Marinobacter qingdaonensis sp. nov., a moderately halotolerant bacterium isolated from intertidal sediment.

A Gram-stain-negative, aerobic, rod-shaped and halotolerant bacterium, designated as strain ASW11-75T, was isolated from intertidal sediments in Qingdao, PR China, and identified using a polyphasic taxonomic approach. Growth of strain ASW11-75T occurred at 10-45 °C (optimum, 37 °C), pH 6.5-9.0 (optimum, pH 8.0) and 0.5-18.0 % NaCl concentrations (optimum, 2.5 %). Phylogenetic analyses based on 16S rRNA gene sequences and 1179 single-copy orthologous clusters indicated that strain ASW11-75T is affiliated with the genus Marinobacter. Strain ASW11-75T showed highest 16S rRNA gene sequence similarity to 'Marinobacter arenosus' CAU 1620T (98.5 %). The digital DNA-DNA hybridization and average nucleotide identity values between strain ASW11-75T and its closely related strains (Marinobacter salarius R9SW1T, Marinobacter similis A3d10T, 'Marinobacter arenosus' CAU 1620T, Marinobacter sediminum R65T, Marinobacter salinus Hb8T, Marinobacter alexandrii LZ-8T and Marinobacter nauticus ATCC 49840T) were 19.8-24.5 % and 76.6-80.7 %, respectively. The predominant cellular fatty acids were C16 : 0, C18 : 1 ω9c and C16 : 0 N alcohol. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminophospholipid and two unidentified lipids. The major isoprenoid quinone was ubiquinone-9. The genomic DNA G+C content was 62.2 mol%. Based on genomic and gene function analysis, strain ASW11-75T had lower protein isoelectric points with higher ratios of acidic residues to basic residues and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt. The results of polyphasic characterization indicated strain ASW11-75T represents a novel Marinobacter species, for which the name Marinobacter qingdaonensis sp. nov. with the type strain ASW11-75T is proposed. The type strain is ASW11-75T (=KCTC 82497T=MCCC 1K05587T).

Effects of ESPCS mode nursing on the surgical tolerance, gastrointestinal tract recovery and self­management efficacy of patients with colon cancer.

Colon cancer is a common gastrointestinal malignant tumor. In addition to conventional treatment, thoughtful and comprehensive aftercare should be given to patients. The present study aimed to explore the effects of explain-simulate-practice-communication-support (ESPCS) model nursing on the surgical tolerance, gastrointestinal recovery and self-management efficacy of patients with colon cancer. The clinical data of 136 patients with colon cancer diagnosed and treated at the Second Affiliated Hospital of Harbin Medical University (Harbin, China) from June 2020 to April 2022 were retrospectively analyzed and a total of 84 patients met the inclusion criteria. A total of 42 patients who underwent conventional nursing were included in the conventional nursing group and 42 patients who underwent ESPCS model nursing were included in the ESPCS model nursing group. Surgical tolerance, gastrointestinal recovery, self-management efficacy (Cancer Self-Management Efficacy Scale), quality of life (Comprehensive Quality of Life Inventory-74) and nursing satisfaction were analyzed. Slightly higher proportions of excellent and good surgical tolerance were found in the ESPCS model nursing group (97.62%) compared with those in the conventional nursing group (85.71%); however, no significant difference was shown (P>0.05). Compared with the conventional nursing group, the time needed for gastric tube removal, bowel sound recovery, anal exhaust, first defecation, general food intake and the time until getting out of bed was significantly shorter in the ESPS model nursing group (all P<0.05). Before the intervention, no statistically significant difference was found between the indicators in the Cancer Self-Management Efficacy Scale of the two groups (all P>0.05). After the intervention, the ESPCS model nursing group had significantly higher scores for positive attitude, stress relief and self-determination than the conventional nursing group (all P<0.05). Before intervention, there was no statistically significant difference in the indicators of CQOLI-74 between the two groups (P>0.05). After the intervention, the ESPCS model nursing group also had significantly higher scores for social function, psychological function, life state and somatic function compared with the conventional nursing group (all P<0.05). Higher satisfaction of patients was found in the ESPCS mode group (95.24%) compared with that in the conventional nursing group (78.57%) (P<0.05). Overall, ESPCS mode nursing could effectively elevate the surgical tolerance of patients with colon cancer, promote the recovery of gastrointestinal function, increase self-management efficacy, and improve the quality of life and nursing satisfaction, which is certainly worthy of clinical promotion.

The efficacy and safety of vonoprazan in quadruple therapy for Helicobacter pylori eradication: a comparative study.

Background: The efficacy and optimal dose of the new acid-suppressant vonoprazan (VPZ) for quadruple therapy remain uncertain. This study aimed to compare the efficacy and safety of 20 mg VPZ daily (VOD) and 20 mg VPZ twice daily (VTD) with a proton pump inhibitor (PPI) twice daily in quadruple therapy. Methods: We retrospectively analyzed the data of 954 patients treated with quadruple therapy to eradicate Helicobacter pylori. Eradication rates and adverse events were compared between the VOD and VTD groups, and between the VOD and PPI groups. Multivariate analysis was conducted to identify the predictors of eradication failure. Results: Eradication was successful in 875 (91.7%) of the 954 patients. The total, initial, and rescue eradication rates in the VOD group were 92.1%, 93.3%, and 77.8%, respectively. In both the crude and multivariate analyses, the VOD group showed eradication rates comparable to those of the VTD and PPI groups (all P > 0.05). Age > 60 years (odds ratio [OR] = 2.165, P = 0.012) and use of rescue therapy (OR = 3.496, P < 0.001) were independent risk factors for eradication failure, whereas VPZ at a low dosing frequency of 20 mg daily was not. A total of 787 patients (82.5%) were followed up (mean follow-up time, 6.7 ± 2.0 months). Compared with the VOD group, the VTD group was more likely to experience adverse events (OR = 2.073, P = 0.035). Conclusion: VPZ at a low dose of 20 mg daily is an effective and safe component of the quadruple therapy for H.pylori eradication.

Alteromonas arenosi sp. nov., a novel bioflocculant-producing bacterium, isolated from intertidal sand.

A novel Gram-stain-negative, strictly aerobic and bioflocculant-producing bacterium, designated as ASW11-36T, was isolated from an intertidal sand collected from coastal areas of Qingdao, PR China. Growth occurred at 15-40 °C (optimum, 30 °C), pH 7.0-9.0 (optimum, pH 7.5) and with 1.5-7.0% (w/v) NaCl (optimum, 2.5-3.0%). In the whole-cell fatty acid pattern prevailed C16:0 and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The major isoprenoid quinone was determined to be Q-8 and the major polar lipids were phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), one unidentified aminolipid (AL), one unidentified glycolipid (GL), and two lipids (L1, L2). Based on the phylogenetic analyses of 16S rRNA gene sequences and 618 single-copy orthologous clusters, strain ASW11-36T could represent a novel member of the genus Alteromonas and was closely related to Alteromonas flava P0211T (98.4%) and Alteromonas facilis P0213T (98.3%). The pairwise average nucleotide identity and digital DNA-DNA hybridization values of the ASW11-36T genome assembly against the closely related species genomes were 71.8% and 21.7%, respectively, that clearly lower than the proposed thresholds for species. Based on phenotypic, phylogenetic, and chemotaxonomic analyses, strain ASW11-36T is considered to represent a novel species of the genus Alteromonas, for which the name Alteromonas arenosi sp. nov. is proposed. The type strain is ASW11-36T (= KCTC 82496T = MCCC 1K05585T). In addition, the strain yielded 65% of flocculating efficiency in kaolin suspension with CaCl2 addition. The draft genome of ASW11-36T shared abundant putative CAZy family related genes, especially involved in the biosynthesis of exopolysaccharides, implying its potential environmental and biological applications.

Synthesis and Bioevaluation of 3-(Arylmethylene)indole Derivatives: Discovery of a Novel ALK Modulator with Antiglioblastoma Activities.

Glioblastoma is the most common brain tumor, with high recurrence and low survival rates. An integrative bioinformatics analysis demonstrated that anaplastic lymphoma kinase (ALK) is a promising therapeutic target for glioblastoma. We designed and synthesized a series of 3-(arylmethylene)indole derivatives, which were further evaluated for antiproliferative activity using glioma cell lines. Among them, compound 4a significantly inhibited the viability of glioblastoma cells. With favorable pharmacokinetic characteristics and blood-brain barrier permeability, 4a improved the survival rate and inhibited the growth of orthotopic glioblastoma. The Phospho-Totum system revealed that ALK was a potential target for the antiglioblastoma activity of 4a. Further experiments indicated that 4a might be a novel ALK modulator, which interacted with the extracellular ligand-binding domain of ALK, thus selectively induced ERK-mediated autophagy and apoptosis. Our findings provide an alternative ALK-based targeting strategy and a new drug candidate for glioblastoma therapy.

An offline to online cognitive behavioral stress management caring program effectively improves psychological pressure, spiritual well-being, and quality of life in postoperative hepatocellular carcinoma patients.

BACKGROUND: This study designed an offline to online cognitive behavioral stress management (OOCBSM) caring program, intending to investigate its effect on mental health and quality of life (QoL) using multiple scales in postoperative hepatocellular carcinoma (HCC) patients. METHODS: 254 postoperative HCC patients were randomly (1:1) allocated into OOCBSM (included a 10-week offline CBSM and subsequent online CBSM until M6) and normal care (NC) groups (10-week NC). Hospital anxiety-and-depression scale (HADS), Zung's self-reporting anxiety (SAS) and depression scale (SDS), FACIT-SP, European quality-of-life-5 dimensions (EQ-5D), and quality-of-life questionnaire-core30 (QLQ-C30) were assessed over 6 months (M). RESULTS: HADS-defined-anxiety rates at M3 (P = 0.036) and M6 (P = 0.025), SAS-defined-anxiety rate at M6 (P = 0.049), HADS-defined-depression rates at M3 (P = 0.026) and M6 (P = 0.049), and SDS-defined-depression rates at M3 (P = 0.015) and M6 (P = 0.043) were all lower in OOCBSM group compared to NC group. Furthermore, FACIT-SP scores at M1 (P = 0.004), M3 (P = 0.003), and M6 (P<0.001) were higher in OOCBSM group compared with NC group. EQ-5D scores at M1 (P = 0.025) and M3 (P = 0.030) but not M6 (P = 0.128), and QLQ-C30-symptom score at M3 (P = 0.014) but not M1 (P = 0.198) and M6 (P = 0.058) were lower in OOCBSM group versus NC group; QLQ-C30-global-health-status scores at M3 (P = 0.027) and M6 (P = 0.001) but not M1 (P = 0.312), QLQ-C30-function scores at M3 (P = 0.005) and M6 (P = 0.001) but not M1 (P = 0.084) were higher in OOCBSM group versus NC group. Patients with younger ages or higher education benefited more from OOCBSM. CONCLUSION: OOCBSM improves psychological pressure, spiritual well-being, and QoL in postoperative HCC patients, especially in those with younger ages or higher education.

A decision tree model to predict liver cirrhosis in hepatocellular carcinoma patients: a retrospective study.

Background: The severity of liver cirrhosis in hepatocellular carcinoma (HCC) patients is essential for determining the scope of surgical resection. It also affects the long-term efficacy of systemic anti-tumor therapy and transcatheter arterial chemoembolization (TACE). Non-invasive tools, including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 (FIB-4), and γ-glutamyl transferase to platelet ratio (GPR), are less accurate in predicting cirrhosis in HCC patients. We aimed to build a novel decision tree model to improve diagnostic accuracy of liver cirrhosis. Patients and Methods: The Mann-Whitney U test, χ2 test, and multivariate logistic regression analysis were used to identify independent cirrhosis predictors. A decision tree model was developed using machine learning algorithms in a training cohort of 141 HCC patients. Internal validation was conducted in 99 HCC patients. The diagnostic accuracy and calibration of the established model were evaluated using receiver operating characteristic (ROC) and calibration curves, respectively. Results: Sex and platelet count were identified as independent cirrhosis predictors. A decision tree model integrating imaging-reported cirrhosis, APRI, FIB-4, and GPR was established. The novel model had an excellent diagnostic performance in the training and validation cohorts, with area under the curve (AUC) values of 0.853 and 0.817, respectively. Calibration curves and the Hosmer-Lemeshow test showed good calibration of the novel model. The decision curve analysis (DCA) indicated that the decision tree model could provide a larger net benefit to predict liver cirrhosis. Conclusion: Our developed decision tree model could successfully predict liver cirrhosis in HCC patients, which may be helpful in clinical decision-making.

Co-delivery of EGCG and melittin with self-assembled fluoro-nanoparticles for enhanced cancer therapy.

PURPOSE: Melittin (MPI) is a potential anticancer peptide due to its abilities of antitumor and immunomodulatory functions. Epigallocatechin-3-Ogallate (EGCG), a major extract of green tea, has shown great affinity for various types of biological molecules, especially for peptide/protein drugs. The aim of this study is to prepare a fluoro- nanoparticle (NP) formed by self-assembly of fluorinated EGCG (FEGCG) and MPI, and evaluate the effect of fluorine modification on MPI delivery and their synergistic antitumor effect. METHODS: Characterization of FEGCG@MPI NPs was determined by dynamic light scattering (DLS) and transmission electron microscope (TEM). Biology functions of FEGCG@MPI NPs were detected by hemolysis effect, cytotoxicity, apoptosis, cellular uptake with confocal microscopy and flow cytometry. The protein expression levels of Bcl-2/Bax, IRF, STATT-1, P-STAT-1, and PD-L1 were determined via western blotting. A transwell assay and wound healing assay were used to detect the cell migration and invasion. The antitumor efficacy of FEGCG@MPI NPs was demonstrated in a subcutaneous tumor model. RESULTS: Fluoro-nanoparticles could be formed by self-assembly of FEGCG and MPI, and fluorine modification on EGCG could ameliorate the side effect and delivery of MPI. The promoted therapeutics of FEGCG@MPI NPs could be achieved by regulating PD-L1 and apoptosis signaling, which might involve pathways of IRF, STAT-1/pSTAT-1, PD-L1, Bcl-2, and Bax in vitro. Moreover, FEGCG@MPI NPs could significantly inhibit the growth of tumor in vivo. CONCLUSIONS: FEGCG@MPI NPs may offer a potential platform and promising strategy in cancer therapy.

Curcumin Induces Ferroptosis in A549 CD133+ Cells through the GSH-GPX4 and FSP1-CoQ10-NAPH Pathways.

BACKGROUND: Cancer stem cells (CSCs) are characterized by an ability for unlimited proliferation and efficiency of self-renewal. The targeting of lung CSCs (LCSCs)-related signaling pathways represent a promising therapeutic strategy for treatment of lung cancer. Ferroptosis a potential strategy for LCSCs treatment, and curcumin cloud induce ferroptosis. In this study, we aimed to observe the effects of curcumin on LCSCs via ferroptosis-related pathways. METHODS: In this study, A549 cluster of differentiation (CD)133+ and A549 CD133- cells were isolated using magnetic bead-based separation. Colony formation and sphere formation assays, as well as cells injection in non-obese diabetes/severe combined immune deficiency (NOD/SCID) mice, were used to analyze the tumorigenic ability of cells differentially expressing CD133. A549 CD133+ cells were treated with different doses of curcumin (0, 10, 20, 40, 80 µM). Cell viability, glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) expressions were measured. The 50% inhibitory concentration (IC50) of curcumin, two ferroptosis inducers, inhibitor of GPX4 (RSL3) and inhibitor of FSP1 (iFSP1), and a ferroptosis inhibitor, ferrostatin-1 (Fer-1), were used to investigate the mechanism underlying the effect of curcumin on ferroptosis in A549 CD133+ cells. RESULTS: A549 CD133+ cells had greater tumorigenic ability than A549 cells. Curcumin treatment suppressed the expressions of GPX4 (glutathione peroxidase 4) and FSP1 in A549 CD133+ cells, thereby inducing ferroptosis. RSL3 and iFSP1 respectively suppressed the GSH (glutathione)-GPX4 and FSP1 (ferroptosis suppressor protein 1)-CoQ10 (coenzyme Q10)-nicotinamide adenine dinucleotide (NADH) pathways in A549 CD133+ cells. However, the roles of curcumin were blocked by Fer-1 treatment. CONCLUSIONS: In this study, curcumin induced ferroptosis through inhibiting the GSH-GPX4 and FSP1-CoQ10-NADH pathways in A549 CD133+ cells, resulting in the inhibition of their self-renewal potential.

SOX9/NFIA promotes human ovarian cancer metastasis through the Wnt/ß-catenin signaling pathway.

To our knowledge, Sex-determining Region Y box 9 (SOX9) has been in connection with a wide range of human cancers. Nevertheless, there remains uncertainty regarding SOX9's role in metastasizing ovarian cancer. In our study, SOX9 was investigated in relation to tumor metastasis in ovarian cancer as well as its potential molecular mechanisms. First, we exhibited an apparent higher expression of SOX9 in ovarian cancer tissues and cells than in normative ones, and the prognosis of patients whose SOX9 levels were high was markedly lower than that of patients whose SOX9 levels were low. Besides, highly expressed SOX9 was correlated with high grade serous carcinoma, poor tumor differentiation, high serum CA125 and lymph node metastasis. Second, SOX9 knockdown exhibited striking inhibition of the migration and invasive ability of ovarian cancer cells, whereas SOX9 overexpression had an inverse role. At the same time, SOX9 could promote ovarian cancer intraperitoneal metastasis in a nude mice in the vivo. In a similar way, SOX9 knockdown dramatically decreased the expression of nuclear factor I-A (NFIA), ß-catenin as well as N-cadherin but had an increased in E-cadherin expression, as opposed to the results when SOX9 was overexpressed. Furthermore, NFIA silencing inhibited the expression of NFIA, ß-catenin and N-cadherin, in the same way that E-cadherin expression was promoted. In conclusion, this study shows that SOX9 has a promotional effect on human ovarian cancer and that SOX9 promotes the metastasis of tumors by upregulating NFIA and activating on a Wnt/ß-catenin signal pathway. SOX9 could be a novel focus for earlier diagnosis, therapy and prospective evaluation in ovarian cancer.

Conversion therapy for massive hepatocellular carcinoma: A case report and literature review.

Key Clinical Message: For potentially resectable HCC, a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used. Abstract: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. The best treatment for HCC is radical surgical resection, but 70%-80% of patients are ineligible for surgery. Although conversion therapy is an established treatment strategy for various solid tumors, there is no uniform protocol for treating HCC. In this case, we present a 69-year-old male patient diagnosed with massive HCC with Barcelona clinical liver cancer (BCLC) stage B. Because of the insufficient volume of the future liver remnant, we believed radical surgical resection was temporarily impossible. Therefore, the patient received conversion therapy, including four cycles of transcatheter arterial embolization (TAE) and hepatic arterial infusion chemotherapy (HAIC-Folfox), lenvatinib (8 mg orally once a day), and tislelizumab (an anti-PD-1 antibody, 200 mg intravenously once every 3 weeks). Fortunately, the patient achieved a good treatment response (smaller lesions and improved liver function) and underwent radical surgery finally. There was no clinical evidence of recurrence at 6 months of follow-up. For potentially resectable HCC, this case reveals that a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used.

Distinct Roles of Ena ATP Family Proteins in Sodium Accumulation, Invasive Growth, and Full Virulence in Colletotrichum gloeosporioides.

Colletotrichum gloeosporioides, a significant fungal pathogen of crops and trees, causes large economic losses worldwide. However, its pathogenic mechanism remains totally unclear. In this study, four Ena ATPases (Exitus natru-type adenosine triphosphatases), homology of yeast Ena proteins, were identified in C. gloeosporioides. Gene deletion mutants of ΔCgena1, ΔCgena2, ΔCgena3, and ΔCgena4 were obtained through the method of gene replacement. First, a subcellular localization pattern indicated that CgEna1 and CgEna4 were localized in the plasma membrane, while the CgEna2 and CgEna3 were distributed in the endoparasitic reticulum. Next, it was found that CgEna1 and CgEna4 were required for sodium accumulation in C. gloeosporioides. CgEna3 was required for extracellular ion stress of sodium and potassium. CgEna1 and CgEna3 were involved in conidial germination, appressorium formation, invasive hyphal development, and full virulence. The mutant of ΔCgena4 was more sensitive to the conditions of high concentrations of ion and the alkaline. Together, these results indicated that CgEna ATPase proteins have distinct roles in sodium accumulation, stress resistance, and full virulence in C. gloeosporioides.

Development and Validation of Prognostic Nomograms Based on Lymph Node Ratio for Young Patients with Gastric Cancer: A SEER-Based Study.

PURPOSE: To investigate the role of lymph node ratio (LNR) in young patients with gastric cancer (GC) and develop nomograms to predict the survival of young GC patients. METHODS: This retrospective study enrolled stage I-III GC patients before the age of 40 between 2010 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazards models were used to determine the prognosticators and create the nomograms incorporating LNR to predict overall survival (OS) and cancer-specific survival (CSS). The discriminating superiority of the nomograms was examined using calibration curves, C-index, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and integrated discrimination improvement (IDI) by comparing with the TNM staging. The performance of the nomograms for risk stratification was analyzed by the Kaplan-Meier method. RESULTS: Based on the significant prognosticators identified in multivariate survival analysis, the nomograms were established and showed LNR as the third strongest predictor. The C-index of the nomograms for OS and CSS were higher than those of the TNM staging (OS: 0.773 vs 0.665; CSS: 0.769 vs 0.666). The ROC curves for the nomograms to predict survival exhibited superior sensitivity and specificity when compared with the TNM staging. The calibration plots, DCA curves, and IDI values of the nomograms also demonstrated adequate fit and ideal net benefit in prediction and clinical utility. The Kaplan-Meier analysis observed remarkable differences in patients divided into different risk subgroups (P < .001). CONCLUSIONS: These results found the clinical outperformance of the LNR-based nomograms for predicting survival in young stage I-III GC patients. Our nomograms may improve accuracy of survival risk prediction and facilitate individualized care of young stage I-III GC patients.

HMGCL-induced ß-hydroxybutyrate production attenuates hepatocellular carcinoma via DPP4-mediated ferroptosis susceptibility.

BACKGROUND: Metabolic disorder is an essential characteristic of tumor development. Ketogenesis is a heterogeneous factor in multiple cancers, but the effect of ketogenesis on hepatocellular carcinoma (HCC) is elusive. METHODS: We aimed to explain the role of ketogenesis-related hydroxy-methyl-glutaryl-CoA lyase (HMGCL) on HCC suppression. Expression pattern of HMGCL in HCC specimens was evaluated by immunohistochemistry (IHC). HMGCL was depleted or overexpressed in HCC cells to investigate the functions of HMGCL in vitro and in vivo. The anti-tumor function of HMGCL was studied in subcutaneous xenograft and Trp53Δhep/Δhep; c-Myc-driven HCC mouse models. The mechanism of HMGCL-mediated tumor suppression was studied by IHC, western blot (WB) and Cut & Tag. RESULTS: HMGCL depletion promoted HCC proliferation and metastasis, whereas its overexpression reversed this trend. As HMGCL catalyzes ß-hydroxy-butyric acid (ß-OHB) production, we discovered that HMGCL increased acetylation at histone H3K9, which further promoted the transcription of dipeptidyl peptidase 4 (DPP4), a key protein maintains intracellular lipid peroxidation and iron accumulation, leading to HCC cells vulnerability to erastin- and sorafenib-induced ferroptosis. CONCLUSION: Our study identified a critical role of HMGCL on HCC suppression, of which HMGCL regulated H3K9 acetylation through ß-OHB and modulating the expression of DPP4 in a dose-dependent manner, which led to ferroptosis in HCC cells.

Uterine Anteroposterior Diameter Measured by Transvaginal Sonography is a Predictor for Dysmenorrhea in Patients With and Without Endometriosis: A Pilot Study.

PURPOSE: The aim of this study was to determine the correlation between uterine diameters and menstrual abdominal pain intensity in patients with and without endometriosis (EM), and the independent influence of EM on the pain intensity. METHODS: Uterine diameters and the diagnosis of adenomyosis were ascertained by transvaginal ultrasonography (TVS). Menstrual abdominal pain intensity was estimated by visual analog scale (VAS). Linear regression was used to figure out the impact of uterine diameters and EM on the VAS scores. Logistic regression was used to calculate the correlation between uterine diameters and the diagnosis of adenomyosis. The cutoff values of uterine anteroposterior diameter (AD) to predict dysmenorrhea (VAS ≥ 4) and the diagnosis of adenomyosis were determined by receiver operating characteristic curves. RESULTS: There were 220 patients with and 233 patients without EM included. Uterine AD independently correlated with the VAS scores in patients with (B = .230, P = .000) and without (B = .203, P = .000) EM. A uterine AD of 39.5 mm predicted dysmenorrhea in both groups. The presence of EM increased the VAS scores by 1.151 points when controlling for uterine diameters. Uterine AD also independently correlated with the diagnosis of adenomyosis under TVS in patients with (OR = 1.212, 95% CI = 1.130-1.301; P = .000) and without (OR = 1.192, 95% CI = 1.123-1.263; P = .000) EM. A uterine AD of 38.5 and 39.5 mm predicted the diagnosis of adenomyosis under TVS in patients with and without EM, respectively. CONCLUSIONS: Increased uterine AD, which is probably ascribed to adenomyosis, plays an important role in augmented menstrual abdominal pain intensity. Meanwhile, the presence of EM reinforces the pain.

Adsorption and Gas-Sensing Properties of Agn (n = 1-4) Cluster Doped GeSe for CH4 and CO Gases in Oil-Immersed Transformer.

The adsorption mechanism of CO and CH4 on GeSe, modified with the most stable 1-4 Ag-atom clusters, is studied with the help of density functional theory. Adsorption distance, adsorption energy, total density of states (TDOS), projected density of states (PDOS), and molecular orbital theory were all used to analyze the results. CO was found to chemisorb exothermically on GeSe, independent of Ag cluster size, with Ag4-GeSe representing the optimum choice for CO gas sensors. CH4, in contrast, was found to chemisorb on Ag-GeSe and Ag2-GeSe and to physisorb on Ag3-GeSe and Ag4-GeSe. Here, Ag GeSe was found to be the optimum choice for CH4 gas sensors. Overall, our calculations suggest that GeSe modified by Ag clusters of different sizes could be used to advantage to detect CO and CH4 gas in ambient air.

Manipulating Offense and Defense Signaling to Fight Cold Tumors with Carrier-Free Nanoassembly of Fluorinated Prodrug and siRNA.

Chemoimmunotherapy has shown great potential to activate an immune response, but the immunosuppressive microenvironment associated with T cell exhaustion remains a challenge in cancer therapy. The proper immune-modulatory strategy to provoke a robust immune response is to simultaneously regulate T-cell exhaustion and infiltration. Here, a new kind of carrier-free nanoparticle is developed to simultaneously deliver chemotherapeutic drug (doxorubicin, DOX), cytolytic peptide (melittin, MPI), and anti-TOX small interfering RNA (thymocyte selection-associated high mobility group box protein, TOX) using a fluorinated prodrug strategy. In this way, the enhanced immunogenic cell death (ICD) induced by the combination of DOX and MPI can act as "offense" signaling to increase CD8+ T-cell infiltration, while the decreased TOX expression interfered with siTOX can serve as "defense" signaling to mitigate CD8+ T-cell exhaustion. As a result, the integration of DOX, MPI, and siTOX in such a bifunctional system produced a potent antitumor immune response in liver cancer and metastasis, making it a promising delivery platform and effective strategy for converting "cold" tumors into "hot" ones.

Structural characterization of a soluble polysaccharide SSPS1 from soy whey and its immunoregulatory activity in macrophages.

A soluble soybean polysaccharide SSPS1 with a molecular weight of 2737 kDa was extracted and purified from soy whey. SSPS1 was composed of glucose (97.3 %) and a small amount of mannose (2.7 %). Structural analysis results suggested that SSPS1 had a â†’ 6)-α-d-Glcp-(1 â†’ glucan structure, with a trace amount of α-d-Glcp-(1 â†’ connected to the main chain via O-3. In vitro immunological experiments suggested that SSPS1 enhanced the growth rate and phagocytic activity of RAW 264.7 macrophages. In addition, SSPS1 stimulated the secretion of cytokines (TNF-α, INF-ß, IL-6 and IL-1ß) as well as nitric oxide (NO) production through upregulating the expression of the related genes and proteins in RAW 264.7 cells. This study provided a new method for efficient utilization of soy whey, and the results indicate that SSPS1 extracted from soy whey could be used as a novel immunomodulator.

Real-world data analysis of immune checkpoint inhibitors in stage III-IV adenocarcinoma and squamous cell carcinoma.

BACKGROUND: This study was designed to investigate the clinical application, efficacy, and safety of immune checkpoint inhibitors (ICIs) in the treatment of lung cancer in the real world. METHODS: A retrospective, observational analysis was conducted on patients treated with ICIs in four tertiary hospitals in the region from January 2015 to March 2021, to evaluate the clinical efficacy of ICIs single-agent or combined chemotherapy and anti-vascular drugs in the first-line or second-line treatment of patients with lung cancer. RESULTS: Three hundred and fifteen patients were enrolled in this study. In patients with stage III-IV adenocarcinoma and Squamous cell carcinoma, the objective response rate (ORR) and disease control rate (DCR) were 35.5% (87/245) and 93.5% (229/245), respectively, the median progression-free survival (PFS) was 10.8 months, and the median overall survival (OS) was not reached. A total of 132 patients received ICIs as the first-line treatment, the median treatment cycle was 8 cycles (2-20 cycles), the short-term efficacy ORR was 38.6%, DCR was 93.9%, and the median PFS was 11.4 months. One hundred thirteen patients received ICIs treatment as second-line treatment, the median treatment cycle was five cycles (2-10 cycles), the short-term efficacy ORR was 31.9%, DCR was 92.9%, and the median PFS was 10.0 months. There were no statistically significant differences in ORR, DCR, or median PFS with ICIs as the first-line treatment compared with the second-line treatment(P > 0.05). The results of subgroup analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), epidermal growth factor receptor (EGFR) mutation status, pathological type and number of treatment lines were not correlated with median PFS(P > 0.05). However, there were statistically significant differences in programmed death-ligand 1(PD-L1) expression, corticosteroid interference, and antibiotic (Abx) treatment among all groups (P < 0.05). In terms of safety, the overall incidence of adverse reactions in 315 patients was 62.5%, and the incidence of immune-related adverse events (irAEs) was 13.7%. Grade 1-2 and 3-4 incidence of adverse events were 34.9 and 27.65%, respectively. There were four patients who experienced fatal irAEs, two cases were liver damage leading to liver failure, one case was immune related pneumonia, and one case was immune related myocarditis. CONCLUSION: In the real world, ICIs has a good effect on patients with lung cancer and significantly improves ORR and PFS.