Chloramphenicol-imprinted polychitosan bounded with carbon dots as fluorescent sensor, dispersive sorbent, and drug carrier.

Chitosan, an abundant natural polysaccharide, was conjugated with carbon dots (CDs) and self-polymerized with chloramphenicol (CAP) templates to synthesize CD-incorporated and molecularly CAP-imprinted polychitosan (CD-MIC). The CD-MIC was used for fluorescent sensing, dispersive sorption, and dosage release of CAP at different pH levels. The sphere of action mechanism, approved by emission and excitation fluorescence, UV-Vis absorption, and fluorescence lifetime measurements, regulated the fluorescence static quenching. By the Perrin model, the quenching extent was linearly correlated to CAP within 0.17 - 33.2 µM (LOD = 37 nM) at pH 7.0. With an imprinting factor of 3.1, the CD-MIC was more selective for CAP than CD, although it was less sensitive to CAP. The recoveries of 5.0 µM CAP from milk matrix were 95% (RSD = 2.3%) for CD-MIC probes and 62% (RSD = 4.5%) for CD. The Langmuir and pseudo-second-order models preferably described the isothermal and kinetic sorptions of CAP into the imprinted cavities in CD-MICs, respectively. The Weber - Morris kinetic model showed three stages involved in intraparticle diffusion, which was pH-dependent and gradually arduous at the later stage, and showed external diffusion partly engaged in the diffusion mechanism. The 20 - 70% of CAP formulated in CAP-embedded CD-MICs were released in 8 - 48 h. The release percentage was lower at pH 7.0 than at pH 5.0 and 9.0, but the equilibrium time was shorter. At pH 7.0, the release percentage reached 45% at 10 min and slowly increased to 51% at 24 h.

CT radiomics features of meso-esophageal fat in predicting overall survival of patients with locally advanced esophageal squamous cell carcinoma treated by definitive chemoradiotherapy.

OBJECTIVE: To investigate the value of CT radiomics features of meso-esophageal fat in the overall survival (OS) prediction of patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: A total of 166 patients with locally advanced ESCC in two medical centers were retrospectively analyzed. The volume of interest (VOI) of meso-esophageal fat and tumor were manually delineated on enhanced chest CT using ITK-SNAP. Radiomics features were extracted from the VOIs by Pyradiomics and then selected using the t-test, the Cox regression analysis, and the least absolute shrinkage and selection operator. The radiomics scores of meso-esophageal fat and tumors for OS were constructed by a linear combination of the selected radiomic features. The performance of both models was evaluated and compared by the C-index. Time-dependent receiver operating characteristic (ROC) analysis was employed to analyze the prognostic value of the meso-esophageal fat-based model. A combined model for risk evaluation was constructed based on multivariate analysis. RESULTS: The CT radiomic model of meso-esophageal fat showed valuable performance for survival analysis, with C-indexes of 0.688, 0.708, and 0.660 in the training, internal, and external validation cohorts, respectively. The 1-year, 2-year, and 3-year ROC curves showed AUCs of 0.640-0.793 in the cohorts. The model performed equivalently compared to the tumor-based radiomic model and performed better compared to the CT features-based model. Multivariate analysis showed that meso-rad-score was the only factor associated with OS. CONCLUSIONS: A baseline CT radiomic model based on the meso-esophagus provide valuable prognostic information for ESCC patients treated with dCRT.

Fluorescence determination of tannic acid imprinted in conjugated hypercrosslinked polymers by Friedel-Crafts acylation.

A molecularly imprinted hypercrosslinked polymer (HCP) was synthesized from the polymerization of mesitylene monomer, terephthaloyl chloride crosslinker, and tannic acid (TA) template through FeCl3-catalyzed Friedel-Crafts acylation. The TA-imprinted HCP (TAHCP) was capable of IUPAC Type I mesoporosity, with specific surface area of 1258 m2 g-1, monolayer adsorption capacity of 289 cm2 g-1, pore sizes ranging from 4.4 to 12.6 Å, amorphous morphology, and characteristic absorption and emission bands. The extended π-conjugation framework of TAHCP was endowed with 385-nm fluorescent emission at 310-nm excitation. The fluorescence intensity of TAHCP could be dynamically quenched by TA and was linearly correlated with 20-1000 nM TA concentrations on the Stern-Volmer plot in the optimized conditions of pH 5.5 buffer, 100 µg mL-1 TAHCP, and 3.5 min equilibrium. The relative standard deviation (RSD) for 50 nM TA was 3.4% (n = 5), and the limit of detection was 6.2 nM based on the 3σ of the TA blanks). For 50nM TA, the imprinted factor was calculated to be 7.8, and the selectivity for 250 nM interferents, including ions, organic acids, saccharides, amino acids, and caffeine, which are commonly found in beverages, was 7.5-9.5, except for gallic acid (1.2). The recoveries of TA spiked in tea and juice beverages at three levels (10-150 nM) were 93.6-101.9% (RSD = 3.6-4.3%).

Enhanced stent visualization system for percutaneous coronary intervention in patients with chronic kidney disease: effects on contrast media volume and radiation exposure.

OBJECTIVE: We aimed to assess the impact of using enhanced stent visualization (ESV) systems on contrast media volume and radiation dose in percutaneous coronary intervention (PCI), especially for patients with chronic kidney disease (CKD). BACKGROUND: Coronary heart disease (CHD) is associated with chronic kidney disease (CKD), as they share a similar pathological pathway. In addition, the iodinated contrast media used for angiography is a risk factor for contrast-associated acute kidney injury (CA-AKI), which could aggravate the progression of CKD. We hypothesized that ESV systems have the potential to reduce the use of contrast media as well as the radiation dose; however, few studies have reported the impact on contrast media with the use of ESV systems. METHODS: We retrospectively collected 124 patients with acute coronary syndrome who underwent PCI from May 2020 to July 2021. The patients were divided into the ESV-guided group (n = 64) and angiography-guided group (n = 60). Procedural parameters, including contrast media volume, radiation exposure (in Air Kerma-AK and Dose Area Product-DAP), number of cines, cine frames, fluoroscopy and procedure time, were recorded and analysed. RESULTS: The groups were comparable regarding the patient characteristics. There was a significant reduction in contrast media volume (174.7 ± 29.6 ml vs.132.6 ± 22.3 ml, p = 0.0001), radiation exposure (776 (499 - 1200) mGy vs. 1065 (791 - 1603) mGy, p = 0.002 in AK; 43 (37 - 73) Gycm2 vs. 80 (64 - 133) Gycm2, p = 0.030 in DAP) and procedure time (53.06 ± 21.20 min vs. 72.00 ± 30.55 min, p = 0.01) with the use of ESV systems. Similar results were observed in the subgroup analysis for the patients with CKD. CONCLUSION: This study suggested that the use of ESV is associated with reduced contrast media usage, radiation dose and procedure time during PCI. The same results were observed in a subgroup analysis in patients with CKD, and this shows that ESV-guided PCI has the potential to reduce renal impairment and mitigate the progression of CKD for those CHD patients with CKD.

Imprinted ß-ketoenamine-linked covalent organic frameworks as dispersive sorbents for the fluorometric determination of timolol.

Timolol accompanied the formation of fluorescent ß-ketoenamine-linked covalent organic frameworks (COFs) via the Sc(Tof)3-catalyzed condensation of derivated carbaldehyde and hydrazide in a 1,4-dioxane/mesitylene porogen to construct timolol-imprinted COFs (TICOFs). With high imprinting factors, the synthesis-optimized TICOFs were characterized by fluorescence, UV-Vis spectrometry, X-ray diffraction, N2 adsorption/desorption analyses, scanning electron microscopy, and FTIR spectrometry. The TICOF fluorescence measured at 390 nm/510 nm is dynamically quenched by timolol and was thus utilized to quantify timolol in a linear range of 25-500 nM with a LOD of 8 nM. The TICOF recovered 99.4% of 0.5% timolol maleate in a commercial eye drop (RSD = 1.1%, n = 5). In addition, TICOF was used as a dispersive sorbent to recover 95% of 2.0 nM timolol from 20 mg of TICOF in 25 mL phosphate buffer. Dilution factors of 25 and 75 were the maximum tolerated proportions of the urine and serum matrix spiked with 2.0 nM timolol to reach recoveries of 92.4% and 90.3%, respectively.

Effective and Efficient Pretreatment of Polyimide Substrates by Capacitively Coupled Plasma for Coating the Composites of Tetracycline-Imprinted Polymers and Quantum Dots: Comparison with Chemical Pretreatment.

Composites of tetracycline (Tc)-imprinted polymethacrylates and quantum dots have been coated on chemically pretreated polyimide substrates (PIs) as fluorescent sensors. In this study, PIs were pretreated by capacitively coupled plasma (CCP) before coating the same composites on them. For the first time, to fabricate sensors by plasma modification of PIs, the CCP conditions, including plasma gas, flow rate, radio frequency generation power, and duration time, the fabrication details, including coating, baking, and stripping steps, and the sample loading process were optimized to perform a linear decrease in fluorescent intensity with Tc concentrations in the range of 5.0-3000 µM (R2 = 0.9995) with a limit of detection of 0.2 µM (S/N = 3, relative standard deviation (RSD) = 2.2%). The selectivity of the stripped PIs was evaluated by the imprinting factors (IFs) for Tc (IF = 7.2), other Tc analogues (IF = 3.4-5.3), and steroids (IF ≈ 1) and by the recoveries of 5.0 µM Tc from bovine serum albumin at 300 µg∙mL-1 (98%, RSD = 3.2%), fetal bovine serum at 1.5 ppt (98%, RSD = 2.8%), and liquid milk (94.5%, RSD = 5.3%). The superiority of the present plasma-treated-based sensor over the previous chemically-treated one in fabrication efficiency and detection effectiveness was clear.

Early Renal-Protective Effects of Remote Ischemic Preconditioning in Elderly Patients with Non-ST-Elevation Myocardial Infarction (NSTEMI).

BACKGROUND With the wide clinical application of angiography, contrast-enhanced nephropathy (CIN) has become the third-leading cause of acute kidney injury (AKI). Remote ischemic preconditioning (RIPC) is a non-fatal ischemia-reperfusion injury that can provide protection against lethal ischemia-reperfusion. This study aimed to assess the effect of RIPC on CIN in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). MATERIAL AND METHODS Patients were randomly divided into 2 groups with 119 patients in each group treated with interventional therapy. Patients in the RIPC group received distal ischemic preconditioning 2 h before contrast exposure, while patients in the control group received a sham RIPC procedure. Incidence of CIN was the primary outcome. Changes in creatinine, NGAL, and KIM-1 after contrast administration were secondary outcomes. RESULTS CIN occurred in a total of 27 (12.3%) patients, including 12 (10.1%) in the RIPC group and 15 (15.1%) in the control group (P=0.329). RIPC treatment significantly reduced the levels of NGAL (P=0.024) and KIM-1 (P=0.007) at 12 h after contrast administration, suggesting RIPC treatment reduces sub-clinical renal damage. Subgroup analysis revealed that significant reduction of KIM-1 and NGAL by RIPC, mainly occurring in patients with a Mehran risk score of 6-10. CONCLUSIONS Although RIPC did not significantly reduce CIN incidence in elderly patients with NSTEMI, the application of more sensitive biomarkers - NGAL and KIM-1 - indicated a reduction of sub-clinical renal damage by RIPC, especially in the early stage of injury. As a simple and well-tolerated method, RIPC may be a potentially feasible option to prevent CIN.

Excitation-independent dual emissions of carbon dots synthesized by plasma irradiation of ionic liquids: Ratiometric fluorometric determination of norfloxacin and mercury(II).

The capacitively coupled plasma (CCP) discharge of an ionic liquid solution of citric acid produces carbon dots (CDs) with excitation-independent fluorescent dual-emissions peaking at 410 nm and 480 nm. The intensity of the purple photoluminescence at 410 nm increases with (a) the flow rate of O2 plasma gas supply from 2.0 to 30 standard cubic centimeters per minute (sccm), (b) the 2-h exposure of the CDs to 254 nm light, and (c) the 8-h immersion of the CDs in a solution of NaBH4. The UV exposure and the hydride immersion reduce the fluorescence intensity peaking at 480 nm, which is highest at 5.0 and 10 sccm. The two emissive states were revealed by UV-vis absorption, XPS spectra, and time-resolved fluorescence. Control of the O2 flow rate can simply tune the ratiometric fluorescence of the CCP-CDs. The CDs obtained from 5 and 30 sccm O2 supplies present a high-intensity ratio (I480 nm/I410 nm ≈ 3.35) and a low one (≈ 0.48), respectively. The 480 nm fluorescence of the former CDs is quenched by mercury(II) ions in the 0.2 to 50 µM concentration range. The 410 nm fluorescence of the latter CDs is enhanced by norfloxacin in the 25 nM to 1.0 µM concentration range. The detection limits are 75 nM for Hg(II) and 7.3 nM for norfloxacin. Graphical abstract Schematic presentation of the effect of the oxygen flow rate in capacitively coupled radio frequency (RF) plasma on the formed CDs. The emission can be quenched by Hg2+ or enhanced by norfloxacin.

Chemoselective Synthesis of Structurally Diverse 3,4-Dihydroquinazoline-2(1H)-thiones and 4H-Benzo[d][1,3]thiazines.

An efficient, mild, and substrate/catalyst-controlled chemoselective reaction of o-isothiocyanato-(E)-cinnamaldehyde with amines has been established, producing three types of six-membered heterocycles: 2-(4H-benzo[d][1,3]thiazin-4-yl)acetaldehydes, 2-(2-thioxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetaldehydes, and (E)-4-(2-methoxyvinyl)-4H-benzo[d][1,3]thiazines. The reaction scopes were quite broad and excellent yield was achieved. This method is extremely efficient and practical and can be conducted on a gram-scale with slightly inferior reactivity under catalyst-free conditions at low cost, making it an ideal alternative to existing methods.

Sensitive Detection of 8-Nitroguanine in DNA by Chemical Derivatization Coupled with Online Solid-Phase Extraction LC-MS/MS.

8-Nitroguanine (8-nitroG) is a major mutagenic nucleobase lesion generated by peroxynitrite during inflammation and has been used as a potential biomarker to evaluate inflammation-related carcinogenesis. Here, we present an online solid-phase extraction (SPE) LC-MS/MS method with 6-methoxy-2-naphthyl glyoxal hydrate (MTNG) derivatization for a sensitive and precise measurement of 8-nitroG in DNA. Derivatization optimization revealed that an excess of MTNG is required to achieve complete derivatization in DNA hydrolysates (MTNG: 8-nitroG molar ratio of 3740:1). The use of online SPE effectively avoided ion-source contamination from derivatization reagent by washing away all unreacted MTNG before column chromatography and the ionization process in mass spectrometry. With the use of isotope-labeled internal standard, the detection limit was as low as 0.015 nM. Inter- and intraday imprecision was <5.0%. This method was compared to a previous direct LC-MS/MS method without derivatization. The comparison showed an excellent fit and consistency, suggesting that the present method has satisfactory effectiveness and reliability for 8-nitroG analysis. This method was further applied to determine the 8-nitroG in human urine. 8-NitroG was not detectable using LC-MS/MS with derivatization, whereas a significant false-positive signal was detected without derivatization. It highlights the use of MTNG derivatization in 8-nitroG analysis for increasing the method specificity.

Three new benzolactones from Lavandula angustifolia and their bioactivities.

Three new benzolactones (1-3), together with four known ones (4-7), were isolated from the whole herb of Lavandula angustifolia. Their structures were established on the basis of detailed spectroscopic analysis (1D- and 2D-NMR, HRESIMS, UV, and IR) and comparison with data reported in the literature. New compounds were evaluated for their anti-tobacco mosaic virus (TMV) activities and cytotoxic activities. The results revealed that compounds 1-3 showed obvious anti-TMV activities with inhibition rates of 26.9, 30.2, and 28.4%, which were at the same grade as positive control. Compounds 1-3 also showed weak inhibitory activities against some tested human tumor cell lines with IC50 values in the range of 32.1-7.6 µM.

Chemical Chaperone 4-Phenylbutyric Acid Reduces Cardiac Ischemia/Reperfusion Injury by Alleviating Endoplasmic Reticulum Stress and Oxidative Stress.

BACKGROUND Cardiovascular diseases are the leading cause of death in many countries and myocardial ischemia-reperfusion (I/R) injury is the cause of many serious heart diseases. Recent reports suggested that endoplasmic reticulum (ER) stress is associated with the progress of ischemia/reperfusion (I/R) injury. In a previous study, we illustrated that 4-phenylbutyric acid (4-PBA) reduces I/R-induced cell death in vitro through inhibiting the ER stress-initiated cell apoptosis. In the present study we investigated whether 4-PBA improves heart function in isolated rat hearts subjected to I/R and elucidated the potential mechanisms involved in 4-PBA-induced cardioprotective effects. MATERIAL AND METHODS The isolated rat hearts were subjected to global ischemia and reperfusion in the absence or presence of 4-PBA. Hemodynamic parameters (LVSP, LVEDP, ±dP/dtmax, and HR) were monitored and histopathological examination was applied. The biomarkers related to oxidative stress were detected by LDH, ROS, MDA, CK, SOD, and GSH-Px kits. A TUNEL apoptosis assay kit was used to detect apoptosis. The expression levels of ER stress and apoptosis proteins were evaluated by Western blotting. RESULTS We found that 4-PBA (5 mM, 10 mM) pretreatment significantly attenuated cardiac dysfunction and depressed oxidative stress induced by I/R. Moreover, I/R activated the ER stress proteins Grp78 and PERK, which are all decreased by 4-PBA. 4-PBA pretreatment also inhibited the expression of CHOP, Caspase-12, and Bax, reduced the phosphorylation of JNK, and enhanced the expression of anti-apoptotic protein Bcl-2. CONCLUSIONS We elucidated the significant protective effects of 4-PBA against I/R injuries by inhibition of ER stress, oxidative stress, and their associated apoptosis.

Trace analysis of methylated and hydroxymethylated cytosines in DNA by isotope-dilution LC-MS/MS: first evidence of DNA methylation in Caenorhabditis elegans.

From 1986 to the present, the popular research model organism Caenorhabditis elegans has been thought to completely lack DNA methylation and seems to have lost DNA methylation enzymes from its genomes. In the present study, we report the development of a sensitive and selective assay based on LC-MS/MS to simultaneously measure 5-methyl-2'-deoxycytidine (5-mdC) and 5-hydroxymethyl-2'-deoxycytidine (5-hmdC) in DNA hydrolysates. With the use of isotope internal standards ([2H3]5-mdC and [2H3]5-hmdC) and online solid-phase extraction, the detection limits of 5-mdC and 5-hmdC were estimated to be 0.01 and 0.02 pg respectively, which correspond to a 0.000006% and 0.00001% methylation and hydroxymethylation level. This method was applied to investigate whether DNA methylation/hydroxymethylation exists in C. elegans. The present study for the first time demonstrates that 5-mdC is present in C. elegans genomic DNA (0.0019-0.0033% of cytosine methylated) using LC-MS/MS, whereas another epigenetic modification, 5-hmdC, is not detectable. Furthermore, we found that C. elegans DNA was hypo- or hyper-methylated in a dose-dependent manner by the DNA methyltransferase (DNMT)-inhibiting drug decitabine (5-aza-2'-deoxycytidine) or cadmium respectively. Our data support the possible existence of an active DNA-methylation mechanism in C. elegans, in which unidentified DNMTs could be involved. The present study highlights the importance of re-evaluating the evolutionary conservation of DNA-methylation machinery in nematodes which were traditionally considered to lack functional DNA methylation.

Direct analysis of tobacco-specific nitrosamine NNK and its metabolite NNAL in human urine by LC-MS/MS: evidence of linkage to methylated DNA lesions.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its urinary metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are the most investigated carcinogenic biomarkers of tobacco-specific nitrosamines. Here, we report the development of a sensitive and selective assay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) to simultaneously measure urinary NNK and NNAL. With the use of isotope internal standards and online solid-phase extraction, urine samples were directly analyzed without prior sample purification. The detection limits of this method were 0.13 and 0.19 pg on column for NNK and NNAL, respectively. Inter- and intra-day imprecision was <10 %. Mean recovery of NNK and NNAL in urine was 99-100 %. This method was applied to measure urinary NNK and NNAL in 101 smokers and 40 nonsmokers to assess tobacco exposure. Urinary nicotine, cotinine, N3-methyladenine (N3-MeA), and N7-methylguanine (N7-MeG) were also measured by isotope-dilution LC-MS/MS methods. The results showed that urinary NNK was not observed in all smokers. Urinary free NNAL (0.10 ± 0.09 ng/mg creatinine) and total NNAL (0.17 ± 0.14 ng/mg creatinine) were detected in all smokers. Urinary concentrations of NNAL were significantly correlated with nicotine, cotinine, N3-MeA, and N7-MeG in smokers (P < 0.001). This method enables the direct and simultaneous measurement of NNK and NNAL in urine using only 50 µL of urine. This study first demonstrated in human that urinary tobacco-specific nitrosamines metabolite (NNAL) are highly correlated with their resulting methylated DNA lesions in urine, which may help to substantiate an increased cancer risk associated with tobacco smoke exposure.

Prior Clinico-Radiological Features Informed Multi-Modal MR Images Convolution Neural Network: A novel deep learning framework for prediction of lymphovascular invasion in breast cancer.

BACKGROUND: Current methods utilizing preoperative magnetic resonance imaging (MRI)-based radiomics for assessing lymphovascular invasion (LVI) in patients with early-stage breast cancer lack precision, limiting the options for surgical planning. PURPOSE: This study aimed to develop a sophisticated deep learning framework called "Prior Clinico-Radiological Features Informed Multi-Modal MR Images Convolutional Neural Network (PCMM-Net)" to improve the accuracy of LVI prediction in breast cancer. By incorporating multiparameter MRI and prior clinical knowledge, PCMM-Net should enhance the precision of LVI assessment. METHODS: A total of 341 patients with breast cancer were randomly divided into training and validation groups at a ratio of 7:3. Imaging features were extracted from T1-weighted, T2-weighted, and contrast-enhanced T1-weighted MRI sequences. Stepwise univariate and multivariate logistic regression were employed to establish a clinico-radiological model for LVI prediction. The radiomics model was built using redundancy and the least absolute shrinkage and selection operator. Then, two deep learning frameworks were developed: the Multi-Modal MR Images Convolutional Neural Network (MM-Net), which does not consider prior radiological features, and PCMM-Net, which incorporates multiparameter MRI and prior clinical knowledge. Receiver operating characteristic curves were used, and the corresponding areas under the curves (AUCs) were calculated for evaluation. RESULTS: PCMM-Net achieved the highest AUC of 0.843. The clinico-radiological features displayed the lowest AUC value of 0.743, followed by MM-Net with an AUC of 0.774, and radiomics with an AUC of 0.795. CONCLUSIONS: This study introduces PCMM-Net, an innovative deep learning framework that integrates prior clinico-radiological features for accurate LVI prediction in breast cancer. PCMM-Net demonstrates excellent diagnostic performance and facilitates the application of precision medicine.

Body composition and inflammation variables as the potential prognostic factors in epithelial ovarian cancer treated with Olaparib.

Background: Epithelial ovarian cancer (EOC) is a significant cause of mortality among gynecological cancers. While Olaparib, a PARP inhibitor, has demonstrated efficacy in EOC maintenance therapy, individual responses vary. This study aims to assess the prognostic significance of body composition and systemic inflammation markers in EOC patients undergoing initial Olaparib treatment. Methods: A retrospective analysis was conducted on 133 EOC patients initiating Olaparib therapy. Progression-free survival (PFS) was assessed through Kaplan-Meier analysis and Cox proportional hazards regression. Pre-treatment computed tomography images were utilized to evaluate body composition parameters including subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), skeletal muscle area index (SMI), and body mineral density (BMD). Inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), serum albumin, and hemoglobin levels, were also measured. Results: The median follow-up duration was 16 months (range: 5-49 months). Survival analysis indicated that high SATI, high VATI, high SMI, high BMD, low NLR, and low PLR were associated with decreased risk of disease progression (all p < 0.05). Multivariate analysis identified several factors independently associated with poor PFS, including second or further lines of therapy (HR = 2.16; 95% CI = 1.09-4.27, p = 0.027), low VATI (HR = 3.79; 95% CI = 1.48-9.70, p = 0.005), low SMI (HR = 2.52; 95% CI = 1.11-5.72, p = 0.027), low BMD (HR = 2.36; 95% CI = 1.22-4.54, p = 0.010), and high NLR (HR = 0.31; 95% CI = 0.14-0.69, p = 0.004). Subgroup analysis in serous adenocarcinoma patients revealed distinct prognostic capabilities of SATI, VATI, SMI, PLR, and NLR. Conclusion: Body composition and inflammation variables hold promise as predictors of therapeutic response to Olaparib in EOC patients. Understanding their prognostic significance could facilitate tailored treatment strategies, potentially improving patient outcomes.

Progesterone Enhances Niraparib Efficacy in Ovarian Cancer by Promoting Palmitoleic-Acid-Mediated Ferroptosis.

Poly (adenosine 5'-diphosphate-ribose) polymerase inhibitors (PARPi) are increasingly important in the treatment of ovarian cancer. However, more than 40% of BRCA1/2-deficient patients do not respond to PARPi, and BRCA wild-type cases do not show obvious benefit. In this study, we demonstrated that progesterone acted synergistically with niraparib in ovarian cancer cells by enhancing niraparib-mediated DNA damage and death regardless of BRCA status. This synergy was validated in an ovarian cancer organoid model and in vivo experiments. Furthermore, we found that progesterone enhances the activity of niraparib in ovarian cancer through inducing ferroptosis by up-regulating palmitoleic acid and causing mitochondrial damage. In clinical cohort, it was observed that progesterone prolonged the survival of patients with ovarian cancer receiving PARPi as second-line maintenance therapy, and high progesterone receptor expression combined with low glutathione peroxidase 4 (GPX4) expression predicted better efficacy of PARPi in patients with ovarian cancer. These findings not only offer new therapeutic strategies for PARPi poor response ovarian cancer but also provide potential molecular markers for predicting the PARPi efficacy.

Clinical characteristics and risk factors in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases.

Objective: To investigate the clinical characteristics and risk factors of patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. Methods: A retrospective analysis of general clinical data was conducted on patients with SARS-CoV-2 omicron infection complicated with hypertension, coronary heart disease, and heart failure admitted to one hospital in Guangdong Province from December 1, 2022, to February 28, 2023. Clinical symptoms, laboratory tests, imaging examinations, treatment, and clinical outcomes were collected. Multivariate logistic regression analysis was used to analyze the risk factors for mortality in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. ROC curves were drawn to evaluate the predictive value of CRP, D-dimer, and CK-MB in predicting the risk of death. Results: A total of 364 confirmed cases were included, divided into the asymptomatic group, mild to moderate group, and severe to critically ill group based on the symptoms of COVID-19. There were 216 males (59.34%) and 148 females (40.66%), with a median age of 75 years. The differences between the three groups in terms of sex and age were statistically significant (p < 0.05). The top three underlying diseases were hypertension (288 cases, 79.12%), coronary heart disease (100 cases, 27.47%), and diabetes (84 cases, 23.08%). The differences in unvaccinated and triple-vaccinated patients among the three groups were statistically significant (p < 0.05). The common respiratory symptoms were cough in 237 cases (65.11%) and sputum production in 199 cases (54.67%). In terms of laboratory tests, there were statistically significant differences in neutrophils, lymphocytes, red blood cells, C-reactive protein, D-dimer, aspartate aminotransferase, and creatinine among the three groups (p < 0.05). In imaging examinations, there were statistically significant differences among the three groups in terms of unilateral pulmonary inflammation, bilateral pulmonary inflammation, and bilateral pleural effusion (p < 0.05). There were statistically significant differences among the three groups in terms of antibiotic treatment, steroid treatment, oxygen therapy, nasal cannula oxygen inhalation therapy, non-invasive ventilation, and tracheal intubation ventilation (p < 0.05). Regarding clinical outcomes, there were statistically significant differences among the three groups in terms of mortality (p < 0.05). Multivariate logistic regression analysis showed that CRP (OR = 1.012, 95% CI = 1.004-1.019) and D-dimer (OR = 1.117, 95% CI = 1.021-1.224) were independent risk factors for patient mortality. The predictive value of CRP, D-dimer, and CK-MB for the risk of death was assessed. D-dimer had the highest sensitivity (95.8%) in predicting patient mortality risk, while CRP had the highest specificity (84.4%). Conclusion: For patients with COVID-19 and concomitant cardiovascular diseases without contraindications, early administration of COVID-19 vaccines and booster shots can effectively reduce the mortality rate of severe cases. Monitoring biomarkers such as CRP, D-dimer, and CK-MB and promptly providing appropriate care can help mitigate the risk of mortality in patients.

Optimization of global DNA methylation measurement by LC-MS/MS and its application in lung cancer patients.

Global analyses of DNA methylation contribute important insights into biology and the wide-ranging role of DNA methylation. We describe the use of online solid-phase extraction and isotope-dilution liquid chromatography/tandem mass spectrometry (LC-MS/MS) for the simultaneous measurement of 5-methyl-2'-deoxycytidine (5-medC) and 2'-deoxycytidine (dC) in DNA. With the incorporation of isotope internal standards and online enrichment techniques, the detection limit of this method was estimated to be as low as 0.065 pg which enables human global DNA methylation detection using only picogram amounts of DNA. This method was applied to assess the optimal amounts of enzymes required for DNA digestion regarding an accurate global DNA methylation determination and completeness of digestion and to determine global methylation in human tumor adjacent lung tissue of 79 lung cancer patients. We further determined methylated (N7-methylguanine (N7-meG), O (6)-methylguanine (O (6)-meG), and N3-methyladenine (N3-meA)) and oxidized DNA lesions (8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)) in lung cancer patients by LC-MS/MS. Optimization experiments revealed that dC was liberated from DNA much more readily than 5-medC by nuclease P1 and alkaline phosphatase (AP) in DNA, which could lead to an error in the global DNA methylation measurement following digestion with insufficient enzymes. Nuclease P1 showed more differential activity for 5-medC and dC than AP. Global DNA methylation levels in adenocarcinoma and squamous cell carcinoma patients were similar in the range of 3.16-4.01 %. Global DNA methylation levels were not affected by smoking and gender and were not correlated with N7-meG or 8-oxodG in lung cancer patients. Levels of O (6)-meG and N3-meA were however found to be undetectable in all lung tissue samples.

A novel immune-related model to predict prognosis and responsiveness to checkpoint and angiogenesis blockade therapy in advanced renal cancer.

Background: Immune checkpoint blockade (ICB) and anti-angiogenic drug combination has prolonged the survival of patients with advanced renal cell carcinoma (RCC). However, not all patients receive clinical benefits from this intervention. In this study, we aimed to establish a promising immune-related prognostic model to stratify the patients responding to ICB and anti-angiogenic drug combination and facilitate the development of personalized therapies for patients with RCC. Materials and methods: Based on clinical annotations and RNA-sequencing (RNA-seq) data of 407 patients with advanced RCC from the IMmotion151 cohort, nine immune-associated differentially expressed genes (DEGs) between responders and non-responders to atezolizumab (anti-programmed death-ligand 1 antibody) plus bevacizumab (anti-vascular endothelial growth factor antibody) treatment were identified via weighted gene co-expression network analysis. We also conducted single-sample gene set enrichment analysis to develop a novel immune-related risk score (IRS) model and further estimate the prognosis of patients with RCC by predicting their sensitivity to chemotherapy and responsiveness to immunotherapy. IRS model was further validated using the JAVELIN Renal 101 cohort, the E-MTAB-3218 cohort, the IMvigor210 and GSE78220 cohort. Predictive significance of the IRS model for advanced RCC was assessed using receiver operating characteristic curves. Results: The IRS model was constructed using nine immune-associated DEGs: SPINK5, SEMA3E, ROBO2, BMP5, ORM1, CRP, CTSE, PMCH and CCL3L1. Advanced RCC patients with high IRS had a high risk of undesirable clinical outcomes (hazard ratio = 1.91; 95% confidence interval = 1.43-2.55; P < 0.0001). Transcriptome analysis revealed that the IRS-low group exhibited significantly high expression levels of CD8+ T effectors, antigen-processing machinery, and immune checkpoints, whereas the epithelial-mesenchymal transition pathway was enriched in the IRS-high group. IRS model effectively differentiated the responders from non-responders to ICB combined with angiogenesis blockade therapy or immunotherapy alone, with area under the curve values of 0.822 in the IMmotion151 cohort, 0.751 in the JAVELIN Renal 101 cohort, and 0.776 in the E-MTAB-3218 cohort. Conclusion: IRS model is a reliable and robust immune signature that can be used for patient selection to optimize the efficacy of ICB plus anti-angiogenic drug therapies in patients with advanced RCC.