Performance in the Fundamentals of Laparoscopic Surgery: Does it reflect global rating scales in the Objective Structured Assessment of Technical Skills in porcine laparoscopic surgery?

Objective: To correlate the utility of the Fundamentals of Laparoscopic Surgery (FLS) manual skills program with the Objective Structured Assessment of Technical Skills (OSATS) global rating scale in evaluating operative performance. Methods: The Asian Urological Surgery Training and Educational Group (AUSTEG) Laparoscopic Upper Tract Surgery Course implemented and validated the FLS program for its usage in laparoscopic surgical training. Delegates' basic laparoscopic skills were assessed using three different training models (peg transfer, precision cutting, and intra-corporeal suturing). They also performed live porcine laparoscopic surgery at the same workshop. Live surgery skills were assessed by blinded faculty using the OSATS rating scale. Results: From March 2016 to March 2019, a total of 81 certified urologists participated in the course, with a median of 5 years of post-residency experience. Although differences in task time did not reach statistical significance, those with more surgical experience were visibly faster at completing the peg transfer and intra-corporeal suturing FLS tasks. However, they took longer to complete the precision cutting task than participants with less experience. Overall OSATS scores correlated weakly with all three FLS tasks (peg transfer time: r=-0.331, r 2=0.110; precision cutting time: r=-0.240, r 2=0.058; suturing with intra-corporeal knot time: r=-0.451, r 2=0.203). Conclusion: FLS task parameters did not correlate strongly with OSATS globing rating scale performance. Although FLS task models demonstrated strong validity, it is important to assimilate the inconsistencies when benchmarking technical proficiency against real-life operative competence, as evaluated by FLS and OSATS, respectively.

Analysis of the thermal insulation performance of cement with waste glass powder in geothermal well.

To improve the heat extraction efficiency from the wellbore fluids to the stratum in the geothermal well, thermal insulation cement, which contains of waste glass powder as a heat-insulating material, is proposed to apply in geothermal well's middle and upper sections in the paper. Effect of such glass powers on mechanic and thermal property of thermal insulation cement was then investigated. Various tests were carried out to measure compressive strength, thermal conductivity, microstructure porosity etc. parameters of the thermal insulation cement. Results showed that the waste glass powder would enhance its the compressive strength and improve its the thermal insulation performance. Correlation study between contents of the added waste glass powder in geothermal cements and its mechanic and thermal property was conducted. It was found that thermal insulation cement exhibited its optimum performance when the added content of glass powers was 20% in weight. Analysis of the microstructure porosity with SEM found that the pores in thermal insulation cement with added waste glass powders were mostly closed, tiny and even, and therefore contributed to the compressive strength of the thermal insulation cement; such pores would be also beneficial to improving its thermal insulation performance.

Safety and effectiveness of LEO stents for dual stent-assisted embolization combined with IA and IV intra-procedural infusion of tirofiban in the treatment of wide-necked intracranial bifurcation aneurysms.

Objective: To evaluate the safety and efficacy of employing LEO stents in dual stent-assisted embolization (DSAE) for wide-necked intracranial bifurcation aneurysms, and to assess the effectiveness of combined IA and IV intra-procedural infusion of tirofiban in mitigating perioperative complications. Methods: Clinical data and follow-up images from 562 patients with wide-necked intracranial bifurcation aneurysms treated at First Affiliated Hospital of Army Medical University from 2018-2022 were collected. Among them, 65 received DSAE with LEO stents. The study observed treatment success rates, procedure-related complications, perioperative thromboembolic events (TEs) and hemorrhagic events (HEs), immediate postoperative modified Raymond-Roy classification (mRR), and follow-up imaging. Glasgow Outcome Scale (GOS) at discharge and clinical follow-ups were recorded. Results: The study enrolled 65 patients (mean age: 56.77 ± 10.07) with wide-necked intracranial bifurcation aneurysms. Among them, 58 had unruptured aneurysms, 7 ruptured (Hunt-Hess II-III). All aneurysms were successfully embolized without significant stent or bleeding complications. Only one case had intraoprative thrombosis; two postoperative ischemic incidents occurred within three days, no severe bleeding events. Immediate imaging showed modified Raymond-Roy classification: mRRC I (92.3%), mRRC II (4.6%), mRRC III b (3.1%). A total of 43 patients were followed up postoperatively with DSA. Among them, 41 patients exhibited mRRC I, while 2 patients exhibited mRRC II. No aneurysm was recanalized. Discharge GOS: GOS 5-60, GOS 4-1, GOS 3-4. One patient, GOS 1, died from lung cancer; others improved. Conclusion: The utilization of LEO stents for dual stent-assisted embolization of wide-necked intracranial bifurcation aneurysms demonstrated remarkable success and safety, yielding favorable postoperative outcomes and no instances of aneurysm recurrence. The concomitant administration of perioperative antiplatelet medications alongside IA and IV intra-procedural infusion of tirofiban effectively attenuated thromboembolic events (TEs) without concomitant elevations in bleeding risks.

Sex Differences in Outcome of Aneurysmal Subarachnoid Hemorrhage and Its Relation to Postoperative Cerebral Ischemia.

BACKGROUND: Whether there is a sex difference in the outcome of aneurysmal subarachnoid hemorrhage (aSAH) remains controversial, and clarifying the role of women in postoperative cerebral ischemic events can help us to understand its relationship with poor prognosis. Therefore, the purpose of this study was to elucidate the relationship between the three aspects of sex differences, postoperative cerebral ischemia, and poor prognosis after aSAH. METHODS: A total of 472 patients admitted within 72 h after aSAH between January 2018 and December 2022 were included. We systematically analyzed the characteristics of sex differences in aSAH and explored the relationship between delayed cerebral ischemia (DCI), surgery-related cerebral infarction (SRCI), and poor prognosis (modified Rankin Scale > 2). RESULTS: Compared with women, men were in worse condition and had more intracerebral hematoma (p = 0.001) on admission, whereas women were older (p < 0.001) and had more multiple aneurysms (p = 0.002). During hospitalization, men were more likely to experience emergency intubation (p = 0.036) and tracheotomy (p = 0.013). Women achieved functional independence at discharge at a similar rate to men (p = 0.394). Among postoperative complications, the incidence of DCI (22% vs. 12%, p = 0.01) and urinary tract infection (p = 0.022) was significantly higher in women. After adjusting for age, multivariable regression analysis showed that hypertension (odds ratio [OR] 2.139, 95% confidence interval [CI] 1.027-4.457), preoperative rerupture (OR 12.240, 95% CI 1.491-100.458), pulmonary infection (OR 2.297, 95% CI 1.070-4.930), external ventricular drainage placement (OR 4.382, 95% CI 1.550-12.390), bacteremia (OR 14.943, 95% CI 1.412-158.117), SRCI (OR 8.588, 95% CI 4.092-18.023), venous thrombosis (OR 5.283, 95% CI 1.859-15.013), higher modified Fisher grades (p = 0.003), and Hunt-Hess grades (p = 0.035) were associated with poor prognosis, whereas DCI (OR 1.394, 95% CI 0.591-3.292) was not an independent risk factor for poor prognosis. The proportion of patients who fully recovered from cerebral ischemia was higher in the DCI group (p < 0.001) compared with the SRCI group, and more patients were discharged with modified Rankin Scale > 2 in the SRCI group (p = 0.005). CONCLUSIONS: Women have a higher incidence of DCI, but there is no sex difference in outcomes after aSAH, and poor prognosis is associated with worse admission condition and perioperative complications. SRCI is a strong independent risk factor for poor prognosis, whereas DCI is not.

Irreversible Electroporation for the Focal Treatment of Prostate Cancer: A Systematic Review.

PURPOSE: Irreversible electroporation (IRE) is a promising alternative treatment for low-intermediate-risk localized prostate cancer. In this systematic review we aim to evaluate the safety profile and functional and oncological outcomes of this new technique. MATERIALS AND METHODS: A systematic review of the literature was performed on PubMed, EMBASE, and Scopus up to 24 August 2023. Nineteen studies were analyzed, including 12 prospective studies and 7 retrospective studies. A total of 1,452 patients underwent IRE as the sole primary treatment modality. RESULTS: The in-field clinically significant prostate cancer rate was reported between 0%-15.6% in the repeat biopsy. The retreatment rate was reported from 8% to 36.6%. The 3 years failure-free survival was presented between 90%-96.8%. The post-operative pad-free rate ranged between 96.7%-100%. Greater heterogeneity exists considering the change in erectile function. The most common reported complications were urinary tract infection and hematuria. Major complications were rare. CONCLUSIONS: These results underline that IRE achieves favorable oncological control with an excellent safety profile, in the meantime preserving patients' urinary and erectile function.

Is atezolizumab plus bevacizumab as first-line therapy for unresectable hepatocellular carcinoma superior to lenvatinib? a systematic review and meta­analysis.

BACKGROUND: This meta-analysis was dedicated to evaluating the effectiveness and safety of Atezolizumab plus Bevacizumab (Atez/Bev) and Lenvatinib (LEN) as first-line systematic therapy for unresectable hepatocellular carcinoma (u-HCC). METHODS: The prospective protocol for this study was registered with the PROSPERO (Registration number: CRD42022356874). Literature searches were conducted in PubMed, EMBASE database Cochrane Library, and Web Science to determine all clinical controlled studies that reported Atez/Bev and LEN for treating u-HCC. We. evaluated as primary end-point overall survival (OS) and progression-free survival (PFS), as well as other outcomes such as tumor response and adverse events (AEs).Quality assessment and data extraction of studies were conducted independently by three reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software. RESULTS: 12 retrospective cohort studies (RCSs) involving a total of 4948 patients were finally included. The results showed that compared with LEN, Atez/Bev can improve the patient's PFS (HR = 0.80, 95% CI: 0.72 ~ 0.88; p < 0.0001) and reduce the rate of overall AEs (OR = 0.46 95% CI: 0.38 ~ 0.55, p < 0.00001) and grade ≥ 3 AEs (OR = 0.43; 95% CI: 0.36 ~ 0.51, p < 0.00001), while there is no difference between OS and treatment responses rate (objective response rate, disease control rate, complete response, partial response, progressive disease, and stable disease) between two groups. In addition, the subgroup analysis shows that Atez/Bev can promote the OS of patients with viral hepatitis. (HR = 0.79, 95% CI: 0.67 ~ 0.95; p = 0.01), while LEN has an advantage in improving OS in patients with Child-Pugh grade B liver function (HR = 1.98, 95% CI: 1.50 ~ 2.63; p < 0.00001). CONCLUSION: Current evidence shows that compared with LEN, Atez/Bev has more advantages in PFS and safety in treating u-HCC and can improve the OS of patients with viral. LEN has advantages in improving the OS of patients with grade B liver function. However, more multicenter randomized controlled experiments are needed in the future to verify our results.

Peripheral cytokine interleukin-10 alleviates perihematomal edema after intracerebral hemorrhage via interleukin-10 receptor/JAK1/STAT3 signaling.

AIMS: The extent of perihematomal edema following intracerebral hemorrhage (ICH) significantly impacts patient prognosis, and disruption of the blood-brain barrier (BBB) exacerbates perihematomal edema. However, the role of peripheral IL-10 in mitigating BBB disruption through pathways that link peripheral and central nervous system signals remains poorly understood. METHODS: Recombinant IL-10 was administered to ICH model mice via caudal vein injection, an IL-10-inhibiting adeno-associated virus and an IL-10 receptor knockout plasmid were delivered intraventricularly, and neurobehavioral deficits, perihematomal edema, BBB disruption, and the expression of JAK1 and STAT3 were evaluated. RESULTS: Our study demonstrated that the peripheral cytokine IL-10 mitigated BBB breakdown, perihematomal edema, and neurobehavioral deficits after ICH and that IL-10 deficiency reversed these effects, likely through the IL-10R/JAK1/STAT3 signaling pathway. CONCLUSIONS: Peripheral IL-10 has the potential to reduce BBB damage and perihematomal edema following ICH and improve patient prognosis.

USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

Exhaustive clinical examination of etiology and initial response to first-line treatment in 577 children with infantile epileptic spasm syndrome children: A 5-year retrospective observational study.

OBJECTIVE: Employing whole-exome sequencing (WES) technology to investigate the etiology of infantile epileptic spasm syndrome (IESS), and determining whether different etiologies exhibit phenotypic variations, while elucidating the potential associated factors, might improve short-term responses to first-line treatment. METHODS: We retrospectively evaluated patients with IESS admitted for treatment between January 2018 and June 2023. Clinical phenotypic differences among etiological classifications and clinical manifestations were analyzed. Variable selection using the best subset method was performed, followed by logistic regression analysis to identify the factors influencing treatment response. RESULTS: A total of 577 patients were included; 412 completed trio-WES. Magnetic resonance imaging abnormalities were detected in 387 patients (67.1%). Patients with etiology as structural abnormalities were likelier to have non-spasms at the initial seizure onset. A total of 532 patients completed the first-line treatment; 273 patients received it for the first time at our hospital (initial response rates: 30.1% and 42.1%, respectively). The response group had a lower proportion of early-onset seizures (≤3 months) than the no-response group (11.3% vs. 23.7%, p < 0.01 and 11.3% vs. 21.5%, p = 0.03, respectively). Logistic regression analysis indicated that earlier initiation of first-line treatment was associated with a higher likelihood of an initial response. However, the etiological classification did not have a significant impact on the initial response. INTERPRETATION: IESS patients with structural abnormalities are more likely to present with non-spasm seizures at initial onset. Early initiation of first-line treatment is crucial; however, initial responses may be less favorable when seizures occur in early infancy.

Expanding the clinical phenotype and genetic spectrum of GEMIN5 disorders: Early-infantile developmental and epileptic encephalopathies.

BACKGROUND: Several biallelic truncating and missense variants of the gem nuclear organelle-associated protein 5 (GEMIN5) gene have been reported to cause neurodevelopmental disorders characterized by cerebellar atrophy, intellectual disability, and motor dysfunction. However, the association between biallelic GEMIN5 variants and early-infantile developmental and epileptic encephalopathies (EIDEEs) has not been reported. PURPOSE: This study aimed to expand the phenotypic spectrum of GEMIN5 and explore the correlations between epilepsy and molecular sub-regional locations. METHODS: We performed whole-exome sequencing in two patients with EIDEE with unexplained etiologies. The damaging effects of variants were predicted using multiple in silico tools and modeling. All reported patients with GEMIN5 pathogenic variants and detailed neurological phenotypes were analyzed to evaluate the genotype-phenotype relationship. RESULTS: Novel biallelic GEMIN5 variants were identified in two unrelated female patients with EIDEE, including a frameshift variant (Hg19, chr5:154284147-154284148delCT: NM_015465: c.2551_c.2552delCT: p.(Leu851fs*30)), a nonsense mutation (Hg19, chr5:154299603-154299603delTinsAGA: NM_015465: c.1523delTinsAGA: p.(Leu508*)), and two missense variants (Hg19, chr5:154282663T > A: NM_015465: c.2705T > A: p.(Leu902Gln) and Hg19, chr5:154281002C > G: NM_015465: c.2911C > G: p.(Gln971Glu)), which were inherited from asymptomatic parents and predicted to be damaging or probably damaging using in silico tools. Except p.Leu508*, all these mutations are located in tetratricopeptide repeat (TPR) domain. Our two female patients presented with seizures less than 1 month after birth, followed by clusters of spasms. Brain magnetic resonance imaging suggests dysgenesis of the corpus callosum and cerebellar hypoplasia. Video electroencephalogram showed suppression-bursts. Through a literature review, we found 5 published papers reporting 48 patients with biallelic variants in GEMIN5. Eight of 48 patients have epilepsy, and 5 patients started before 1 year old, which reminds us of the relevance between GEMIN5 variants and EIDEE. Further analysis of the 49 GEMIN5 variants in those 50 patients demonstrated that variants in TPR-like domain or RBS domain were more likely to be associated with epilepsy. CONCLUSIONS: We found novel biallelic variants of GEMIN5 in two individuals with EIDEE and expanded the clinical phenotypes of GEMIN5 variants. It is suggested that the GEMIN5 gene should be added to the EIDEE gene panel to aid in the clinical diagnosis of EIDEE and to help determine patient prognosis.

The Role of Peripheral Inflammatory Markers and Coagulation Factors in Patients with Central Nervous System (CNS) Immune Disease and Glioma.

OBJECTIVE: Gliomas are associated with high rates of disability and mortality, and currently, there is a lack of specific and sensitive biomarkers for diagnosis. The ideal biomarkers should be detected early through noninvasive methods. Our research aims to develop a rapid, convenient, noninvasive diagnostic method for gliomas, as well as for grading and differentiation. METHOD: We retrospectively collected data from patients who underwent surgery for glioma, trigeminal neuralgia/hemifacial spasmschwannoma, and those diagnosed with multiple sclerosis at our institution from January 2018 to December 2020. Inflammatory markers and coagulation factor levels were collected on admission, and neutrophil count (NLR), (WBC count minus neutrophil count) / lymphocyte count, platelet count / lymphocyte count, lymphocyte count / monocyte count, and albumin count [g/L] + total lymphocyte count × 5 were calculated for patients. Analyze the significance of biomarkers in the diagnosis and grading of gliomas, the diagnosis of MS, and the differential diagnosis of them. RESULTS: We evaluated 155 healthy individuals, 64 trigeminal neuralgia/hemifacial spasm patients, 47 MS patients, 316 schwannoma patients, and 814 with glioma patients. Compared with healthy controls and MS group, the preoperative levels of NLR, (WBC count minus neutrophil count) / lymphocyte count, D-dimer, Fibrinogen, Antithrobin, and Factor VIII of glioma patients were significantly higher in glioma patients and positively correlated with the grade of glioma. Conversely, 0020 lymphocyte count / Monocyte count and albumin count [g/L] + total lymphocyte count × 5 were significantly lower and negatively correlated with glioma grading. ROC curves confirmed that for the diagnosis of glioma, NLR showed a maximum area under the curve value of 0.8616 (0.8322-0.8910), followed by D-dimer and Antithrombin, with area under the curve values of 0.8205 (0.7601-0.8809) and 0.8455 (0.8153-0.8758), respectively. NLR and d-dimer also showed great sensitivity in the diagnosis of MS and differential diagnosis with gliomas. CONCLUSIONS: Our study demonstrated that multiple inflammatory markers and coagulation factors could be utilized as biomarkers for the glioma diagnosis, grading, and differential diagnosis of MS. Furthermore, the combination of these markers exhibited high sensitivity and specificity.

Preparation and Performance of Ceramic Tiles with Steel Slag and Waste Clay Bricks.

Steel slag and waste clay bricks are two prevalent solid waste materials generated during industrial production. The complex chemical compositions of these materials present challenges to their utilization in conventional alumina silicate ceramics manufacturing. A new type of ceramic tile, which utilizes steel slag and waste clay brick as raw materials, has been successfully developed in order to effectively utilize these solid wastes. The optimal composition of the ceramic material was determined through orthogonal experimentation, during which the effects of the sample molding pressure, the soaking time, and the sintering temperature on the ceramic properties were studied. The results show that the optimal ceramic tile formula was 45% steel slag, 35% waste clay bricks, and 25% talc. The optimal process parameters for this composition included a molding pressure of 25 MPa, a sintering temperature of 1190 °C, and a soaking time of 60 min. The prepared ceramic tile samples had compositions in which solid waste accounted for more than 76% of the total material. Additionally, they possessed a modulus of rupture of more than 73.2 MPa and a corresponding water absorption rate of less than 0.05%.

Wood-converted porous carbon decorated with MIL-101(Fe) derivatives for promoting photo-Fenton degradation of ciprofloxacin.

In response to the escalating concerns over antibiotics in aquatic environments, the photo-Fenton reaction has been spotlighted as a promising approach to address this issue. Herein, a novel heterogeneous photo-Fenton catalyst (Fe3O4/WPC) with magnetic recyclability was synthesized through a facile two-step process that included in situ growth and subsequent carbonization treatment. This catalyst was utilized to expedite the photocatalytic decomposition of ciprofloxacin (CIP) assisted by H2O2. Characterization results indicated the successful anchoring of MIL-101(Fe)-derived spindle-like Fe3O4 particles in the multi-channeled wood-converted porous carbon (WPC) scaffold. The as-synthesized hybrid photocatalysts, boasting a substantial specific surface area of 414.90 m2·g-1 and an excellent photocurrent density of 0.79 µA·cm-2, demonstrated superior photo-Fenton activity, accomplishing approximately 100% degradation of CIP within 120 min of ultraviolet-light exposure. This can be attributed to the existence of a heterojunction between Fe3O4 and WPC substrate that promotes the migration and enhances the efficient separation of photogenerated electron-hole pairs. Meanwhile, the Fe(III)/Fe(II) redox circulation and mesoporous wood carbon in the catalyst synergistically enhance the utilization of H2O and accelerate the formation of •OH radicals, leading to heightened degradation efficiency of CIP. Experiments utilizing chemical trapping techniques have demonstrated that •OH radicals are instrumental in the CIP degradation process. Furthermore, the study on reusability indicated that the efficiency in removing CIP remained at 89.5% even through five successive cycles, indicating the structural stability and excellent recyclability of Fe3O4/WPC. This research presented a novel pathway for designing magnetically reusable MOFs/wood-derived composites as photo-Fenton catalysts for actual wastewater treatment.

Association between cardiometabolic index and depression: National Health and Nutrition Examination Survey (NHANES) 2011-2014.

BACKGROUND: Emerging evidence suggests a common pathophysiological basis for metabolic disorders and mental diseases. Despite the existence of reports suggesting a strong connection between dyslipidemia and depression, a comprehensive and reliable indicator to identify depression is still lacking. Cardiometabolic index (CMI) is an integrated index calculated from three vital metabolic indicators, including triglyceride (TG), high-density lipoprotein cholesterol (HDLC) and waist height ratio (WHtR). OBJECTIVE: This study aims to explore the association between CMI and depression. METHODS: Cross-sectional data of participants with complete information of CMI, depression, and other covariates were obtained from the National Health and Nutrition Examination Survey (NHANES). Weighted student's t-test and Chi-square test were used to identify the differences between two groups. Weighted multivariate logistic regression model, restricted cubic spline (RCS) regression analysis, subgroup analysis and interaction tests were conducted to explore the association between CMI and depression. Receiver operating curve (ROC) analysis and area under the curve (AUC) were also utilized to evaluate the performance of CMI in identifying depression. RESULTS: A positive correlation between CMI and depression was observed in 3794 participants included in the study, which was further confirmed to be non-linear via RCS regression analysis, with two significant inflection points being identified, including 0.9522 and 1.58. In the crude or adjusted models, individuals with a CMI level ≥ 0.9522 exhibited remarkably increased risk for developing depression. CMI got an AUC of 0.748 in identifying depression. Subgroup analyses and interaction tests indicate that the association between CMI and depression remained consistent across different subgroups and was not modified by other covariates except drinking. Those who are current drinkers and with a high CMI are more susceptible to suffer depression. CONCLUSIONS: An elevated CMI is linked to increased risk for depression. Addressing dyslipidemia and improving lipid levels may potentially lower the risk for depression.

Perioperative complications of arteriovenous tirofiban administration versus oral dual antiplatelet therapy for stent-assisted embolization treated aneurysmal subarachnoid hemorrhage: A retrospective, controlled cohort analysis.

BACKGROUND: Major perioperative complications of stent-assisted embolization treated for aneurysmal subarachnoid hemorrhage patients include the formation of thromboembolic events (TEs) and hemorrhagic events (HEs), for which antiplatelet protocols play a key role. METHODS: We conducted a single-center retrospective analysis to compare the differences between arteriovenous tirofiban administration with traditional oral dual antiplatelet therapy (DAPT). A total of 417 consecutive patients were enrolled. General clinical characteristics, as well as the perioperative ischemic and hemorrhagic events, were retracted in digital documents. Logistic regression was conducted to identify both risk and protective factors of perioperative TEs and HEs. RESULTS: Perioperative TEs occurred in 21 patients, with an overall perioperative TEs rate of approximately 5.04%; among these patients, the incidence of perioperative TEs in the tirofiban group was less than that in the DAPT group. Additionally, 66 patients developed perioperative HEs, with an incidence of approximately 15.83%; among these patients, the incidence of perioperative HEs was less than that in the DAPT group. No significant differences were seen between the two groups in terms of the mRS score at the time of discharge. CONCLUSION: This study indicated that an improved perioperative antiplatelet drug tirofiban was an independent protective factor for perioperative TEs in stent-assisted embolization of ruptured intracranial aneurysms, but it did not impart an elevated risk of perioperative HEs and had no significant effects on the near-term prognosis of the patients.

Altered expression of the Plexin-B2 system in tuberous sclerosis complex and focal cortical dysplasia IIb lesions.

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.

Computation-Aided Phylogeny-Oriented Engineering of ß-Xylosidase: Modification of "Blades" to Enhance Stability and Activity for the Bioconversion of Hemicellulose to Produce Xylose.

Hemicellulose is a highly abundant, ubiquitous, and renewable natural polysaccharide, widely present in agricultural and forestry residues. The enzymatic hydrolysis of hemicellulose has generally been accomplished using ß-xylosidases, but concomitantly increasing the stability and activity of these enzymes remains challenging. Here, we rationally engineered a ß-xylosidase from Bacillus clausii to enhance its stability by computation-aided design combining ancestral sequence reconstruction and structural analysis. The resulting combinatorial mutant rXYLOM25I/S51L/S79E exhibited highly improved robustness, with a 6.9-fold increase of the half-life at 60 °C, while also exhibiting improved pH stability, catalytic efficiency, and hydrolytic activity. Structural analysis demonstrated that additional interactions among the propeller blades in the catalytic module resulted in a much more compact protein structure and induced the rearrangement of the opposing catalytic pocket to mediate the observed improvement of activity. Our work provides a robust biocatalyst for the hydrolysis of agricultural waste to produce various high-value-added chemicals and biofuels.

Latent classes of symptom trajectories among major depressive disorder patients in China.

OBJECTIVE: This study aimed to understand the long-term symptom trajectories of Chinese patients with major depressive disorder (MDD) using piecewise latent growth modeling and growth mixture modeling. The investigation also aimed to identify the baseline characteristics indicative of poorer treatment outcomes. METHODS: A total of 558 outpatients with MDD were assessed using a sequence of surveys. The Hamilton Rating Scale for Depression (HRSD), Hamilton Anxiety Rating Scale (HAMA), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to evaluate baseline depression, anxiety, and cognitive function. Depression symptom severity was subsequently measured at the 1-month, 2-month, 6-month, 1-year, and 2-year follow-ups. RESULTS: Results indicated three depressive symptomology trajectories, including (a) severe, improving class (12.72 %), (b) partially responding, later deteriorating class (6.09 %), and (c) moderate, improving class (81.18 %). Logistic regression analyses showed that a history of cardiovascular disease (CVD) increased the odds of belonging to the partially responding, later deteriorating class, whereas higher baseline depression increased the odds of belonging to the severe, improving class compared to the moderate, improving class. Patients who experienced less depression relief during the first month of treatment had a lower probability of belonging to the moderate, improving class. LIMITATIONS: Participant attrition in this study may have inflated the estimated rate of treatment-resistant patients. CONCLUSIONS: The burden of CVD and poorer initial treatment response are plausible risk factors for poorer treatment outcomes, highlighting targets for intervention in Chinese MDD patients.

Divergent electroencephalogram resting-state functional network alterations in subgroups of autism spectrum disorder: a symptom-based clustering analysis.

Autism spectrum disorder (ASD) is characterized by etiological and phenotypic heterogeneity. Despite efforts to categorize ASD into subtypes, research on specific functional connectivity changes within ASD subgroups based on clinical presentations is limited. This study proposed a symptom-based clustering approach to identify subgroups of ASD based on multiple clinical rating scales and investigate their distinct Electroencephalogram (EEG) functional connectivity patterns. Eyes-opened resting-state EEG data were collected from 72 children with ASD and 63 typically developing (TD) children. A data-driven clustering approach based on Social Responsiveness Scales-Second Edition and Vinland-3 scores was used to identify subgroups. EEG functional connectivity and topological characteristics in four frequency bands were assessed. Two subgroups were identified: mild ASD (mASD, n = 37) and severe ASD (sASD, n = 35). Compared to TD, mASD showed increased functional connectivity in the beta band, while sASD exhibited decreased connectivity in the alpha band. Significant between-group differences in global and regional topological abnormalities were found in both alpha and beta bands. The proposed symptom-based clustering approach revealed the divergent functional connectivity patterns in the ASD subgroups that was not observed in typical ASD studies. Our study thus provides a new perspective to address the heterogeneity in ASD research.

Infantile epileptic spasm syndrome as a new NR2F1 gene phenotype.

INTRODUCTION: NR2F1 pathogenetic variants are associated with the Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS). Recent studies indicate that BBSOAS patients not only have visual impairments but may also have developmental delays, hypotonia, thin corpus callosum and epileptic seizures. However, reports of BBSOAS occurrence along with infantile epileptic spasm syndrome (IESS) are rare. METHODS: Here, we report three cases involving children with IESS and BBSOAS caused by de novo NR2F1 pathogenetic variants and summarize the genotype, clinical characteristics, diagnosis and treatment of them. RESULTS: All three children experienced epileptic spasms and global developmental delays, with brain Magnetic Resonance Imaging (MRI) suggesting abnormalities (thinning of the corpus callosum or widened extracerebral spaces) and two of the children exhibiting abnormal visual evoked potentials. CONCLUSIONS: Our findings indicate that new missense NR2F1 pathogenetic variants may lead to IESS with abnormal visual evoked potentials. Thus, clinicians should be aware of the Bosch-Boonstra-Schaaf optic atrophy syndrome and regular monitoring of the fundus, and the optic nerve is necessary during follow-up.