Objective: To investigate the effects of the sphingosine-1-phosphate receptor-2 (S1PR2) inhibitor JTE-013 on pulmonary fibrosis in silicosis mice and its underlying molecular mechanisms. Methods: In October 2024, 40 SPF male C57BL/6J mice were randomly divided into control group, JTE-013 control group, silicosis model group, and JTE-013 treatment group. A silicosis model was established by non-exposure intratracheal instillation of SiO(2) suspension. One week after model was establishment, mice in the JTE-013 treatment group were intraperitoneally injected with JTE-013 (10 mg/kg, twice a week for a total of 6 times), while mice in other groups were intraperitoneally injected with the same volume of normal saline. After 28 d of modeling, the lung coefficients of mice in each group were detected. The lung tissues were stained with HE, Masson, and Sirius Red to assess pathological damage and collagen deposition. The content of hydroxyproline (HYP) was determined. The expressions of S1PR2, epithelial-mesenchymal transition (EMT) marker proteins [E-cadherin (E-cad), Vimentin, α-smooth muscle actin (α-SMA) ], and Ras homolog family member A/Rho-related coiled helix kinase 1 (RhoA/ROCK1) pathway proteins were detected by protein immunoblotting method. Human alveolar epithelial A549 cells were cultured in vitro. The cells were divided into normal control group (cultured in complete medium for 26 h), JTE-013 control group (cultured in medium prepared to 1 μmol/L JTE-013 solution for 26 h), SiO(2) treatment group (cultured for 2 h with normal medium, then treated with 50 μg/ml SiO(2) suspension for 24 h), and SiO(2)+JTE-013 treatment group (pre-treated with 1 μmol/L JTE-013 for 2 h, then added 50 μg/ml SiO(2) suspension for 24 h). After group intervention, the expression levels of S1PR2, EMT-related proteins, RhoA and ROCK1 in the cells were detected. For the normally distributed measurement data, one-way ANOVA analysis of variance was used for inter-group comparison, and LSD-t test was used for pairwise comparison. Results: Compared with the control group, the mice in the silicosis model group had a significant decrease in body weight, and their lung coefficient and HYP content were significantly increased (P<0.05), silicotic nodules formed in the lungs, accompanied by collagen deposition. And the expression levels of SIPR2 protein, EMT-related proteins Vimentin, α-SMA, and the RhoA and ROCK1 proteins in signaling pathway were significantly increased, while the expression level of the epithelial marker E-cad was significantly decreased (P<0.05). Compared with the silicosis model group, the mice in the JTE-013 treatment group had a significantly increase in body weight, the lung coefficient and HYP content were significantly decreased (P<0.05), the pulmonary fibrosis was significantly reduced. And the expression levels of SIPR2 protein, EMT-related proteins Vimentin, α-SMA, and the RhoA and ROCK1 proteins in the signaling pathway were significantly decreased, while the expression level of the epithelial marker E-cad was significantly increased (P<0.05). In the in vitro experiments, compared with the normal control group, the expression levels of EMT-related proteins Vimentin, α-SMA and the proteins RhoA and ROCK1 in the signaling pathway in the SiO(2) treatment group were significantly increased, while the expression level of the epithelial marker E-cad was significantly decreased (P<0.05). Compared with the SiO(2) group, the expression levels of EMT-related proteins Vimentin, α-SMA, and the proteins RhoA and ROCK1 in the signaling pathway in the SiO(2)+JTE-013 treatment group were significantly decreased, while the expression level of the epithelial marker E-cad was significantly increased (P<0.05) . Conclusion: JTE-013 can alleviate the pulmonary fibrosis in silicosis mice, which may be related to the inhibition of the EMT process through the RhoA/ROCK1 signaling pathway.

A persistently crooked nose refers to a condition in which the deviation of the nasal pyramid from the facial midline remains or reappears after the rhinoplasty surgery. Asymmetries in any compartment of the nose are among the main concerns of patients seeking revision rhinoplasty. Therefore, mastering surgical techniques to address these issues is essential to achieve success in revision cases. In this article, we discuss various surgical techniques, present case examples, and provide supplementary revision rhinoplasty videos performed by the senior author to enhance understanding.

Revision rhinoplasty remains one of the most demanding procedures in facial plastic surgery, challenging not only because of the altered anatomy, deficiencies of structural support, and complex 3-dimensional morphology of the nose, but also because of the varying degrees of scarring. Although the open approach dominates contemporary revision rhinoplasty practice, the endonasal technique remains a valuable option in appropriately selected patients. By preserving the skin-soft tissue envelope and the intrinsic ligamentous support of the nose, endonasal revision offers advantages including reduced edema, avoidance of external scars, and maintenance of a more natural nasal appearance and feel.

In a standard septoplasty, most of the quadrangular cartilage is resected while preserving an L-strut to maintain structure of the nose. Deviation may recur due to contractile forces causing flexure or torsion of the L-strut, which may be reduced by modifying the shape of the L-strut chondrotomy. Alternatively, deviations may have been insufficiently addressed by the initial septoplasty. Grafting techniques are often used to address deviations of the L-strut, and repositioning of the posterior septal angle may be required when displaced off the anterior nasal spine. With certain severe sepal deformities, extracorporeal septoplasty may be a more effective option.

Acute kidney injury (AKI) is common in patients with acute coronary syndrome (ACS). However, understanding its prevalence, risk factors and prognosis remains incomplete. We identified 21328 patients admitted for chest pain to a regional hospital in 2021; 6685 had confirmed ACS. AKI episodes were identified by the serum creatinine criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) AKI guideline. The rates of recovery and inpatient, 30-day and 90-day mortality rates were analyzed. Multi-variable analysis showed that ACS was independently associated with AKI (adjusted odds ratio [OR] 2.327; 95% confidence interval [CI] 2.130-2.542; p < 0.0001). Subgroup analysis showed that ACS was independently associated with AKI on admission (adjusted OR 2.516, 95% CI 2.305-2.746, p < 0.0001) but not new-onset AKI during hospitalization. Other factors associated with AKI were similar between patients with and without ACS. AKI in patients with ACS had similar rate of recovery as those without ACS (p = 0.4). Multi-variable logistic regression showed that both ACS types in AKI were associated with higher inpatient, 30-day and 90-day mortality rates, and they had a synergistic effect. Other factors associated with inpatient, 30-day and 90-day mortality rates of patients with AKI were similar between patients with and without ACS. We conclude that ACS was associated with a higher incidence of AKI, and the risk was mainly associated with AKI on admission. The recovery rates from AKI were similar between patients with and without ACS, but the presence of AKI and ACS synergistically increased the inpatient, 30-day and 90-day mortality rates.

Crossed cerebellar diaschisis (CCD) is characterized by reduced perfusion and metabolism in the cerebellar hemisphere contralateral to a supratentorial lesion. In large-vessel occlusion acute ischemic stroke (LVO-AIS), CCD may result from hemodynamic impairment, structural injury, or both. From a blood-oxygenation-level-dependent cerebrovascular reactivity (BOLD-CVR) imaging database, we identified patients with anterior-circulation LVO-AIS who underwent BOLD-CVR MRI within 7 days of symptom onset. Patients were stratified into those with persistent occlusion (non-endovascular thrombectomy, non-EVT) and those imaged after successful reperfusion (EVT). CCD was defined by a cerebellar asymmetry index > 12%. Associations between CCD and imaging markers of structural injury (infarct lesion volume) and hemodynamic impairment (steal phenomenon volume) as well as associations with 90-day functional outcome were assessed using logistic regression models. Sensitivity analyses included multiple imputation and best-/worst-case scenarios for missing outcomes. Seventy-nine patients were included (23 EVT, 56 non-EVT). CCD was present in 35% of EVT and 41% of non-EVT patients. In non-EVT patients, CCD was independently associated with larger steal phenomenon volumes (adjusted OR 1.99; 95% CI 1.12-3.73), but not infarct size. In EVT patients, CCD was associated with larger infarct lesions (adjusted OR 5.75; 95% CI 1.41-68.92) but not steal phenomenon volume. CCD predicted poorer 90-day outcome only in non-EVT patients in complete-case analysis, but this association was not robust in sensitivity analyses. CCD in acute LVO-AIS reflects different mechanisms depending on occlusion status: hemodynamic impairment under persistent occlusion and structural injury after reperfusion. BOLD-CVR imaging provides insight into CCD, though larger studies are needed to clarify its prognostic value.

Repeat stereotactic radiosurgery (SRS) is a treatment option for residual brain arteriovenous malformations (AVMs) following incomplete response to an initial SRS, and this study aimed to clarify the long-term outcomes. Patients who underwent repeat SRS between 1990 and 2022 were retrospectively analyzed. Primary outcome was a favorable patient outcome, defined as AVM obliteration without post-SRS hemorrhage or symptomatic T2 signal change/late radiation-induced complications (LRICs). Fifty-eight patients with a median follow-up of 97 months were analyzed. Six patients (10.3%) experienced recurrent hemorrhage between the initial and repeat SRS, indicating high risk of hemorrhage in this cohort. Favorable patient outcome was achieved in 41 patients (70.7%), with 3- and 5-year cumulative rates of 68.1% and 79.2%. Maximum dose was associated with a favorable patient outcome (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.01-1.14; p = 0.016). AVM obliteration was achieved in 47 patients (81.0%), with 3- and 5-year rates of 69.2% and 85.0%. Three patients (5.2%) experienced post-repeat SRS hemorrhage, with an annual hemorrhage rate of 1.66%/person-year. Five patients (8.6%) experienced LRICs requiring resection with 5- and 10-year rates of 4.0% and 6.9%. T2 signal change after initial SRS (HR 17.11, 95% CI 1.06-276.55; p = 0.046) and initial maximum diameter > 25 mm (HR 21.12, 95% CI 1.01-442.76; p = 0.049) were associated with LRICs. Repeat SRS demonstrated long-term favorable outcomes in patients at a high risk of hemorrhage. A longer follow-up duration is important, as in the case of LRICs, which could be predicted by T2 signal change and nidus size before repeat SRS.

The perinatal period is a high-risk time for stroke, with possible lifelong effects. We aimed at identifying factors associated with long-term neurological outcomes and post-stroke epilepsy in patients with neonatal arterial ischemic stroke (NAIS). We analyzed patients with NAIS from the Italian Registry of Infantile Thrombosis (RITI). Associations between clinical variables and outcomes (neurological deficits and epilepsy at last follow-up) were evaluated using univariate logistic regression. Among the 181 patients included (56.2% male), seizures were the most common initial symptom (79.4%). Stroke was left-sided in 62.0%, and bilateral in 15.0%; multiple lesions were reported in 32.5%. The middle cerebral artery territory was most frequently involved. One patient had a new infarction during hospitalization, and one died. At follow-up (median 21 months), no further recurrences or deaths occurred; neurological deficits were reported in 38.8%, and post-stroke epilepsy in 12.0% (among these latter, prior acute seizures occurred in 86.7%). At univariate regression, factors significantly associated with long-term neurological deficits were higher maternal age (p = 0.031); urgent cesarean (p < 0.001); lower gestational age (p = 0.033); neurological deficits at discharge (p < 0.001); seizures at last follow-up (p = 0.008). Factors significantly associated with post-stroke epilepsy were need for acute-phase assisted ventilation (p = 0.001); radiological brainstem involvement (p = 0.037); and longer admission duration (p = 0.050).

 Mortality and recurrence after NAIS are rare, but neurological deficits occur in about 40%, and epilepsy in 12%. Perinatal and clinical factors may predict adverse outcomes and epilepsy.

• The perinatal period is a high-risk window for neonatal arterial ischemic stroke (NAIS), with seizures as the most common presenting symptom. Mortality and recurrent strokes after NAIS are rare, but long-term neurological deficits and post-stroke epilepsy are recognized complications.

• In this registry-based cohort, specific perinatal and clinical factors-such as higher maternal age, urgent cesarean delivery, lower gestational age, neurological deficits at discharge, and seizures at follow-up-were significantly associated with long-term neurological impairments. • Risk factors for post-stroke epilepsy were identified, including need for acute-phase assisted ventilation, radiological brainstem involvement, and longer hospital stays, providing new insights for early prognostication and follow-up strategies.

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel oral agents for treating anemia in chronic kidney disease (CKD), with potential effects on lipid modulation. We aimed to systematically evaluate the effects of HIF-PHIs on lipid profiles and cardiovascular outcomes in CKD patients.

PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase (Ovid) were searched for randomized controlled trials comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in dialysis-dependent (DD) or nondialysis-dependent (NDD) CKD patients. Primary outcomes included changes in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C). Secondary outcomes included cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and all-cause mortality.

A total of 20 trials involving 12,155 patients were analyzed in this review. Roxadustat significantly reduced LDL-C (mean difference [MD], -16.07 mg/dL; 95% CI, -17.92 to -14.21; 14 randomized controlled trials [RCTs], 10,510 patients), total cholesterol (MD, -25.25 mg/dL; 95% CI, -29.70 to -20.81; 10 RCTs, 5,538 patients), triglycerides (MD, -19.70 mg/dL; 95% CI, -30.78 to -8.61; 9 RCTs, 4,616 patients), but also decreased HDL-C (MD, -4.91 mg/dL; 95% CI, -6.80 to -3.02; 9 RCTs, 5,132 patients). Desidustat significantly reduced LDL-C and total cholesterol, but showed no significant effects on triglycerides or HDL-C, whereas molidustat showed no significant lipid-lowering effects. Overall, treatment with HIF-PHIs was not associated with significant differences in cardiovascular death (RR, 1.00; 95% CI, 0.84 to 1.18; 10 RCTs, 9,371 patients), myocardial infarction (RR, 1.12; 95% CI, 0.90 to 1.38; 15 RCTs, 11,265 patients), stroke (RR, 1.18; 95% CI, 0.86 to 1.61; 14 RCTs, 11,136 patients), or all-cause mortality (RR, 1.06; 95% CI, 0.96 to 1.17; 19 RCTs, 11,903 patients), compared with ESAs or placebo.

Roxadustat showed the most substantial lipid-lowering effects, while desidustat showed significant reductions in LDL-C and total cholesterol but no significant effects on triglycerides or HDL-C, and molidustat showed no significant effects. Despite these changes in lipid profiles, no significant differences in cardiovascular outcomes were observed for these three HIF-PHIs, compared with ESAs or placebo.

This pilot study aimed to evaluate early outcomes of a composite graft constructed from two saphenous veins (SVs) with a single inflow source in coronary artery bypass grafting (CABG) for patients with an atherosclerotic ascending aorta. The analysis focused on prevention of embolic events and early graft patency.

The analysis included 17 patients who underwent CABG using the left internal thoracic artery (LITA) to the left anterior descending artery (LAD), combined with a composite graft constructed from two saphenous veins (SVs) with a single inflow source. The SV composite graft was anastomosed to non-LAD coronary territories.

Intraoperative flow and pulsatility index values of the SV grafts were satisfactory. No major complications, including new cerebrovascular embolic events, were observed. The early patency rate of SV anastomoses was 90%; all four occlusions among the total 40 anastomoses occurred in the Y-shaped composite graft.

A composite graft constructed from two SVs with a single inflow source appears to reduce the risk of embolic events by minimizing manipulation of the atherosclerotic ascending aorta. However, the configuration of the proximal SV anastomoses may affect early graft patency. Specifically, the risk of early failure appears to be higher in the Y-shaped configuration than in the V-shaped configuration.