Ningxin Decoction （柴芩衡枢宁神汤）； for sanjiao pivot dysfunction syndrome， treatment should prescribe Chaigui Tongshu Dashen Decoction （柴归通枢达神饮）； for gallbladder function disorder syndrome， treatment should apply Wendan Qishu Shoushen Decoction （温胆启枢守神汤）. Throughout the treatment process， the concept of "simultaneous treatment of cancer and depression" is implemented to smooth the shaoyang pivot， block the vicious cycle where cancer toxin and emotional abnormalities mutually reinforce each other.