Imaging-guided companion diagnostics in radiotherapy by monitoring APE1 activity with afterglow and MRI imaging.

Companion diagnostics using biomarkers have gained prominence in guiding radiotherapy. However, biopsy-based techniques fail to account for real-time variations in target response and tumor heterogeneity. Herein, we design an activated afterglow/MRI probe as a companion diagnostics tool for dynamically assessing biomarker apurinic/apyrimidinic endonuclease 1(APE1) during radiotherapy in vivo. We employ ultrabright afterglow nanoparticles and ultrasmall FeMnOx nanoparticles as dual contrast agents, significantly broadening signal change range and enhancing the sensitivity of APE1 imaging (limit of detection: 0.0092 U/mL in afterglow imaging and 0.16 U/mL in MRI). We devise longitudinally and transversely subtraction-enhanced imaging (L&T-SEI) strategy to markedly enhance MRI contrast and signal-to-noise ratio between tumor and normal tissue of living female mice. The combined afterglow and MRI facilitate both anatomical and functional imaging of APE1 activity. This probe enables correlation of afterglow and MRI signals with APE1 expression, radiation dosage, intratumor ROS, and DNA damage, enabling early prediction of radiotherapy outcomes (as early as 3 h), significantly preceding tumor size reduction (6 days). By monitoring APE1 levels, this probe allows for early and sensitive detection of liver organ injury, outperforming histopathological analysis. Furthermore, MRI evaluates APE1 expression in radiation-induced abscopal effects provides insights into underlying mechanisms, and supports the development of treatment protocols.

Enhancing Fractionated Cancer Therapy: A Triple-Anthracene Photosensitizer Unleashes Long-Persistent Photodynamic and Luminous Efficacy.

Conventional photodynamic therapy (PDT) is often limited in treating solid tumors due to hypoxic conditions that impede the generation of reactive oxygen species (ROS), which are critical for therapeutic efficacy. To address this issue, a fractionated PDT protocol has been suggested, wherein light irradiation is administered in stages separated by dark intervals to permit oxygen recovery during these breaks. However, the current photosensitizers used in fractionated PDT are incapable of sustaining ROS production during the dark intervals, leading to suboptimal therapeutic outcomes (Table S1). To circumvent this drawback, we have synthesized a novel photosensitizer based on a triple-anthracene derivative that is designed for prolonged ROS generation, even after the cessation of light exposure. Our study reveals a unique photodynamic action of these derivatives, facilitating the direct and effective disruption of biomolecules and significantly improving the efficacy of fractionated PDT (Table S2). Moreover, the existing photosensitizers lack imaging capabilities for monitoring, which constraints the fine-tuning of irradiation parameters (Table S1). Our triple-anthracene derivative also serves as an afterglow imaging agent, emitting sustained luminescence postirradiation. This imaging function allows for the precise optimization of intervals between PDT sessions and aids in determining the timing for subsequent irradiation, thus enabling meticulous control over therapy parameters. Utilizing our novel triple-anthracene photosensitizer, we have formulated a fractionated PDT regimen that effectively eliminates orthotopic pancreatic tumors. This investigation highlights the promise of employing long-persistent photodynamic activity in advanced fractionated PDT approaches to overcome the current limitations of PDT in solid tumor treatment.

LDCT screening results among eligible and ineligible screening candidates in preventive health check-ups population: a real world study in West China.

To compare the LDCT screening results between eligible and ineligible screening candidates in preventive health check-ups population. Using a real-world LDCT screening results among people who took yearly health check-up in health management center of West China Hospital between 2006 and 2017. Objects were classified according to the China National Lung Cancer Screening Guideline with Low-dose Computed Tomography (2018 version) eligibility criteria. Descriptive analysis were performed between eligible and ineligible screening candidates. The proportion of ineligible screening candidates was 64.13% (10,259), and among them there were 4005 (39.04%) subjects with positive screenings, 80 cases had a surgical lung biopsy. Pathology results from lung biopsy revealed 154 cancers (true-positive) and 26 benign results (false-positive), the surgical false-positive biopsy rate was 4.17%, and ineligible group (7.69%) was higher than eligible group (2.47%), P < 0.05. Further, in ineligible screening candidates, the proportion of current smokers was higher among males compared to females (53.85% vs. 4.88%, P < 0.05). Of the 69 lung cancer patients detected in ineligible screening candidates, lung adenocarcinoma accounts for a high proportion of lung cancers both in male (75.00%) and female (85.00%). The proportion of ineligible screening candidates and the surgical false-positive biopsy rate in ineligible candidates were both high in health check-ups population.

Noninvasive Imaging of Tumor Glycolysis and Chemotherapeutic Resistance via De Novo Design of Molecular Afterglow Scaffold.

Chemotherapeutic resistance poses a significant challenge in cancer treatment, resulting in the reduced efficacy of standard chemotherapeutic agents. Abnormal metabolism, particularly increased anaerobic glycolysis, has been identified as a major contributing factor to chemotherapeutic resistance. To address this issue, noninvasive imaging techniques capable of visualizing tumor glycolysis are crucial. However, the currently available methods (such as PET, MRI, and fluorescence) possess limitations in terms of sensitivity, safety, dynamic imaging capability, and autofluorescence. Here, we present the de novo design of a unique afterglow molecular scaffold based on hemicyanine and rhodamine dyes, which holds promise for low-background optical imaging. In contrast to previous designs, this scaffold exhibits responsive "OFF-ON" afterglow signals through spirocyclization, thus enabling simultaneous control of photodynamic effects and luminescence efficacy. This leads to a larger dynamic range, broader detection range, higher signal enhancement ratio, and higher sensitivity. Furthermore, the integration of multiple functionalities simplifies probe design, eliminates the need for spectral overlap, and enhances reliability. Moreover, we have expanded the applications of this afterglow molecular scaffold by developing various probes for different molecular targets. Notably, we developed a water-soluble pH-responsive afterglow nanoprobe for visualizing glycolysis in living mice. This nanoprobe monitors the effects of glycolytic inhibitors or oxidative phosphorylation inhibitors on tumor glycolysis, providing a valuable tool for evaluating the tumor cell sensitivity to these inhibitors. Therefore, the new afterglow molecular scaffold presents a promising approach for understanding tumor metabolism, monitoring chemotherapeutic resistance, and guiding precision medicine in the future.

Emerging biomedical imaging-based companion diagnostics for precision medicine.

The tumor heterogeneity, which leads to individual variations in tumor microenvironments, causes poor prognoses and limits therapeutic response. Emerging technology such as companion diagnostics (CDx) detects biomarkers and monitors therapeutic responses, allowing identification of patients who would benefit most from treatment. However, currently, most US Food and Drug Administration-approved CDx tests are designed to detect biomarkers in vitro and ex vivo, making it difficult to dynamically report variations of targets in vivo. Various medical imaging techniques offer dynamic measurement of tumor heterogeneity and treatment response, complementing CDx tests. Imaging-based companion diagnostics allow for patient stratification for targeted medicines and identification of patient populations benefiting from alternative therapeutic methods. This review summarizes recent developments in molecular imaging for predicting and assessing responses to cancer therapies, as well as the various biomarkers used in imaging-based CDx tests. We hope this review provides informative insights into imaging-based companion diagnostics and advances precision medicine.

Organic Afterglow Nanoparticles in Bioapplications.

Organic afterglow nanoparticles are unique optical materials that emit light long after cessation of excitation. Due to their advantages of no need for real-time light excitation, avoiding autofluorescence, low imaging background, high signal-to-background ratio, deep tissue penetration, and high sensitivity, afterglow imaging technology has been widely used in cell tracking, biosensing, cancer diagnosis, and cancer therapy, which provides an effective technical method for the acquisition of molecular information with high sensitivity, specificity and real-time at the cellular and living level. In this review, we summarize and illustrate the recent progress of organic afterglow imaging, focusing on the mechanism of organic afterglow materials and their biological application. Furthermore, we also discuss the potential challenges and the further directions of this field.

The rational design of nanozymes for imaging-monitored cancer therapy.

Nanozymes are nanoscale materials that display enzyme-like properties, which have been improved to eliminate the limitations of natural enzymes and further broaden the use of conventional artificial enzymes. In the last decade, the research and exploration of nanozymes have attracted considerable attention in the chemical and biological fields, especially in the fields of biomedicine and tumor therapy. To date, plenty of nanozymes have been developed with the single or multiple activities of natural enzymes, including peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), glucose oxidase (GOx). Tumor-characteristic metabolites can be transformed into toxic substances under the catalysis of nanozymes to kill tumor cells. However, the therapeutic effects of nanozymes greatly depend on their catalytic activity, which displays a lot of differences in vitro and in vivo. Moreover, the complex tumor environment (low pH, high H2O2 and GSH concentration, hypoxia, etc.) plays an important role in affecting their catalytic activity. Besides, the uncontrollable catalysis of nanozymes may lead to the destruction of normal tissues. To solve these problems, researchers have exploited several imaging methods to monitor the reaction processes during catalysis, including optical imaging methods (fluorescence and chemiluminescence), photoacoustic imaging, and magnetic resonance imaging. In this review, we have summarized the development of tumor treatment using nanozymes in recent years, along with the current imaging tools to monitor the catalyzing activity of nanozymes. Representative examples have been elaborated on to show the current development of these imaging tools. We hope this review will provide some instructive perspectives on the development of nanozymes and promote the applications of imaging-guided tumor therapeutics.

Semiconducting Polymer Nanoparticles-Manganese Based Chemiluminescent Platform for Determining Total Antioxidant Capacity in Diabetic Mice.

The total antioxidant capacity (TAC) is a key indicator of the body's resistance to oxidative stress injury in diabetic patients. The measurement of TAC is important for effectively evaluating the redox state to prevent and control the occurrence of diabetes complications. However, there is a lack of a simple, convenient, and reliable method to detect the total antioxidant capacity in diabetes. Herein, we design a novel chemiluminescent platform based on semiconducting polymer nanoparticles-manganese (SPNs-MnVII) to detect the total antioxidant capacity of urine in diabetic mice. We synthesize semiconducting polymer nanoparticles with four different structures and discover the ability of MnVII to produce singlet oxygen (1O2) that is employed to excite thiophene-based SPNs (PFODBT) to emit near-infrared chemiluminescence. Notably, the chemiluminescent intensity has a good linear relationship with the concentration of MnVII (detection limit: 2.8 µM). Because antioxidants (e.g., glutathione or ascorbic acid) can react with MnVII, such a chemiluminescent tool of SPNs (PFODBT)-MnVII can detect the glutathione or ascorbic acid with a larger responsive range. Furthermore, the total antioxidant capacity of urine from mice is evaluated via SPNs (PFODBT)-MnVII, and there are statistically significant differences between diabetic and healthy mice. Thus, this new chemiluminescent platform of SPNs (PFODBT)-MnVII is convenient, efficient, and sensitive, which is promising for monitoring antioxidant therapy of diabetes.

Zinc-Carnosine Metallodrug Network as Dual Metabolism Inhibitor Overcoming Metabolic Reprogramming for Efficient Cancer Therapy.

The targeting of tumor metabolism as a novel strategy for cancer therapy has attracted tremendous attention. Herein, we develop a dual metabolism inhibitor, Zn-carnosine metallodrug network nanoparticles (Zn-Car MNs), which exhibits good Cu-depletion and Cu-responsive drug release, causing potent inhibition of both OXPHOS and glycolysis. Notably, Zn-Car MNs can decrease the activity of cytochrome c oxidase and the content of NAD+, so as to reduce ATP production in cancer cells. Thereby, energy deprivation, together with the depolarized mitochondrial membrane potential and increased oxidative stress, results in apoptosis of cancer cells. In result, Zn-Car MNs exerted more efficient metabolism-targeted therapy than the classic copper chelator, tetrathiomolybdate (TM), in both breast cancer (sensitive to copper depletion) and colon cancer (less sensitive to copper depletion) models. The efficacy and therapy of Zn-Car MNs suggest the possibility to overcome the drug resistance caused by metabolic reprogramming in tumors and has potential clinical relevance.

Prediction Models for Sleep Quality Among College Students During the COVID-19 Outbreak: Cross-sectional Study Based on the Internet New Media.

BACKGROUND: COVID-19 has been reported to affect the sleep quality of Chinese residents; however, the epidemic's effects on the sleep quality of college students during closed-loop management remain unclear, and a screening tool is lacking. OBJECTIVE: This study aimed to understand the sleep quality of college students in Fujian Province during the epidemic and determine sensitive variables, in order to develop an efficient prediction model for the early screening of sleep problems in college students. METHODS: From April 5 to 16, 2022, a cross-sectional internet-based survey was conducted. The Pittsburgh Sleep Quality Index (PSQI) scale, a self-designed general data questionnaire, and the sleep quality influencing factor questionnaire were used to understand the sleep quality of respondents in the previous month. A chi-square test and a multivariate unconditioned logistic regression analysis were performed, and influencing factors obtained were applied to develop prediction models. The data were divided into a training-testing set (n=14,451, 70%) and an independent validation set (n=6194, 30%) by stratified sampling. Four models using logistic regression, an artificial neural network, random forest, and naïve Bayes were developed and validated. RESULTS: In total, 20,645 subjects were included in this survey, with a mean global PSQI score of 6.02 (SD 3.112). The sleep disturbance rate was 28.9% (n=5972, defined as a global PSQI score >7 points). A total of 11 variables related to sleep quality were taken as parameters of the prediction models, including age, gender, residence, specialty, respiratory history, coffee consumption, stay up, long hours on the internet, sudden changes, fears of infection, and impatient closed-loop management. Among the generated models, the artificial neural network model proved to be the best, with an area under curve, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 0.713, 73.52%, 25.51%, 92.58%, 57.71%, and 75.79%, respectively. It is noteworthy that the logistic regression, random forest, and naive Bayes models achieved high specificities of 94.41%, 94.77%, and 86.40%, respectively. CONCLUSIONS: The COVID-19 containment measures affected the sleep quality of college students on multiple levels, indicating that it is desiderate to provide targeted university management and social support. The artificial neural network model has presented excellent predictive efficiency and is favorable for implementing measures earlier in order to improve present conditions.

Concomitant Diseases and Co-contribution on Progression of Liver Stiffness in Patients with Hepatitis B Virus Infection.

BACKGROUND: The association between hepatitis B and concomitant diseases, such as fatty liver, T2DM, MetS, and Hp infection, remains unclear. AIM: The present study was to illustrate the association and explore the co-contribution on abnormal transaminase and progression of liver stiffness. METHODS: A total of 95,998 participants underwent HBsAg screening in West China Hospital from 2014 to 2017. Multivariable logistic regression was used to determine the adjusted odds ratios. RESULTS: The prevalence of HBsAg-positive rate was 8.30% of our included study population. HBsAg positive was associated with negative risk of fatty liver (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.65-0.78, p < 0.001) and MetS (OR 0.74, 95% CI 0.67-0.84, p < 0.001), and with positive risk of Hp infection (OR 1.09, 95% CI 1.02-1.17, p = 0.012) and T2DM (OR 1.18, 95% CI 1.01-1.40, p = 0.043). Besides, HBsAg-positive patients with T2DM had higher risk of elevated ALT (OR 2.09, 95% CI 1.69-2.83, p < 0.001 vs OR 1.59, 95% CI 1.51-1.68, p < 0.001), AST (OR 2.69, 95% CI 1.98-3.65, p < 0.001 vs OR 1.89, 95% CI 1.76-2.02, p < 0.001) than HBV alone. In addition to HBV, T2DM also can increase the risk of liver fibrosis (OR 3.23, 95% CI 1.35-7.71, p = 0.008) and cirrhosis (OR 4.31, 95% CI 1.41-13.20, p = 0.010). CONCLUSION: Hepatitis B patients have a lower risk of fatty liver and MetS, and a higher risk of T2DM and Hp infection. Besides, T2DM might be possibly associated with abnormal liver transaminase and fibrosis progression in HBsAg-positive patients.

Precisely controlling the cellular internalization of DNA-decorated semiconductor polymer nanoparticles for drug delivery.

Nonspecific adhesivity of nanoparticles to cells is regarded as a significant issue of nanomedicine, which brings about many serious drawbacks in applications, including low detection sensitivity, non-targeted biotoxicity and poor diagnostic accuracy. Here, we propose for the first time, DNA-decorated semiconductor polymer nanoparticles (SPN-DNAs), whose adhesivity can be significantly alleviated by controlling the density and thickness of DNA layers. This property is demonstrated to be independent of external conditions such as temperature, concentration, incubation time, ionic strength and cell lines. The mechanism of this phenomenon is also discussed. Finally, based on minimized nonspecific adhesivity to cells, a triggered nanoswitch can be constructed to control cellular internalization and drug delivery.

A novel afterglow nanoreporter for monitoring cancer therapy.

Rationale: Immunogenic cell death (ICD)-associated immunogenicity evoked through reactive oxygen species (ROS) is an efficient way to fight against the immune-dysfunctional microenvironment, so as to provoke potent anti-tumor immunity. However, the unknown ROS dose during cancer therapies may induce adverse immune responses (e.g., insufficient ICD, toxicity toward normal tissues or immune system). Methods: Herein, we developed a pyrido pyrazine - thiophene based semiconducting polymer as novel near-infrared (NIR) organic afterglow nanoparticles for the real-time visualization of self-generated ROS, during photodynamic-mediated immunogenic cell death. Specifically, we introduced the strong "acceptor" (pyrido pyrazine) into thiophene based semiconducting polymer to redshift emission wavelength, and further modulate the "donor" to afford more afterglow reaction sites and reducing ΔEst, so as to enhance luminescence intensity. Results: The semiconducting polymer-based afterglow nanoparticles exhibit strong afterglow emission with longer-wavelength emission (> 800 nm), compared with the reported organic afterglow nanoparticles (e.g., MEHPPV, PFODBT or Chlorin, < 690 nm), which endows this afterglow nanoparticles with a greatly improvement of signal to noise ratio. Moreover, the photodynamic effect of this afterglow nanoparticles can induce immunogenic cell death of cancer cells and further cause immune responses in mice. Conclusions: The NIR afterglow signal presents a good relationship with ROS generation, immunogenic cell death and outcome of treatment. Therefore, it was able to provide a non-invasive tool for predicting the degree of ICD that occurs during ROS-mediated cancer therapy and may contribute to precise immunotherapy.

Overcoming Hypoxia-Induced Ferroptosis Resistance via a 19 F/1 H-MRI Traceable Core-Shell Nanostructure.

Lipid peroxides accumulation induced ferroptosis is an effective cell death pathway for cancer therapy. However, the hypoxic condition of tumor microenvironment significantly suppresses the efficacy of ferroptosis. Here, we design a novel nanoplatform to overcome hypoxia-induced ferroptosis resistance. Specifically, we synthesize a novel kind of perfluorocarbon (PFOB)@manganese oxide (MnOx) core-shell nanoparticles (PM-CS NPs). Owing to the good carrier of O2 as fuel, PM-CS NPs can induce higher level of ROS generation, lipid peroxidation and GSH depletion, as well as lower activity of GPX4, compared with MnOx NPs alone. Moreover, the supplement of O2 can relieve tumor hypoxia to break down the storage of intracellular lipid droplets and increase expression of ACSL4 (a symbol for ferroptosis sensitivity). Furthermore, upon stimulus of GSH or acidity, PM-CS NPs exhibit the "turn on" 19 F-MRI signal and activatable T1 /T2 -MRI contrast for correlating with the release of Mn. Finally, PM-CS NPs exert high cancer inhibition rate for ferroptosis based therapy via synergetic combination of O2 -mediated enhancement of key pathways of ferroptosis.

Association of serum pepsinogens and gastrin-17 with Helicobacter pylori infection assessed by urea breath test.

Background: Association of gastric atrophy or cancer with levels of serum pepsinogens, gastrin-17 and anti-Helicobacter pylori IgG antibody have been extensively studied. However, the association of serum pepsinogen and gastrin-17 with H. pylori infection has not been studied in a large population. Aim: To investigate the impact of H. pylori infection on serum levels of pepsinogens and gastrin-17. Methods: A total of 354, 972 subjects who underwent health check-ups were included. Serum levels of pepsinogens and gastrin-17 were measured using the enzyme-linked immunosorbent assay. H. pylori infection was detected using 14C-urea breath test (UBT). Multivariable logistic regression analysis was used to investigate the association of serum pepsinogen and gastrin-17 with H. pylori infection. Results: H. pylori prevalence was 33.18% in this study. The mean levels of pepsinogens and gastrin-17 were higher, while the mean pepsinogen-I/II ratio were lower among H. pylori-positive than -negative subjects. In H. pylori-positive subjects, pepsinogen and gastrin-17 levels correlated positively, whereas the pepsinogen-I/II ratio correlated negatively with UBT values (e.g., the mean serum level of pepsinogen-I in subjects with UBT values in the range of 100-499dpm, 500-1499dpm, and ≥1500dpm was 94.77 ± 38.99, 102.77 ± 43.59, and 111.53 ± 47.47 ng/mL, respectively). Compared with H. pylori-negative subjects, the adjusted odds ratio (aOR) of having pepsinogen-I ≤ 70 ng/mL in the three H. pylori-positive but with different UBT value groups was 0.31 (p<0.001), 0.16 (p<0.001), and 0.08 (p<0.001), respectively; while the aOR of having G-17>5.70 pmol/L was 4.56 (p<0.001), 7.43 (p<0.001), and 7.12 (p<0.001). This suggested that H. pylori-positive subjects with higher UBT values were less likely to have pepsinogen-I ≤70 ng/mL (a serum marker for gastric atrophy), but more likely to have gastrin-17 >5.70 pmol/L (a marker for peptic ulcer). Conclusions: H. pylori-positive subjects with higher UBT values are unlikely to have gastric atrophy, but may have greater risk of severe gastritis or peptic ulcers. Our study suggests that H. pylori-positive patients with high UBT values may benefit the most from H. pylori eradication.

Metal-fluorouracil networks with disruption of mitochondrion enhanced ferroptosis for synergistic immune activation.

Rationale: Ferroptosis drugs inducing cancer immunogenic cell death (ICD) have shown the potential of immunotherapy in vivo. However, the current ferroptosis drugs usually induce the insufficient immune response because of the low ROS generation efficiency. Methods: Herein, we design zinc-fluorouracil metallodrug networks (Zn-Fu MNs), by coordinating Zn and Fu via facile one-pot preparation, to inactivate mitochondrial electron transport for enhanced ROS production and immune activation. Results: Zn-Fu MNs can be responsive toward acidity and adenosine triphosphate (ATP) with the release of Fu and Zn2+, during which Zn2+ can induce mitochondrion disruption to produce ROS, resulting in ferroptosis of cancer cells and 5-Fu interferes with DNA synthesis in nuclei with 19F-MRI signal to be switched on for correlating drug release. With the synergistic effect of DNA damage and ferroptosis, the cancer cells are forced to promote ICD. Thereby, Zn-Fu MNs exhibit the excellent immune response without any other antigens loading. As a result, the infiltration of T cells within tumor and activation of immune cells in spleen have been greatly enhanced. Conclusions: Combined DNA damage and ferroptosis, Zn-Fu MNs induce the violent emission of tumor associated antigens within cancer cells which will sensitize naive dendritic cells and promote the activation and recruitment of cytotoxic T lymphocytes to exterminate cancer cells. Therefore, the obtained Zn-Fu MNs as ferroptosis inducers can effectively remodel immunosuppressive tumor microenvironment and activate antitumor immune reaction.

Ternary Alloy PtWMn as a Mn Nanoreservoir for High-Field MRI Monitoring and Highly Selective Ferroptosis Therapy.

Ferroptosis exhibits potential to damage drug-resistant cancer cells. However, it is still restricted with the "off-target" toxicity from the undesirable leakage of metal ions from ferroptosis agents, and the lack of reliable imaging for monitoring the ferroptosis process in living systems. Herein, we develop a novel ternary alloy PtWMn nanocube as a Mn reservoir, and further design a microenvironment-triggered nanoplatform that can accurately release Mn ions within the tumor to increase reactive oxygen species (ROS) generation, produce O2 and consume excess glutathione for synergistically enhancing nonferrous ferroptosis. Moreover, this nanoplatform exerts a responsive signal in high-field magnetic resonance imaging (MRI), which enables the real-time report of Mn release and the monitoring of ferroptosis initiation through the signal changes of T1 -/T2 -MRI. Thus, our nanoplatform provides a novel strategy to store, deliver and precisely release Mn ions for MRI-guided high-specificity ferroptosis therapy.

Elevated thyroid-stimulating hormone levels are associated with poor sleep: a cross-sectional and longitudinal study.

PURPOSE: Poor sleep accompanied by elevated TSH (thyroid stimulating hormone) levels is not uncommon since TSH secretion is controlled by the circadian rhythm. However, the relationship between poor sleep and TSH elevation is unclear; hence, we aimed to elucidate this relationship by conducting a cross-sectional and longitudinal study. METHODS: Participants with isolated elevated (N = 168) and normal (N = 119) TSH concentrations were recruited, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess the sleep status. Subjects with an isolated TSH elevation were followed up longitudinally. The serum TSH concentration was remeasured after sleep status improved. RESULTS: The proportions of poor sleep and occasional poor sleep in subjects with isolated TSH elevation were significantly higher than those with normal TSH levels (70.24% vs. 49.58%, p = 0.001; 9.52% vs. 1.68%, p = 0.006). Subjects with isolated TSH elevation had significantly higher PSQI scores in the subjective sleep quality, sleep latency, sleep duration, and habitual sleep efficiency dimensions than those with normal TSH levels (all p < 0.05). Poor sleep was significantly associated with isolated TSH elevation in the multiple logistic regression analysis [odds ratio (OR) = 2.396, p = 0.001]. Among subjects with an isolated TSH elevation at baseline, the percentage of TSH normalization was significantly higher in those who slept better than in those who still slept poorly (85.42% vs. 6.45%, p < 0.001). CONCLUSIONS: This study revealed that isolated elevated TSH concentrations normalize when the sleep status is improved; hence, we recommend that clinicians thoroughly assess the sleep status of patients and remeasure TSH concentrations after sleep status improves.

Abnormal transaminase and lipid profiles in coexisting diseases in patients with fatty liver: a population study in Sichuan.

Among chronic liver diseases, fatty liver has the highest incidence worldwide. Coexistence of fatty liver and other chronic diseases, such as diabetes, hepatitis B virus (HBV) and Helicobacter pylori (Hp) infection, is common in clinical practice. The present study was conducted to analyze the prevalence and association of coexisting diseases in patients with fatty liver and to investigate how coexisting diseases contribute to abnormal transaminase and lipid profiles. We enrolled participants who were diagnosed with fatty liver via ultrasound in the physical examination center of West China Hospital. Multivariable logistic regression was used to determine the adjusted odds ratios (ORs). We found that 23.6% of patients who underwent physical examinations were diagnosed with fatty liver. These patients had higher risks of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and hypertension and a lower risk of HBV infection. The risks of Hp infection and hyperthyroidism did not statistically differ. When fatty liver coexisted with T2DM, MetS and thyroid dysfunction, it conferred a higher risk of elevated transaminase. Fatty liver was positively correlated with triglycerides, cholesterol and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with HBV; thus, HBV had a neutralizing effect on lipid metabolism when coexisting with fatty liver. In conclusion, patients with fatty liver that coexists with T2DM, MetS and thyroid dysfunction are more prone to elevated transaminase levels. Patients with both fatty liver and HBV may experience a neutralizing effect on their lipid metabolism. Thus, lipid alterations should be monitored in these patients during antiviral treatment for HBV.

Two-dimensional intermetallic PtBi/Pt core/shell nanoplates overcome tumor hypoxia for enhanced cancer therapy.

The design of multifunctional nanoplatforms is of great importance for improving hypoxia-induced therapeutic outcomes, especially for overcoming radiotherapy (RT) tolerance. Here, two-dimensional intermetallic PtBi/Pt nanoplates (PtBi NPs) were designed as a therapeutic platform to in situ generate oxygen, and thereby overcome tumor hypoxia for boosting photothermal/radiotherapy (PTT/RT). With high X-ray attenuation coefficient, PtBi NPs exhibited outstanding radiotherapy sensitization characteristics. Moreover, the high photothermal effect of PtBi NPs could promote the catalytic activity of PtBi NPs to achieve a synergistic PTT/RT effect. PEGylated PtBi NPs (PtBi-PEG) exhibited excellent biocompatibility, prolonged blood circulation time and enhanced tumor accumulation. Finally, PtBi-PEG showed excellent trimodal contrast enhancement for infrared (IR) imaging, photoacoustic (PA) imaging and X-ray imaging, facilitating imaging-guided cancer therapy. Thus, our work highlights PtBi-PEG as a novel multifunctional theranostic nanoplatform with great potential for future multimodal imaging-guided synergistic cancer therapy.