Evaluation of the clinical efficacy of using an inverted triangular cannulated compression screw in combination with positive or negative buttress reduction for the healing of femoral neck fractures.

OBJECTIVE: We aimed to compare the clinical efficacy of inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction in the healing of femoral neck fractures. METHODS: Between October 2017 and March 2021, 55 patients with femoral neck fractures underwent treatment using inverted triangular cannulated compression screws combined with Gotfried positive or negative buttress reduction. Among these patients, 29 received inverted triangular cannulated compression screws combined with Gotfried positive buttress reduction treatment. This group consisted of 16 males and 13 females, with an average age of 43.45 ± 8.23 years. Additionally, 26 patients received inverted triangular cannulated compression nails combined with Gotfried negative buttress reduction treatment. This group included 14 males and 12 females, with an average age of 41.96 ± 8.69 years. Postsurgery, various measurements were taken, including the degree of shortening of the femoral neck, degree of bone nonunion, degree of fixation failure, degree of ischemic necrosis of the femoral head, and Harris score of the hip joint. RESULTS: All patients were followed up for a minimum of 18 months. The group that underwent treatment with an inverted triangular cannulated compression screw combined with Gotfried positive buttress reduction did not experience any cases of bone nonunion, fixation failure, or ischemic necrosis of the femoral head. In the group that received treatment with inverted triangle cannulated compression screws combined with Gotfried negative buttress reduction, there was one case of bone nonunion, three cases of early fixation failure, and one case of ischemic necrosis. Ultimately, five patients (19.23% of the total) underwent joint replacement surgery. The average shortening lengths in the vertical plane were 4.07 ± 1.98 mm and 8.08 ± 3.54 mm, respectively. In the horizontal plane, the average shortening lengths were 3.90 ± 1.57 mm and 7.77 ± 3.31 mm, respectively. At the last follow-up, the group that received Gotfried positive buttress reduction had a greater Harris hip joint score. CONCLUSION: The success rate of combining inverted triangular cannulated compression screws with Gotfried positive buttress reduction surgery is relatively high. This surgical approach effectively prevents femoral neck shortening and improves hip joint function. Moreover, it is crucial to avoid negative buttress reduction when managing femoral neck fractures.

Association of hepatocellular carcinoma risk with polymorphisms in tumour necrosis factor alpha gene in a Chinese Han population.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Studies have shown that the tumour necrosis factor alpha (TNF-α) plays an important role in the development of HCC; however, the association between genetic variations of TNF-α and HCC is not yet fully understood. To evaluate the correlation of TNF-α polymorphisms with HCC, we randomly selected 327 HCC patients and 432 healthy controls, all these subjects reported Han nationality. Genotyping of four TNF-α SNPs (rs1799724, rs1800629, rs1799964 and rs1800610) was performed using the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) method. Distributions of rs1799964 genotypes and rs1800610 alleles were found to be significantly different between cases and controls (p = .011, p = .001). The recessive model of rs1799964 significantly increased HCC risk (p = .0015), while the dominant and over-dominant models of rs1800610 significantly reduced HCC risk (p = .0096, p = .014). Haplotype analysis of the four TNF-α SNPs revealed that the TGTA haplotype was associated with a reduced HCC risk (p = .0033, OR = 0.53), while the TGTG haplotype was associated with an increased HCC risk (p = .0032, OR = 9.69). These findings indicated that specific TNF-α polymorphisms may be associated with the susceptibility to HCC.

Nrf2-mediated redox balance alleviates LPS-induced vascular endothelial cell inflammation by inhibiting endothelial cell ferroptosis.

Ferroptosis plays an important role in inflammation and oxidative stress. Whether ferroptosis is involved in the inflammation of vascular endothelial cells and its regulation mechanism remains unclear. We estimated the correlation between serum iron ion levels and the inflammation index of 33 patients with arteriosclerosis. In vitro, HUVECs with or without ferrostatin-1 were exposed to Lipopolysaccharide. Corresponding cell models to verify the target signaling pathway. The results showed that serum iron ion levels had a significant positive correlation with N ratio, N/L, LDL level, and LDL/HDL (P < 0.05), and a negative correlation with L ratio (P < 0.05) in the arteriosclerosis patients. In vitro, ferroptosis is involved in HUVECs inflammation. Ferrostatin-1 can rescue LPS-induced HUVECs inflammation by decreasing HMGB1/IL-6/TNF-α expression. Nrf2 high expression could protect HUVECs against ferroptosis by activating the GPX4/GSH system, inhibiting ferritinophagy, and alleviating inflammation in HUVECs by inhibiting HMGB1/IL-6/TNF-α expression. It also found that Nrf2 is a key adaptive regulatory factor in the oxidative damage of HUVECs induced by NOX4 activation. These findings indicated that ferroptosis contributed to the pathogenesis of vascular endothelial cell damage by mediating endothelial cell inflammation. Nrf2-mediated redox balance in vascular inflammation may be a therapeutic strategy in vascular diseases.

EGR1/NOX4 pathway regulates oxidative stress and further facilitates fibrosis progression in keloids responses to TGF-ß1.

BACKGROUND: As classic benign fibroproliferative tumors, keloids remain a major therapeutic challenge due to their complex pathological mechanisms. OBJECTIVE: To determine the functional role of transforming growth factor ß1 (TGF-ß1)/early growth response factor-1 (EGR1)/NADPH oxidases 4 (NOX4) axis in the pathogenesis of keloid fibrosis. METHODS: Differentially expressed genes in keloid tissues and normal skins were analyzed by RNA sequencing. Then, the human skin fibroblast cell line was treated with TGF-ß1 at a dose of 10 ng/mL in order to stimulate the TGF-ß1/SMAD pathway and the pathway was blocked using the SB431542. Furthermore, EGR1/NOX4 was over-expressed and inhibited by transfecting overexpression plasmids and small interfering RNAs, respectively. The levels of intracellular reactive oxygen species were measured using the DCFH-DA assay, and the expression levels of fibrosis-related genes were assessed by Western blot analysis. Alternately, dual-luciferase reporter analysis verified the targeting relationship between EGR1 and NOX4. RESULTS: The TGF-ß1/SMAD signaling pathway was significantly activated in keloid tissues to promote dermal fibrosis. The level of ROS was increased in keloid fibroblasts. Moreover, TGF-ß1 could facilitate the expression of EGR1 through regulating the SMAD pathway in keloids and promoting the fibrotic phenotype of keloid fibroblasts. EGR1 could regulate the production of ROS by targeting NOX4. Furthermore, NOX4-derived ROS could promote fibrotic-like phenotype of keloid fibroblasts and play an important role in keloid fibrosis. CONCLUSION: Our findings provide new insights into the mechanisms of the TGF-ß1/EGR1/NOX4 pathway in keloid fibrosis, and the TGF-ß1/EGR1/NOX4 axis may serve as a potential therapeutic target for keloids.

Dysregulation of EZH2/miR-138-5p Axis Contributes to Radiosensitivity in Hepatocellular Carcinoma Cell by Downregulating Hypoxia-Inducible Factor 1 Alpha (HIF-1α).

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase involved in cell proliferation, invasion, angiogenesis, and metastasis in various cancers, including hepatocellular carcinoma (HCC). However, the role and molecular mechanisms of EZH2 in HCC radiosensitivity remain unclear. Here, we show that EZH2 is upregulated in HCC cells and the aberrantly overexpressed EZH2 is associated with the poor prognosis of HCC patients. Using miRNA databases, we identified miR-138-5p as a regulator of EZH2. We also found that miR-138-5p was suppressed by EZH2-induced H3K27me3 in HCC cell lines. MiR-138-5p overexpression and EZH2 knockdown enhanced cellular radiosensitivity while inhibiting cell migration, invasion, and epithelial-mesenchymal transition (EMT). Analysis of RNA-seq datasets revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was the main enrichment pathway for differential genes after miR-138-5p overexpression or EZH2 knockdown. Expression level of HIF-1α was significantly suppressed after miR-138-5p overexpression or silencing of EZH2. HIF-1α silencing mitigated resistance of HCC cells and inhibited EMT. This study establishes the EZH2/miR-138-5p/HIF-1α as a potential therapeutic target for sensitizing HCC to radiotherapy.