Melatonin improves maternal sleep deprivation-induced learning and memory impairment, inflammation, and synaptic dysfunction in murine male adult offspring.

INTRODUCTION: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown. METHODS: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting. RESULTS: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. CONCLUSIONS: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.

Epstein-Barr Virus Infection-Associated Facial Swelling: A Case Report.

Maxillofacial soft tissue swelling is a common clinical symptom with various etiologies. While odontogenic space infection is the most common cause, it is crucial not to overlook maxillofacial swellings caused by specific pathogenic infections and other local factors. This paper reports the case of an adult patient with right-sided swelling of his face, persistent oral mucosal ulcers, and recurrent hyperthermia for 30 days. He had received various antibiotics for the initial diagnosis of "right buccal space infection," but the antibiotics did not have any effect on his symptoms. None of the blood tests, histological examinations, bone marrow biopsies, and immune-related tests produced diagnostic findings. A diagnosis of Epstein-Barr virus (EBV) infection was finally confirmed by biopsy tissue genomics sequencing and quantitative analysis of EBV nucleic acid. In this report, we describe the diagnosis and treatment process for this patient and suggest that facial swelling could be an important clinical symptom of EBV infection.

Vestibular Rehabilitation of Patient with Hypertrophic Olivary Degeneration: A Case Report.

Background Hypertrophic olivary degeneration (HOD) is a rare disorder that typically develops in the weeks to months following a structural brainstem or cerebellar lesion in the Guillain-Mollaret triangle (GMT). Clinically, patients with HOD present with palatal myoclonus and nystagmus, which are difficult to treat and rarely resolve. Purpose The purpose of this case is to present the results of vestibular and balance assessments of a patient with bilateral HOD before and after vestibular rehabilitation. Methods This case report describes a 43-year-old trucker who presented with dizziness, blurred vision, and balance problems for more than 10 months, accompanied by new-onset tremors and ataxia for more than 6 months. The patient's characteristic clinical manifestations were palatal myoclonus and nystagmus. Magnetic resonance imaging (MRI) revealed bilateral HOD after an acute pontine hemorrhage. Comprehensive vestibular and balance assessments were performed. Results Vestibular and balance assessments demonstrated nystagmus, impaired vestibulo-ocular reflex (VOR), optokinetic reflex (OKR), and balance function. Following 4 months of vestibular rehabilitation, the patient's eye symptoms and balance function were improved. Conclusions The case presented here highlights the rare clinical manifestations of HOD after pontine hemorrhage. Vestibular rehabilitation training may be beneficial for the recovery of patients with HOD.

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline.

A new method for the synthesis of heterocyclic systems containing tetrazole and tetrahydroisoquinoline is developed via the performance of one-pot Ugi-azide and Heck cyclization reactions. The integration of the multicomponent and post-condensation reactions in one-pot maximizes the pot-, atom-, and step-economy (PASE).

Observation of bound valence excited electronic states of deprotonated 2-hydroxytriphenylene using photoelectron, photodetachment, and resonant two-photon detachment spectroscopy of cryogenically cooled anions.

Polycyclic aromatic hydrocarbons (PAHs) are common atmospheric pollutants, and they are also ubiquitous in the interstellar medium. Here, we report the study of a complex O-containing PAH anion, the deprotonated 2-hydroxytriphenylene (2-OtPh-), using high-resolution photoelectron imaging and photodetachment spectroscopy of cryogenically cooled anions. Vibrationally resolved photoelectron spectra yield the electron affinity of the 2-OtPh radical as 2.629(1) eV and several vibrational frequencies for its ground electronic state. Photodetachment spectroscopy reveals bound valence excited electronic states for the 2-OtPh- anion, with unprecedentedly rich vibronic features. Evidence is presented for a low-lying triplet state (T1) and two singlet states (S1 and S2) below the detachment threshold. Single-color resonant two-photon photoelectron spectroscopy uncovers rich photophysics for the 2-OtPh- anion, including vibrational relaxation in S1, internal conversion to the ground state of 2-OtPh-, intersystem crossing from S2 to T1, and a long-lived autodetaching shape resonance about 1.3 eV above the detachment threshold. The rich electronic structure and photophysics afforded by the current study suggest that 2-OtPh- would be an interesting system for pump-probe experiments to unravel the dynamics of the excited states of this complex PAH anion.

Genomic landscape and functional characterization of structural variations in schizophrenia and bipolar disorder.

Multiple types of variations have been postulated to confer risk of schizophrenia and bipolar disorder, but majority of present GWAS solely focused on SNPs or small indels, and the impacts of structural variations (SVs) remain less understood. Nevertheless, accumulating evidence suggest that SVs may explain the association signals in certain GWAS hits. Here, we conducted pairwise linkage disequilibrium (LD) analyses of SNPs and SVs in populations from 1000 Genomes Project. Among the 299 psychiatric GWAS loci, 1213 SVs showed an LD of r2 > 0.1 with GWAS risk SNPs, and 66 of them were in moderate to strong LD (r2 > 0.6) with at least one GWAS risk SNP. Nine SVs were subject to further explorative analyses, including eQTL analysis in DLPFC, luciferase reporter gene assays, CRISPR/Cas9-mediated genome deletion and RT-qPCR. These assays highlighted several functional SVs showing regulatory effects on transcriptional activities, and some risk genes (e.g., BORCS7, GNL3) affected by the SVs were also annotated. Finally, mice overexpressing Borcs7 in the mPFC exhibited schizophrenia-like behaviors, such as abnormal prepulse inhibition and social dysfunction. These data suggest that SNPs association signals at GWAS loci might be driven by SVs, highlighting the necessities of considering such variants in future.

Multi-Responsive Peptide-Based Ultrathin Nanosheets Prepared by a Horizontal Monolayer Assembly.

In this study, peptide-based self-assembled nanosheets with a thickness of approximately 1 nm were prepared using a hierarchical covalent physical fabrication strategy. The covalent alternating polymerization of helical peptide E3 with an azobenzene (AZO) structure yielded copolymers CoP(E3-AZO), which physically self-assembled into ultrathin nanosheets in an unanticipated two-dimensional horizontal monolayer arrangement. This special monolayer arrangement enabled the thickness of the nanosheets to be equal to the cross-sectional diameter of a single linear copolymer, which is a rare phenomenon. Molecular dynamics simulations suggested that the synergistic effect of multiple molecular interactions drives the self-assembly of CoP(E3-AZO) into nanosheets and that various methods, including phototreatment, pH adjustment, the addition of additives, and introduction of cosolvents, can alter the molecular interactions and modulate the self-assembly of CoP(E3-AZO), yielding diverse nanostructures. Remarkably, the ultrathin nanosheets selectively inhibited cancer cells at certain concentrations.

Complete Laparoscopic Type C2 Radical Surgery for Cervical Stump Cancer: No-Look and No-Touch Techniques.

BACKGROUND: Due to previous surgical history and subsequent adhesions between pelvic organs, surgery for cervical stump cancer (CSC) is technically more challenging than surgery for cervical cancer with an intact uterus.1 We aimed to illustrate the related anatomy, surgical steps and techniques of complete laparoscopic type C2 radical surgery (CLRS) for early-stage CSC. METHODS: CLRS for six patients with CSC was performed from January 2021 to January 2022. We demonstrated the detailed skills of parametrial management during CLRS for CSC in case 5 by means of a video. A 58-year-old woman diagnosed with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIA1 CSC received CLRS through five operative ports (Fig. 1). RESULTS: The magnetic resonance imaging (MRI) scans and gross appearance of the specimen are shown in Fig. 2. The median age and body mass index (BMI) of the six patients were 53 years and 23.8, respectively. The median blood loss was 275 mL; the median time of operation was 218 min; the median length of hospitalization was 15 days; and the median time to recover urinary function was 12 days. One patient underwent postoperative radiation for pathologically proven adenocarcinoma with deep stromal invasion,2 while the other five did not. After a median follow-up of 24 months, no patients experienced complications, recurrence, or death (Table 1). CONCLUSIONS: This study details the skills of CLRS for CSC, especially space development and the 'no-look, no-touch' tumor-free principle. It is helpful for clinicians to perform safe and standardized surgery on patients with early-stage CSC. Fig. 1 Trocar placement of complete laparoscopic type C2 radical surgery for early-stage CSC. CSC cervical stump cancer, S superior, I inferior, R right, L left, U umbilicus Fig. 2 MRI scans and gross appearance of the specimen for case 5 with CSC at FIGO 2018 stage IIA1. The tumor lesion on the cervical stump is indicated by yellow arrows. a Axial T2-weighted image; b DKI image; c ADC map; d sagittal T2-weighted image; e sagittal T1-weighted image; f gross appearance of the surgical specimen. MRI magnetic resonance imaging, CSC cervical stump cancer, FIGO International Federation of Gynecology and Obstetrics, DKI diffusional kurtosis imaging, ADC apparent diffusion coefficient Table 1 Clinicopathological characteristics, operative details, and outcomes of patients with cervical stump cancer Patient no. Age at diagnosis (years) BMI Reasons for subtotal hysterectomy FIGO 2018 stage Histology Operation Operation time (mins) Blood loss (mL) Urinary catheter (days) Hospital stay (days) Complications Depth of invasion LVSI LNs dissected TNM stage Tumor size (mm) Postoperative radiotherapy Follow-up (months) Recurrence Death 1 50 25.9 Uterine myoma IIA1 ASC CLRS+PLND 221 360 10 12 No Middle one-third N 13 T2a1N0M0 16 No 30 No No 2 55 17.3 Uterine myoma IB1 AC CLRS+PLND 191 270 20 12 No Deep one-third N 24 T1b1N0M0 10 Yes 20 No No 3 50 24.8 Uterine myoma IB1 SC CLRS+PLND 295 310 13 15 No Superficial one-third N 21 T1b1N0M0 15 No 25 No No 4 63 30.1 Uterine myoma IB1 SC CLRS+PLND 213 180 6 16 No Superficial one-third N 25 T1b1N0M0 15 No 19 No No 5 58 20.2 Postpartum hemorrhage IIA1 SC CLRS+PLND 220 100 11 14 No Middle one-third N 21 T2a1N0M0 15 No 24 No No 6 46 22.7 Uterine myoma IB1 SC CLRS+PLND 215 120 14 17 No Superficial one-third N 26 T1b1N0M0 12 No 23 No No BMI body mass index, FIGO International Federation of Gynecology and Obstetrics, ASC cervical adenosquamous carcinoma, AC cervical adenocarcinoma, SC cervical squamous carcinoma, CLRS+PLND complete laparoscopic radical surgery and pelvic node dissections, LVSI lymphovascular space invasion, N negative, LNs lymph nodes, TNM tumor node metastasis.

Lower comorbidity scores and severity levels in Veterans Health Administration hospitals: a cross-sectional study.

BACKGROUND: Previous studies found that documentation of comorbidities differed when Veterans received care within versus outside Veterans Health Administration (VHA). Changes to medical center funding, increased attention to performance reporting, and expansion of Clinical Documentation Improvement programs, however, may have caused coding in VHA to change. METHODS: Using repeated cross-sectional data, we compared Elixhauser-van Walraven scores and Medicare Severity Diagnosis Related Group (DRG) severity levels for Veterans' admissions across settings and payers over time, utilizing a linkage of VHA and all-payer discharge data for 2012-2017 in seven US states. To minimize selection bias, we analyzed records for Veterans admitted to both VHA and non-VHA hospitals in the same year. Using generalized linear models, we adjusted for patient and hospital characteristics. RESULTS: Following adjustment, VHA admissions consistently had the lowest predicted mean comorbidity scores (4.44 (95% CI 4.34-4.55)) and lowest probability of using the most severe DRG (22.1% (95% CI 21.4%-22.8%)). In contrast, Medicare-covered admissions had the highest predicted mean comorbidity score (5.71 (95% CI 5.56-5.85)) and highest probability of using the top DRG (35.3% (95% CI 34.2%-36.4%)). CONCLUSIONS: More effective strategies may be needed to improve VHA documentation, and current risk-adjusted comparisons should account for differences in coding intensity.

sRNA expression profile of KPC-2-producing carbapenem-resistant Klebsiella pneumoniae: Functional role of sRNA51.

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has significant challenges to human health and clinical treatment, with KPC-2-producing CRKP being the predominant epidemic strain. Therefore, there is an urgent need to identify new therapeutic targets and strategies. Non-coding small RNA (sRNA) is a post-transcriptional regulator of genes involved in important biological processes in bacteria and represents an emerging therapeutic strategy for antibiotic-resistant bacteria. In this study, we analyzed the transcription profile of KPC-2-producing CRKP using RNA-seq. Of the 4693 known genes detected, the expression of 307 genes was significantly different from that of carbapenem-sensitive Klebsiella pneumoniae (CSKP), including 133 up-regulated and 174 down-regulated genes. Both the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly related to metabolism. In addition, we identified the sRNA expression profile of KPC-2-producing CRKP for the first time and detected 115 sRNAs, including 112 newly discovered sRNAs. Compared to CSKP, 43 sRNAs were differentially expressed in KPC-2-producing CRKP, including 39 up-regulated and 4 down-regulated sRNAs. We chose sRNA51, the most significantly differentially expressed sRNA in KPC-2-producing CRKP, as our research subject. By constructing sRNA51-overexpressing KPC-2-producing CRKP strains, we found that sRNA51 overexpression down-regulated the expression of acrA and alleviated resistance to meropenem and ertapenem in KPC-2-producing CRKP, while overexpression of acrA in sRNA51-overexpressing strains restored the reduction of resistance. Therefore, we speculated that sRNA51 could affect the resistance of KPC-2-producing CRKP by inhibiting acrA expression and affecting the formation of efflux pumps. This provides a new approach for developing antibiotic adjuvants to restore the sensitivity of CRKP.

PITX2 functions as a transcription factor for GPX4 and protects pancreatic cancer cells from ferroptosis.

Ferroptosis inhibits tumor progression in pancreatic cancer cells, while PITX2 is known to function as a pro-oncogenic factor in various tumor types, protecting them from ferroptosis and thereby promoting tumor progression. In this study, we sought to investigate the regulatory role of PITX2 in tumor cell ferroptosis within the context of pancreatic cancer. We conducted PITX2 knockdown experiments using lentiviral infection in two pancreatic cancer cell lines, namely PANC-1 and BxPC-3. We assessed protein expression through immunoblotting and mRNA expression through RT-PCR. To confirm PITX2 as a transcription factor for GPX4, we employed Chromatin Immunoprecipitation (ChIP) and Dual-luciferase assays. Furthermore, we used flow cytometry to measure reactive oxygen species (ROS), lipid peroxidation, and apoptosis and employed confocal microscopy to assess mitochondrial membrane potential. Additionally, electron microscopy was used to observe mitochondrial structural changes and evaluate PITX2's regulation of ferroptosis in pancreatic cancer cells. Our findings demonstrated that PITX2, functioning as a transcription factor for GPX4, promoted GPX4 expression, thereby exerting an inhibitory effect on ferroptosis in pancreatic cancer cells and consequently promoting tumor progression. Moreover, PITX2 enhanced the invasive and migratory capabilities of pancreatic cancer cells by activating the WNT signaling pathway. Knockdown of PITX2 increased ferroptosis and inhibited the proliferation of PANC-1 and BxPC-3 cells. Notably, the inhibitory effect on ferroptosis resulting from PITX2 overexpression in these cells could be countered using RSL3, an inhibitor of GPX4. Overall, our study established PITX2 as a transcriptional regulator of GPX4 that could promote tumor progression in pancreatic cancer by reducing ferroptosis. These findings suggest that PITX2 may serve as a potential therapeutic target for combating ferroptosis in pancreatic cancer.

Acidic fibroblast growth factor inhibits reactive oxygen species-induced epithelial-mesenchymal transdifferentiation in vascular endothelial cells via the miR-155-5p/SIRT1/Nrf2/HO-1 pathway to promote wound healing in diabetic mice.

Background: Diabetic chronic wounds are among the most common and serious complications of diabetes and are associated with significant morbidity and mortality. Endothelial-to-mesenchymal transition (EndMT) is a specific pathological state in which endothelial cells are transformed into mesenchymal cells in response to various stimuli, such as high glucose levels and high oxidative stress. Acidic fibroblast growth factor (aFGF), which is a member of the fibroblast growth factor family, possesses strong antioxidant properties and can promote the differentiation of mesenchymal stem cells into angiogenic cells. Therefore, we investigated the role of aFGF in EndMT in diabetic wounds and analysed the underlying mechanisms. Methods: A diabetic mouse model was used to verify the effect of aFGF on wound healing, and the effect of aFGF on vascular endothelial cells in a high-glucose environment was examined in vitro. We examined the expression of miR-155-5p in a high-glucose environment and the miR-155 downstream target gene SIRT1 by luciferase reporter assays. Results: aFGF promoted wound closure and neovascularization in a mouse model of type 2 diabetes. In vitro, aFGF inhibited the production of total and mitochondrial reactive oxygen species (ROS) in vascular endothelial cells and alleviated epithelial-mesenchymal transdifferentiation in a high-glucose environment. Mechanistically, aFGF promoted the expression of SIRT1 and the downstream targets Nrf2 and HO-1 by negatively regulating miR-155-5p, thereby reducing ROS generation. Conclusions: In conclusion, our results suggest that aFGF inhibits ROS-induced epithelial-mesenchymal transdifferentiation in diabetic vascular endothelial cells via the miR-155-5p/SIRT1/Nrf2/HO-1 axis, thereby promoting wound healing.

An Automated Approach for Predicting HAMD-17 Scores via Divergent Selective Focused Multi-heads Self-Attention Network.

This study introduces the Divergent Selective Focused Multi-heads Self-Attention Network (DSFMANet), an innovative deep learning model devised to automatically predict Hamilton Depression Rating Scale-17 (HAMD-17) scores in patients with depression. This model introduces a multi-branch structure for sub-bands and artificially configures attention focus factors on various branches, resulting in distinct attention distributions for different sub-bands. Experimental results demonstrate that when DSFMANet processes sub-band data, its performance surpasses current benchmarks in key metrics such as mean square error (MSE), mean absolute error (MAE), root mean square error (RMSE), and coefficient of determination (R2). This success is particularly evident in terms of MSE and MAE, where the performance of sub-band data is significantly superior, highlighting the model's potential in accurately predicting HAMD-17 scores. Concurrently, the experiment also compared the model's performance with sub-band and full-band data, affirming the superiority of the selective focus attention mechanism in electroencephalography (EEG) signal processing. DSFMANet, when utilizing sub-band data, exhibits higher data processing efficiency and reduced model complexity. The findings of this study underscore the significance of employing deep learning models based on sub-band analysis in depression diagnosis. The DSFMANet model not only effectively enhances the accuracy of depression diagnosis but also offers valuable research directions for similar applications in the future. This deep learning-based automated approach can effectively ascertain the HAMD-17 scores of patients with depression, thus offering more accurate and reliable support for clinical decision-making.

Design, synthesis, and antibacterial activity of pleuromutilin derivatives.

This paper reports the design, synthesis, and antibacterial activity study of pleuromutilin derivatives with 2-methyl-4-nitroaniline and 2-methoxy-4-nitroaniline side chains at the C22 position. The structures of the new compounds were characterized by 1H-NMR, 13C-NMR and HRMS. The inhibitory activity of the compounds against MSSA, pyogeniccoccus, streptococcus, and MRSA strains was determined using the micro broth dilution method. The results showed that the compounds exhibited certain activity against Gram-positive bacteria, among which compounds A8a, A8b, A8c, A8d, and A7 demonstrated superior antibacterial activity against MSSA, MRSA, and pyogeniccoccus compared to tiamulin, although the derivatives showed lower antibacterial activity against streptococcus compared to the control drug. Based on the favorable in vitro activity of A8c, the time-kill kinetics against MRSA were evaluated, revealing that compound A8c could inhibit bacterial proliferation in a concentration-dependent manner.

Attention deficit hyperactivity disorder in children with epilepsy: a multicenter cross-sectional analysis in China.

BACKGROUND: The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life. METHODS: We carried out a multicenter cross-sectional survey of children with epilepsy across China between March 2022 and August 2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD. RESULTS: Overall, 395 epilepsy patients aged 6-18 years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15 years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD. CONCLUSIONS: While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy.

Tobramycin-resistant small colony variant mutant of Salmonella enterica serovar Typhimurium shows collateral sensitivity to nitrofurantoin.

The increasing antibiotic resistance poses a significant global health challenge, threatening our ability to combat infectious diseases. The phenomenon of collateral sensitivity, whereby resistance to one antibiotic is accompanied by increased sensitivity to another, offers potential avenues for novel therapeutic interventions against infections unresponsive to classical treatments. In this study, we elucidate the emergence of tobramycin (TOB)-resistant small colony variants (SCVs) due to mutations in the hemL gene, which render S. Typhimurium more susceptible to nitrofurantoin (NIT). Mechanistic studies demonstrate that the collateral sensitivity in TOB-resistant S. Typhimurium SCVs primarily stems from disruptions in haem biosynthesis. This leads to dysfunction in the electron transport chain (ETC) and redox imbalance, ultimately inducing lethal accumulation of reactive oxygen species (ROS). Additionally, the upregulation of nfsA/B expressions facilitates the conversion of NIT prodrug into its active form, promoting ROS-mediated bacterial killing and contributing to this collateral sensitivity pattern. Importantly, alternative NIT therapy demonstrates a significant reduction of bacterial load by more than 2.24-log10 cfu/g in the murine thigh infection and colitis models. Our findings corroborate the collateral sensitivity of S. Typhimurium to nitrofurans as a consequence of evolving resistance to aminoglycosides. This provides a promising approach for treating infections due to aminoglycoside-resistant strains.

Effects of intensive psychological intervention on treatment compliance, psychological status, and quality of life of patients with epilepsy.

BACKGROUND: Epilepsy is a nervous system disease characterized by recurrent attacks, a long disease course, and an unfavorable prognosis. It is associated with an enduring therapeutic process, and finding a cure has been difficult. Patients with epilepsy are predisposed to adverse moods, such as resistance, anxiety, nervousness, and anxiety, which compromise treatment compliance and overall efficacy. AIM: To explored the influence of intensive psychological intervention on treatment compliance, psychological status, and quality of life (QOL) of patients with epilepsy. METHODS: The clinical data of 105 patients with epilepsy admitted between December 2019 and July 2023 were retrospectively analyzed, including those of 50 patients who underwent routine intervention (control group) and 55 who underwent intensive psychological intervention (research group). Treatment compliance, psychological status based on the Self-Rating Anxiety Scale (SAS) and Depression Scale Self-Rating Depression Scale (SDS) scores, hope level assessed using the Herth Hope Scale (HHS), psychological resilience evaluated using the Psychological Resilience Scale, and QOL determined using the QOL in Epilepsy-31 Inventory (QOLIE-31) were comparatively analyzed. RESULTS: Treatment compliance in the research group was 85.5%, which is significantly better than the 68.0% of the control group. No notable intergroup differences in preinterventional SAS and SDS scores were identified (P > 0.05); however, after the intervention, the SAS and SDS scores decreased significantly in the two groups, especially in the research group (P < 0.05). The two groups also exhibited no significant differences in preinterventional HHS, Connor-Davidson Resilience Scale (CD-RISC), and QOLIE-31 scores (P > 0.05). After 6 months of intervention, the research group showed evidently higher HHS, CD-RISC, tenacity, optimism, strength, and QOLIE-31 scores (P < 0.05). CONCLUSION: Intensive psychological intervention enhances treatment compliance, psychological status, and QOL of patients with epilepsy.

Establishment and evaluation of a prognostic model for patients with unresectable gastric cancer liver metastases.

BACKGROUND: Liver metastases (LM) is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer (GC). The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis, thereby enhancing the ability to evaluate patient outcomes. AIM: To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis, thereby enhancing patient outcome assessment. METHODS: Retrospective analysis was conducted on clinical data pertaining to GCLM (type III), admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018. The dataset was divided into a development cohort and validation cohort in a ratio of 2:1. In the development cohort, we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients. Subsequently, we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis, calibration curves, and clinical decision curves. A nomogram was created to visually represent the prediction model, which was then externally validated using the validation cohort. RESULTS: A total of 372 patients were included in this study, comprising 248 individuals in the development cohort and 124 individuals in the validation cohort. Based on Cox analysis results, our final prediction model incorporated five independent risk factors including albumin levels, primary tumor size, presence of extrahepatic metastases, surgical treatment status, and chemotherapy administration. The 1-, 3-, and 5-years Area Under the Curve values in the development cohort are 0.753, 0.859, and 0.909, respectively; whereas in the validation cohort, they are observed to be 0.772, 0.848, and 0.923. Furthermore, the calibration curves demonstrated excellent consistency between observed values and actual values. Finally, the decision curve analysis curve indicated substantial net clinical benefit. CONCLUSION: Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model, demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.

Oxytocin ameliorates cognitive impairments by attenuating excitation/inhibition imbalance of neurotransmitters acting on parvalbumin interneurons in a mouse model of sepsis-associated encephalopathy.

Inflammation plays a crucial role in the initiation and progression of sepsis, and it also induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy (SAE). Parvalbumin (PV) interneurons are pivotal contributors to cognitive processes in various central dysfunctions including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid (GABA)ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to the SAE mice induced by lipopolysaccharide (LPS). Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence analysis demonstrated decreased PV expression in the cornu ammonis 1 (CA1) region of the hippocampus following LPS treatment, which was alleviated by oxytocin. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to improved cognitive function. In conclusion, cognitive function improved after oxytocin treatment. The number of PV neurons in the hippocampal CA1 region and the balance of excitatory/inhibitory synaptic transmission on PV interneurons, as well as changes in local field potential gamma oscillations in the hippocampal CA1 region, may represent its specific mechanisms.

Copper-Bearing Metal-Organic Framework with Mucus-Penetrating Function for the Multi-Effective Clearance of Mucosal Colonized Helicobacter pylori.

Helicobacter pylori colonizes over 50% of people worldwide. Biofilm formation through penetrating gastric mucus and resistance acquired by H. pylori markedly reduces the efficacy of traditional antibiotics. The present triple therapy and bismuth-based quadruple therapy inevitably causes intestinal flora disturbance and fails to address the excessive H. pylori-triggered inflammatory response. Herein, a mucus-permeable therapeutic platform (Cu-MOF@NF) that consists of copper-bearing metal-organic framework (Cu-MOF) loaded with nitrogen-doped carbon dots and naturally active polysaccharide fucoidan is developed. The experimental results demonstrate that Cu-MOF@NF can penetrate the mucus layer and hinder H. pylori from adhering on gastric epithelial cells of the stomach. Notably, released Cu2+ can degrade the polysaccharides in the biofilm and interfere with the cyclic growing mode of "bacterioplankton ↔ biofilm", thereby preventing recurrent and persistent infection. Compared with traditional triple therapy, the Cu-MOF@NF not only possesses impressive antibacterial effect (even include multidrug-resistant strains), but also improves the inflammatory microenvironment without disrupting the balance of intestinal flora, providing a more efficient, safe, and antibiotic-free new approach to eradicating H. pylori.