Purpose: To investigate risk factors, treatment strategies, and outcomes of endophthalmitis associated with severe fungal keratitis. Methods: Data from 392 patients diagnosed with fungal keratitis were retrospectively examined. Patients had severe disease that was refractory to topical or systemic antifungal therapy, and the infection involved the endothelium or perforated the cornea. The incidence and risk factors for endophthalmitis, and treatment outcomes were evaluated. Results: Thirty-seven of 392 patients (9.4%) had endophthalmitis. Multivariate logistic regression revealed the following risk factors for endophthalmitis: topical steroid use (odds ratio [OR] = 6.35, 95% confidence interval [CI]: 2.01–20.08), previous corneal laceration suturing (OR = 5.05, 95% CI: 1.11–22.93), large corneal ulcer size (≥10-mm diameter; OR = 4.43, 95% CI: 1.71–11.50), hypopyon (OR = 11.05, 95% CI: 2.12–57.55), and aphakia (OR = 15.45, 95% CI: 1.59–149.82). Thirty of the 37 eyes (81.1%) with endophthalmitis were saved by penetrating keratoplasty, vitrectomy, or intravitreal antifungal injection; 7 eyes (18.9%) were eviscerated. Conclusion: Most patients with endophthalmitis secondary to corneal fungal infection were successfully managed by penetrating keratoplasty, vitrectomy, or intravitreal antifungal therapy. Multiple risk factors for endophthalmitis were identified. Timely diagnosis and risk factor assessment were essential for ensuring early surgical intervention for fungal keratitis–related endophthalmitis.

Fluid shear stress (FSS) plays a crucial role for cell migration within bone cavities filled with interstitial fluid. Whether the local wall FSS distribution on cell surface depends on the global gradient FSS of flow field should be clarified to explain our previous experimental observation. In this study, finite element models of discretely distributed or hexagonal closely packed cells adherent on the bottom plate in a modified plate flow chamber with different global FSS gradient were constructed. Fluid-solid coupling simulation of wall fluid shear stress on cells was performed, and two types of data analysis methods were used. The results showed that the profile of local FSS distribution on cell surface coincides with the angle of cell migration determined in the previous study, suggesting that RAW264.7 osteoclast precursors may sense the global FSS gradient and migrate toward the low-FSS region under a high gradient. For hexagonal closely packed cells, this profile on the surface of central cells decreased along with the increase of cell spacing, which may be caused by the higher local FSS difference along the direction of FSS gradient in the regions close to the bottom plate. This study may explain the phenomenon of the targeted migration of osteoclast precursors under gradient FSS field and further provide insights into the mechanism of mechanical stimulation-induced bone remodeling.

During mechanical stimulation-induced bone remodeling, interstitial fluid around microcracks may produce a flow field with gradient fluid shear stress (FSS). Osteoclast precursors can sense this gradient FSS and migrate toward the low FSS region. However, the local distribution of wall FSS on bone cells under a flow field with globally gradient FSS remains unknown. In this study, finite element models of a modified plate flow chamber with cells were constructed. The effect of oscillatory flow with different FSS levels and cell spacings or frequencies on the distribution of local wall FSS around cells was simulated by using a fluid–solid coupling method. Results showed that the polarization of wall FSS distribution in a cell decreased with the increase in cell spacing. At a low FSS level, the frequency of oscillatory flow had a minimal effect on the wall FSS distribution. At a high FSS level, the increase in flow frequency enhanced the fluctuation of local wall FSS distribution on cells. These results provide a basis for future research on the flow-induced migration of osteoclast precursors and clarify the mechanism of mechanical stimulation-induced bone resorption.

Bone is one of the hardest tissues in the human body, but it can undergo microcracks under long‐term and periodic mechanical loads. The Newton iterative method was used to calculate the steady state, and the effects of different inlet and outlet pressures, trabecular gap width and height, and microcrack’s depth and width on the fluid shear stress (FSS) were studied, and the gradient of FSS inside the microcrack was analyzed. The results show that the pressure difference and trabecular gap heigh are positively correlated with the FSS (the linear correlation coefficients R ² were 0.9768 and 0.96542, respectively). When the trabecular gap width was 100 μm, the peak of FSS decreased by 28.57% compared with 800 and 400 μm, and the gradient of FSS inside the microcrack was 0.1–0.4 Pa/mm. This study can help people more intuitively understand the internal fluid distribution of trabecular bone and provide a reliable theoretical basis for the subsequent construction of gradient FSS devices in vitro.

The skeleton is able to adapt to mechanical loading through bone remodeling, i.e. bone resorption followed by bone formation. The osteoclasts close to microdamages are believed to initiate bone resorption, but whether local mechanical loading such as fluid flow regulates recruitment and differentiation of osteoclast precursors at the site of bone resorption has yet to be investigated. In the present study, finite element analysis first revealed that there exists low fluid shear stress (FSS) field inside microdamage. Basing on a custom-made device of cone-and-plate fluid chamber, finite element analysis and particle image velocimetry measurement were performed to verify the formation of gradient FSS flow field. Furthermore, the effects of gradient FSS on the migration, aggregation, and fusion of osteoclast precursors were observed. Results showed that osteoclast precursor RAW264.7 cells migrate along radial direction toward the region with lower FSS during exposure to gradient FSS stimulation for 40 min, obviously deviating from the direction of actual fluid flow indicated by fluorescent particles. When inhibiting calcium signaling pathway with gadolinium and thapsigargin, cell migration toward low-FSS region was significantly reduced. For other cell lines, MC3T3-E1, PDLF, rMSC and MDCK, gradient FSS stimulation did not lead to the low-FSS-inclined migration. After being cultured under gradient FSS stimulation for 6 days, the density of RAW264.7 cells and the ratio of TRAP-positive multinucleated osteoclasts in low-FSS region were significantly higher than those in high-FSS region. Therefore, osteoclast precursor cells may have special ability to sense FSS gradient and tend to actively migrate toward low-FSS region, which is regulated by calcium signaling pathway.