Ischemic stroke (IS), a leading cause of morbidity and mortality worldwide, primarily results from blood clot formation in cerebral vessels, leading to vessel occlusion, reduced cerebral blood flow, and subsequent tissue ischemia. While thrombolytic therapies and mechanical thrombectomy remain cornerstone treatments for restoring blood flow, their clinical efficacy is significantly limited by the narrow therapeutic window, which underscores the critical need for novel, safe, and effective therapeutic strategies. In this review, we present an intensive analysis of four pathophysiological stages of IS progression and their intervention targets, and evaluate both established and emerging therapeutic strategies with the molecular mechanisms underpinning these methods, aiming to enhance the understanding of IS intervention. Additionally, we discuss current challenges in IS therapy, emphasizing the importance of timely, stage-specific approaches to optimize therapeutic outcomes. Finally, we highlight some promising research directions and innovations to advance IS field.

Objective:To investigate and evaluate the clinical efficacy and safety of a modified anterior approach for transpupillary silicone oil removal combined with phacoemulsification and intraocular lens (IOL) implantation.Methods:A retrospective case-control study. A total of 148 patients (148 eyes) who underwent silicone oil removal combined with cataract surgery at the Department of Ophthalmology, Guangdong Provincial People's Hospital between January 2020 and November 2024 were included in the study. All affected eyes underwent preoperative examinations including best-corrected visual acuity (BCVA), intraocular pressure, corneal topography, and optical coherence tomography (OCT). Based on the method of silicone oil removal, the eyes were divided into two groups: group A (modified anterior approach transpupillary silicone oil removal combined with phacoemulsification and IOL implantation, 99 eyes) and group B (standard pars plana vitrectomy for silicone oil removal combined with phacoemulsification and IOL implantation, 49 eyes). The surgical duration, changes in BCVA and intraocular pressure at 1 day, 7 days, and 1 month postoperatively, as well as the incidence of complications such as corneal edema and its resolution, conjunctival congestion, iris prolapse, posterior capsule rupture, nucleus drop, IOL position, residual silicone oil in the vitreous cavity or anterior chamber, vitreous hemorrhage, recurrent retinal detachment (RD), and choroidal detachment or hemorrhage, were compared between the two groups. The independent sample t-test was used for the comparison of measurement data between the two groups, and the χ2 test was used for the comparison of count data. Results:The operation time of group A and group B was (17.01±1.28) min and (31.62±2.32) min, respectively. The operation time of group A was significantly shorter than that of group B, and the difference was statistically significant ( t=?41.002, P<0.001). The comparison of BCVA ( t =?0.561, ?0.833, ?1.386) and IOP ( t=?0.055, 1.375, ?0.507) between the two groups of affected eyes before surgery and at 1 day and 7 days after surgery showed no statistically significant differences ( P>0.05). There was no silicone oil residual in group A, while 3 eyes in group B were observed with silicone oil residual (6.1%, 3/49). Neovascular glaucoma was observed in one eye. Compared to group A, group B exhibited a statistically significant increase in the incidence of postoperative conjunctival congestion, silicone oil retention, and posterior capsular opacification ( χ2=10.600, 6.187, 92.617; P<0.05). In contrast, no statistically significant differences were observed between the groups in the incidence of corneal edema or recurrent retinal detachment (RD) ( χ2=0.272, 1.557; P>0.05). No intraoperative complications, such as iris prolapse, posterior capsular rupture, nucleus drop, zonular dehiscence, choroidal detachment, or hemorrhage, occurred in any of the operated eyes. Furthermore, no postoperative complications, including corneal endothelial decompensation, IOL displacement, or endophthalmitis, were observed during the follow-up period. Conclusion:Compared to the conventional pars plana approach for silicone oil removal combined with cataract surgery, the modified anterior perfusion transpupillary approach demonstrated significantly shorter surgical duration and a reduced incidence of postoperative complications.

Dyslipidemia is one of the common metabolic disorders in type 2 diabetes mellitus,often coexisting with insulin resistance and central obesity to form metabolic syndrome,significantly increasing the risk of macrovascular and microvascular complications in diabetic patients.Non-high-density lipoprotein cholesterol(non-HDL-C)refers to the sum of cholesterol contained in other lipopro-teins except high-density lipoprotein cholesterol(HDL-C).In recent years,the importance of non-HDL-C in the management of diabetic complications has garnered increasing attention,and it has been established as a major lipid-lowering target along with low-density lipoprotein cholesterol(LDL-C)in the latest expert consensus on lipid management for Chinese diabetic patients.Clinical studies have demonstrated that non-HDL-C is closely associated with residual cardiovascular risk and recurrent stroke risk in diabetic patients,as well as carotid plaque vulnerability and the development of peripher-al arterial disease.Additionally,non-HDL-C is also closely related to diabetic nephropathy and reti-nopathy in type 2 diabetes mellitus,and achieving long-term control of non-HDL-C levels can reduce the risk of chronic kidney disease.This article summarized the relationship between non-HDL-C and complications of type 2 diabetes mellitus and elucidated its significance as a future clinical therapeutic target.

Objective:To investigate and evaluate the clinical efficacy and safety of a modified anterior approach for transpupillary silicone oil removal combined with phacoemulsification and intraocular lens (IOL) implantation.Methods:A retrospective case-control study. A total of 148 patients (148 eyes) who underwent silicone oil removal combined with cataract surgery at the Department of Ophthalmology, Guangdong Provincial People's Hospital between January 2020 and November 2024 were included in the study. All affected eyes underwent preoperative examinations including best-corrected visual acuity (BCVA), intraocular pressure, corneal topography, and optical coherence tomography (OCT). Based on the method of silicone oil removal, the eyes were divided into two groups: group A (modified anterior approach transpupillary silicone oil removal combined with phacoemulsification and IOL implantation, 99 eyes) and group B (standard pars plana vitrectomy for silicone oil removal combined with phacoemulsification and IOL implantation, 49 eyes). The surgical duration, changes in BCVA and intraocular pressure at 1 day, 7 days, and 1 month postoperatively, as well as the incidence of complications such as corneal edema and its resolution, conjunctival congestion, iris prolapse, posterior capsule rupture, nucleus drop, IOL position, residual silicone oil in the vitreous cavity or anterior chamber, vitreous hemorrhage, recurrent retinal detachment (RD), and choroidal detachment or hemorrhage, were compared between the two groups. The independent sample t-test was used for the comparison of measurement data between the two groups, and the χ2 test was used for the comparison of count data. Results:The operation time of group A and group B was (17.01±1.28) min and (31.62±2.32) min, respectively. The operation time of group A was significantly shorter than that of group B, and the difference was statistically significant ( t=?41.002, P<0.001). The comparison of BCVA ( t =?0.561, ?0.833, ?1.386) and IOP ( t=?0.055, 1.375, ?0.507) between the two groups of affected eyes before surgery and at 1 day and 7 days after surgery showed no statistically significant differences ( P>0.05). There was no silicone oil residual in group A, while 3 eyes in group B were observed with silicone oil residual (6.1%, 3/49). Neovascular glaucoma was observed in one eye. Compared to group A, group B exhibited a statistically significant increase in the incidence of postoperative conjunctival congestion, silicone oil retention, and posterior capsular opacification ( χ2=10.600, 6.187, 92.617; P<0.05). In contrast, no statistically significant differences were observed between the groups in the incidence of corneal edema or recurrent retinal detachment (RD) ( χ2=0.272, 1.557; P>0.05). No intraoperative complications, such as iris prolapse, posterior capsular rupture, nucleus drop, zonular dehiscence, choroidal detachment, or hemorrhage, occurred in any of the operated eyes. Furthermore, no postoperative complications, including corneal endothelial decompensation, IOL displacement, or endophthalmitis, were observed during the follow-up period. Conclusion:Compared to the conventional pars plana approach for silicone oil removal combined with cataract surgery, the modified anterior perfusion transpupillary approach demonstrated significantly shorter surgical duration and a reduced incidence of postoperative complications.

Objective:To analyze independent factors for treatment-requiring retinopathy of prematurity (TR-ROP) and establish a predictive nomogram model for TR-ROP.Method:A retrospective cohort study. A total of 6 998 preterm infants who were born at Guangdong Women's and Children's Hospital between January 1, 2012 and March 31, 2022 and were screened for retinopathy of prematurity (ROP) were included in the study. TR-ROP was defined as type 1 ROP and aggressive ROP; 22 independent factors including general information, maternal perinatal conditions, interventions and neonatal diseases related to ROP were collected. The infants were divided at the level at an 8:2 ratio according to clinical experience, with 5 598 in the training cohort and 1 400 in the validation cohort. t test was used for comparison of quantitative data and χ 2 test was used for comparison of counting data between groups. Multivariate logistic regression analysis was carried out for the indicators with differences in the univariate analysis. The visualized regression analysis results of R software were used to obtain the histogram. The accuracy of the nomogram was verified by C-index and receiver operating characteristic curve (ROC curve). Results:Among the 6 998 children tested, 4 069 were males and 2 920 were females. Gestational age was (33.69±3.19) weeks; birth weight was (2 090±660) g. There were 376 cases of TR-ROP (5.4%, 376/6 998). The results of multivariate logistic regression analysis showed that gestational age [odds ratio ( OR) =0.63, 95% confidence interval ( CI) 0.47-0.85, P=0.002], intrauterine distress ( OR=0.30, 95% CI 0.10-0.99, P=0.048), bronchopulmonary dysplasia ( OR=0.23, 95% CI 0.09-0.60, P=0.003), hypoxic-ischemic encephalopathy ( OR=5.40, 95% CI 1.45-20.10, P=0.012), blood transfusion history ( OR=4.05, 95% CI 1.50-10.95, P=0.006) were the independent influencing factors of TR-ROP. Based on this and combined with birth weight, a nomogram prediction model was established. The C-index of the training set and validation set were 0.940 and 0.885, respectively, and the area under ROC curve were 0.945 (95% CI 0.930-0.961) and 0.931 (95% CI 0.876-0.986), respectively. The sensitivity and specificity were 86.2%, 94.0% and 83.2%, 93.3%, respectively. Conclusions:Gestational age, intrauterine distress, bronchopulmonary dysplasia, hypoxic-ischemic encephalopathy and blood transfusion history are the independent factors influencing the occurrence of TR-ROP. The TR-ROP nomogram prediction model based on independent influencing factors has high sensitivity and specificity.

Background: Neuroblastoma (NB) is a malignant pediatric tumor requiring new therapies. Accumulating evidence has confirmed that micro RNAs play critical roles in NB metastasis. Dihydroartemisinin (DHA) is capable of inhibiting the growth of NB cells. The primary objective of the current investigation was to characterize a newly discovered microRNA, miR-32-5p, in terms of the functional role, underlying mechanism of action, and potential synergistic therapeutic impact in the context of NB metastasis. Materials and methods: Real-time quantitative polymerase chain reaction and Western blotting were employed to assess the expression levels of miR-32-5p and its target, vacuolar protein sorting 4B (VPS4B). Furthermore, Transwell assay was utilized to evaluate in vitro cell migration and invasion, whereas a metastasis xenograft model was established in nude mice via caudal vein injections. Results: Gene Expression Omnibus database and real-time quantitative polymerase chain reaction analysis showed that miR-32-5p was downregulated in human NB samples and NB cell lines, in comparison with the normal tissue and cell lines. Inhibiting miR-32-5p induced the migration and invasion of NB cells, whereas overexpression of miR-32-5p prevented the migration and invasion in NB cell lines. Furthermore, VPS4B was identified as the direct target of miR-32-5p and the miR-32-5p reduction associated with NB metastasis upregulated the expression of VPS4B. Conversely, overexpression of VPS4B reversed the suppressive effects ofmiR-32-5p onNB cells. Moreover, miR-32-5p increased the sensitivity to DHA both in NB cells and in the metastasis xenograft model of nude mice. Conclusions: The downregulation of miR-32-5p in NB regulates NB metastasis by targeting VPS4B. Moreover, miR-32-5b can improve the sensitivity of DHA in the xenograft mouse model. Our findings have important implications for the combined application of miR-32-5p and DHA in the treatment of NB.

The objective was to report a relatively rare case of fulminant type 1 diabetes(FT1 DM)complicated with acute pancreatitis(AP),to summarize the characteristics as well as experience of diag-nosis and treatment,and to explore its pathogenesis.Clinical data of a case of FT1DM complicated with AP in the Department of Endocrinology of our hospital were analyzed retrospectively.A 66-year-old male presented with acute fever and abdominal pain,accompanying with the significantly elevated pancreatic enzymes,and his abdominal CT scan showed exudation around the pancreas.The clinical manifestations mentioned above were consistent with the diagnosis of AP.Five days after onset,the patient developed clinical symptoms,such as obvious thirst,polyuria,polyasthenia and fatigue.Meanwhile,his plasma glucose increased significantly and the diabetic ketoacidosis(DKA)occurred.The patient's fasting and postprandial 2 hours C peptide decreased significantly(all 0.02 μg/L),glycated hemoglobin level was not high(6％),and his islet-related autoantibodies were undetectable.Thus,the patient could be diag-nosed with FT1DM.After the treatment of fasting,fluid replacement,anti-infection,somatostatin,anti-coagulation and intravenous insulin sequential subcutaneous insulin pump,the patient gained the allevia-tion of pancreatitis,restoration of oral intake,and relatively stable blood glucose levels.Summarizing the characte-ristics of this case and reviewing the literature,FT1DM complicated with AP was relatively rare in FT1DM.Its common characteristics were described below:(1)Most cases started with AP and the blood glucose elevated within 1 week,or some cases had the simultaneously onset of AP and FT1DM.(2)The clinical course of AP was short and relieved no more than 1 week;Pancreatic imaging could completely return to normal within 1 to 4 weeks after onset.(3)The etiology of AP most was idiopathic;The elevation of pancreatic enzyme level was slight and the recovery was rapidly compared with AP of other etiologies.FT1DM could be complicated with AP,which was different from the physiological mani-festations of pancreatic disease in general FT1DM patients.Virus infection mignt be the common cause of AP and FT1DM,and AP might be the early clinical manifestation of some FT1DM.The FT1DM patients developed with abdominal pain was easy to be missed,misdiagnosed and delayed,which should receive more attention in clinic.

Objective:To design a simulated navigation scheme of cranial puncture based on three dimensional (3D) infrared optical locator,so as to achieve accurately puncture of trigeminal nerve semilunar node and ensure maximization of the effect of clinical surgery. Methods:The experiment used computed tomography (CT) to scan skull phantom,and imported its data into 3D Slicer system. Spatial coordinates of skull phantom,surgical tool,surgical needle and needle tips were converted to 3D Slicer through the 3D optical locator and 3D Slicer's image guided therapy (IGT) module,so as to display the relationship of spatial position between needle tip and skull model in real-time,and to verify the accuracy of actual measurement of 3D optical locator,and the located accuracy of navigation scheme of skull puncture. Results:After the verification of 10 verification tests,the defined accuracy of 3D optical locator reached 0.2 mm. The operation of virtual world of 3D Slicer system can real-timely and accurately correspond with that of real world. The measured result of simulated navigation and position was (0.87±0.49) mm. Conclusion:The testing results verify the accuracy of navigation of simulated cranial puncture,which has favorable effect,and which can provide a reference for planning navigation scheme before percutaneous puncture balloon compression (PBC) surgery.

Objective:To design a simulated navigation scheme of cranial puncture based on three dimensional (3D) infrared optical locator,so as to achieve accurately puncture of trigeminal nerve semilunar node and ensure maximization of the effect of clinical surgery. Methods:The experiment used computed tomography (CT) to scan skull phantom,and imported its data into 3D Slicer system. Spatial coordinates of skull phantom,surgical tool,surgical needle and needle tips were converted to 3D Slicer through the 3D optical locator and 3D Slicer's image guided therapy (IGT) module,so as to display the relationship of spatial position between needle tip and skull model in real-time,and to verify the accuracy of actual measurement of 3D optical locator,and the located accuracy of navigation scheme of skull puncture. Results:After the verification of 10 verification tests,the defined accuracy of 3D optical locator reached 0.2 mm. The operation of virtual world of 3D Slicer system can real-timely and accurately correspond with that of real world. The measured result of simulated navigation and position was (0.87±0.49) mm. Conclusion:The testing results verify the accuracy of navigation of simulated cranial puncture,which has favorable effect,and which can provide a reference for planning navigation scheme before percutaneous puncture balloon compression (PBC) surgery.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the pathophysiology of sepsis, but the exact mechanism remains debatable. In this study, we investigated the associations among the serum levels of PAI-1, the incidence of 4G/5G promoter PAI-1 gene polymorphisms, immunological indicators, and clinical outcomes in septic patients. METHODS: A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study, with 28-day mortality as the primary outcome. The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms (SNPs) were examined. Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1, serum level of PAI-1, and 28-day mortality. RESULTS: The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1 (4G/4G and 4G/5G) (Odds ratio [OR]: 2.49; 95% confidence interval [CI]: 1.09, 5.68). Furthermore, a high serum level of PAI-1 strongly influenced 28-day mortality (OR 3.36; 95% CI 1.51, 7.49). The expression and activation of neutrophils (OR 0.96; 95% CI 0.93, 0.99), as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils (OR: 1.00; 95% CI: 1.00, 1.00), were both regulated by the genotype of PAI-1. CONCLUSIONS Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1, which might contribute to mortality by affecting neutrophil activity. Thus, patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Humans ; Middle Aged ; Young Adult ; Genotype ; Neutrophils ; Plasminogen Activator Inhibitor 1/genetics* ; Polymorphism, Single Nucleotide/genetics* ; Retrospective Studies ; Sepsis/genetics*