Bioinformatics analysis identifies TGF-ß signaling pathway-associated molecular subtypes and gene signature in diabetic foot.

The role of transforming growth factor ß (TGF-ß) in inflammation and immune response is established, but the mechanism of TGF-ß signaling pathway-related genes (TRGs) in diabetic foot ulcer (DFU) is not fully understood. We aimed to investigate the contribution of TRGs in the identification, molecular categorization, and immune infiltration of DFU through bioinformatics analysis. TGF-ß signaling pathway is activated in DFU. 33 TRGs were upregulated. Regression analysis revealed TGFBR1 and TGFB1 as significant differential expression core genes, validated by quantitative real-time PCR. The diagnostic model with core genes had high clinical validity (AUC = 0.909). Core gene expression was associated with immune cell infiltration. A total of 5672 genes showed differential expression in TGF-related patterns, with differences in biological functions and immune infiltration. TGF-ß signaling pathway may be critical in DFU development.

Ginsenoside Rg5 promotes wound healing in diabetes by reducing the negative regulation of SLC7A11 on the efferocytosis of dendritic cells.

Background: ginsenoside Rg5 is a rare ginsenoside with known hypoglycemic effects in diabetic mice. This study aimed to explore the effects of ginsenoside Rg5 on skin wound-healing in the Leprdb/db mutant (db/db) mice (C57BL/KsJ background) model and the underlying mechanisms. Methods: Seven-week-old male C57BL/6J, SLC7A11-knockout (KO), the littermate wild-type (WT), and db/db mice were used for in vivo and ex vivo studies. Results: Ginsenoside Rg5 provided through oral gavage in db/db mice significantly alleviated the abundance of apoptotic cells in the wound areas and facilitated skin wound healing. 50 µM ginsenoside Rg5 treatment nearly doubled the efferocytotic capability of bone marrow-derived dendritic cells (BMDCs) from db/db mice. It also reduced NF-κB p65 and SLC7A11 expression in the wounded areas of db/db mice dose-dependently. Ginsenoside Rg5 physically interacted with SLC7A11 and suppressed the cystine uptake and glutamate secretion of BMDCs from db/db and SLC7A11-WT mice but not in BMDCs from SLC7A11-KO mice. In BMDCs and conventional type 1 dendritic cells (cDC1s), ginsenoside Rg5 reduced their glycose storage and enhanced anaerobic glycolysis. Glycogen phosphorylase inhibitor CP-91149 almost abolished the effect of ginsenoside Rg5 on promoting efferocytosis. Conclusion: ginsenoside Rg5 can suppress the expression of SLC7A11 and inhibit its activity via physical binding. These effects collectively alleviate the negative regulations of SLC7A11 on anaerobic glycolysis, which fuels the efferocytosis of dendritic cells. Therefore, ginsenoside Rg5 has a potential adjuvant therapeutic reagent to support patients with wound-healing problems, such as diabetic foot ulcers.

Machine learning-based nomogram for 30-day mortality prediction for patients with unresectable malignant biliary obstruction after ERCP with metal stent: a retrospective observational cohort study.

BACKGROUND: This study aimed to investigate the risk factors for 30-day mortality in patients with malignant biliary obstruction (MBO) after endoscopic retrograde cholangiopancreatography (ERCP) with endobiliary metal stent placement. Furthermore, we aimed to construct and visualize a prediction model based on LASSO-logistic regression. METHODS: Data were collected from 245 patients who underwent their first ERCP with endobiliary metal stent placement for unresectable MBO between June 1, 2013, and August 31, 2021. Univariable and multivariable logistic regression analyses were conducted to identify the risk factors for 30-day mortality. We subsequently developed a logistic regression model that incorporated multiple parameters identified by LASSO regression. The model was visualized and the nomogram was plotted. Risk stratification was performed based on nomogram-derived scores. RESULTS: The 30-day mortality rate was 10.7% (23/245 patients). Distant metastasis, total bilirubin, post-ERCP complications, and successful drainage were independent risk factors of 30-day mortality. The variables screened by LASSO regression, including distant metastasis, total bilirubin, post-ERCP complications, and successful drainage, were incorporated into the logistic model. The results were visualized through a nomogram based on the model. To assess the model's performance, discrimination was evaluated using the area-under-the-curve values obtained from receiver operating characteristic analyses with 10-fold cross-validation in the training group and validated in the testing group. The calibration curve showed the good predictive ability of the model. Decision curve analysis is used to evaluate the clinical application of nomogram. Finally, we performed risk stratification based on the risk calculated using the nomogram. Patients were assigned to the low-, moderate-, and high-risk groups based on their probability scores. The Kaplan-Meier survival curves for the different nomogram-based groups were significantly different (p < 0.001). CONCLUSIONS: We developed a nomogram using the LASSO-logistic regression model to forecast the 30-day mortality rate in patients who had undergone ERCP with endobiliary metal stent placement due to MBO. This nomogram can assist in identifying individuals at high-risk of 30-day mortality following ERCP.

Percutaneous robot-assisted screw fixation for nondisplaced pelvic fractures: a good choice?

PURPOSE: To compare the merits and demerits of percutaneous robot-assisted screw fixation for nondisplaced pelvic fractures with other treatments via long-term follow-up. METHODS: This was a retrospective analysis of nondisplaced pelvic fractures treated between January 2015 and December 2021. The number of fluoroscopy exposures, operative duration, intraoperative blood loss, surgical complications, screw placement accuracy and Majeed score were compared among the nonoperative group (24 cases), open reduction and internal fixation (ORIF) group (45 cases), free-hand empirical screw fixation (FH) group (10 cases) and robot-assisted screw fixation (RA) group (40 cases). RESULTS: There was less intraoperative blood loss in the RA and FH groups than in the ORIF group. The number of fluoroscopy exposures in the RA group was lower than that in the FH group but much higher than that in the ORIF group. There were five cases of wound infection in the ORIF group and no surgical complications in the FH or RA group. The medical expenses were higher in the RA group than in the FH group, with no significant difference from the ORIF group. The Majeed score was lowest in the nonoperative group three months after injury (64.5±12.0) but lowest in the ORIF group one year after injury (88.6±4.1). CONCLUSION: Percutaneous RA for nondisplaced pelvic fractures is effective and minimally invasive and does not increase medical expenses compared with ORIF. Therefore, it is the best choice for patients with nondisplaced pelvic fractures.

The efficacy of "TiRobot"orthopaedic robot-assisted VS conventional fluoroscopic percutaneous screw fixation of the sacroiliac joint.

PURPOSE: This study is to compare the precision and safety of the orthopaedic robot with conventional fluoroscopy for assisted percutaneous sacroiliac joint screw implantation. METHODS: Retrospective analysis was performed on the clinical data of 57 patients with unstable posterior pelvic ring injuries who were admitted and met the criteria between January 2017 and January 2022. All of these patients underwent percutaneous sacroiliac joint screw implantation, and their clinical data were split into two groups based on the surgical technique: a RA group (robot-assisted implantation, 30 patients, 54 screws) and a CF group (conventional fluoroscopic freehand implantation, 27 patients, 42 screws). There were 96 screws placed in total. The durations of the two groups' operations, fluoroscopy examinations, fluoroscopy doses, total number of fluoroscopies, and intra-operative guide pin applications were noted and compared. On post-operative CT scans, the placement of each screw was assessed using the Gertzbein-Robbins classification. Finally, imaging Matta criteria were used to assess the sacroiliac joint fracture reduction. The Majeed functional score was used to assess clinical function. RESULTS: Both groups successfully completed 57 procedures in total. In both groups, there were no consequences from vascular injury, wound infection, or urinary tract infection. Additionally, there were no complications from robotic-induced nerve injury, operating time, fluoroscopic dose, and the frequency of fluoroscopic; the number of percutaneous punctures in the RA group was lower than that of the CF group.There were statistically significant differences between the aforementioned data (P < 0.05). The modified Matta evaluated the effectiveness of fracture reduction. In the RA group, there was no statistically significant difference between the CF group (P > 0.05). According to the modified Gertzbein-Robbins classification criteria, the 54 screws implanted in the RA group were classified as follows: class A (45), class B (5), class C (4), and class D (0); the accuracy rate of the implants was 92.59%. Forty-two screws implanted in the CF group, 30 screws were defined class A, class B (3), class C (7), and class D (2). The accuracy rate of the implants was 78.57%(χ2 = 3.967, P < 0.05). There was a statistically significant difference between the two groups. The Majeed score 30 patients in RA group, one month post-operation, 16 considered exceptional, eight decent, six moderate, and zero bad. Post-operation more than six months,25 recorded exceptional, five decent. By the time,27 patients in CF group,12 exceptional grade, eight decent, six moderate, and one bad,one month post-operation. Post-operation more than six months,22 recorded exceptional, five decent.Both group (P > 0.05). CONCLUSION: "TiRobot" robot-assisted screw implant treatment for unstable posterior pelvic ring injury has a greater success rate than traditional surgery as compared to conventional percutaneous screw implant. It is a precise, secure, and minimally invasive surgical technique that can also be applied to severe pelvic injuries even congenital sacral deformities.

Optimal position and apex-subchondral bone distance of cannulated screws for internal fixation of femoral neck fracture: A radiological study.

To determine the optimal position of three cannulated screws in an inverted triangle pattern for internal fixation of femoral neck fractures, including the apex-subchondral bone distance, computed tomography (CT) images of the hip were processed using the MIMICS (Materialize Interactive Medical Image Control System) Research software. Points adjacent to the inferior, anterosuperior, and posterior cortex of the femoral neck were selected on the axial view. Subsequently, the positions of these points were adjusted to maximize the area between them, and splines were drawn in the coronal and sagittal planes to represent the cannulated screws. Finally, the virtual anteroposterior and lateral fluoroscopy images of the proximal femur and splines were created and the parameters calculated. Finite element analysis showed this fixation scheme provides stronger fracture support and stability. Twenty patients with femoral neck fractures (Modified group), with the area and perimeter of the triangle formed on axial postoperative CT images, including the shortest distance from the tip of the screw to the subchondral bone was compared with 23 matched patients for whom the conventional inverted isosceles triangle configuration of screws for internal fixation was used (Conventional group). The area and perimeter of the stabilization screws were larger, with a shorter apex-subchondral bone distance for the Modified group. There was no incidence of screw penetration in the femoral neck or head in either group, and all fractures healed within a follow-up period of 10 months. The modified screw placement method is simple and safe and provides greater fracture stability than the conventional empirical method of fixation.

Robot-assisted vs traditional percutaneous freehand for the scaphoid fracture treatment: a retrospective study.

PURPOSE: The purpose of this study was to assess the efficiency, safety, and accuracy of cannulated screw fixation using a robot-assisted method compared with a traditional percutaneous freehand method. METHODS: This retrospective clinical study included 18 patients with scaphoid fracture who underwent cannulated screw fixation by robot-assisted technique or traditional percutaneous freehand technique from June 2018 to June 2020. All patients were divided into the robot-assisted group (9 patients) or the traditional surgery group (9 patients). The operation time, blood loss, number of intra-operative fluoroscopies, fracture healing time, Mayo wrist function score, and screw implantation accuracy were recorded in the two groups. RESULTS: The average age of the robot-assisted group was 37.9 ± 10.6 years (with a range of 30 to 52 years), there were eight males and one female, and there were six cases of scaphoid fracture on the right side and three on the left side. The average pre-operative time was 2.8 ± 0.7 days (ranging from 1 to 3 days). The average age of the traditional surgery group was 31.6 ± 6.8 years (with a range of 20 to 45 years), there were eight males and one female, and there were five cases of scaphoid fracture on the right side and four on the left side. The average pre-operative time was 2.1 ± 0.8 days (with a range of 2 to 4 days). The number of intra-operative fluoroscopies was 24.4 ± 3.5 in the traditional surgery group, whereas it was only 10.1 ± 1.9 in the robot-assisted group, which was significantly lower (P < 0.05). The average operation time of the traditional operation group was 48.4 ± 12.2 min, and that of the robot-assisted group was 32.6 ± 4.2 minutes, which was significantly shorter (P < 0.05). The angles between the actual screw position and the central axis of the scaphoid on both the coronal and sagittal post-operative CT images were 8.3° ± 2.3° and 8.8° ± 1.6° for the traditional operation group and 3.8° ± 0.8° and 4.3° ± 1.2° for the robot-assisted group, so the accuracy of the robot-assisted group was significantly higher (P < 0.05). There were no significant differences between the two groups in wrist function recovery or fracture healing time. CONCLUSION: Robot-assisted treatment of scaphoid fracture is more accurate than traditional freehand technology, with shorter operation time and fewer intra-operative fluoroscopies. There is no difference between the two surgical techniques in intra-operative bleeding, post-operative fracture healing, or functional recovery. Robot-assisted surgery is a safe, effective, and accurate method for treating scaphoid fracture.

A systematic review and meta-analysis of elastic stockings for prevention of thrombosis after orthopedic surgery.

BACKGROUND: To investigate the preventive effect of elastic stockings on deep vein thrombosis (DVT) after orthopedic surgery by literature search and meta-analysis. METHODS: PubMed, Embase and Cochrane were selected as the search database platforms to search the literature of randomized controlled trials related to elastic stockings and DVT published from 2008 to date. Revman 5.3.5 software was used for statistical analysis of the data to obtain forest and funnel plots. RESULTS: In this study, 90 studies were initially screened and 7 were finally included, covering a total of 3,116 patients. Meta-analysis showed that the 7 studies had statistical heterogeneity (I2=32%, P=0.18), so a random effect model was used. The obtained statistic was [odds ratio (OR) =0.59, 95% confidence interval (CI): (0.34, 1.03)], the statistical effect size was Z=1.84, P=0.07, and the difference was not statistically significant, so a stepwise sensitivity analysis was performed by the exclusion method. One study was excluded, and the remaining 6 showed homogeneity (I2=0%, P=0.46). They were analyzed by subgroup according to the type of operation: ankle surgery or hip and knee arthroplasty. The internal literatures of each subgroup were homogeneous: ankle surgery subgroup (I2=0%, P=0.43), hip and knee arthroplasty subgroup (I2=0%, P=0.88). Therefore, fixed effect mode analysis was used, and the effect size of elastic stockings after ankle surgery was Z=3.65, P=0.0003, while the effect size of elastic stockings in the hip and knee arthroplasty subgroup was Z=1.23, P=0.22. DISCUSSION: Elastic stockings had an obvious preventive effect on DVT in patients undergoing ankle surgery, but not in patients undergoing lumbar, knee or spinal surgery. It is necessary to combine anticoagulant drugs and other physical therapies to prevent DVT.

Hydrogen sulfide inhibits calcium and phosphorus loss after fracture by negatively regulating glucocorticoid/glucocorticoid receptor α.

AIMS: Post-fracture calcium and phosphorus excretion is greater than influx, which might be caused by stress. Glucocorticoid is known to enhance calcium and phosphorous excretion, and hydrogen sulfide (H2S) has been shown to exert inhibitory effects on glucocorticoid. Therefore, this study explored whether H2S could inhibit calcium and phosphorus loss after fracture by regulating glucocorticoid and/or its receptor. MAIN METHODS: The following properties were analyzed in rats with femur fractures: serum and urinary calcium and phosphorus (by colorimetry); bone turnover markers alkaline phosphatase, serum type 1 collagen amino terminal peptide, type 1 procollagen carboxy terminal peptide, and anti-tartaric acid phosphatase (by ELISA); factors related to calcium-phosphorus metabolism including glucocorticoid, parathyroid hormone, calcitonin, fibroblast growth factor 23, and 1,25(OH)2D3 (by ELISA); and sulfhydration of glucocorticoid receptor α in the kidney (by immunoprecipitation linked biotin-switch assay), after supplementing with mifepristone, the H2S donor GYY4137 or H2S generating enzyme inhibitors aminooxyacetic acid and propargylglycine. KEY FINDINGS: Serum H2S decreased and glucocorticoid secretion increased in rats post-fracture. The glucocorticoid receptor inhibitor mifepristone partly blunted calcium and phosphorus loss. Furthermore, supplementation with GYY4137 reduced glucocorticoid secretion; inhibited glucocorticoid receptor α activity by sulfhydration; downregulated vitamin D 1α-hydroxylase expression; and upregulated 24-hydroxylase, calbindin-D28k, and sodium phosphate cotransporter 2a expression in the kidney; thereby inhibiting calcium and phosphorus loss induced by fracture. Moreover, inhibiting endogenous H2S generation showed opposite effects. SIGNIFICANCE: Our findings suggest that H2S antagonized calcium and phosphorus loss after fracture by reducing glucocorticoid secretion and inhibiting glucocorticoid receptor α activity by sulfhydration.

TiRobot-Assisted Percutaneous Cannulated Screw Fixation in the Treatment of Femoral Neck Fractures: A Minimum 2-Year Follow-up of 50 Patients.

OBJECTIVE: To assess the long-term clinical efficacy of TiRobot-assisted percutaneous cannulated screw fixation in the treatment of femoral neck fractures. METHODS: This retrospective study included 50 patients with unilateral femoral neck fractures who were treated with TiRobot-assisted percutaneous cannulated screw fixation from September 2017 to May 2018. After at least 2 years of follow-up, the results of treatment, including operation duration, frequency of fluoroscopy use, intraoperative bleeding, hospital stay, medical expense, screw placement accuracy, rate of fracture healing and necrosis of the femoral head, and Harris hip scores at the last follow up, were recorded and compared with those of 83 matched patients who underwent conventional manual positioning surgery. RESULTS: The TiRobot group had longer operation duration (83.3 ± 31.2 min vs 44.1 ± 14.8 min) and higher medical expenses (28,407.1 ± 7498.0 yuan vs 22,672.3 ± 4130.3 yuan) than the conventional group. The TiRobot group had significantly less intraoperative bleeding (11.3 ± 7.3 mL vs 51.6 ± 40.4 mL) and shorter hospital stay (8.6 ± 2.8 days vs 11.1 ± 3.41 days) than the conventional group. Screw parallelism (1.32° ± 1.85° vs 2.54° ± 2.99° on anteroposterior radiograph; 1.42° ± 2.25° vs 3.09° ± 3.63° on lateral radiograph) and distance between screws (58.44 ± 10.52 mm vs 39.69 ± 12.17 mm) were significantly improved. No significant difference was found between the two groups in terms of the use of fluoroscopy (40.1 ± 28.5 times vs 38.6 ± 21.0 times) and Harris hip scores at the last follow-up (93.2 ± 10.3 points vs 88.4 ± 11.9 points). Two cannulated screws penetrated the femoral head during manual insertion in the conventional group but not in the TiRobot group. The rate of nonunion and necrosis of the femoral head in the TiRobot group was reduced compared with that in the conventional group (0 vs 7.2%; 6.0% vs 24.1%). CONCLUSION: TiRobot-assisted percutaneous cannulated screw fixation of femoral neck fractures is accurate and minimally invasive and helps in reducing late complications, particularly necrosis of the femoral head and nonunion of fractures.

Effect of changes in serum levels of endogenous hydrogen sulfide on fracture healing: Study protocol clinical trial (SPIRIT compliant).

BACKGROUND: Fracture is a common disease; many factors affect fracture healing. Recent studies have confirmed that hydrogen sulfide (H2S) plays an essential role in bone formation, but most of these studies are drawing conclusions based on animal experiment; whether H2S could promote fracture healing in patients is still unclear. We aim to investigate the change of serum H2S in fracture patients, and analyze its effort on fracture healing. METHODS: This is a single-center, prospective cohort study. Patients with spinal or limb fracture will be recruited. Patient's serum and urine will be collected at baseline for examination (serum H2S, ß-CTX, OC, PINP, 25-OH-VitD3, S-CTX, urinary calcium, and urinary creatinine). All patients will be followed-up for 24 months in outpatients settings, the image of X-ray or CT will be reviewed and fracture healing will be judged by 2 experienced orthopedic physicians. The difference in serum parameters especially H2S will be compared between patients with fracture healed within 9 months and those with fracture unhealed at 9 months. DISCUSSION: Results of the trial could provide insight into influence of H2S on fracture healing. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of School of Medicine UESTC & Sichuan Provincial People's Hospital Ethics Committee. All the participants will be asked to provide written informed consent before data collection. The findings of the study will be published in peer-reviewed journals and will be presented at national or international conferences.