The genetic causal relationship between type 2 diabetes, glycemic traits and venous thromboembolism, deep vein thrombosis, pulmonary embolism: a two-sample Mendelian randomization study.

OBJECTIVE: To investigate the genetic underpinnings of the association between type 2 diabetes (T2D), glycemic indicators such as fasting glucose (FG), fasting insulin (FI), and glycated hemoglobin (GH), and venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), thereby contributing novel insights to the scholarly discourse within this domain. METHODS: Genome-wide association study (GWAS) summary data pertaining to exposures (T2D, FG, FI, GH) and outcomes (VTE, DVT, PE) were acquired from the IEU Open GWAS database, encompassing participants of European descent, including both male and female individuals. Two-sample Mendelian randomization (MR) analyses were conducted utilizing the TwoSampleMR and MRPRESSO packages within the R programming environment. The primary analytical approach employed was the random-effects inverse variance weighted (IVW) method. Heterogeneity was assessed via Cochran's Q statistic for MR-IVW and Rucker's Q statistic for MR-Egger. Horizontal pleiotropy was evaluated using the intercept test of MR Egger and MR pleiotropy residual sum and outlier (MR-PRESSO) analysis, with the latter also employed for outlier detection. Additionally, a "Leave one out" analysis was conducted to ascertain the influence of individual single nucleotide polymorphisms (SNPs) on MR results. RESULTS: The random-effects IVW analysis revealed a negative genetic causal association between T2D) and VTE (P = 0.008, Odds Ratio [OR] 95% confidence interval [CI] = 0.896 [0.827-0.972]), as well as between FG and VTE (P = 0.002, OR 95% CI = 0.655 [0.503-0.853]), GH and VTE (P = 0.010, OR 95% CI = 0.604 [0.412-0.884]), and GH and DVT (P = 0.002, OR 95% CI = 0.413 [0.235-0.725]). Conversely, the random-effects IVW analysis did not detect a genetic causal relationship between FI and VTE (P > 0.05), nor between T2D, FG, or FI and DVT (P > 0.05), or between T2D, FG, FI, or GH and PE (P > 0.05). Both the Cochran's Q statistic for MR-IVW and Rucker's Q statistic for MR-Egger indicated no significant heterogeneity (P > 0.05). Moreover, the intercept tests of MR Egger and MR-PRESSO suggested the absence of horizontal pleiotropy (P > 0.05). MR-PRESSO analysis identified no outliers, while the "Leave one out" analysis underscored that the MR analysis was not influenced by any single SNP. CONCLUSION: Our investigation revealed that T2D, FG, and GH exhibit negative genetic causal relationships with VTE at the genetic level, while GH demonstrates a negative genetic causal relationship with DVT at the genetic level. These findings furnish genetic-level evidence warranting further examination of VTE, DVT, and PE, thereby making a contribution to the advancement of related research domains.

The association between admission mean corpuscular volume and preoperative deep venous thrombosis in geriatrics hip fracture: a retrospective study.

OBJECTIVE: This study evaluated the association between admission MCV and preoperative deep vein thrombosis (DVT) in geriatric hip fractures. METHODS: Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of the patients were collected at the largest trauma center in northwest China. MCV was measured at admission and converted into a categorical variable according to the quartile. Multivariate binary logistic regression and generalized additive model were used to identify the linear and nonlinear association between MCV and preoperative DVT. Analyses were performed using EmpowerStats and the R software. RESULTS: A total of 1840 patients who met the criteria were finally enrolled and divided into four groups according to their MCV levels. The mean MCV was 93.82 ± 6.49 (80.96 to 105.91 fL), and 587 patients (31.9%) were diagnosed with preoperative DVT. When MCV was a continuous variable, the incidence of preoperative DVT increased with mean corpuscular volume. In the fully adjusted model, admission MCV was positively correlated with the incidence of preoperative DVT (OR: 1.03; 95% CI: 1.01-1.05; P = 0.0013). After excluding the effect of other factors, each additional 1fL of MCV increased the prevalence of preoperative DVT by 1.03 times as a continuous variable. CONCLUSION: MCV was linearly associated with preoperative DVT in geriatric patients with hip fractures and could be considered a predictor of DVT risk. The MCV may contribute to risk assessment and preventing adverse outcomes in the elderly. STUDY REGISTRATION: This study is registered on the website of the Chinese Clinical Trial Registry (ChiCTR: ChiCTR2200057323).

The association between admission serum albumin and preoperative deep venous thrombosis in geriatrics hip fracture: a retrospective study of 1819 patients with age ≥ 65 years.

OBJECTIVE: This study evaluated the association between serum albumin levels and preoperative deep vein thrombosis (DVT) in geriatric hip fractures. METHODS: Older adult patients with hip fractures were screened between January 2015 and September 2019. The demographic and clinical characteristics of the patients were collected. Multivariate binary logistic regression and generalized additive model were used to identify the linear and nonlinear association between albumin levels and preoperative DVT. Analyses were performed using EmpowerStats and the R software. RESULTS: A total of 1819 patients were included in this study. The average age was 79.37 ± 6.88 years. There were 550 males and 1269 females. The preoperative albumin was 38.19 ± 4.07 g/L. There were 580 (31.89%) preoperative DVTs. Multivariate binary logistic regression showed that albumin level was associated with preoperative DVT (odds ratio [OR] = 0.94, 95% confidence interval [CI]: 0.91-0.97, P = 0.0002) after adjusting for confounding factors. The fully adjusted model showed a DVT risk decrease of 6% when albumin concentration increased by one g/L after controlling for confounding factors. In addition, the trend test and propensity score matching also showed a stable linear correlation between albumin level and preoperative DVT. CONCLUSION: Serum albumin is associated with preoperative DVT in geriatric patients with hip fractures, and it could be considered a predictor for the risk of DVT. REGISTRATION ID: ChiCTR2200057323.

Association between Neutrophil Levels on Admission and All-Cause Mortality in Geriatric Patients with Hip Fractures: A Prospective Cohort Study of 2,589 Patients.

Objective: To evaluate the association between neutrophil levels and all-cause mortality in geriatric hip fractures. Methods: Elderly patients with hip fractures were screened between January 2015 and September 2019. Demographic and clinical characteristics of the patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between neutrophil levels and mortality. Analyses were performed using Empower Stats and R software. Results: A total of 2,589 patients were included in this study. The mean follow-up period was 38.95 months. During the study period, 875 (33.80%) patients died due to various causes. Linear multivariate Cox regression models showed that neutrophil levels were associated with mortality after adjusting for confounding factors, when neutrophil concentration increased by 1∗109/L, the mortality risk increased by 3% (HR = 1.03, 95% CI: 1.00-1.06, and P=0210). Neutrophil concentration was used as a categorical variable; we only found statistically significant differences when neutrophil levels were high (HR = 1.27, 95% CI:1.05-1.52, and P=0.0122). In addition, the results are stable in P for trend and propensity score matching sensitivity analysis. Conclusions: Neutrophil levels are associated with mortality in geriatric hip fractures and could be considered a predictor of death risk in the long-term. This study is registered with the Chinese Clinical Trial Registry (ChiCTR) as number ChiCTR2200057323.

SdrG gene activated joint surface membrane protein PTPRJ to induce periprosthetic joint infection after total hip arthroplasty.

WHAT IS KNOWN AND OBJECTIVE: Up to now, no study focused on the role of SdrG in PJI after THA. To explore the mechanism of periprosthetic joint infection (PJI) after total hip arthroplasty (THA). METHODS: Joint fluid and blood were collected from patients with PJI after THA, aseptic loosening of the joints or bacterial infection after traumatic fractures of the extremities alone. The expression of SdrG in the 3 groups was determined by agarose gel electrophoresis. The expression of protein tyrosine phosphatase receptor J (PTPRJ) was measured by immunohistochemistry method. The platelet adhesion rate was determined by biochemical analysis. The content of D-dimer, CRP and ESR in blood was determined by latex agglutination method. Multiple linear correlation analysis was used to analyse the correlation between PJI and the expression of PTPRJ protein, platelet adhesion rate, D-dimer content, CRP and ESR. RESULTS AND DISCUSSION: The expression of SdrG and PTPRJ in PJI group was markedly increased compared to the other 2 groups. The platelet adhesion rate in PJI group was markedly larger compared to aseptic loosening and simple wound infection group, and the rate in simple wound infection group was larger than aseptic loosening group. The level of D-dimer, CRP and ESR in PJI group was higher than that of the other groups. The expression of PTPRJ protein, D-dimer content, CRP and ESR was all closely related to PJI, while platelet adhesion rate had no correlation with PJI. WHAT IS NEW AND CONCLUSION: SDRG gene around joint prosthesis was over-expressed, which activated joint surface membrane protein PTPRJ and then induced platelet aggregation to reduce joint function.

miR-140-3p regulates the osteogenic differentiation ability of bone marrow mesenchymal stem cells by targeting spred2-mediated autophagy.

Understanding the function and regulatory mechanism of miR-140-3p on the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Alizarin Red staining, Alkaline phosphatase (ALP) staining, and ALP activity were used to detect the ability osteogenic differentiation. miR-140-3p or Spred2 overexpression into BMSCs using lentiviral vectors and the result were analyzed by Reverse transcription quantitative polymerase chain reaction (RT-qPCR). The relation between miR-140-3p and Spred2 was examined by luciferase reporter assay. CCK8 assay was used to detect the proliferation of BMSCs. RT-qPCR and Western blot analysis were both used to detect altered gene and protein in osteogenic differentiation of BMSCs, respectively. The BMSCs which were induced for 21 days were analyzed by Alizarin Red staining, (ALP) staining and ALP activity. RT-qPCR analysis showed that overexpressed miR-140-3p promotes osteogenic differentiation. Western blots results indicated that the overexpression of Spred2 suppressed miR-140-3p. Luciferase reporter assay indicated that Spred2 can integrate with miR-140-3p directly. Meanwhile, the protein level of ALP, OCN, and Runx2, the markers of chondrogenesis, was increased when miR-140-3p increased or Spred2 overexpressed in the osteoinductive medium applied to the BMSCs. Our study demonstrated the association between miR-140-3p and Spred2 in osteogenic differentiation of BMSCs for the first time. Furthermore, our detections also revealed that Spred2-induced autophagic signaling accelerates the progress of osteogenic differentiation ability of BMSCs.

The traditional experience strategy (TES) and combined ultrasonography examination (CUE) for the treatment of lateral compression type 1 pelvic fractures: a historical control study.

BACKGROUND: It is difficult to judge the stability of lateral compression type-1 (LC-1) pelvic fracture, as it is often based on static images of the pelvis. Compared with the traditional experience strategy, ultrasonography examination may be able to distinguish operative and conservative patients before definitive treatment. However, in previous studies, we have not compared the outcomes between traditional experience strategy (TES group) and combined ultrasonography examination (CUE group). Thus, the aim of the study is comparing the differences between TES and CUE strategy, to identify the value of ultrasonography examination. METHODS: Medical records system for patients with LC-1 pelvic fractures who were treated with TES and CUE strategy were included. Patients' baseline characteristics, treatment strategy, and function were recorded at follow-up. Functional outcomes were evaluated using the Majeed grading system. RESULTS: In total, 77 patients with LC-1 pelvic fractures were included in the study. There were 42 and 35 patients in TES and CUE group, respectively. Compared to TES group (69 %), there were less proportion patients chosen the operative treatment in CUE group (43 %, P = 0.021). The volume of intraoperative blood loss in CUE operative group was more than TES operative group (P = 0.037). There were more patients with complete sacral fracture in CUE operative group than TES operative group (P = 0.002). The Majeed scores in CUE conservative group was higher than TES conservative group (P = 0.008). The overall Majeed scores in CUE group was higher than that in TES group (P = 0.039). CONCLUSIONS: The ultrasonography examination could relatively accurately identify the unstable LC-1 pelvis than the traditional experience strategy, the operative rate could be reduced and the overall function of LC-1 patients could be improved under the ultrasonography examination. LEVEL OF EVIDENCE: Level III.

The effect of new preoperative preparation method compared to conventional method in complex acetabular fractures: minimum 2-year follow-up.

OBJECTIVE: This study aimed to compare the efficacy and safety of the new method including 3D printing-based preoperative planning, surgical workshop, and contouring of the plate versus conventional method in the surgical treatment of complex acetabular fractures. METHODS: We retrospectively analyzed the data in a cohort of 88 patients of complex acetabular fracture with mean 29.95 ± 4.84 months (24-41 months) follow-up. Patients were divided into two groups. Group 1 consisting of 41 patients were performed previewed surgery with a 3D printing-based pre-contoured plate on a 3D printing model. Group 2, comprised of 47 patients, were treated by the traditional contoured plate technique. The quality of reduction was assessed using criteria described by Matta. Functional outcome was evaluated using Modified Postel Merle D'Aubigne score. A custom-made quiz was used to evaluate the chief assistant. RESULTS: The study showed no significant differences in measured preoperative variables except for the age between the Group 1 and Group 2 (p > 0.05). Compared with the Group 2, the intraoperative blood loss, operative time was significantly decreased in Group 1 (p < 0.05). There were no significant statistical differences in the quality of reduction and Modified Postel Merle D'Aubigne score (p > 0.05). The result of evaluation of assistant in Group 1 was significantly high than in Group 2 (p < 0.05). CONCLUSION: 3D printing-based pre-contoured plate is a more effective and reliable method than traditional contoured plate technique for treating the complex acetabular fractures. Meanwhile, the 3D printing is a useful orthopedic surgical education tool which can improve the understanding of the complex acetabular fracture for a young surgeon.

Comparison of posterior ring fixation with combined anterior and posterior ring fixation for the treatment of lateral compression type 2 pelvic fractures.

PURPOSE: The aim of surgical treatment for lateral compression type 2 (LC-2) pelvic fractures is to enable early mobilization and provide pain relief. Anterior and posterior ring fixation is usually performed simultaneously, with the goal of providing good biomechanical stability. However, it is unclear whether anterior ring fixation is necessary. This study therefore aimed to determine the feasibility of isolated posterior ring fixation for LC-2 pelvic fractures. METHODS: Records of patients with LC-2 pelvic fractures were extracted from a medical database. Patients who underwent posterior pelvic ring fixation alone (PR fixation group) or anterior and posterior ring fixation (APR fixation group) were included. Patients' operative characteristics, time to clinical healing, length of hospital stay, time to weight bearing, and complications were recorded at follow-up. Radiography was used to assess healing and fracture displacement. Functional outcomes were evaluated using the Majeed grading system. RESULTS: The PR fixation group included 44 patients, and the APR fixation group included 49 patients. Operative time, intra-operative blood loss, units of blood transfused, intra-operative fluid administered, and post-operative drainage were lower in the PR fixation group than in the APR fixation group. Length of hospital stay was also shorter in the PR fixation group than in the APR fixation group. Although the frequency (8/44) of fracture displacement in the superior ramus prior to union was high in the PR fixation group, no significant differences in time to weight bearing, time to clinical healing, or Majeed scores were found between the groups at follow-up. CONCLUSIONS: Isolated posterior ring fixation for LC-2 pelvic fractures is feasible; patients who underwent treatment with this technique had functional outcomes similar to that of those who underwent anterior and posterior ring fixation.

Treatment of capitellar and trochlear fractures with posterior comminution: minimum 2-year follow-up.

HYPOTHESIS: This study aimed to evaluate the safety and efficacy of the fixation of Dubberley type B capitellar and trochlear fractures using dorsolateral anatomic plates with support of the distal humerus (DAPSDHs). METHODS: Fifteen patients with Dubberley type B capitellar and trochlear fractures (two type 1B, five type 2B, and eight type 3B) were treated through the extended lateral approach, and fixation was achieved with DAPSDHs. Radiographic evaluation was performed, and range of motion of the elbow and forearm was recorded. Functional outcomes were assessed using the Mayo Elbow Performance Score and Disabilities of the Arm, Shoulder and Hand score. RESULTS: The mean follow-up period was 32.5 months (range, 24-54 months). Fracture union was achieved in all cases. At the final follow-up, range of motion was as follows: flexion, 123.7° ± 8.1° (range, 110°-135°); lack of extension, 11.0° ± 7.1° (range, 5°-30°); pronation, 81.7° ± 5.6° (range, 70°-90°); and supination, 78.7° ± 5.2° (range, 70°-85°). At the final follow-up, the mean Disabilities of the Arm, Shoulder and Hand score was 11.9 ± 4.0 (range, 4.2-20.8) and the mean Mayo Elbow Performance Score was 89.0 ± 7.1 (range, 70-95). The outcome was rated as excellent in 12 patients (80.0%), good in 2 (13.3%), and fair in 1 (6.7%). Avascular necrosis of the capitellum developed in 1 patient. One patient had implant irritation. Heterotopic ossification developed in 1 patient. Ten patients returned to their previous activity levels. CONCLUSION: Capitellar and trochlear fractures with posterior comminution are safely and effectively treated through the extended lateral approach using DAPSDHs, resulting in good radiographic and functional outcomes.

Minimally invasive stabilisation of posterior pelvic ring instabilities with pedicle screws connected to a transverse rod.

PURPOSE: The goal was to evaluate the clinical outcomes, quality of reduction and complications of pelvic fractures treated by minimally invasive stabilisation of posterior pelvic ring instabilities with pedicle screws connected to a transverse rod. METHODS: Retrospective analysis of prospectively collected data in a consecutive patient series with pelvic fractures treated by minimally invasive stabilisation of posterior pelvic ring instabilities with pedicle screws between January 2010 and January 2016. The functional outcomes evaluated by Majeed scores, and fracture reduction results were evaluated using the Tornetta and Matta standard. As well as recording the duration of the surgical procedure, intraoperative blood loss, the times of intra-operative fluoroscopy and complications. RESULTS: A total of 29 patients (15 men and 14 women; age range, 21-72 years; mean, 40.8 years) could be followed-up after an average of 38.2 ± 21.3 months (range, 12-84 months). According to the AO/OTA classification, there were 24 patients with B2 injury and five patients with C1 injury of the pelvic ring. For the sacral fractures, according to Denis classification, four cases were zone I fractures and 25 cases were zone II fractures. The duration of the surgical procedure, intra-operative blood loss and the times of intra-operative fluoroscopic of the posterior-ring surgical procedure was 28.2 ± 4.6 minutes (range, 20-38 minutes), 46.7 ± 4.9 ml (range, 39-56 ml), and 13.1 ± 1.6 seconds (range, 10-17 seconds) respectively. Posterior-ring fracture reduction was excellent in 11 patients and 15 were good, three cases were fair; the excellent and good rate was 89.7% (26/29). At the final follow-up, the function result was rated as excellent in ten cases, good in 16, fair in three, and poor in zero cases; the excellent and good rate was 89.7% (26/29). There was no incision infection, intra-operative neurovascular injury, pedicle screw loose or breakage, and non-union of the posterior arch did not occur. Two patients requested removal of the fixator: one patient with breakage of the anterior pelvic ring internal fixator, and the pedicle screw was also taken out in the same operative session; another one with moderate pain on the posterior pelvic ring. CONCLUSIONS: Minimally invasive stabilisation of posterior-pelvic-ring instabilities with pedicle screw connected to a transverse rod may be a good alternative to sacroiliac screw fixation because it is quick, safe and associated with a good functional outcome; thus being a useful option in patients who do not qualify for sacroiliac screw fixation.

Etanercept alleviates early brain injury following experimental subarachnoid hemorrhage and the possible role of tumor necrosis factor-α and c-Jun N-terminal kinase pathway.

Cerebral inflammation plays a crucial role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). This study investigated the effects of c-Jun N-terminal kinase (JNK) inhibitor SP600125, acetylcholine (Ach), etanercept, and anti-TNF-α on cellular apoptosis in the cerebral cortex and the hippocampus, in order to establish the role of JNK and TNF-α in EBI. The SAH model was established using an endovascular puncture protocol. The reliability of the EBI model was determined by phosphorylated-Bad (pBad) immunohistochemistry. Neurological scores were recorded and western blot was used to detect the expression of JNK and TNF-α, and TUNEL assay was used to mark apoptotic cells. The results showed that pBad positive cells were evenly distributed in the cerebral cortex at different time points. The highest expression of pBad was reached 1 day after SAH, and pJNK and TNF-α reached their peak expression at 2 days after SAH. SP600125, Ach, and etanercept significantly decreased the level of pJNK and TNF-α in the cerebral cortex and the hippocampus. In addition, SP600125 and etanercept reduced cellular apoptosis in the cerebral cortex and the hippocampus and significantly improved neurological scores at 2 days after SAH potentially via inhibition of the JNK-TNF-α pathway. Ach reduced cellular apoptosis only in the cerebral cortex. It is possible that JNK induces TNF-α expression, which in turn enhances JNK expression in EBI after SAH, leading to increased apoptosis in the cerebral cortex and the hippocampus. Thus, our results indicate that that etanercept may be a potential therapeutic agent to alleviate EBI.

The rapid lipopolysaccharide-induced release of matrix metalloproteinases 9 is suppressed by simvastatin.

A rapid increase in matrix metalloproteinase-9 (MMP-9) expression by stimulated leukocytes is common in many diseases. Recent evidence suggests that the beneficial effects of statins are mediated in part by the suppression of MMP-9 release. In this study, we investigated the effect of statin on MMP-9 expression and its antagonist, tissue inhibitor of metalloproteinase-1 (TIMP-1) in LPS-stimulated leukocytes. Rat neutrophils and monocytes were stimulated with lipopolysaccharide (LPS) in the presence of simvastatin. MMP-9 secretion and mRNA expression were analyzed using ELISA and RT-PCR, respectively. Total MMP-9 protein production was measured by Western blot analysis. Potential signal transduction pathways responsible for MMP-9 production were investigated using luciferase reporter assays (NF-κB), pull-down assays (RhoA), and pharmacological inhibition. Our data show that MMP-9 and TIMP-1 expression are differentially induced by LPS in neutrophils and monocytes. We showed that rapid MMP-9 release occurred mainly via secretion from intracellular stores. Moreover, we showed that statin significantly suppressed LPS-induced MMP-9 release and mRNA expression in a time- and concentration-dependent manner. We also evaluated that simvastain postponed the rapid LPS-induced MMP-9 release for about 20 min. In conclusion, we demonstrated that the suppressive effect of simvastatin on LPS-stimulated MMP-9 release does not occur via the NF-κB pathway and the MAPKs pathway, but via the RhoA/ROCK pathway.

Gamma knife radiosurgery (GKRS) for pineal region tumors: a study of 147 cases.

BACKGROUND: The purpose of this study is to evaluate the effectiveness of gamma knife radiosurgery (GKRS) in the treatment of pineal region tumors (PRTs). METHODS: We retrospectively reviewed 147 cases of PRTs primarily treated with GKRS at our hospital between 1999 and 2009. Mean follow-up time was 67 months (range 60.5-100.1). The local tumor control rates (LTCRs) and overall survival rates were calculated to evaluate the results of the GKRS treatment. RESULTS: At 2 months after GKRS, tumor volume was significantly reduced in 91 cases (61.9%). At 6 months, average tumor volume was 4.2 cm(3) as compared to 8.47 cm(3) before GKRS. By 1 year after GKRS, the tumor completely disappeared in 57 patients. Fourteen patients underwent second treatment, and one patient had third treatment. The overall survival rates were 72.1% at 3 years and 66.7% at 5 years for all patients and 62.4% at 3 years and 54.5% at 5 years for germ cell tumors (GCTs). The LTCRs were 94.30% at 3 years and 90.80% at 5 years for all patients and 88.00% at 3 years and 77.27% at 5 years for GCTs. CONCLUSIONS: GKRS is an effective and safe modality that can be widely used to PRTs as the primary therapy.

Advances in research of the neuroprotective mechanisms of cerebral ischemic postconditioning.

Ischemic postconditioning refers to controlling reperfusion blood flow during reperfusion after ischemia, which can induce an endogenous neuroprotective effect and reduce ischemia-reperfusion injury. Activation of endogenous neuroprotective mechanisms plays a key role in protecting against brain ischemia-reperfusion injury. The mechanisms of cerebral ischemic postconditioning are not completely clear, and the following aspects may be involved: downregulation of oxidative stress, attenuating mitochondrial dysfunction, attenuating endoplasmic reticulum stress, accelerating the elimination of glutamate, increasing rCBF, inhibiting apoptosis, inhibiting autophagy, and regulating signal transduction.