Impact of Sinus CT Severity Score on the Outcomes of Endoscopic Sinus Surgery in Eosinophilic CRSwNP.

BACKGROUND: Eosinophilic chronic rhinosinusitis with nasal polyps (eos-CRSwNP), especially those with diffuse disease as indicated by CT scans, has high recurrence rate and low control rate after endoscopic sinus surgery (ESS). Most of them are difficult to treat. OBJECTIVE: This study sought to identify if eos-CRSwNP patients were to undergo surgery earlier, while the disease is still limited on CT, they might achieve better postoperative outcomes. METHODS: This study enrolled eos-CRSwNP patients with different degree of sinus involvement who underwent primary ESS and compared the surgical outcomes of the patients exhibiting mild sinus involvement with those displaying severe sinus involvement. The demographic data, preoperative disease severity, and surgery outcomes at 1 year postoperatively were collected. CRS control status was the primary endpoint to evaluate the outcomes. RESULTS: This study included 118 patients with at least one-year follow-up. The overall uncontrolled rate was 33.1% at 1 year postoperatively. The best cut-off value for CT Lund-Mackay (L-M) score was 13 to predict the uncontrolled status (AUC = 0.67). Then, patients were divided into the mild group (L-M < 13, n = 70) and the severe group (L-M ≥ 13, n = 48) according to L-M score. The follow-up data indicated that 24.3% of patients (17/70) in the mild group and 45.8% of patients (22/48) in the severe group were uncontrolled (p = 0.015). Postoperative endoscopic score in the mild group was significantly better than those in the severe group (p = 0.002). CONCLUSION: ESS performed on eos-CRSwNP patients with mild sinus involvement have better postoperative outcomes at 1 year than patients with severe sinus involvement. LEVELS OF EVIDENCE: Level 3 Laryngoscope, 2024.

CCL9/CCR1 axis-driven chemotactic nanovesicles for attenuating metastasis of SMAD4-deficient colorectal cancer by trapping TGF-ß.

SMAD4 deficiency in colorectal cancer (CRC) is highly correlated with liver metastasis and high mortality, yet there are few effective precision therapies available. Here, we show that CCR1+-granulocytic myeloid-derived suppressor cells (G-MDSCs) are highly infiltrated in SMAD4-deficient CRC via CCL15/CCR1 and CCL9/CCR1 axis in clinical specimens and mouse models, respectively. The excessive TGF-ß, secreted by tumor-infiltrated CCR1+-G-MDSCs, suppresses the immune response of cytotoxic T lymphocytes (CTLs), thus facilitating metastasis. Hereby, we develop engineered nanovesicles displaying CCR1 and TGFBR2 molecules (C/T-NVs) to chemotactically target the tumor driven by CCL9/CCR1 axis and trap TGF-ß through TGF-ß-TGFBR2 specific binding. Chemotactic C/T-NVs counteract CCR1+-G-MDSC infiltration through competitive responding CCL9/CCR1 axis. C/T-NVs-induced intratumoral TGF-ß exhaustion alleviates the TGF-ß-suppressed immune response of CTLs. Collectively, C/T-NVs attenuate liver metastasis of SMAD4-deficient CRC. In further exploration, high expression of programmed cell death ligand-1 (PD-L1) is observed in clinical specimens of SMAD4-deficient CRC. Combining C/T-NVs with anti-PD-L1 antibody (aPD-L1) induces tertiary lymphoid structure formation with sustained activation of CTLs, CXCL13+-CD4+ T, CXCR5+-CD20+ B cells, and enhanced secretion of cytotoxic cytokine interleukin-21 and IFN-γ around tumors, thus eradicating metastatic foci. Our strategy elicits pleiotropic antimetastatic immunity, paving the way for nanovesicle-mediated precision immunotherapy in SMAD4-deficient CRC.

Associations of multiple risk factors with prenatal depression and anxiety: Evidence from the Tianjin Birth Cohort (TJBC) study.

BACKGROUND: Antenatal mental disorders are associated with maternal and fetal adverse events. Previous studies have been focused on the postpartum period, rather than pregnancy, yet the association of risk factors with prenatal depression and anxiety through pregnancy has been rarely reported. This study aimed to identify the risk factors of prenatal depression and anxiety, and access their potential roles in developing mental disorders during pregnancy. METHODS: This is a prospective study in 6470 participants from the Tianjin Birth Cohort in China (TJBC). The degree of prenatal depression and anxiety was evaluated using a questionnaire of Self-Rating Depression scale (SDS) and Self-Rating Anxiety Scale (SAS), which was given to pregnant women at 15-27 (Stage-2), and 28-41 (Stage-3) gestational weeks. The questionnaire also collected demographic, personal, and lifestyle information. The association of different factors with SDS/SAS score was examined by logistic regression analysis. RESULTS: We observed an overall depression rate of 12.4 % and an overall anxiety rate of 7.7 % during pregnancy in the TJBC. In the Stage-2, the depression rate was 14.5 % and the anxiety rate was 9.5 %. In the Stage-3, the depression rate dropped to 9.7 % while the anxiety rate dropped to 5.3 %. With univariate analysis, we found that age, education, social support, marriage satisfaction, secondhand smoke (SHS), sleeping time and stress were common factors of prenatal mental health. Working status, family income, gravidity, smoking, electronic using, recreational activities were associated with depression risk, whereas BMI, disease history, changing eating habits, and feeding animal were associated with anxiety risk. Using logistic regression, we found that low education level, low social support, low marriage satisfaction, thyroid disfunction, Stage-2(second trimester), and stress were related to prenatal mental health. CONCLUSION: The prevalence anxiety and depression in Tianjin is normal as national level. Age appropriateness, a good education level, sufficient social support, marital satisfaction, normal thyroid function, and absence of stress are associated with relieving depression and anxiety during gestation. However, due to individual difference, expectant mothers should seek professional support and guidance to address their mental health needs during gestation.

Surgical treatment of unilateral acquired superior oblique muscle palsy in adults by inferior oblique belly transposition: a retrospective analysis.

PURPOSE: Evaluate and analyze the efficacy of inferior oblique belly transposition (IOBT) in treating adult patients with diplopia and small-angle hypertropia caused by mild to moderate inferior oblique overaction (IOOA) secondary to acquired superior oblique palsy (SOP). METHODS: Nine adult patients with diplopia and small-angle hypertropia associated with mild to moderate IOOA secondary to unilateral acquired SOP were included in the current retrospective study. All patients received the IOBT procedure between February 2019 and May 2023 at The Second People's Hospital of Jinan and were followed up for more than 6 months after the surgery. During the procedure, the belly of the inferior oblique muscle was fixed to the sclera at 5 mm posterior to the temporal insertion of the inferior rectus muscle. The following indicators were reviewed pre- and post-surgery: the vertical deviation (VD) in the primary position and in the Bielschowsky test, the fovea disc angle (FDA) of the affected eye, changes in IOOA, and diplopia. RESULTS: After IOBT, the VD in the primary position decreased from 7.22△ ± 1.72△ (range 4△-10△) to 1.22△ ± 1.30△ (range 0△-3△). The VD in the Bielschowsky test decreased from 13.00△ ± 1.80△ to 3.22△ ± 1.09△. The FDA decreased from 10.02° ± 3.34° to 6.26° ± 1.91°. The grade of IOOA was reduced from 2.00 (1.00, 2.00) to 0.00 (0.00, 1.00). All changes were statistically significant (P < 0.001 or P = 0.006). Diplopia was resolved completely for all patients. CONCLUSIONS: IOBT can effectively treat adults with diplopia and small-angle hypertropia caused by mild to moderate IOOA secondary to acquired SOP.

Sequential dual-locking strategy using photoactivated Pt(IV)-based metallo-nano prodrug for enhanced chemotherapy and photodynamic efficacy by triggering ferroptosis and macrophage polarization.

Selective activation of Pt(IV) prodrugs within tumors has emerged as a promising strategy in tumor treatment. Although progress has been made with photo- and ultrasound-activated Pt(IV) prodrugs, concerns remain over the non-specific activation of photosensitizers (PS) and the potential for phototoxicity and chemical toxicity. In this study, a sequential dual-locked Pt(IV) nano-prodrug that can be activated by both the acidic tumor microenvironment and light was developed. The Pt(IV) prodrug was prepared by conjugating PS-locked Pt(IV) to a polymeric core, which was then chelated with metallo iron to lock its photoactivity and form a metallo-nano prodrug. Under acidic tumor microenvironment conditions, the metallo-nano prodrug undergoes dissociation of iron, triggering a reduction process in oxaliplatin under light irradiation, resulting in the activation of both chemotherapy and photodynamic therapy (PDT). Additionally, the prodrug could induce metallo-triggered ferroptosis and polarization of tumor-associated macrophages (TAM), thereby enhancing tumor inhibition. The dual-lock strategy employed in a nanoparticle delivery system represents an expansion in the application of platinum-based anticancer drugs, making it a promising new direction in cancer treatment.

Evolutionary and Expression Analysis of the Pig MAGE Gene Family.

The melanoma-associated antigen (MAGE) family found in eukaryotes plays a crucial role in cell proliferation and differentiation, spermatogenesis, neural development, etc. This study explored the validation and evolution of MAGE genes in eukaryotic genomes and their distribution and expression patterns in pigs. In total, 249 MAGE genes were found on 13 eukaryotic species. In total, 33, 25, and 18 genes were located on human, mouse, and pig genomes, respectively. We found eight, four, and three tandemly duplicated gene clusters on the human, mouse, and pig genomes, respectively. The majority of MAGE genes in mammals are located on the X chromosome. According to the phylogenetic analysis, the MAGE family genes were classified into 11 subfamilies. The NDN gene in zebrafish (DreNDN) was the root of this evolutionary tree. In total, 10 and 11 MAGE genes on human and mouse genomes, respectively, exhibited a collinearity relationship with the MAGE genes on pig genomes. Taking the MAGE family genes in pigs, the MAGE subfamilies had similar gene structures, protein motifs, and biochemical attributes. Using the RNA-seq data of Duroc pigs and Rongchang pigs, we detected that the expression of type I MAGE genes was higher in reproductive tissues, but type II MAGE genes were predominantly expressed in the brain tissue. These findings are a valuable resource for gaining insight into the evolution and expression of the MAGE family genes.

[Corrigendum] Ophiopogonin B suppresses the metastasis and angiogenesis of A549 cells in vitro and in vivo by inhibiting the EphA2/Akt signaling pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, for the scratch­wound assay experiments shown in Fig. 3C, two images appeared to overlap [specifically, the '0 h / Control' and 0 h / OP­B (5 µmol/l) data panels], albeit with different magnification and after a 180° rotation. The authors have examined their original data, and realize that an inadvertent error was made in assembling the images in the figure; specifically, the images of 5 and 10 µmol/l OP­B treatment for 0 h were both misused. The corrected version of Fig. 3, showing all the correct data for Fig. 3C, is shown on the next page. Note that these errors did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. They also apologize to the readership for any inconvenience caused. [Oncology Reports 40: 1339­1347, 2018; DOI: 10.3892/or.2018.6531].

[Coblation-assisted endoscopic excision of juvenile nasopharyngeal angiofibroma and outcomes].

Objective:To summarize the procedures and efficacy of surgical treatment for Andrew stage Ⅰ-Ⅲ juvenile nasopharyngeal angiofibroma（JNA）. Methods:A total of 12 patients with JNA who underwent surgery from 2016 to 2021 were enrolled, including 1 case in stage Ⅰ, 3 cases in stage Ⅱ, and 8 cases in stage Ⅲ. JNA was resected by transnasal endoscopic approach alone, or combined with transoral approach or Caldwell-Luc approach was performed. Results:Eleven cases underwent complete resection without recurrence and 1 case had residual tumor. There were no serious complications. The median intraoperative blood loss was 200 mL, and 1 patient received blood transfusion. The median operative time was 110 minutes. Conclusion:JNA in Andrew stage Ⅰ-Ⅲ can be quickly and completely resected by standardized surgical procedures using endoscopy and coblation technology.

Uncommon P1 Anchor-featured Viral T Cell Epitope Preference within HLA-A*2601 and HLA-A*0101 Individuals.

The individual HLA-related susceptibility to emerging viral diseases such as COVID-19 underscores the importance of understanding how HLA polymorphism influences peptide presentation and T cell recognition. Similar to HLA-A*0101, which is one of the earliest identified HLA alleles among the human population, HLA-A*2601 possesses a similar characteristic for the binding peptide and acts as a prevalent allomorph in HLA-I. In this study, we found that, compared with HLA-A*0101, HLA-A*2601 individuals exhibit distinctive features for the T cell responses to SARS-CoV-2 and influenza virus after infection and/or vaccination. The heterogeneous T cell responses can be attributed to the distinct preference of HLA-A*2601 and HLA-A*0101 to T cell epitope motifs with negative-charged residues at the P1 and P3 positions, respectively. Furthermore, we determined the crystal structures of the HLA-A*2601 complexed to four peptides derived from SARS-CoV-2 and human papillomavirus, with one structure of HLA-A*0101 for comparison. The shallow pocket C of HLA-A*2601 results in the promiscuous presentation of peptides with "switchable" bulged conformations because of the secondary anchor in the median portion. Notably, the hydrogen bond network formed between the negative-charged P1 anchors and the HLA-A*2601-specific residues lead to a "closed" conformation and solid placement for the P1 secondary anchor accommodation in pocket A. This insight sheds light on the intricate relationship between HLA I allelic allomorphs, peptide binding, and the immune response and provides valuable implications for understanding disease susceptibility and potential vaccine design.

Essential oil from Chimonanthus nitens Oliv. Leaves ameliorate inflammation and oxidative stress in LPS-induced ALI through NF-κB and Nrf2 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Initial investigative research indicated that the essential oil from Chimonanthus nitens Oliv. Leaves (CLO) significantly reduces lung tissues inflammation and effectively repairs Acute lung injury (ALI) mice model. However, the mechanism underlying is not clear, and the impacts of CLO on oxidative stress require further investigation. AIM OF THE STUDY: The purpose of the experiment was to validate the influence of CLO in ALI model mice, as well as its potential mechanisms. MATERIALS AND METHODS: Lipopolysaccharide-induced establishment of the A549 cell inflammation model, and ALI mice model was established by intrathecal administration of LPS. RESULTS: CLO significantly reduced the release of inflammatory cytokines in A549 cells, lowered MDA and ROS levels, and enhanced SOD activity. Animal experiment results showed that CLO dramatically decreased white blood cell count, the expression of inflammatory cytokines, and the destruction of alveolar structures. CLO enhances the activity of antioxidant enzymes. Western Blot and q-PCR analyses have revealed that the mechanism of CLO is correlation with the NF-κB and Nrf2 signaling pathways in cellular and animal models. Pathway inhibitor experiments indicated that there might be functional crosstalk between these two pathways. CONCLUSIONS: CLO may regulate inflammation and oxidative stress in LPS-induced ALI through NF-κB and Nrf2 signaling pathways. This finding could be novel in the pharmacological treatment of ALI.

Wedelolactone suppresses breast cancer growth and metastasis via regulating TGF-ß1/Smad signaling pathway.

OBJECTIVE: Breast cancer is a malignant tumor with high invasion and metastasis. TGF-ß1-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of breast cancer. Wedelolactone (Wed) is extracted from herbal medicine Ecliptae Herba, which is reported to have antineoplastic activity. Here, we aimed to elucidate the efficacy and mechanism of Wed against breast cancer. METHODS: The effects of Wed on migration and invasion of 4T1 were detected. The expression of EMT-related markers was detected by Western blot and qPCR. The 4T1 orthotopic murine breast cancer model was established to evaluate the therapeutic effect of Wed on the growth and metastasis of breast cancer through TGF-ß1/Smad pathway. RESULTS: Wed inhibited the proliferation, migration and invasion of 4T1. It exhibited concentration-dependent inhibition of p-Smad2/3. Wed also reversed the expression of EMT-markers induced by TGF-ß1. In addition, Wed suppressed the growth and metastasis of breast cancer in mice. It also affected p-Smad3 expression as well as EMT-related genes, suggesting that its anti-breast cancer effect may be related to the TGF-ß1/Smad pathway. CONCLUSION: Wed reverses EMT by regulating TGF-ß1/Smad pathway, potentially serving as a therapeutic agent for breast cancer. Wed is expected to be a potential drug to inhibit TGF-ß1/Smad pathway-related diseases.

Corrigendum to "MiR-423-5p is a novel endogenous control for the quantification of circulating miRNAs in human esophageal squamous cell carcinoma" [Heliyon Volume 9, Issue 4, April 2023, Article e14515].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e14515.].

Clinical efficacy of CDK4/6 inhibitor plus endocrine therapy in HR-positive/HER2-0 and HER2-low-positive metastatic breast cancer: a secondary analysis of PALOMA-2 and PALOMA-3 trials.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with traditional endocrine therapy (ET) are now the recommended first-line treatment for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (MBC). However, the benefits of adding CDK4/6 inhibitors to ET in HER2-low-positive and HER2-0 subgroups remain unclear. We aimed to assess the effectiveness of CDK4/6 inhibitors in combination with ET in patients with HR-positive, HER2-low-positive and HER2-0 MBC. METHODS: This secondary analysis assessed progression-free survival (PFS) among HER2-low-positive and HER2-0 patients enrolled in the double-blind, placebo-controlled randomised clinical trials PALOMA-2 and PALOMA-3. The study included 1186 HER2-negative, HR-positive female patients, with available immunohistochemistry (IHC) and/or in situ hybridization (ISH) results, across 17 countries enrolled between February 2013 and August 2014. HER2-low-positive status was defined by IHC 1+ or 2+ with negative ISH, and HER2-zero by IHC 0. Data analyses were conducted between March and May 2023. In the PALOMA-2 trial, patients were randomly assigned to receive either palbociclib or placebo, in combination with letrozole in the first-line treatment for HR-positive MBC. Patients in the PALOMA-3 study, who had progression or relapse during previous ET, were randomly allocated to receive either palbociclib plus fulvestrant or placebo plus fulvestrant. The primary endpoint was investigator-assessed PFS. Kaplan-Meier approach and Cox proportional hazards model were applied to estimate the association of treatment strategies with PFS among HER2-0 and HER2-low-positive populations. The two trials are registered with ClinicalTrials.gov, number NCT01740427 and NCT01942135. FINDINGS: Of the 666 patients with MBC from the PALOMA-2 study, there were 153 HER2-0 and 513 HER2-low-positive patients. In the HER2-0 population, no significant difference in PFS was observed between the palbociclib-letrozole and placebo-letrozole groups (hazard ratio = 0.79, 95% confidence interval [CI] 0.48-1.30, p = 0.34). In the HER2-low-positive population, palbociclib-letrozole demonstrated a significantly lower risk of PFS than placebo-letrozole group (hazard ratio = 0.52, 95% CI 0.41-0.66, p < 0.0001). The PALOMA-3 study analysed 520 patients with MBC. Within the 153 HER2-0 patients, the palbociclib-fulvestrant group showed a significantly longer PFS than the placebo-fulvestrant group (hazard ratio = 0.54, 95% CI 0.30-0.95, p = 0.034). Among the 367 HER2-low-positive patients, palbociclib-fulvestrant improved PFS (hazard ratio = 0.39, 95% CI 0.28-0.54, p < 0.0001). INTERPRETATION: The combination of a CDK4/6 inhibitor with ET significantly improved PFS in HER2-low-positive patients, while for HER2-0 patients, benefits were primarily observed in patients who had progressed on previous ET. Furthermore, HER2-0 patients may derive limited benefits from first-line CDK4/6 inhibitor treatment. Further work is needed to validate these findings and to delineate patient subsets that are most likely to benefit from the combination of CDK4/6 inhibitors and ET as first-line treatments. FUNDING: None.

Radiation-based immunogenic vaccine combined with a macrophage "checkpoint inhibitor" for boosting innate and adaptive immunity against metastatic colon cancers.

Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors. Especially, X-ray- induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants. However, we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines, which can specifically bind with the MerTK receptor on macrophages, acting as a "checkpoint" to facilitate immune silence in the tumor microenvironment. Therefore, we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250, a macrophage MerTK "checkpoint inhibitor," for treating peritoneal carcinomatosis in colon cancer. By incorporating UNC2250 into the treatment regimen, immunosuppressive efferocytosis of macrophages, which relies on MerTK-directed recognition of phosphatidylserine on vaccines, was effectively blocked. Consequently, the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages, thereby simultaneously eliciting robust adaptive and innate immunity. This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.

Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy.

To investigate the impact of goal-directed fluid therapy (GDFT) on postoperative cognitive dysfunction (POCD) in elderly patients with colorectal cancer, we conducted a randomized controlled trial. Eighty elderly patients who underwent elective laparoscopic radical resection of colorectal cancer were randomly assigned to either the GDFT group or the conventional fluid therapy group. The primary outcome was the incidence of POCD during the initial 7 postoperative days, while secondary outcomes included inflammatory marker levels such as interleukin-6 (IL-6) and S100ß protein, hemodynamics, level of lactic acid, postoperative functional recovery, and complications. Among 88 randomized patients, 80 were evaluable for the primary outcome. The incidence of POCD was significantly lower in the GDFT group (15.0%) compared to the conventional fluid therapy group (30.0%), with the highest occurrence observed on day 3 postoperatively in both groups (P < 0.05). IL-6 and S100ß concentrations were consistently lower in the GDFT group than in the conventional fluid therapy group at the corresponding time points (P < 0.05). The GDFT group exhibited more stable perioperative hemodynamics and lower lactate levels (P < 0.05). Moreover, patients in the GDFT group exhibited better postoperative functional recovery indicators and a lower incidence of postoperative complications (P < 0.05). In summary, GDFT appears to reduce the incidence of early POCD, accelerate postoperative recovery, and enhance overall prognosis.

Study on the interaction protein of transcription factor Smad3 based on TurboID proximity labeling technology.

TurboID is a highly efficient biotin-labelling enzyme, which can be used to explore a number of new intercalating proteins due to the very transient binding and catalytic functions of many proteins. TGF-ß/Smad3 signaling pathway is involved in many diseases, especially in diabetic nephropathy and inflammation. In this paper, a stably cell line transfected with Smad3 were constructed by using lentiviral infection. To further investigate the function of TGF-ß/Smad3, the protein labeling experiment was conducted to find the interacting protein with Smad3 gene. Label-free mass spectrometry analysis was performed to obtain 491 interacting proteins, and the interacting protein hnRNPM was selected for IP and immunofluorescence verification, and it was verified that the Smad3 gene had a certain promoting effect on the expression of hnRNPM gene, and then had an inhibitory effect on IL-6. It lays a foundation for further study of the function of Smad3 gene and its involved regulatory network.

Prognostic Significance of the Cachexia Index in Patients with Non-Small-Cell Lung Cancer and Brain Metastases after Stereotactic Radiotherapy.

Background: The cachexia index (CXI) has been proposed as a novel biomarker of cancer cachexia. We aimed to investigate the association between CXI and survival outcomes after stereotactic radiotherapy (SRT) in patients with non-small cell lung cancer (NSCLC) and brain metastases. Methods: Data from 145 patients with NSCLC, who underwent SRT for brain metastases between April 2016 and August 2020, were retrospectively analyzed. Cachexia index was calculated as skeletal muscle index (SMI) × serum albumin level/neutrophil-to-lymphocyte ratio, whereas SMI was calculated from computed tomography images captured at the L1 level. Kaplan-Meier curves and Cox proportional hazards models were used to assess progression-free survival (PFS) and overall survival (OS). The prognostic values of CXI and other cachexia biomarkers were assessed using receiver operating characteristic (ROC) curve analysis. Results: Lower pretreatment CXI (<30.8) was significantly associated with older age (P = .039), lower Karnofsky performance score (P = .009), and a high likelihood of extracranial metastases (P = .001). Patients with a lower pretreatment CXI had a significantly shorter PFS and OS than those with a higher CXI (P < .001). Multivariate analysis revealed that pretreatment CXI was an independent risk factor for both PFS, hazard ratio (HR) = 2.375; 95% confidence interval (CI) = 1.610-3.504; P < .001, and OS, HR = 2.340; 95% CI = 1.562-3.505; P < .001. Compared with other biomarkers, pretreatment CXI had the highest area under the ROC curve value for prognostic assessment, reaching 0.734. Moreover, the loss of CXI was a strong risk factor for survival independent of pretreatment CXI (P = .011). Conclusions: Cachexia index may serve as a clinically useful tool for predicting survival outcomes of patients with NSCLC and brain metastases who undergo SRT.

Dexmedetomidine mitigates acute kidney injury after coronary artery bypass grafting: a prospective clinical trial.

INTRODUCTION AND OBJECTIVES: To evaluate the impact of dexmedetomidine impact on cardiac surgery-associated acute kidney injury (CSA-AKI), kidney function, and metabolic and oxidative stress in patients undergoing coronary artery bypass grafting with heart-lung machine support. METHODS: A randomized double-masked trial with 238 participants (50-75 years) undergoing coronary artery bypass grafting was conducted from January 2021 to December 2022. The participants were divided into Dex (n=119) and NS (n = 119) groups. Dex was administered at 0.5 mcg/kg over 10minutes, then 0.4 mcg/kg/h until the end of surgery; the NS group received equivalent saline. Blood and urine were sampled at various time points pre- and postsurgery. The primary outcome measure was the incidence of CSA-AKI, defined as the occurrence of AKI within 96hours after surgery. RESULTS: The incidence of CSA-AKI was significantly lower in the Dex group than in the NS group (18.26% vs 32.46%; P=.014). Substantial increases were found in estimated glomerular filtration rate value at T4-T6 (P<.05) and urine volume 24hours after surgery (P<.01). Marked decreases were found in serum creatinine level, blood glucose level at T1-T2 (P<.01), blood urea nitrogen level at T3-T6 (P<.01), free fatty acid level at T2-T3 (P<.01), and lactate level at T3-T4 (P<.01). CONCLUSIONS: Dex reduces CSA-AKI, potentially by regulating metabolic disorders and reducing oxidative stress. Registered with the Chinese Clinical Study Registry (No. ChiCTR2100051804).

Outcomes of endoscopic sinus surgery in patients with central compartment atopic disease.

Background: Central compartment atopic disease (CCAD) is a subtype of chronic rhinosinusitis (CRS). Research focusing on the endoscopic sinus surgery (ESS) outcomes of CCAD is limited. This study aimed to evaluate the outcomes of ESS in CCAD and compared to 2 following subtypes: chronic rhinosinusitis with nasal polyps (CRSwNP) and concomitant polypoid disease in the central compartment (CRSwNP/CC) and CRSwNP not otherwise specified (CRSwNP NOS). Methods: This case-control study enrolled patients with bilateral CRSwNP who underwent ESS and had at least 1 year of follow-up. Patients were classified into CCAD, CRSwNP/CC, and CRSwNP NOS. The demographic data, preoperative disease severity, and surgery outcomes, including CRS control status, endoscopic score, and symptom scores at 1 year postoperatively, were collected. We defined well controlled and partly controlled as appropriate disease control. Results: This study screened 259 patients and enrolled 138 patients with complete medical records and 1-year follow-up (CCAD N = 51, CRSwNP/CC N = 55, CRSwNP NOS N = 32). Among them, appropriate disease control was achieved in 84.3% of patients (43/51) in the CCAD group, 69.1% (38/55) in the CRSwNP/CC group, and 93.7% (30/32) in the CRSwNP NOS group (P = 0.029). Then we performed post-hoc analysis using appropriate disease control and uncontrolled. There was a significant difference between CRSwNP/CC and CRSwNP NOS (P = 0.007), but no significant difference compared CCAD group to CRSwNP/CC group (P = 0.065) and CRSwNP NOS group (P = 0.199). There were significant differences in endoscopic E-score among groups (P < 0.001). In post-hoc analysis, we found that CRSwNP/CC (Median [IQR], 33.32 [42.14]) had a significantly worse E-score than CCAD (8.33 [16.67]) and CRSwNP NOS (4.17 [8.30]). Also, postoperative olfactory visual analog scale (VAS) scores significantly differed among groups (P = 0.043). However, post-hoc analysis showed no difference between any 2 groups. There were no differences in postoperative VAS scores of obstruction (P = 0.159), rhinorrhea (P = 0.398), and headache/facial pain (P = 0.092). Conclusion: Most CCAD patients had good surgical outcomes 1 year after surgery. Meanwhile, the CRSwNP/CC group had the fewest patients under appropriate disease control.

Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome.

Image 1.