PTSD prevalence and factors in intern nursing students after COVID-19 full liberalization in China: a cross-sectional study.

Objective: This study aimed to assess the prevalence of post-traumatic stress disorder (PTSD) and its influencing factors among intern nursing students after the full liberalization of the COVID-19 prevention and control policy in China. Methods: Participants completed the online survey from January 14 to January 19, 2023. A demographic questionnaire, COVID-19 and internship-related questionnaire, the Fear of COVID-19 scale, the Primary Care PTSD Screen, and the Connor-Davidson Resilience Scale were used to conduct the online survey. Results: Of 438 participants, 88.4% tested positive for COVID-19 in the last 6 months. The prevalence of fear, resilience, and PTSD was 16.9, 15.5, and 11.2%, respectively. Direct care of COVID patients in hospital (OR = 2.084, 95%CI 1.034 ~ 4.202), the experience of occupational exposure (OR = 2.856, 95%CI 1.436 ~ 5.681), working with an experienced team (OR = 2.120, 95%CI 1.070 ~ 4.198), and fear COVID-19 (OR = 8.269, 95%CI 4.150 ~ 16.479) were significantly and positively associated with PTSD in nursing internship students. Conclusion: After COVID-19 full liberalization in China, intern nursing students still experienced pandemic-related mental distress, which can bring PTSD. Adequate support and counseling should be provided, as needed, to intern nursing students who are about to enter the workforce and have experienced severe PTSD symptoms related to COVID-19. Our findings indicated that should understand the importance of screening, formulate intervention strategies and preventive measures to address psychosocial problems, and provide coping skills training to intern nursing students.

Long non-coding RNA LIP interacts with PARP-1 influencing the efficiency of base excision repair.

In recent years, various long non-coding RNAs (lncRNAs) involved in DNA damage response (DDR) have been identified and studied to deepen our understanding. However, there are rare reports on the association between lncRNAs and base excision repair (BER). Our designed DNA microarray identified dozens of functionally unknown lncRNAs, and their transcription levels significantly increased upon exposure to DNA damage inducers. One of them, named LIP (Long noncoding RNA Interacts with PARP-1), exhibited a significant alteration in transcription in response to methyl methanesulfonate (MMS) and temozolomide (TMZ) treatments. LIP knockdown or knockout cell lines are sensitive to MMS and TMZ, indicating that LIP plays a crucial role in DDR. The loss or insufficiency of LIP significantly influences the efficiency of BER in human cells, and it suggests that LIP participates in the BER pathway. The interaction between LIP and a key factor in BER, poly (ADP-ribose) polymerase 1 (PARP-1), has been confirmed. We identified and characterized LIP, a lncRNA, which is involved in DDR, significantly influences BER efficiency, and interacts with the BER key factor PARP-1. This advances our understanding of the connection between lncRNAs and BER, presenting the potential for the discovery of new drug targets.

Injectable Nanocomposite Immune Hydrogel Dressings: Prevention of Tumor Recurrence and Anti-Infection after Melanoma Resection.

Complex wound repair due to tumor recurrence and infection following tumor resection presents significant clinical challenges. In this study, a bifunctional nanocomposite immune hydrogel dressing, SerMA-LJC, is developed to address the issues associated with repairing infected damaged tissues and preventing tumor recurrence. Specifically, the immune dressing is composed of methacrylic anhydride-modified sericin (SerMA) and self-assembled nanoparticles (LJC) containing lonidamine (Lon), JQ1, and chlorine e6 (Ce6). In vitro and in vivo experiments demonstrate that the nanocomposite hydrogel dressing can trigger immunogenic cell death (ICD) and has a potent anti-tumor effect. Moreover, this dressing can mitigate the acidic microenvironment of tumor cells and suppress the overexpression of PD-L1 on the tumor cell surface, thereby altering the immunosuppressive tumor microenvironment and augmenting the anti-tumor immune response. Further, the RNA sequencing analysis revealed that the hydrogel dressing significantly impacts pathways associated with positive regulation of immune response, apoptotic process, and other relevant pathways, thus triggering a potent anti-tumor immune response. More importantly, the dressing generates a substantial amount of reactive oxygen species (ROS), which can effectively kill Staphylococcus aureus and promote infectious wound healing. In conclusion, this dual-function nanocomposite immune hydrogel dressing exhibits promise in preventing tumor recurrence and promoting infectious wound healing.

Study on the Quality Variation and Internal Mechanisms of Frozen Oatmeal Cooked Noodles during Freeze-Thaw Cycles.

Frozen staple food, attributed to its favorable taste and convenience, has a promising development potential in the future. Frequent freezing and thawing, however, will affect its quality. This study simulated several freeze-thaw cycles (FTC) that may occur during the cold chain process of frozen oatmeal cooked noodles (FOCN) production to consumption. The quality changes and their mechanisms were elucidated using methods such as differential scanning calorimetry (DSC), low-field nuclear magnetic resonance (LF-NMR), Fourier-transform infrared spectroscopy (FTIR), confocal laser scanning microscopy (CLSM), texture analysis, and sensory evaluation. The freezable water content of the FOCN decreased because of the FTC treatment, and the relative content of total water in FOCN also decreased accordingly. The increase in ß-Turn after FTC induced disorder in the secondary structure of proteins, causing the protein microstructure to become loose and discontinuous, which in turn reduced the water-holding capacity of FOCN. Additionally, FTC reduced the chewiness and sensory score of FOCN. This research will contribute a theoretical foundation for optimizing the cold chain process.

An Anti-Oxidative Bioink for Cartilage Tissue Engineering Applications.

Since chondrocytes are highly vulnerable to oxidative stress, an anti-oxidative bioink combined with 3D bioprinting may facilitate its applications in cartilage tissue engineering. We developed an anti-oxidative bioink with methacrylate-modified rutin (RTMA) as an additional bioactive component and glycidyl methacrylate silk fibroin as a biomaterial component. Bioink containing 0% RTMA was used as the control sample. Compared with hydrogel samples produced with the control bioink, solidified anti-oxidative bioinks displayed a similar porous microstructure, which is suitable for cell adhesion and migration, and the transportation of nutrients and wastes. Among photo-cured samples prepared with anti-oxidative bioinks and the control bioink, the sample containing 1 mg/mL of RTMA (RTMA-1) showed good degradation, promising mechanical properties, and the best cytocompatibility, and it was selected for further investigation. Based on the results of 3D bioprinting tests, the RTMA-1 bioink exhibited good printability and high shape fidelity. The results demonstrated that RTMA-1 reduced intracellular oxidative stress in encapsulated chondrocytes under H2O2 stimulation, which results from upregulation of COLII and AGG and downregulation of MMP13 and MMP1. By using in vitro and in vivo tests, our data suggest that the RTMA-1 bioink significantly enhanced the regeneration and maturation of cartilage tissue compared to the control bioink, indicating that this anti-oxidative bioink can be used for 3D bioprinting and cartilage tissue engineering applications in the future.

A novel adjustable PHBV basement film for enhancing the efficacy of glaucoma surgery by inhibiting scar formation.

Trabeculectomy is the primary surgical approach used to treat glaucoma, but scarring of the filtering passage (filtering bleb) after surgery often leads to treatment failure. To address this issue, we have developed a drug release system called RSG/Pd@ZIF-8 PHBV film. This system enables the sustained release of an anti-fibrosis drug, aiming to prevent scarring. In vitro, the film has the function of continuous Rosiglitazone (RSG) release, with accelerated release after laser irradiation. The antibacterial experiments revealed that the film exhibited antibacterial rates of 87.0 % against E.coli and 97.1 % against S.aureus, respectively. Moreover, we confirmed its efficacy in a rabbit eye model undergoing trabeculectomy. After implantation of the film, we observed a prolonged postoperative period for reducing intraocular pressure (IOP), increased survival rate of filtering blebs, and improved long-term surgical outcomes in vivo. Additionally, the film exhibited excellent biosafety. In summary, the designed sustained-release film in this study possesses the aforementioned functionalities, allowing for the regulation of anti-scarring drug release without causing harm post-surgery. This personalized and precise anti-scarring strategy represents a significant advancement.

Natural self-healing injectable hydrogels loaded with exosomes and berberine for infected wound healing.

Complete and rapid healing of infected skin wounds remains a challenge in current clinical treatment. In this study, we prepared a self-healing injectable CK hydrogel by crosslinking two natural polysaccharides, carboxymethyl chitosan and oxidized konjac glucomannan, based on the Schiff base bond. To enhance the biological function of the hydrogel, we multi-functionalized hydrogen by loading it with berberine (BBR) and stem cell-derived exosomes (Exo), forming a composite hydrogel, CK@BBR&Exo, which could be injected directly into the wound through a needle and adhered to the wound. Furthermore, the self-healing properties of CK@BBR&Exo increased its usefulness and service life. Additionally, the drug-loaded CK@BBR&Exo hydrogel was versatile, inhibiting bacterial growth, regulating the inflammatory response, and promoting neovascularization in infected skin wounds, thus achieving the rapid healing of infected skin wounds. These results suggest that the CK@BBR&Exo-injectable self-healing hydrogel is an ideal dressing for treating infected skin wounds.

Tanshinone IIA Facilitates Efficient Cartilage Regeneration under Inflammatory Factors Caused Stress via Upregulating LncRNA NEAT1_2.

(1) Background: Osteoarthritis (OA) is a crippling condition characterized by chondrocyte dedifferentiation, cartilage degradation, and subsequent cartilage defects. Unfortunately, there is a lack of effective medicines to facilitate the repair of cartilage defects in OA patients. In this study, we investigated the role of lncRNA NEAT1_2 in maintaining the chondrocyte phenotype and identified tanshinone IIA(TAN) as a natural medicine that enhances NEAT1_2 levels, resulting in efficient cartilage regeneration under inflammatory cytokines. (2) Methods: The transcriptional levels of NEAT1_2 and cartilage phenotype-related genes were identified by RT-qPCR. The siRNA interference approach was utilized to silence NEAT1_2; the Alamar Blue assay was performed to determine chondrocyte viability under inflammatory conditions. To evaluate the concentrations of collagen type II and glycosaminoglycans distributed by chondrocytes in vitro and in vivo, immunohistochemical staining and Safranin O staining were used. (3) Results: IL-1ß suppresses NEAT1_2 and genes related to the chondrocytic phenotype, whereas TAN effectively upregulates them in a NEAT1_2-dependent manner. Consistently, TAN alleviated chondrocyte oxidative stress inhibited cartilage degradation by modulating the relevant genes and promoted efficient cartilage regeneration in vitro and in vivo when chondrocytes are exposed to inflammatory cytokines. (4) Conclusions: TAN enhances the expression of NEAT1_2 inhibited by IL-1ß and affects the transcription of chondrocytic phenotype-related genes, which promotes cartilage regeneration in an inflammatory environment.

Molecular underpinnings underlying behaviors changes in the brain of juvenile common carp (Cyrinus carpio) in response to warming.

INTRODUCTION: Global warming is increasing interest in how aquatic animals can adjust their physiological performance and cope with temperature changes. Therefore, understanding the behavioral changes and molecular underpinnings in fish under warming is crucial for both the individual and groups survival. This could provide experimental evidence and resource for evaluating the impact of global warming. OBJECTIVE: Three genetic families of common carp (Cyprinus carpio) were generated. These juveniles were constructed short-term (4 days) and long-term (30 days) warming groups to investigate the effects of warming on behavioral responses and to elucidate the potential underlying mechanisms of warming-driven behavior. METHODS: Behavioral tests were used to explore the effects of short- and long-term exposure to warming on the swimming behavior of C. carpio. Brain transcriptome combined with measurement of nervous system activity was used to further investigated the comprehensive neuromolecular mechanisms under warming. RESULTS: Long-term warming groups had a more significant impact on the decline of swimming behavior in juvenile C. carpio. Furthermore, brain comparative transcriptomic analysis combined with measurement of nervous system activity revealed that genes involved in cytoskeletal organization, mitochondrial regulation, and energy metabolism are major regulators of behavior in the juvenile under warming. Importantly, especially in the long-term warming groups, enrichment analysis of associated gene expression suggested functional alterations of synaptic transmission and signal transduction leading to swimming function impairment in the central nervous system, as revealed by behavioral tests. CONCLUSIONS: Our study provides evidence of the neurogenomic mechanism underlying the decreased swimming activity in juvenile C. carpio under warming. These findings have important implications for understanding the impacts of climate change on aquatic ecosystems and the organisms that inhabit them.

Optimizing Voice Recognition Informatic Robots for Effective Communication in Outpatient Settings.

Aim/Objective Within the dynamic healthcare technology landscape, this research aims to explore patient inquiries within outpatient clinics, elucidating the interplay between technology and healthcare intricacies. Building upon the initial intelligent guidance robot implementation shortcomings, this investigation seeks to enhance informatic robots with voice recognition technology. The objective is to analyze users' vocal patterns, discern age-associated vocal attributes, and facilitate age differentiation through subtle vocal nuances to enhance the efficacy of human-robot communication within outpatient clinical settings. Methods This investigation employs a multi-faceted approach. It leverages voice recognition technology to analyze users' vocal patterns. A diverse dataset of voice samples from various age groups was collected. Acoustic features encompassing pitch, formant frequencies, spectral characteristics, and vocal tract length are extracted from the audio samples. The Mel Filterbank and Mel-Frequency Cepstral Coefficients (MFCCs) are employed for speech and audio processing tasks alongside machine learning algorithms to assess and match vocal patterns to age-related traits. Results The research reveals compelling outcomes. The incorporation of voice recognition technology contributes to a significant improvement in human-robot communication within outpatient clinical settings. Through accurate analysis of vocal patterns and age-related traits, informatic robots can differentiate age through nuanced verbal cues. This augmentation leads to enhanced contextual understanding and tailored responses, significantly advancing the efficiency of patient interactions with the robots. Conclusion Integrating voice recognition technology into informatic robots presents a noteworthy advancement in outpatient clinic settings. By enabling age differentiation through vocal nuances, this augmentation enhances the precision and relevance of responses. The study contributes to the ongoing discourse on the dynamic evolution of healthcare technology, underscoring the complex synergy between technological progression and the intricate realities within healthcare infrastructure. As healthcare continues to metamorphose, the seamless integration of voice recognition technology marks a pivotal stride in optimizing human-robot communication and elevating patient care within outpatient settings.

Spliceosomal protein U2B″ delays leaf senescence by enhancing splicing variant JAZ9ß expression to attenuate jasmonate signaling in Arabidopsis.

The regulatory framework of leaf senescence is gradually becoming clearer; however, the fine regulation of this process remains largely unknown. Here, genetic analysis revealed that U2 small nuclear ribonucleoprotein B (U2B″), a component of the spliceosome, is a negative regulator of leaf senescence. Mutation of U2B″ led to precocious leaf senescence, whereas overexpression of U2B″ extended leaf longevity. Transcriptome analysis revealed that the jasmonic acid (JA) signaling pathway was activated in the u2b″ mutant. U2B″ enhances the generation of splicing variant JASMONATE ZIM-DOMAIN 9ß (JAZ9ß) with an intron retention in the Jas motif, which compromises its interaction with CORONATINE INSENSITIVE1 and thus enhances the stability of JAZ9ß protein. Moreover, JAZ9ß could interact with MYC2 and obstruct its activity, thereby attenuating JA signaling. Correspondingly, overexpression of JAZ9ß rescued the early senescence phenotype of the u2b″ mutant. Furthermore, JA treatment promoted expression of U2B″ that was found to be a direct target of MYC2. Overexpression of MYC2 in the u2b″ mutant resulted in a more pronounced premature senescence than that in wild-type plants. Collectively, our findings reveal that the spliceosomal protein U2B″ fine-tunes leaf senescence by enhancing the expression of JAZ9ß and thereby attenuating JA signaling.

Berberine oleanolic acid complex salt grafted hyaluronic acid/silk fibroin (BOA-g-HA/SF) composite scaffold promotes cartilage tissue regeneration under IL-1ß caused stress.

Since inflammatory cytokines cause stress to chondrocytes and the failure of cartilage defects repair with cartilage tissue engineering, it is necessary to develop a scaffold to maintain cartilage regeneration under inflammatory factors caused stress. Following a berberine-oleanolic acid (OA) complex salt (BOA) was grafted to hyaluronic acid (HA) to obtain water soluble BOA-g-HA, it mixed with silk fibroin (SF) to prepared 4 solutions, which contained 30 mg/mL SF and 0.75, 1.5, 2.25, and 3.0 mg/mL BOA-g-HA respectively. They were lyophilized to fabricate BOA-g-HA/SF-1, BOA-g-HA/SF-2, BOA-g-HA/SF-3, and BOA-g-HA/SF-4 composite scaffolds respectively. All prepared scaffolds displayed porous network structure and exhibited promising mechanical properties for tissue engineering applications. Among them, the BOA-g-HA/SF-3 composite scaffold showed the highest influence on maintaining chondrocytic phenotype of chondrocytes under IL-1ß induced stress. Following SF, HA/SF, and BOA-g-HA/SF-3 composite scaffolds with seeded chondrocytes were treated with IL-1ß induction for 1 week, specimens were incubated with cell culture medium for 3 week or were subcutaneously implanted into nude mice for 4 weeks. The results demonstrated that the BOA-g-HA/SF-3 composite scaffold promotes cartilage tissue regeneration in vitro and in vivo under IL-1ß caused stress, suggesting that it can be potential applied for repairing cartilage defects in osteoarthritis patients.

A sturgeon cartilage extracellular matrix-derived bioactive bioink for tissue engineering applications.

Three-dimensional (3D) bioprinting provides a promising strategy for tissue and organ engineering, and extracellular matrix (ECM)-derived bioinks greatly facilitate its applications in these areas. Decellularized sturgeon cartilage ECM (dSC-ECM)-derived bioinks for cartilage tissue engineering were fabricated with methacrylate-modified dSC-ECM (dSC-ECMMA) and sericin methacrylate (SerMA), which optimizedthe mechanical properties of their solidified hydrogels.dSC-ECM induces chondrocytes to form cell clusters and subsequently reduces their proliferation, but the proliferation of encapsulated chondrocytes was normal in solidified dSC-ECM-5 bioink samples, which contain 5 mg/mL dSC-ECMMA. Hence, this bioink was selected for further investigation. Lyophilized dSC-ECM-5 hydrogels showed connected pore microstructure, which is suitable for cell migration and nutrients transportation. ThisdSC-ECM-5 bioink exhibited high fidelity and good printability by testing via a 3D bioprinting system, and the chondrocytes loaded in printed hydrogel products were viable and able to grow, following incubation, in the cell culture medium. Solidified dSC-ECM-5 and SerMA bioinks loaded with chondrocytes were subcutaneously implanted into nude mice for 4 weeks to test the suitability of the bioink for cartilage tissue engineering. Compared to the SerMA bioink, the dSC-ECM-5 bioink significantly enhanced cartilage tissue regeneration and maturation in vivo, suggesting the potential of this bioink to be applied in cartilage tissue engineering in the future.

Pan-cancer analysis of the prognostic and immunological role of matrix metalloproteinase 9.

Matrix metalloproteinase 9 (MMP9), a zinc ion-dependent endopeptidase, is one of the most complex matrix metalloproteinases in the gelatinase family. During tissue remodeling, MMP9 leads to gelatin and collagen degradation, which in turn promotes tumor invasion and metastasis. However, comprehensive pan-cancer analysis has not been performed for MMP9. In addition, the diagnostic and prognostic value of MMP9 as a cancer biomarker remain poorly understood, as well as the utility of MMP9 expression as a predictor of immunological responses. Based on a comprehensive analysis of bioinformatics information, we investigated MMP9 expression in different cancers, correlations between MMP9 expression and cancer prognosis and gene mutations, and relationships between MMP9 expression and immune cell infiltration. Our results indicated that MMP9 was highly expressed in most malignant cancers. MMP9 expression was significantly positively or negatively associated with the clinical prognoses of patients with different kinds of cancer. Furthermore, MMP9 expression significantly correlated with infiltrating cells and the expression levels of immune checkpoint genes. This pan-cancer analysis provides comprehensive information on the potential value of MMP9 as a theranostic biomarker.

Impact of campus living conditions on Chinese medical school students' mental health during the COVID-19 campus lockdown: the chain mediating role of cognitive reappraisal and expression suppression.

Objective: To investigate the effect of changes in campus living conditions related to the Corona Virus Disease 2019 (COVID-19) pandemic on medical school students' mental health status, to explore the mediating role of emotion regulation strategies, and to provide effective suggestions for promoting medical school students' mental health. Methods: A self-report questionnaire, an emotion regulation questionnaire (ERQ), and psychological questionnaires for emergent events of public health (PQEEPH) were used to interview 998 medical school students who experienced campus lockdowns during the COVID-19 pandemic. Results: The mean total PQEEPH score was 3.66 ± 3.06. The degrees of inconvenience in daily life and change in routine and expression suppression as an emotion regulation strategy were significantly positively correlated with all PQEEPH dimensions. Cognitive reappraisal was significantly negatively associated with depression, neurosis, obsessive-compulsive anxiety, and hypochondriasis (ps < 0.05). Cognitive reappraisal and expression suppression demonstrated a chain mediating role between the degree of inconvenience in life and mental health and between the degree of change in routine and mental health (F = 32.883, 41.051, ps < 0.05). Conclusion: Campus lockdown management significantly impacts medical school students' mental health. Extensive use of cognitive reappraisal and expression suppression can reduce students' adverse psychological reactions during campus lockdowns to an extent.

Transcription Factors-Regulated Leaf Senescence: Current Knowledge, Challenges and Approaches.

Leaf senescence is a complex biological process regulated at multiple levels, including chromatin remodeling, transcription, post-transcription, translation, and post-translational modifications. Transcription factors (TFs) are crucial regulators of leaf senescence, with NAC and WRKY families being the most studied. This review summarizes the progress made in understanding the regulatory roles of these families in leaf senescence in Arabidopsis and various crops such as wheat, maize, sorghum, and rice. Additionally, we review the regulatory functions of other families, such as ERF, bHLH, bZIP, and MYB. Unraveling the mechanisms of leaf senescence regulated by TFs has the potential to improve crop yield and quality through molecular breeding. While significant progress has been made in leaf senescence research in recent years, our understanding of the molecular regulatory mechanisms underlying this process is still incomplete. This review also discusses the challenges and opportunities in leaf senescence research, with suggestions for possible strategies to address them.

Photoinhibiting via simultaneous photoabsorption and free-radical reaction for high-fidelity light-based bioprinting.

Light-based 3D bioprinting is now employed widely to fabricate geometrically complex constructs for various biomedical applications. However, the inherent light scattering defect creates significant challenges in patterning dilute hydrogels to form high-fidelity structures with fine-scale features. Herein, we introduce a photoinhibiting approach that can effectively suppress the light scattering effect via a mechanism of simultaneous photoabsorption and free-radical reaction. This biocompatible approach significantly improves the printing resolution (~1.2 - ~2.1 pixels depending on swelling) and shape fidelity (geometric error less than 5%), while minimising the costly trial-and-error procedures. The capability in patterning 3D complex constructs using different hydrogels is demonstrated by manufacturing various scaffolds featuring intricate multi-sized channels and thin-walled networks. Importantly, cellularised gyroid scaffolds (HepG2) are fabricated successfully, exhibiting high cell proliferation and functionality. The strategy established in this study promotes the printability and operability of light-based 3D bioprinting systems, allowing numerous new applications for tissue engineering.

Impact of endogenous glucocorticoid on response to immune checkpoint blockade in patients with advanced cancer.

Background: Previous studies indicate that exogenous use of glucocorticoid (GC) affects immune checkpoint inhibitor (ICI) efficacy. However, there is a paucity of clinical data evaluating the direct impact of endogenous GC on the efficacy for cancer patients with immune checkpoint blockade. Methods: We first compared the endogenous circulating GC levels in healthy individuals and patients with cancer. We next retrospectively reviewed patients with advanced cancer with PD-1/PD-L1 inhibitor alone or combination therapy in a single center. The effects of baseline circulating GC levels on objective response rate (ORR), durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS) were analyzed. The association of the endogenous GC levels with circulating lymphocytes, cytokines levels, and neutrophil to lymphocyte ratio, and tumor infiltrating immune cells, were systematically analyzed. Results: The endogenous GC levels in advanced cancer patients were higher than those in early-stage cancer patients as well as healthy people. In the advanced cancer cohort with immune checkpoint blockade (n=130), patients with high baseline endogenous GC levels (n=80) had a significantly reduced ORR (10.0% vs 40.0%; p<0.0001) and DCB (35.0% vs 73.5%, p=0.001) compared to those with low endogenous GC levels (n=50). The increased GC levels was significantly associated with reduced PFS (HR 2.023; p=0.0008) and OS (HR 2.809; p=0.0005). Moreover, statistically significant differences regarding PFS, and OS were also detected after propensity score matching. In a multivariable model, the endogenous GC was identified as an independent indicator for predicting PFS (HR 1.779; p=0.012) and OS (HR 2.468; p=0.013). High endogenous GC levels were significantly associated with reduced lymphocytes (p=0.019), increased neutrophil to lymphocyte ratio (p=0.0009), and increased interleukin-6 levels (p=0.025). Patients with high levels of endogenous GC had low numbers of tumor infiltrating CD3+ (p=0.001), CD8+ T (p=0.059), and CD4+ T (p=0.002) cells, and the numbers of circulating PD-1+ NK cells (p=0.012), and the ratio of CD8+PD-1+ to CD4+PD-1+ (p=0.031) were higher in patients with high levels of endogenous GC compared to low levels of endogenous GC. Conclusion: Baseline endogenous GC increase executes a comprehensive negative effect on immunosurveillance and response to immunotherapy in real-world cancer patients accompanied with cancer progression.

Clinical characteristics and management of immune checkpoint inhibitor-related cardiotoxicity: A single-center experience.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy in the past decade and amplify T-cell-mediated immune responses by disrupting immunoinhibitory signals. The augmented T-cell immune response has led to a range of immune-related adverse effects (irAEs). Immune-related cardiotoxicity has been reported in case series but has been underappreciated due to difficulties in diagnosis. This article describes epidemiological, clinical presentation, subtype, and treatment data and a new systematic framework for the clinical management of cardiotoxicity. Methods: Data were extracted for cancer patients who received ICIs in a single center between January 1, 2020, and February 28, 2022. ICI-associated cardiotoxicity was clinically diagnosed based on clinical presentations, biochemical biomarkers, and imaging features. Results: We identified a total of 12 (2.46%) cases of ICI-related cardiotoxicity from 487 patients who received PD-1 or PD-L1 inhibitors. All patients were diagnosed with advanced or metastatic solid tumors. The severity of ICI-related cardiotoxicity ranged from subclinical cardiac abnormalities (subclinical type) with only asymptomatic troponin-I (TnI) elevations (25.0%) to symptomatic cardiac abnormalities (clinical type) (75.0%). Patients with symptomatic cardiac abnormalities had several manifestations, including tachyarrhythmia (16.7%), bradyarrhythmia (41.7%), or cardiac failure (8.3%). The median immunotherapy exposure time was 1.5 doses (range: 1 to 5), and the median time from the initial immunotherapy to the onset of ICI-related cardiotoxicity was 33.5 days (IQR: 20.3 to 46.8). Most patients, including those with subclinical cardiac abnormalities, were administered systemic corticosteroids (58.3%). One (8.3%) patient was put on mechanical ventilation, one (8.3%) received plasma exchange therapy, one (8.3%) was implanted with a pacemaker, and one (8.3%) was admitted to the ICU. Three patients with symptomatic cardiac abnormalities (25.0%) died, and other patients presented with significant clinical improvement with good outcomes. Conclusion: ICI-related cardiotoxicity is uncommon but critical with a high mortality rate and poor prognosis, especially for a small group of patients with symptomatic cardiac abnormalities. More attention should be given to cardiotoxicity associated with ICIs, and these patients should be given baseline examinations and biochemical analyses before and after the initiation of immunotherapy, intensive cardiac assessments, an accurate and rapid diagnosis, and timely multidisciplinary management with immunosuppressive agents and other necessary clinical interventions.

Lack of association between leptin concentrations and cystic fibrosis: A meta-analysis and regression.

Background: Leptin (LEP) acts as a proinflammatory cytokine and may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to assess the quantitative difference in leptin status between CF patients and non-CF controls. Methods: In this study, the researchers conducted systematic searches of various databases, such as PubMed, Excerpta Medica Database, Google Scholar, Web of Science, and the China National Knowledge Infrastructure. The data collected from the above databases were assessed using the Stata 11.0 and R 4.1.3 software. The correlation coefficients and the Standardized Mean Differences (SMD) were employed to assess the effect size. A combination analysis was also carried out with the help of either a fixed-effects or random-effects model. In addition, the single-cell sequencing GSE193782 dataset was obtained to determine the mRNA expression levels of LEP and leptin receptor (LEPR) in the bronchoalveolar lavage fluid, to verify the different leptin expression between the CF patients and healthy controls. Results: A total of 919 CF patients and 397 controls from 14 articles were included in this study. CF patients and non-CF controls showed similar serum/plasma leptin levels. Gender, specimen testing, age, and study design were all taken into account for carrying out subgroup analyses. The results revealed no variations in serum/plasma leptin levels between the controls and CF patients in the various subgroups. Female CF patients exhibited higher leptin concentrations compared to male CF patients, and male healthy individuals showed lower leptin levels than female healthy participants. Aside from the fact that serum/plasma leptin appeared to be favorably linked to fat mass and BMI, the findings in this study also indicated that serum/plasma concentrations were not associated with Forced Expiratory Volume in the first second (FEV1). No statistically significant differences were observed in the leptin and leptin receptor mRNA expression levels between the healthy controls and CF patients. The leptin receptor and leptin expression levels in alveolar lavage fluid were low in various cells, without any distinctive distribution patterns. Conclusions: The current meta-analysis indicated the absence of significant differences in leptin levels between CF patients and healthy individuals. Gender, fat mass, and BMI may all be correlated with leptin concentrations. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022380118.