The risk factors for postoperative temporary vocal cord paralysis after thyroid cancer surgery: an observational retrospective cohort study.

OBJECTIVE: To analyze the potential factors influencing new-onset postoperative transient vocal cord paralysis (VCP) in thyroid cancer patients. METHODS: Case information of 8,340 thyroid cancer patients hospitalized at XX from January 2018 to December 2020 was collected retrospectively and analyzed. The possible influencing factors were analyzed using a chi-square test, rank-sum test, and multiple logistic regression analysis. A nomogram was used to construct the clinical prediction model that was validated in the validation set by ROC, calibration curves, and DCA. RESULTS: The STROCSS guideline was followed to conduct a retrospective cohort study. A total of 8,340 patients, including 1,817 (21.8%) men and 6,523 (78.2%) women, were enrolled in this study. The rate of temporary VCP was 3.6% (308/8,340). Based on the results of postoperative laryngoscopy, the patients were divided into VCP group and non-VCP group. Comparative analysis between the groups revealed that potential factors associated with postoperative transient VCP were tumor location on the dorsal side of the gland (P = 0.042), ultrasound showing a maximum nodal diameter > 1 cm (P = 0.002), multifocal carcinoma (P < 0.001), invasion of surrounding tissue (P = 0.005), lymph node metastases in the central compartment (P = 0.034), lateral cervical lymph node metastasis (P < 0.001), and prolonged operation (P < 0.001). A multiple logistic regression analysis showed that the independent risk factors in postoperative transient VCP were T stage (OR = 1.411, P = 0.013, 95% CI: 1.075-1.853), multifocal carcinoma (OR = 1.532, P = 0.013, 95% CI: 1.095-2.144), and duration of surgery (OR = 1.009, P < 0.001, 95% CI: 1.006-1.012). Finally, a clinical prediction model was established via a nomogram and was validated in the validation set, although its diagnostic efficacy needs to be improved further. CONCLUSION: High T stage, multifocal carcinoma, and prolonged operation time may be independent risk factors for the occurrence of postoperative transient VCP in patients undergoing initial surgery for thyroid cancer.

The association between gout flares and monosodium urate burden assessed using musculoskeletal ultrasound in patients with gout.

Background: Ultrasound (US) has a high sensitivity in detecting monosodium urate (MSU) deposition in gout patients. However, the value of US in predicting gout flares has been reported only in a few monocentric studies. Objective: To investigate the association between gout flares in the previous year and US-detected MSU burden using two different US scores. Design: A retrospective study. Methods: Patients with gout were consecutively recruited to undergo musculoskeletal US examinations of their knees, ankles, and feet. The score derived from Outcome Measure in Rheumatology (hereinafter referred to as MSU score) and musculoskeletal US features-based (hereinafter referred to as MSKF score) were used to quantify the MSU burden of gout. Odds ratios for frequent gout flares were calculated. Results: We enrolled 1894 patients with gout (mean age: 45 years; gout duration: 5 years; males: 96.1%), experiencing a median of three flares over the past year. Of these, 428 (22.6%) patients reported frequent (⩾7) gout flares. The MSU and MSKF median scores were 6 and 9, respectively. For each five-point increase in MSU and MSKF score, the odds ratio of frequent gout flares increased 1.13-fold and 1.24-fold, respectively. The area under the curve (AUC) for the MSU and MSKF score was 0.635 [95% confidence interval (CI): 0.604-0.665] and 0.688 (95% CI: 0.659-0.718), respectively, (AUC difference 0.054, p value for AUC difference < 0.001). Conclusion: The MSU and MSKF scores were significantly associated with the number of gout flares in the previous year. The MSKF score outperformed the MSU score in terms of frequent gout flare discrimination.

A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance.

CRISPR homing gene drive is a potent technology with considerable potential for managing populations of medically and agriculturally significant insects. It induces a bias in the inheritance of the drive allele in progeny, rapidly spreading the desired gene construct throughout the population. Homing drives operate by Cas9 cleavage followed by homology-directed repair, copying the drive allele to the wild-type chromosome. However, resistance alleles formed by end-joining repair pose a significant obstacle to the spread of the drive. To address this challenge, we create a homing drive targeting the essential but haplosufficient hairy gene in Drosophila melanogaster. Our strategy involves eliminating nonfunctional resistance alleles, which are recessive lethal, while rescuing drive-carrying individuals with a recoded version of hairy. The drive inheritance rate is moderate, and multigenerational cage studies show drive spread to 96%-97% of the population. However, the drive fails to reach the whole population due to the formation of functional resistance alleles, despite use of four gRNAs. These alleles have a large deletion but likely utilize an alternate start codon, and they have a small fitness advantage over the drive. Thus, revised design strategies targeting more essential regions of a target gene may often be necessary to avoid such functional resistance, even when using multiplexed gRNAs. Replacement of the native 3' UTR of the rescue element with a homolog from another species increases drive inheritance by 13%-24%. This was possibly because of reduced homology between the rescue element and nearby native DNA, which could also be an important design consideration for gene drives that utilize rescue elements.

Adiponectin Inhibits the Progression of Obesity-Associated Papillary Thyroid Carcinoma Through Autophagy.

CONTEXT: Obesity is a risk factor for the development of papillary thyroid cancer (PTC). However, the molecular mechanisms by which obesity promotes PTC are unclear. OBJECTIVE: This study aims to identify adipokines that are linked to PTC progression. METHODS: An adipokine antibody array was used to determine the serum levels of 40 adipokines in normal-weight and obese PTC patients. Enzyme-linked immunosorbent assay was used to determine the serum levels of adiponectin. Recombinant human adiponectin was produced by human adipose-derived stem cells and used to treat PTC cells. Cell proliferation and migration were evaluated using the CCK8 and Transwell assays. Bioinformatics analysis was used to predict mechanisms by which adiponectin affects PTC. RESULTS: Adipokines differentially expressed between normal-weight and obese patients showed a gender-dependent pattern. Obese PTC patients had a significantly lower serum adiponectin level than normal-weight patients, especially in female individuals. Adiponectin levels were negatively correlated with aggressive features of PTC, including tumor diameter > 1 cm, extrathyroidal extension, and lymph node metastasis. Recombinant human adiponectin inhibited the proliferation and migration of human PTC cells in vitro. Bioinformatics analysis identified adiponectin receptor 2 (ADIPOR2) and the autophagy pathway as possible mediators of adiponectin function in TC. In vitro experiments confirmed that adiponectin activated autophagy in PTC cells. These findings shed new lights into the role and mechanisms of adiponectin in TC pathogenesis. CONCLUSION: Adiponectin is involved in development of obesity-related PTC. Adiponectin can directly inhibit thyroid cancer growth and metastasis through the autophagy pathway.

Attentional focus differentially modulates the corticospinal and intracortical excitability during dynamic and static exercise.

Although attentional focus affects motor performance, whether corticospinal excitability and intracortical modulations differ between focus strategies depending on the exercise patterns remains unclear. In the present study, using single- and paired-pulse transcranial magnetic stimulation and peripheral nerve stimulation, we demonstrated changes in the cortical and spinal excitability under external focus (EF) and internal focus (IF) conditions with dynamic or static exercise. Participants performed the ramp-and-hold contraction task of right index finger abduction against an object (sponge or wood) with both exercises. They were asked to concentrate on the pressure on the sponge/wood induced by finger abduction under the EF condition, and on the index finger itself under the IF condition. Motor-evoked potential (MEP) and F-wave in the premotor, phasic, or tonic phase, and short- and long-interval intracortical inhibition (SICI and LICI, respectively), and intracortical facilitation (ICF) in the premotor phase were examined by recording surface electromyographic activity in the right first dorsal interosseous muscle. Increments in the MEP amplitude were larger under the EF condition than under the IF condition in the dynamic, but not static, exercise. The F-wave, SICI, and LICI did not differ between focus conditions in both exercises. In the dynamic exercise, interestingly, ICF was greater under the EF condition than under the IF condition and positively correlated with the MEP amplitude. These results indicate that corticospinal excitability and intracortical modulations to attentional focus differ depending on exercise patterns, suggesting that attentional focus differentially affects the central nervous system responsible for diverse motor behaviors.NEW & NOTEWORTHY We investigated attentional focus-dependent corticospinal and intracortical modulations in dynamic or static exercise. The corticospinal excitability was modulated differentially depending on the focus of attention during dynamic, but not static exercise. Although the reduction of intracortical GABAergic inhibition was comparable between focus conditions in both exercises, intracortical facilitation was smaller when focusing on the internal environments in the dynamic exercise, resulting in lower activation of the corticospinal tract.

Noticeable effect of lower baseline amplitude on the predictive accuracy of intraoperative amplitude changes for postoperative vocal cord palsy: a prospective cohort study.

BACKGROUND: To explore the effect of lower baseline amplitude on its predictive accuracy of postoperative vocal cord paralysis (VCP) in monitored thyroid surgery. MATERIALS AND METHODS: Clinical and electrophysiological data were collected during thyroid surgeries performed between November and December 2021 at XXX. Univariate/multivariate regression analysis were applied to these data to examine a possible correlation. A receiver operating characteristic (ROC) curve was used to evaluate predictive efficacy. RESULTS: A total of 631 nerves-at-risk (NAR) were identified in 460 patients who were divided into two groups according to postoperative development of VCP. The VCP group included a higher percentage of NAR with V1<1000 (68.2% vs. 40.7%, respectively; P=0.014) and NAR with R1<1400 (77.3% vs. 47.0%, respectively; P=0.005) compared with the non-VCP group. Multivariate regression analysis further identified V1<1000 (odds ratio (OR)=2.688, P=0.038), R1<1400 (OR=3.484, P=0.018) as independent risk factors for postoperative temporary VCP. The ROC curve showed the AUC value of V signal decline for predicting VCP was 0.87. The diagnostic efficiency of R signal decline reached as high as 0.973. A multivariate logistic regression analysis identified independent risk factors for V1<1000 and these included: higher body mass index (BMI) (OR=1.072, P=0.013), hypertension (OR=1.816, P=0.015), smoking (OR=1.814, P=0.031), and male gender (OR=2.016, P=0.027). CONCLUSION: In our cohort, lower baseline amplitude was an independent risk factor for developing transient postoperative VCP. It also affected the predictive efficacy of intraoperative amplitude changes on VCP. Higher BMI, hypertension, smoking, and male gender may also be closely associated with lower initial amplitude. Thus, maintaining a higher initial amplitude is critical for patient safety during thyroid surgery.

Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives.

BACKGROUND: Pyroptosis, an inflammatory form of programmed cell death, has been implicated in the pathogenesis and progression of several cancers. However, the significance of pyroptosis-related genes (PRGs) in papillary thyroid cancer (PTC) remains unclear. METHODS: Transcriptome and clinical data of PTC patients were obtained from The Cancer Genome Atlas. The expression patterns of PRGs were identified by consensus clustering. A prognostic model for predicting the thyroid cancer-free interval (TCFi) employed five machine learning methods. Enrichment and immune-related analyses were performed to elucidate the role of pyroptosis. The responses to radioactive iodine (RAI), immune checkpoint inhibitors (ICIs), molecular targeted therapy (MTT), and chemotherapy (CTx) were predicted based on pyroptosis-derived features. Additionally, the expression of prognostic PRGs was validated via six external datasets, 16 cell lines, and 20 pairs of clinical samples. RESULTS: PTC patients were classified into three PyroClusters, C1 exhibited BRFA-like tumors with the highest invasiveness and the worst prognosis, C2 presented RAS-like tumors, and C3 was characterized by gene fusion. Nine PRGs (CXCL8, GJA1, H2BC8, IFI27, PRDM1, PYCARD, SEZ6L2, SIGLEC15, TRAF6) were filtered out to construct a PyroScore prognostic model. A derived nomogram demonstrated superior predictive performance than four clinical staging systems. A strong correlation between pyroptosis and tumor immune microenvironment (TIME) remodeling was observed in mechanistic analyses. Patients with a high PyroScore exhibited "hot" tumor immunophenotypes and had a poorer prognosis but could benefit more from ICIs and CTx (such as paclitaxel). Patients with a low PyroScore were more sensitive to RAI and MTT (such as pazopanib and sorafenib). CONCLUSIONS: PyroScore model can effectively predict TCFi in patients with PTC. Dysregulated expression of PRGs is associated with the TIME modeling. Pyroptosis features have potential significance for developing novel therapeutic strategies for PTC patients.

Study of postoperative laryngopharyngeal discomfort: protocol for a single-centre cohort study.

INTRODUCTION: Postoperative laryngopharyngeal discomfort after extubation can lead to severe throat pain, dysphagia, or postoperative tongue oedema. Possible mechanisms include increased oral pressure, obstruction of venous and lymphatic return in the neck, and increased capillary hydrostatic pressure, which leads to oedema of the tongue and upper airway. However, real-time monitoring indicators of anaesthesia are lacking. Therefore, we designed this study to accurately measure the contact force of the tracheal tube on the tongue in different surgical positions during general anaesthesia. METHODS AND ANALYSIS: This prospective single-centre observational study will enrol 54 patients undergoing elective surgery under general anaesthesia for>2 hours with endotracheal tube application from 1 July 2023 to 30 June 2024. Patients will be divided into the supine (Supine group) and high-risk (Flexion group) groups. Dynamic changes in the contact force between the tracheal tube and tongue will be measured using T-Scan technology. All patients will be followed up for 7 days postoperatively. The primary endpoint is postoperative laryngopharyngeal discomfort. Secondary outcomes include the time to the first successful recovery of oral intake of fluids and solid food, and airway-related events. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Ethics Committee of Clinical Research of China-Japan Friendship Hospital (2023-KY-219, approved on 14 September 2023). Informed consent will be obtained during anaesthesia evaluation. This study aims to explore the characteristics of the contact force on the tongue caused by endotracheal intubation in different surgical positions and to provide a better understanding of the risk factors and prevention of postoperative laryngopharyngeal discomfort. The findings of this study will be presented at our hospital, reported on ClinicalTrials.gov, and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05987293.

Purine Metabolic Pathway Alterations and Serum Urate Changes after Oral Inosine Loading in Male Chinese Volunteers.

BACKGROUND: Oral inosine loading is a new method to evaluate the effects of purine on urate metabolism. However, individuals respond differently to acute purine intake, and the effects on the metabolism of other purines remain to be explored. METHODS: 35 male participants are recruited. Participants received 500 mg of inosine orally after an overnight fast, and blood and urine samples are collected before and at various time points over 180 min after inosine administration. RESULTS: The serum urate concentration is significantly different between the hyperuricemia (n = 14) and non-hyperuricemia (n = 16) groups before inosine intake, but there is no in urate change after inosine intake. When grouped according to the baseline estimated glomerular filtration rate (eGFR), the increase in urate level in the high-eGFR group is significantly higher than that in the low-eGFR group (p  =  0.047). The high-eGFR group showed higher levels of serum xanthine and xanthine oxidase (XOD), the key enzyme in urate synthesis, after inosine loading (p < 0.01). CONCLUSIONS: The increase in urate level is positively related to eGFR after oral acute inosine administration, which may have been due to a higher level of XOD.

Accuracy of Force Generation and Preparatory Prefrontal Oxygenation in Ballistic Hand Power and Precision Grips.

It remains unclear whether accurate motor performance and cortical activation differ among grasping forms across several force levels. In the present study, a ballistic target force matching task (20%, 40%, 60%, and 80% of maximum voluntary force) with power grip, side pinch, and pulp pinch was utilized to explore the accuracy of the forces generated as well as the muscular activity of intrinsic and extrinsic hand muscles. By using near-infrared spectroscopy, we also examined bilateral dorsolateral prefrontal cortex (DLPFC) activation during the preparatory phase (initial 10 s) of the task. The accuracy of the power grip and pulp pinch was relatively higher than that of the side pinch, and the electromyographic activity of intrinsic hand muscles exhibited a similar trend for power grip and side pinch, while the opposite muscle recruitment pattern was observed for pulp pinch. The increment of DLPFC oxygenation across force levels differed among grasping forms, with greater activity at relatively higher levels in the power grip and side pinch, and at relatively lower levels in the pulp pinch. Taken together, the differential contribution of the DLPFC may be responsible for force generation depending on different grasping forms and force levels.

GC heterogeneity reveals sequence-structures evolution of angiosperm ITS2.

BACKGROUND: Despite GC variation constitutes a fundamental element of genome and species diversity, the precise mechanisms driving it remain unclear. The abundant sequence data available for the ITS2, a commonly employed phylogenetic marker in plants, offers an exceptional resource for exploring the GC variation across angiosperms. RESULTS: A comprehensive selection of 8666 species, comprising 165 genera, 63 families, and 30 orders were used for the analyses. The alignment of ITS2 sequence-structures and partitioning of secondary structures into paired and unpaired regions were performed using 4SALE. Substitution rates and frequencies among GC base-pairs in the paired regions of ITS2 were calculated using RNA-specific models in the PHASE package. The results showed that the distribution of ITS2 GC contents on the angiosperm phylogeny was heterogeneous, but their increase was generally associated with ITS2 sequence homogenization, thereby supporting the occurrence of GC-biased gene conversion (gBGC) during the concerted evolution of ITS2. Additionally, the GC content in the paired regions of the ITS2 secondary structure was significantly higher than that of the unpaired regions, indicating the selection of GC for thermodynamic stability. Furthermore, the RNA substitution models demonstrated that base-pair transformations favored both the elevation and fixation of GC in the paired regions, providing further support for gBGC. CONCLUSIONS: Our findings highlight the significance of secondary structure in GC investigation, which demonstrate that both gBGC and structure-based selection are influential factors driving angiosperm ITS2 GC content.

Effect of Third Interstitial Fluid on Adverse Outcomes in Patients with Severe Pre-eclampsia and Twin Pregnancy: A 5-year Single-center Retrospective Study.

OBJECTIVE: This study aims to identify the effect of third interstitial fluid on adverse outcomes in twin pregnancies with severe pre-eclampsia, and explore the differences in bad ending between twins and singletons. METHODS: The present retrospective cohort study was conducted on patients with severe pre-eclampsia, who delivered in Tongji Hospital, Wuhan, China, between 2017 and 2022. The adverse outcomes in singleton and twin pregnancies with severe pre-eclampsia were initially investigated. Then, the diverse maternal and fetal consequences between singleton and twin pregnancies in patients with severe pre-eclampsia were compared after merging with the third interstitial fluid. RESULTS: A total of 709 patients were included for the present study. Among these patients, 68 patients had twin pregnancies, and 641 patients had singleton pregnancies. The rate of postpartum hemorrhage (2.81% vs. 13.24%, P<0.001), and admission rate to the Neonatal Intensive Care Unit (NICU) after birth (30.73% vs. 63.24%, P=0.011) were significantly higher in twin pregnancies. The neonatal weight of twins was statistically lower than singletons (1964.73±510.61 g vs. 2142.92±731.25 g, P=0.008). For the groups with the third interstitial fluid, the delivery week (P=0.001) and rate of admission to the NICU after birth were significantly advanced in twin pregnancy group, when compared to singleton pregnancy group (P=0.032), and the length of hospital stay was shorter (P=0.044). Furthermore, there was no statistically significant difference between the twin pregnancy group and the singletony pregnancy group without the third interstitial fluid. CONCLUSION: The maternal and fetal adverse outcomes of patients with severe pre-eclampsia increased in twin pregnancies, when compared to singleton pregnancies. Thus, when patients develop the third interstitial fluid, twin pregnancies would more likely lead to adverse fetal outcomes, when compared to singleton pregnancies, and there would be no significant difference in maternal adverse outcomes. More attention should be given to patients who merge with the third interstitial fluid.

Surgical resection of recurrent differentiated thyroid cancer: patterns, detection, staging, and treatment of 683 patients.

Background: Despite improvements in overall survival, the recurrence of differentiated thyroid cancer (DTC) is becoming more common and remains a challenge necessitating accurate reappraisal of the patient. This study aimed to describe the characteristics, reasons, morbidity, and strategies of second operations for DTC. Methods: This was a retrospective observational study of patients with DTC who underwent a second surgery between June 2008 and June 2021 in the Department of Thyroid Surgery at China-Japanese Union Hospital, Jilin University, P.R. China. All clinical characteristics were recorded, and the analysis was estimated using SPSS. Results: Second surgeries were detected in 683 patients. The proportion of second operations changed with the update of international guidelines from 2015 (P < 0.001). The true recurrence rate progressively increased from 21.3% to 61.5%. The rate of an "absence of preoperative FNA" or an "absence of intraoperative pathology at first surgery" decreased from 49.8% to 12.7%, while that of a "misdiagnosis of preoperative FNA at second surgery" decreased from 10% to 1.8%. The most common tumor location during the second surgery was the lateral lymph nodes (n = 104, 36.5%), with a median time to relapse of 36 months. Completion of thyroidectomy and lymph node dissection correlated with the second operation. Conclusion: After 2015, second surgeries were more standardized, the incidence of complications decreased, and real recurrence became the most common reason for a second DTC surgery.

Lack of action-sentence compatibility effect in non-clinical individuals with high autistic traits.

Introduction: Patients with autism spectrum disorder (ASD) exhibit atypical responses to language use and comprehension. Recently, various degrees of primary autistic symptoms have been reported in the general population. We focused on autistic traits and examined the differences in mechanisms related to language comprehension using the action-sentence compatibility effect (ACE). ACE is a phenomenon in which response is facilitated when the action matches the behavior described in the statement. Methods: In total, 70 non-clinical individuals were divided into low autistic and high autistic groups according to their autism spectrum quotient (AQ) scores. ACEs with adverbs and onomatopoeias were examined using a stimulus set of movement-related sentences. A choice-response task helped determine the correct sentence using antonym adverbs (slow and fast) and onomatopoeia (quick and satto) related to the speed of the movement. Results: The low-AQ group showed ACEs that modulated the reaction time in antonym sentences. The high-AQ group showed less temporal modulation, and their overall reaction time was shorter. The low-AQ group showed faster reaction times for onomatopoeic words; however, the high-AQ group showed a tendency to reverse this trend. In individuals with intermediate autistic traits, the angle effect may be moderated by individual differences in motor skills and experience rather than autistic traits. The stimulus presentation involved a passive paradigm. Discussion: This study provides insight into language comprehension processes in non-clinical individuals ranging from low to high autistic idiosyncrasy and elucidates language and behavior in individuals at different locations on the autistic trait continuum.

Estimating disease-free survival of thyroid cancer based on novel cuprotosis-related gene model.

Background: Cuprotosis is a newly discovered form of cell death that differs from other types of cell death. The aim of this study was to investigate the functional role and a possible prognostic model for thyroid cancer. Methods: TCGA and GEO were used to investigate the differential expression of CRGs in THCA. KEGG and GO enrichment analyses were applied to investigate the possible molecular functions. The features of CRGs were selected by LASSO regression. 20 pairs of samples were randomly collected from the hospital to compare expression between tumor and normal. Results: Among the 19 CRGs related to thyroid cancer recurrence, 16 genes were differentially expressed in thyroid cancer. KEGG analysis showed that the 19 CRGs were mainly enriched in cell death, cell cycle and ribosomal pathways. K-M survival analysis and subsequent multiple logistic regression revealed that the expression of BUB1 and GINS2 were potential risk factors for disease-free survival (DFS) of thyroid cancer. In addition, further LASSO-regression selected the following three DFS-related CRGs: FDX1, BUB1 and RPL3. A novel prognostic prediction model was constructed by nomogram, and the prediction probability for 1-, 3- and 5-year survival approached the actual time. As for the possible mechanisms, FDX1, BUB1 and RPL3 were associated with immune infiltration. The cell model experiment illustrated that the ATM signaling pathway might be involved in thyroid cancer cell death. Conclusion: Three CRG models (FDX1, BUB1, RPL3) could better predict the prognosis of thyroid cancer. Immune cell infiltration and the ATM pathway were the possible mechanisms.

Whole Blood-Derived circUSP10 Acts as a Diagnostic Biomarker in Patients With Early-Stage Non-Small-Cell Lung Cancer.

Accumulating evidence has indicated that differentially expressed noncoding circular RNAs (circRNAs) play essential roles in the occurrence and development of various types of cancer. Here, we aimed to identify and explore the diagnostic value of hsa_circ_0003026 (named circUSP10) in patients with early non-small-cell lung cancer (NSCLC). The differentially expressed circRNAs were screened from the microarray-based assay of human NSCLC tissues and their corresponding noncancerous tissues, and the candidate circRNAs were further verified in patients with NSCLC using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Circulating circUSP10 was isolated from whole blood of healthy people and patients with NSCLC and was detected by RT-qPCR. In addition, the diagnostic value of circUSP10 in early NSCLC was evaluated by receiver operating characteristic (ROC) curve analysis. We found that circUSP10 was upregulated in tumor tissues from patients with early NSCLC and associated with tumor size and tumor-node-metastasis (TNM) stage. Importantly, circUSP10 was obviously upregulated in the whole blood of patients with NSCLC. Additionally, whole blood-derived circUSP10 showed good diagnostic performance for screening early NSCLC and was relatively stable in blood under adverse conditions. These findings demonstrate that circUSP10 may act as a novel biomarker for the diagnosis of early-stage NSCLC, suggesting the potential of circUSP10 in RNA-based therapy for cancer.

Assessment of mental health status among Chinese nursing staff in the intensive care unit: a network analysis.

Backgrounds: Nursing is the key group to provide healthcare services, and it is easy for nursing staff to develop mental health problems. Aims: The study aimed to evaluate prevalence of psychological symptoms in nurses working in an intensive care unit (ICU) and the inter-relationship of associations of psychological symptoms using network analysis. Methods: This study is a cross-sectional design study. The Chinese version of the Symptom Check List-90 (SCL-90) was used to measure the psychological status of ICU nurses. The network structure of psychological symptoms was characterised, and indices of 'Expected influence' were used to identify symptoms central to the network. Network stability was examined using a case-dropping bootstrap procedure. Results: Multiple logistic regression analysis found those who had worked more than 15 years were less likely to experience positive psychological symptoms, whereas nurses working in emergency ICU and other ICUs, nurses working in departments with over 16 beds were more likely to develop psychological symptoms. In addition, 'Anxiety', 'Mental degeneration' and 'Depression' were central symptoms in the network. Conclusions: ICU nurses reported a high level of psychological symptoms, which may affect the quality of their work and worsen public health problems.

Peripheral Blood-Derived CircVPS35L as a Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer.

INTRODUCTION: Circular RNAs (circRNAs) are dysregulated in cancers and are stably expressed in body fluids such as blood. We therefore identified and evaluated the clinical value of a newly found circRNA VPS35L (circVPS35L) as a biomarker for the diagnosis of non-small cell lung cancer (NSCLC). METHODS: Reverse-transcription quantitative PCR (RT-qPCR) was used to determine the expression levels of circVPS35L in tissues, whole blood, and cell lines. The actinomycin D assay and RNase R treatment were utilized to determine the stability of circVPS35L. Receiver operating characteristic (ROC) curve analysis was conducted to predict the diagnostic value of blood-derived circVPS35L in NSCLC. RESULTS: CircVPS35L was found to be downregulated in NSCLC tissues and cell lines. Interestingly, circVPS35L expression was significantly correlated with tumor size (p = 0.0269), histology type (p < 0.0001), and TNM stage (p = 0.0437). Importantly, circVPS35L was poorly expressed in peripheral blood of NSCLC patients when compared with healthy controls and patients with benign lung disease. ROC analysis revealed a higher diagnostic value of circVPS35L than the three conventional tumor markers (CYFR21-1, NSE, and CEA) in patients with NSCLC. Moreover, circVPS35L was highly stable in peripheral blood when exposed to undesirable conditions. CONCLUSION: These findings demonstrate that circVPS35L has great potential as a novel biomarker for the diagnosis of NSCLC and can be used to distinguish NSCLC from benign lung disease.

Mechanism of time-dependent toxicity of quinolone antibiotics on luminescent bacteria Vibrio qinghaiensis sp.-Q67.

Four quinolone antibiotics (ciprofloxacin (CIP), enrofloxacin (ENR), sparfloxacin (SPA), gatifloxacin (GAT)) and their binary mixtures at environmentally relevant concentrations exhibited time-dependent hormesis on Vibrio qinghaiensis sp.-Q67 (Q67). The study aims to investigate the time-dependent toxicity of low-dose pollutants and the occurrence of hormesis. These indicators, total protein (TP), reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and luminescence-related chemicals flavin mononucleotide (FMN), nicotinamide adenine dinucleotide (NADH), were measured to explore the mechanism of hormesis. The results showed a trend of increases in all indicators after 12 h of exposure, reaching maximal effects at 60 h and then decreasing as time progressed. At 36 h, 60 h and 84 h, the results showed a gradual increase followed by a decreasing trend in TP, FMN and NADH as the concentration in the group increased, whereas ROS, CAT, SOD and MDA showed the opposite trend. Notably, the degree of changes was related to the magnitude of hormesis. At low concentrations, the content of ROS and MDA decreased, the activity of CAT and SOD was lower, but the content of TP, FMN, NADH gradually increased, positively correlated with the promotion of Q67. At high concentrations, ROS and MDA content in Q67 increased, triggering the antioxidant defense mechanism (CAT and SOD activity increased), but TP, FMN, NADH content decreased, negatively correlated with the inhibited Q67. Therefore, our findings demonstrated two common patterns in these seven biochemical indicators on Q67. These findings have important practical implications for the ecological risk assessment of antibiotics in aquatic environment.

Pan-Cancer Analysis of the Oncogenic and Prognostic Role of PKM2: A Potential Target for Survival and Immunotherapy.

Background: No pan-cancer study has been conducted till date to explore the comprehensive oncogenic roles of pyruvate kinase M2 (PKM2). Methods: TCGA, TIMER, GEPIA, UALCAN, STRING, and other databases were used to analyze the expression, prognostic roles, epigenetic variants, and possible oncogenic mechanisms of PKM2. Proteomic sequencing data and PRM were applied to validate. Results: PKM2 showed higher expression in majority of cancers, the expression being significantly correlated with the clinical stage. Higher expression of PKM2 was associated with lower OS and DFS in several cancers, such as MESO and PAAD. In addition, the epigenetic variation of PKM2, including gene alteration, mutation type and sites, DNA methylation, and phosphorylation, showed diversity in different cancers. All four methods indicated that PKM2 is positively associated with the immune infiltration of tumor-associated fibroblasts, such as in THCA, GBM, and SARC. Further mechanistic exploration suggested that the ribosome pathway might play an essential role in the regulation of PKM2, and interestingly, four out of ten hub genes were found to be highly related to OS in several cancers. Finally, in thyroid cancer specimen, we validated the expression and potential mechanisms by proteomic sequencing and PRM validation. Conclusion: In the majority of cancers, the higher expression of PKM2 was highly associated with poor prognosis. Further molecular mechanism exploration implied that PKM2 might serve as a potential target for cancer survival and immunotherapy by regulating the ribosome pathway.