Dual-Factor-Controlled Dynamic Precursors Enable On-Demand Thermoset Degradation and Recycling.

Thermosets are well known for their advantages such as high stability and chemical resistance. However, developing sustainable thermosets with degradability and recyclability faces several principal challenges, including reconciling the desired characteristics during service with the recycling and reprocessing properties required at the end of life, establishing efficient methods for large-scale synthesis, and aligning with current manufacturing process. Here a general strategy is presented for the on-demand degradation and recycling of thermosets under mild conditions utilizing dynamic precursors with dual-factor-controlled reversibility. Specifically, dynamic triazine crosslinkers are introduced through dynamic nucleophilic aromatic substitution (SNAr) into the precursor polyols used in polyurethane (PU) synthesis. Upon removal of the catalyst and alcohol, the reversibility of SNAr is deactivated, allowing for the use of standard PU polymerization techniques such as injection molding, casting, and foaming. The resulting cyanurate-crosslinked PUs maintain high stability and diverse mechanical properties of traditional crosslinked PUs, yet offer the advantage of easy on-demand depolymerization for recycling by activating the reversibility of SNAr under specific but mild conditions-a combination of base, alcohol, and mild heat. It is envisioned that this approach, involving the pre-installation of dual-factor-controlled dynamic crosslinkers, can be broadly applied to current thermosetting plastic manufacturing processes, introducing enhanced sustainability.

Chronic subdural hematoma that may be caused by nephrotic syndrome: a case report and literature review.

Background: Chronic subdural hematoma (CSDH) is a common complication of neurosurgery. Craniocerebral trauma is the likely cause. There are no reports relating CSDH with nephrotic syndrome. Its pathogenesis is very rare, and there are no previous reports on treatments for this disease. We report a case of chronic subdural hematoma that may be caused by nephrotic syndrome and review the previous literature on this subject. Case summary: We report a rare case of chronic subdural hematoma that may be caused by nephrotic syndrome. After the patient was admitted to the hospital, relevant laboratory tests were conducted, and a large amount of protein was detected in the patient's urine, indicating hypoproteinaemia and hyperlipidemia. The patient was diagnosed with nephrotic syndrome. After the exclusion of related surgical contraindications, the patient underwent trepanation and drainage of the chronic subdural hematoma. Subsequent treatment with oral atorvastatin was provided after surgery. The patient was transferred to the nephrology department for further treatment of nephrotic syndrome if his neurological condition improved. No neurological sequelae were detected at the follow-up visit 3 months after the operation. Conclusion: Chronic subdural hematomas are rarely caused by nephrotic syndrome. Trepanation and drainage may be considered for patients confirmed to have adequate hematoma liquefaction on imaging and who can tolerate craniotomy. Atorvastatin should be supplemented as prophylactic treatment after the operation. Nephrotic syndrome should be treated as soon as the patient's neurological condition is stable.

RBM25 is required to restrain inflammation via ACLY RNA splicing-dependent metabolism rewiring.

Spliceosome dysfunction and aberrant RNA splicing underline unresolved inflammation and immunopathogenesis. Here, we revealed the misregulation of mRNA splicing via the spliceosome in the pathogenesis of rheumatoid arthritis (RA). Among them, decreased expression of RNA binding motif protein 25 (RBM25) was identified as a major pathogenic factor in RA patients and experimental arthritis mice through increased proinflammatory mediator production and increased hyperinflammation in macrophages. Multiomics analyses of macrophages from RBM25-deficient mice revealed that the transcriptional enhancement of proinflammatory genes (including Il1b, Il6, and Cxcl10) was coupled with histone 3 lysine 9 acetylation (H3K9ac) and H3K27ac modifications as well as hypoxia inducible factor-1α (HIF-1α) activity. Furthermore, RBM25 directly bound to and mediated the 14th exon skipping of ATP citrate lyase (Acly) pre-mRNA, resulting in two distinct Acly isoforms, Acly Long (Acly L) and Acly Short (Acly S). In proinflammatory macrophages, Acly L was subjected to protein lactylation on lysine 918/995, whereas Acly S did not, which influenced its affinity for metabolic substrates and subsequent metabolic activity. RBM25 deficiency overwhelmingly increased the expression of the Acly S isoform, enhancing glycolysis and acetyl-CoA production for epigenetic remodeling, macrophage overactivation and tissue inflammatory injury. Finally, macrophage-specific deletion of RBM25 led to inflammaging, including spontaneous arthritis in various joints of mice and inflammation in multiple organs, which could be relieved by pharmacological inhibition of Acly. Overall, targeting the RBM25-Acly splicing axis represents a potential strategy for modulating macrophage responses in autoimmune arthritis and aging-associated inflammation.

Is intravenous infusion an unrecognized route for internal microplastic human exposure? A general assessment.

As newly recognized environmental pollutants, microplastics (MPs, ≤5 mm in length) have been reported in various human tissues and fluids, including the spleen, liver, heart, blood and blood clots, raising global concerns about their impact on human health. This study investigated the characteristics of MPs in intravenous infusion and the removal of MPs from infusion products by infusion sets fitted with different filters using micro-Fourier Transform Infrared Spectroscopy. MPs were detected in infusion products, with an average abundance of 1.24 ± 1.44 items/unit (2.91 ± 3.91 items/L). The primary types of MPs identified were fragmented particles of polyethene and polypropylene, ranging in size from 15-100 µm. Internal filters in infusion sets played a crucial role in removing MPs, particularly fibrous ones, resulting in a reduction in both abundance and particle size of MPs in the human body. Moreover, this study conducted a general assessment of intravenous microplastic exposure among hospital patients and estimated the global per-person input of MPs via intravenous administration. It is an opportunity for us to gain a deeper understanding of MPs in intravenous infusion and provides guides selecting infusion devices, increasing awareness of associated health risks.

Smartphone-assisted fluorescent microfluidic-chip for sensitive detection of sweat glucose via dual-sensing of O2/H2O2.

A novel smartphone-assisted fluorescent microfluidic-chip was designed for detecting sweat glucose. The microfluidic chip contained six microchambers, each of which was equipped with a glucose sensing membrane incorporating glucose oxidase (GOD), fluorescent O2 probe PtTFPP and H2O2 probe G1. Based upon O2 consumption and H2O2 generation during glucose catalysis by GOD, the chip produced two fluorescence signals towards glucose under single-wavelength excitation, i.e. green fluorescence in response to H2O2 and red fluorescence to O2. The limit of detection (LOD) based on H2O2 monitoring was 0.005 mM, while the LOD based on O2 monitoring was 0.04 mM. Furthermore, the obtained chip was integrated with a smartphone-based portable platform to record RGB values for point-of-care testing of sweat glucose. Glucose calibration (Y = -3.45 + 1.81∗R + 0.68∗G) at 6-min time point was performed by combining R and G channels signals. The dual-monitoring analysis provided a more accurate and reliable verification of glucose detection. This smartphone-assistant optical microfluidic-chip device holds significant potential for portable self-management of glucose in personalized healthcare and clinical diagnosis.

Survival Benefit of Lenvatinib Plus PD-1 Inhibitor with or Without HAIC in Advanced Hepatocellular Carcinoma Beyond Oligometastasis: a Multicenter Cohort Study.

Purpose: The outcome between Lenvatinib plus programmed cell death protein-1 (PD-1) inhibitor and Lenvatinib in HCC beyond oligometastasis was unclear. In this multicenter, we compared the prognosis of Lenvatinib plus PD-1 inhibitor with Lenvatinib in HCC beyond oligometastasis. Patients and Methods: A total of 296 patients from six institutions were included. The patients were divided into two groups: (a) concurrent Lenvatinib plus PD-1 inhibitor treatment (Len+PD-1 group) and (b) Lenvatinib monotherapy (Len group). The primary endpoint was overall survival (OS), the second endpoint was progression-free survival (PFS) and efficacy. Results: The median OS was 20.1 ± 1.2 (17.7-22.5) months and 15.7 ± 1.5 (12.8-18.6) months in the Len+PD-1 and Len groups, respectively. The 12-, 24-, and 36-month OS rates were 79.1%, 39.4%, and 10.7% in the Len+PD-1 group, and 76.3%, 29.7%, and 0% in the Len group, respectively. The OS and PFS rates of the Len+PD-1 group were significantly longer compared with the Len group (hazard ratio [HR], 0.88; 95% confidence index [CI], 0.49-0.94; P = 0.021) and (HR, 0.66; 95% CI, 0.50-0.87; P = 0.003). A subgroup analysis revealed that OS (HR, 0.57; 95% CI, 0.36-0.90; P = 0.016) was improved between the Len+PD-1 and Len groups with hepatic artery infusion chemotherapy (HAIC) treatment, whereas OS (HR, 1.11; 95% CI, 0.68-1.80; P = 0.689) was similar between the Len and Len+PD-1 groups without HAIC. Conclusion: Lenvatinib combined with PD-1 inhibitor significantly improves the survival of HCC beyond oligometastasis. For patients with HAIC, there was obviously significance between Len and Len+PD-1 groups.

Lenvatinib as one of system therapy, is recommended treatment for HCC with multimetastases. The LEAP-002 trial, which evaluated Lenvatinib combined with Pembrolizumab exhibited improved progression-free survival (PFS) and overall survival (OS) compared with Lenvatinib alone. However, the combination efficacy on HCC beyond oligometastasis is unknown. In this multicenter study, we found that Lenvatinib combined with PD-1 inhibitor significantly improved both the OS and PFS and this combination could be recommended for HCC beyond oligometastases. OS and PFS were improved in the Len+PD-1 versus the Len group with hepatic artery infusion chemotherapy (HAIC) treatment, whereas the OS and PFS were similar between the Len and Len+PD-1 groups without HAIC. We provided clinical value that HAIC could be recommended as an effective local therapy to improve the prognosis for advanced HCC.

Hepatic Arterial Infusion Chemotherapy Combined Lenvatinib and PD-1 Inhibitor Showed Improved Survival for Infiltrative Hepatocellular Carcinoma: A Multicenter Cohort Study.

Purpose: Lenvatinib and programmed cell death protein-1 (PD-1) inhibitor on infiltrative hepatocellular carcinoma (HCC) have obtained demonstrated efficacy and still need improvement. Hepatic arterial infusion chemotherapy (HAIC) has shown promising results for advanced HCC. This study aimed to compare the efficacy of HAIC combined Lenvatinib and PD-1 inhibitor versus Lenvatinib combined PD-1 inhibitor for infiltrative HCC. Patients and Methods: A total of 232 patients were enrolled. There were 114 patients received Lenvatinib combined PD-1 inhibitor (Len+PD-1 group) and 118 patients received HAIC combined Lenvatinib and PD-1 inhibitor (HAIC+Len+PD-1 group). Overall survival (OS), progression-free survival (PFS) and safety of patients were compared between the two groups by propensity score-matching (PSM). Results: The 6-, 12-, and 24-month OS rates were 93.8%, 65.1% and 13.4% in Len+PD-1 group, and 100%, 77.3% and 32.1% in HAIC+Len+PD-1 group, respectively. The 3-, 6-, and 12-month PFS rates were 86.4%, 45.7% and 14.1% in Len+PD-1 group, and 95.1%, 59.3% and 25.9% in HAIC+Len+PD-1 group, respectively. The HAIC+Len+PD-1 group had obviously better survival than the Len+PD-1 group both in OS (P=0.002) and PFS (P=0.004). Subgroup analysis revealed that OS in patients with metastasis was improved with HAIC+Len+PD-1 treatment. Patients with alpha-fetoprotein (AFP) response after treatment showed better survival than the non-response. In addition, HAIC+Len+PD-1 group showed manageable adverse events (AEs). Conclusion: Patient with infiltrative HCC, HAIC+Len+PD-1 treatment had longer OS and PFS than Len+PD-1 treatment. Early AFP response was an effective indicator of better survival and tumor response to therapy.

Infiltrative hepatocellular carcinoma (HCC) is an odd group that is not well adjudicated in the current staging systems, and treatment options for patients with infiltrative HCC are challenging with scant and insufficient clinical evidence. In this multi-center study, we innovatively analyzed the outcome of hepatic arterial infusion chemotherapy (HAIC) combined lenvatinib and PD-1 inhibitor (HAIC+Len+PD-1) was associated longer progression-free survival and overall survival than Lenvatinib plus PD-1 inhibitor combination (Len+PD-1) for patient with infiltrative HCC. In addition, further intragroup analysis revealed that OS of patients with and without metastasis in Len+PD-1 group was significant difference. However, no difference was observed in OS for patients with and without metastasis in HAIC+Len+PD-1 group. Patients with alpha-fetoprotein (AFP) response after treatment showed better survival than the non-response. Our research provides evidence that HAIC combined Lenvatinib and PD-1 inhibitor results in clinically significant improvements in infiltrative HCC. It could be recommended as a first choice for infiltrative HCC therapy.

Influencing factors for postpartum depression in women with gestational diabetes mellitus.

Objective: It remains undefined about the association between gestational diabetes mellitus (GDM) and postpartum depression (PPD). Hence, a cross-sectional study was conducted to evaluate the association between GDM and PPD among pregnant women and to investigate the influencing factors for PPD. Methods: From June 2021 to June 2022, 205 parturients with GDM and 201 without GDM were included in the study as the GDM group and the control group, respectively. The collected data from the general information questionnaire and Self Rating Depression Scale (SDS) were statistically analyzed based on binomial logistic regression analyses and generalized linear mixed models (GLMMs). Results: Age at delivery, gestational age, glycosylated hemoglobin, triglyceride, SDS, and proportions of women who had a history of induced abortion or GDM were significantly different between the GDM group and control group (P<0.05). The incidence of PPD in the GDM group was significantly higher than that in the control group. The neonatal body weight and triglyceride in GDM women with PPD were significantly lower than those in GDM women without PPD (P<0.001). The univariate logistic regression analysis demonstrated that educational age was a protective factor, while glycosylated hemoglobin and GDM were risk factors for PPD. The multiple linear regression analysis revealed that neonatal body weight (OR=-0.904, 95%CI: -1.657 to -0.152, P=0.019) and educational age (OR=-0.166, 95%CI: -0.306 to -0.025, P=0.021) were protective factor, while GDM (OR=1.854, 95%CI: 1.027-2.681, P<0.0001) was a risk factor for PPD. Conclusion: GDM may be associated with PPD. Neonatal body weight and educational age were protective factors for PPD, and GDM was a risk factor for PPD. Therefore, more attention should be paid to the mental health status of women with GDM, especially those with lesser educational age and lower neonatal body weight.

The Relationship between Nutritional Status and Thyroid Function among Adults in the USA: NHANES 2007-2012.

Controlled Nutritional Status (CONUT) scores have been developed as quantitative tools that can be employed to gauge the nutritional status of individual patients. However, there has been very little research investigating the association between these CONUT scores and the function of the thyroid. As such, the present study was designed to address this research gap through the evaluation of a representative cohort of American adults. National Health and Nutrition Examination Survey (NHANES) data were herein used to separate subjects into those with normal nutritional status (CONUT score: 0-1) from those who were malnourished (CONUT scores > 1). Associations between these CONUT scores and the function of the thyroid were investigated through linear regression modeling, employing weighted analytical strategies and subgroup analyses. Overall, 8,082 individuals from the NHANES 2007-2012 cohort were enrolled in this analysis. These individuals exhibited a weighted mean CONUT score of 0.72 (0.02). 6661 (weighted proportion: 83.12%) in the normal nutritional status group and 1421 (16.88%) in the malnourished group. In adjusted analyses, subjects who were malnourished were found to present with an increase in FT4 levels (ß = 0.033; p < 0.001 together with reduced TT3 levels (ß = -3.526; p = 0.01). The present data offer evidence in support of higher CONUT scores, which correspond to malnutrition, being related to increases in FT4 levels together with reductions in TT3 levels. More studies will be crucial to further probe the mechanistic drivers of these results.

Tough polyacrylic acid hydrogels with stable swelling and active functionalities enabled by quaternized cellulose nanofibrils and iron ions for absorbent pad interlayers.

Hydrogels are highly sought-after absorbent materials for absorbent pads; however, it is still challenging to achieve a satisfactory balance between mechanical performance, water absorption capacity, and active functionalities. In this work, we presented double-network hydrogels synthesized through acrylic acid (AA) polymerization in the presence of quaternized cellulose nanofibrils (QCNF) and Fe3+. Spectroscopic and microscopic analyses revealed that the combined QCNF and Fe3+ facilitated the formation of double-network hydrogels with combined chemical and physical crosslinking. The synergistic effect of QCNF and Fe3+ resulted in impressive mechanical properties, including tensile strength of 1.98 MPa, fracture elongation of 838.8 %, toughness of 7.47 MJ m-3, and elastic modulus of 0.35 MPa. In comparison to the single-network PAA hydrogel, the PAA/QCNF/Fe3+ (PQFe) hydrogels showed higher and relatively stable swelling ratios under varying pH levels and saline conditions. The PQFe hydrogels exhibited notable antioxidant activity, as evidenced by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and demonstrated effective antibacterial activity against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). These hydrogels show promising potential as an absorbent interlayer in absorbent pads for active food packaging.

Dietary supplementation with Macleaya cordata extract alleviates intestinal injury in broiler chickens challenged with lipopolysaccharide by regulating gut microbiota and plasma metabolites.

Introduction: The prevention and mitigation of intestinal immune challenge is crucial for poultry production. This study investigated the effects of dietary Macleaya cordata extract (MCE) supplementation on the prevention of intestinal injury in broiler chickens challenged with lipopolysaccharide (LPS). Methods: A total of 256 one-day-old male Arbor Acres broilers were randomly divided into 4 treatment groups using a 2×2 factorial design with 2 MCE supplemental levels (0 and 400 mg/kg) and 2 LPS challenge levels (0 and 1 mg/kg body weight). The experiment lasted for 21 d. Results and discussion: The results showed that MCE supplementation increased the average daily feed intake during days 0-14. MCE supplementation and LPS challenge have an interaction on the average daily gain during days 15-21. MCE supplementation significantly alleviated the decreased average daily gain of broiler chickens induced by LPS. MCE supplementation increased the total antioxidant capacity and the activity of catalase and reduced the level of malondialdehyde in jejunal mucosa. MCE addition elevated the villus height and the ratio of villus height to crypt depth of the ileum. MCE supplementation decreased the mRNA expression of pro-inflammatory cytokines interleukin (IL)-6 and IL-8 in the jejunum. MCE addition mitigated LPS-induced mRNA up-expression of pro-inflammatory factors IL-1ß and IL-17 in the jejunum. MCE supplementation increased the abundance of probiotic bacteria (such as Lactobacillus and Blautia) and reduced the abundance of pathogenic bacteria (such as Actinobacteriota, Peptostretococcaceae, and Rhodococcus), leading to alterations in gut microbiota composition. MCE addition altered several metabolic pathways such as Amino acid metabolism, Nucleotide metabolism, Energy metabolism, Carbohydrate metabolism, and Lipid metabolism in broilers. In these pathways, MCE supplementation increased the levels of L-aspartic acid, L-Glutamate, L-serine, etc., and reduced the levels of phosphatidylcholine, phosphatidylethanolamine, thromboxane B2, 13-(S)-HODPE, etc. In conclusion, dietary supplementation of 400 mg/kg MCE effectively improved the growth performance and intestinal function in LPS-challenged broiler chickens, probably due to the modulation of gut microbiota and plasma metabolites.

Addition of Immune Checkpoint Inhibitor Showed Better Efficacy for Infiltrative Hepatocellular Carcinoma Receiving Hepatic Arterial Infusion Chemotherapy and Lenvatinib: A Multicenter Retrospective Study.

Purpose: The prognosis of infiltrative hepatocellular carcinoma (HCC) is dismal. Hepatic arterial infusion chemotherapy (HAIC) plus Lenvatinib (Len) and immune checkpoint inhibitor (ICI) have shown promising results for HCC. However, this three combination therapy on infiltrative HCC is unknown. In this study, we compared HAIC plus lenvatinib (Len) and programmed cell death protein-1 (PD-1) inhibitor with HAIC plus Len for infiltrative HCC. Patients and Methods: This multi-center cohort study included patients with infiltrative HCC who received HAIC combined with Len (HAIC+Len group, n = 173) or HAIC combined with Len and PD-1 inhibitor (HAIC+Len+ICI group, n = 128) as the first-line treatment from January 2019 to December 2021. To balance any intergroup differences, one-to-one propensity score matching (PSM) was applied. Overall survival (OS) and progression-free survival (PFS) were compared between the two groups. Results: After PSM, the median OS was 14.1 ± 1.0 and 16.1 ± 1.4 months in the HAIC+Len and HAIC+Len+ICI groups, respectively. The median PFS was 4.6 ± 0.4 months in the HAIC+Len group and 7.5 ± 0.8 months in the HAIC+Len+ICI group. The HAIC+Len+ICI group showed significantly better OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.90; P = 0.008) and PFS (HR, 0.53; 95% confident index [CI], 0.40-0.70; P < 0.001) compared with the HAIC+Len group. Subgroup analysis revealed that for OS in HCC without metastasis, the addition of PD-1 inhibitor was not significant (HR, 0.68; 95% CI, 0.43-1.07; P = 0.091). No difference was observed in OS between low (2-3 cycles) and high (4-6 cycles) level of HAIC cycles (HR, 0.99; 95% CI, 0.67-1.44; P = 0.938). Conclusion: The HAIC+Len+ICI group had a longer PFS and OS compared with the HAIC+Len group, demonstrating an acceptable safety profile. This triple combination strategy may be an alternative treatment for infiltrative HCC management.

The evidence of HAIC plus Len and PD-1 inhibitors for infiltrative HCC is limited. There was no study to evaluate the efficacy of HAIC combined with Len and PD-1 inhibitors for infiltrative HCC. In this study, we found that HAIC plus Len and PD-1 inhibitor (HAIC+Len+ICI) was associated with longer progression-free survival and overall survival than HAIC plus Len combination (HAIC+Len) for patient with infiltrative HCC. In addition, OS in patients with metastasis was improved with HAIC+Len+ICI treatment. OS in patients without metastasis, addition of PD-1 inhibitor after HAIC and Len was not beneficial. What's more, three cycles of HAIC are adequate, especially for patients with high tumor burden, especially with main branch portal vein tumor thrombus (PVTT). Our research provides new evidence that HAIC+Len+ICI treatment significantly improved the OS and PFS of infiltrative HCC patients compared with those who received HAIC+Len treatment. It provides a strong reference for clinical treatment.

Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances.

Tertiary lymphoid structures (TLSs) are defined as lymphoid aggregates formed in non-hematopoietic organs under pathological conditions. Similar to secondary lymphoid organs (SLOs), the formation of TLSs relies on the interaction between lymphoid tissue inducer (LTi) cells and lymphoid tissue organizer (LTo) cells, involving multiple cytokines. Heterogeneity is a distinguishing feature of TLSs, which may lead to differences in their functions. Growing evidence suggests that TLSs are associated with various diseases, such as cancers, autoimmune diseases, transplant rejection, chronic inflammation, infection, and even ageing. However, the detailed mechanisms behind these clinical associations are not yet fully understood. The mechanisms by which TLS maturation and localization affect immune function are also unclear. Therefore, it is necessary to enhance the understanding of TLS development and function at the cellular and molecular level, which may allow us to utilize them to improve the immune microenvironment. In this review, we delve into the composition, formation mechanism, associations with diseases, and potential therapeutic applications of TLSs. Furthermore, we discuss the therapeutic implications of TLSs, such as their role as markers of therapeutic response and prognosis. Finally, we summarize various methods for detecting and targeting TLSs. Overall, we provide a comprehensive understanding of TLSs and aim to develop more effective therapeutic strategies.

Phenotypic and genotypic characteristics of children with PCDH19 clustering epilepsy in China.

PURPOSE: PCDH19 gene variants, termed PCDH19 clustering epilepsy, represent a distinct etiology of epilepsy. This study aimed to elucidate the clinical manifestations and explore the genotypes and phenotypes of children affected by PCDH19 clustering epilepsy. METHODS: This retrospective study included medical history, magnetic resonance imaging, video-electroencephalography, and genetic analysis of patients diagnosed with PCDH19 Clustering Epilepsy at the Neurology Department of Beijing Children's Hospital from 2015 to 2023. Chi-square tests and logistic regression analyses were conducted to study the factors associated with developmental delay in patients. RESULTS: The age at seizure onset ranged from 5 to 61 months among all 30 patients (median 14 months; IQR 9.25-22.5 months). Among the 30 patients, 29 were female and 1 was male. Clusters of seizures and fever-triggered seizures were observed, with the most prevalent seizure types being focal to bilateral tonic-clonic seizures (FBTCS). Seizures were successfully controlled in 15 patients. Unfortunately, one patient experienced a sudden unexpected death in epilepsy (SUDEP). Additionally, 14 patients had hereditary mutations, 14 had de novo mutations, 1 had both hereditary and de novo mutations, and 1 male patient had a mosaic component mutation of 0.64 due to a somatic mutation. Developmental delays were identified in 17 patients (56.7 %), and 6 patients (20 %) were diagnosed with autism spectrum disorder (ASD). Among the 17 patients, 9 experienced developmental delays before the onset of epilepsy, while 8 were initially normal but later developed developmental delays during disease progression. Statistical analysis revealed that the presence of drug-resistant epilepsy was an independent risk factor for the occurrence of developmental delays (P = 0.020, OR = 9.758, 95 % CI (1.440-66.111)). CONCLUSION: In this study, 13 new potential rare pathogenic variations in PCDH19 clustering epilepsy were identified. The clinical features observed in patients are consistent with known phenotypic features, and we found that patients with drug-resistant epilepsy are more likely to have developmental delays. The severity of the phenotype in patients with PCDH19 variants ranged from drug-responsive seizures to refractory epilepsy.

Lost at SCLC: a review of potential platinum sensitizers.

The expression "lost at sea" means to be confused or perplexed. By extension, lost at SCLC references the current confusion about how to circumvent the chemoresistance, particularly platinum resistance, which so plagues the treatment of extensive-stage small cell lung cancer (ES-SCLC) that in 2012 the US National Cancer Institute (NCI) designated it a "recalcitrant cancer." Over a decade later, despite the approval of immune checkpoint inhibitors and the conditional approval of lurbinectedin, the prognosis for ES-SCLC, and especially platinum-resistant ES-SCLC, has scarcely improved. The focus of this review, which briefly summarizes current treatment options for ES-SCLC, is on five clinical-stage therapies with the potential to successfully reverse the platinum resistance that is perhaps the biggest obstacle to better clinical outcomes.

Development and validation of a nomogram based on Lasso-Logistic regression for predicting splenomegaly secondary to acute pancreatitis.

PURPOSE: Investigate the clinical characteristics of splenomegaly secondary to acute pancreatitis (SSAP) and construct a nomogram prediction model based on Lasso-Logistic regression. METHODS: A retrospective case-control study was conducted to analyze the laboratory parameters and computed tomography (CT) imaging of acute pancreatitis (AP) patients recruited at Xuanwu Hospital from December 2014 to December 2021. Lasso regression was used to identify risk factors, and a novel nomogram was developed. The performance of the nomogram in discrimination, calibration, and clinical usefulness was evaluated through internal validation. RESULTS: The prevalence of SSAP was 9.2% (88/950), with the first detection occurring 65(30, 125) days after AP onset. Compared with the control group, the SSAP group exhibited a higher frequency of persistent respiratory failure, persistent renal failure, infected pancreatic necrosis, and severe AP, along with an increased need for surgery and longer hospital stay (P < 0.05 for all). There were 185 and 79 patients in the training and internal validation cohorts, respectively. Variables screened by Lasso regression, including platelet count, white blood cell (WBC) count, local complications, and modified CT severity index (mCTSI), were incorporated into the Logistic model. Multivariate analysis showed that WBC count ≦9.71 × 109/L, platelet count ≦140 × 109/L, mCTSI ≧8, and the presence of local complications were independently associated with the occurrence of SSAP. The area under the receiver operating characteristic curve was 0.790. The Hosmer-Lemeshow test showed that the model had good fitness (P = 0.954). Additionally, the nomogram performed well in the internal validation cohorts. CONCLUSIONS: SSAP is relatively common, and patients with this condition often have a worse clinical prognosis. Patients with low WBC and platelet counts, high mCTSI, and local complications in the early stages of the illness are at a higher risk for SSAP. A simple nomogram tool can be helpful for early prediction of SSAP.

Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients.

BACKGROUND: Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. METHODS: A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. RESULTS: This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384-73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045-28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48-49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25-25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48-12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09-27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798-0.934) with a sensitivity of 0.761 and specificity of 0.869. CONCLUSION: We established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.

Comparison of resection, ablation and stereotactic body radiation therapy in treating solitary hepatocellular carcinoma ≤ 5 cm: a retrospective, multicenter, cohort study.

BACKGROUND: Few studies have focused on the efficacy of stereotactic body radiation therapy (SBRT) in treating early hepatocellular carcinoma (HCC) for curative intention. This study aims to determine the best option among resection, ablation and SBRT in dealing with single HCC no more than 5 cm. MATERIALS AND METHODS: This multicenter retrospective cohort study included 985 patients from 3 hospitals: 495, 335 and 155 in the resection, ablation and SBRT groups, respectively between January 2014 and December 2021. Subgroup analysis and propensity score matching (PSM) were performed. RESULTS: The SBRT group had unfavorable clinical features including larger tumor size, poorer liver function and more relapsed tumors. The 1-, 3-, and 5-year recurrence free survival (RFS) rates were 84.3%, 66.8% and 56.2% with resection, 73.3%, 49.8% and 37.2% with ablation and 73.2%, 56.4% and 53.6% with SBRT, respectively (P<0.001). The 3-year overall survival (OS) rates were 89.0%, 89.2% and 88.8% in the resection, ablation and SBRT group, respectively (P=0.590). The three modalities resulted in similar RFS and OS after adjusting for clinical factors. Resection provided ideal local tumor control, successively followed by SBRT and ablation. SBRT led to comparable RFS time compared to resection for tumors < 3 cm (HR=0.75, P=0.205), relapsed tumors (HR=0.83, P=0.420) and patients with poor liver function (HR=0.70, P=0.330). In addition, SBRT was superior to ablation regarding RFS when tumors were adjacent to intra-hepatic vessels (HR=0.64, P=0.031). SBRT were more minimally invasive, however, gastrointestinal disorders, hepatic inflammation and myelosuppression occurred more frequently. CONCLUSION: All three approaches could be applied as curative options. Resection remains the best choice for preventing tumor recurrence, and SBRT showed advantages in treating small, recurrent and vascular-type lesions as well as patients with relatively poor liver function.

The splicing factor SF3B1 confers ferroptosis resistance and promotes lung adenocarcinoma progression via upregulation of SLC7A11.

This study aimed to investigate the expression of SF3B1 in non-small cell lung cancer, and its clinical significance, biological function, and molecular mechanisms. SF3B1 mRNA and protein levels were elevated in both lung squamous cell carcinoma and lung adenocarcinoma (LUAD) tissues based on TCGA data and immunohistochemistry. Notably, high SF3B1 expression in LUAD was significantly associated with increased lymph node metastasis. Functional experiments involving SF3B1 knockdown and overexpression demonstrated that SF3B1 facilitated the proliferation, invasion, and migration of LUAD cells. Additionally, the SF3B1 inhibitor pladienolide-B attenuated the aggressive behavior of LUAD cells both in vitro and in vivo. RNA sequencing analysis indicated that differentially expressed genes in the SF3B1 knockdown and SF3B1 inhibitor groups were enriched in ferroptosis-related pathways compared to their respective control groups. The antiferroptotic role of SF3B1 in LUAD cells was validated by detecting glutathione depletion, lipid peroxidation, and observing morphological changes using transmission electron microscopy. This process was confirmed to be independent of apoptosis and autophagy, as evidenced by the effects of the ferroptosis inducer erastin, the apoptosis inhibitor Z-VAD-FMK, and the autophagy inhibitor 3-methyladenine. Rescue experiments indicated that the antiferroptotic role of SF3B1 in LUAD is partially mediated by upregulating the expression of SLC7A11.