RUNX1, FUS, and ELAVL1-induced circPTPN22 promote gastric cancer cell proliferation, migration, and invasion through miR-6788-5p/PAK1 axis-mediated autophagy.

BACKGROUND: An increasing number of studies have demonstrated the association of circular RNAs (circRNAs) with the pathological processes of various diseases and their involvement in the onset and progression of multiple cancers. Nevertheless, the functional roles and underlying mechanisms of circRNAs in the autophagy regulation of gastric cancer (GC) have not been fully elucidated. METHODS: We used transmission electron microscopy and the mRFP-GFP-LC3 dual fluorescent autophagy indicator to investigate autophagy regulation. The cell counting kit-8 assay, colony formation assay, 5-ethynyl-2'-deoxyuridine incorporation assay, Transwell assay, and Western blot assay were conducted to confirm circPTPN22's influence on GC progression. Dual luciferase reporter assays validated the binding between circPTPN22 and miR-6788-5p, as well as miR-6788-5p and p21-activated kinase-1 (PAK1). Functional rescue experiments assessed whether circPTPN22 modulates PAK1 expression by competitively binding miR-6788-5p, affecting autophagy and other biological processes in GC cells. We investigated the impact of circPTPN22 on in vivo GC tumors using a nude mouse xenograft model. Bioinformatics tools predicted upstream regulatory transcription factors and binding proteins of circPTPN22, while chromatin immunoprecipitation and ribonucleoprotein immunoprecipitation assays confirmed the binding status. RESULTS: Upregulation of circPTPN22 in GC has been shown to inhibit autophagy and promote cell proliferation, migration, and invasion. Mechanistically, circPTPN22 directly binds to miR-6788-5p, subsequently regulating the expression of PAK1, which activates protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) phosphorylation. This modulation ultimately affects autophagy levels in GC cells. Additionally, runt-related transcription factor 1 (RUNX1) negatively regulates circPTPN22 expression, while RNA-binding proteins such as FUS (fused in sarcoma) and ELAVL1 (recombinant ELAV-like protein 1) positively regulate its expression. Inhibition of the autophagy pathway can increase FUS expression, further upregulating circPTPN22 in GC cells, thereby exacerbating the progression of GC. CONCLUSION: Under the regulation of the transcription factor RUNX1 and RNA-binding proteins FUS and ELAVL1, circPTPN22 activates the phosphorylation of Akt and Erk through the miR-6788-5p/PAK1 axis, thereby modulating autophagy in GC cells. Inhibition of autophagy increases FUS, which in turn upregulates circPTPN22, forming a positive feedback loop that ultimately accelerates the progression of GC.

Comprehensive profiles of sulfur cycling microbial communities along a mangrove sediment depth.

The sulfur (S) cycle is an important biogeochemical cycle with profound implications for both cellular- and ecosystem-level processes by diverse microorganisms. Mangrove sediments are a hotspot of biogeochemical cycling, especially for the S cycle with high concentrations of S compounds. Previous studies have mainly focused on some specific inorganic S cycling processes without paying specific attention to the overall S-cycling communities and processes as well as organic S metabolism. In this study, we comprehensively analyzed the distribution, ecological network and assembly mechanisms of S cycling microbial communities and their changes with sediment depths using metagenome sequencing data. The results showed that the abundance of gene families involved in sulfur oxidation, assimilatory sulfate reduction, and dimethylsulfoniopropionate (DMSP) cleavage and demethylation decreased with sediment depths, while those involved in S reduction and dimethyl sulfide (DMS) transformation showed an opposite trend. Specifically, glpE, responsible for converting S2O32- to SO32-, showed the highest abundance in the surface sediment and decreased with sediment depths; in contrast, high abundances of dmsA, responsible for converting dimethyl sulfoxide (DMSO) to DMS, were identified and increased with sediment depths. We identified Pseudomonas and Streptomyces as the main S-cycling microorganisms, while Thermococcus could play an import role in microbial network connections in the S-cycling microbial community. Our statistical analysis showed that both taxonomical and functional compositions were generally shaped by stochastic processes, while the functional composition of organic S metabolism showed a transition from stochastic to deterministic processes. This study provides a novel perspective of diversity distribution of S-cycling functions and taxa as well as their potential assembly mechanisms, which has important implications for maintaining mangrove ecosystem functions.

Identification of a longevity gene through evolutionary rate covariation of insect mito-nuclear genomes.

Oxidative phosphorylation, essential for energy metabolism and linked to the regulation of longevity, involves mitochondrial and nuclear genes. The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied, but little is known about whether other nuclear genes not targeted to mitochondria evolutionarily and functionally interact with mitochondrial genes. Here we systematically examined the ERC of mitochondrial and nuclear benchmarking universal single-copy ortholog (BUSCO) genes from 472 insects, identifying 75 non-mitochondria-targeted nuclear genes. We found that the uncharacterized gene CG11837-a putative ortholog of human DIMT1-regulates insect lifespan, as its knockdown reduces median lifespan in five diverse insect species and Caenorhabditis elegans, whereas its overexpression extends median lifespans in fruit flies and C. elegans and enhances oxidative phosphorylation gene activity. Additionally, DIMT1 overexpression protects human cells from cellular senescence. Together, these data provide insights into the ERC of mito-nuclear genes and suggest that CG11837 may regulate longevity across animals.

SETMAR Facilitates the Differentiation of Thyroid Cancer by Regulating SMARCA2-Mediated Chromatin Remodeling.

Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial-mesenchymal transformation (EMT), thyroid differentiation-related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor-based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. Finally, the METTL3-14-WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR-SMARCA2-TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation.

Multidimensional data analysis revealed thyroiditis-associated TCF19 SNP rs2073724 as a highly ranked protective variant in thyroid cancer.

BACKGROUND: Thyroid cancer represents the most prevalent malignant endocrine tumour, with rising incidence worldwide and high mortality rates among patients exhibiting dedifferentiation and metastasis. Effective biomarkers and therapeutic interventions are warranted in aggressive thyroid malignancies. The transcription factor 19 (TCF19) gene has been implicated in conferring a malignant phenotype in cancers. However, its contribution to thyroid neoplasms remains unclear. RESULTS: In this study, we performed genome-wide and phenome-wide association studies to identify a potential causal relationship between TCF19 and thyroid cancer. Our analyses revealed significant associations between TCF19 and various autoimmune diseases and human cancers, including cervical cancer and autoimmune thyroiditis, with a particularly robust signal for the deleterious missense variation rs2073724 that is associated with thyroid function, hypothyroidism, and autoimmunity. Furthermore, functional assays and transcriptional profiling in thyroid cancer cells demonstrated that TCF19 regulates important biological processes, especially inflammatory and immune responses. We demonstrated that TCF19 could promote the progression of thyroid cancer in vitro and in vivo and the C>T variant of rs2073724 disrupted TCF19 protein binding to target gene promoters and their expression, thus reversing the effect of TCF19 protein. CONCLUSIONS: Taken together, these findings implicate TCF19 as a promising therapeutic target in aggressive thyroid malignancies and designate rs2073724 as a causal biomarker warranting further investigation in thyroid cancer.

Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma.

Single-cell transcriptome sequencing (scRNA-seq) provides a higher resolution of cellular differences than bulk RNA-seq, enabling the dissection of cell-type-specific responses to perturbations in papillary thyroid carcinoma (PTC). However, cellular genomic features are highly heterogeneous and have a large number of genes without any expression signals, which hinders the statistical power to identify differentially expressed genes and may generate many false-positive results. To overcome this challenge, we conducted an integrative analysis on two PTC scRNA-seq datasets and cross-validated consistent differential expression. By combining results from 32 common cell types in the two studies, we identified 31 consistently differentially expressed genes (DEGs) across seven cell types, including B cells, endothelial cells, epithelial cells, monocytes, NK cells, smooth muscle cells, and T cells. Functional enrichment analysis revealed that these genes are important for the adaptive immune response and autoimmune thyroid diseases. The additional disease-free survival analysis also confirmed that these 31 genes significantly affected patient survival time in large scale thyroid cancer cohort. Furthermore, we experimentally validated one of the top consistent DEGs as a potential biomarker gene of PTC epithelial cells, KRT7, which may be a upstream gene for the NF-κB signaling pathway. The result shows that KRT7 may promote thyroid cancer metastasis through the epithelial-mesenchymal transition and NF-κB signaling pathway. In summary, our single-cell transcriptome integration-based approach may provide insights into the important role of NF-κB in the underlying biology of the PTC.

The value of the neutrophil to lymphocyte ratio and PLT count for the diagnosis and prediction of COVID-19 severity.

BACKGROUND: COVID-19 and influenza A can cause severe respiratory illness. Differentiating between the two diseases and identifying critically ill patients in times of epidemics become a challenge for frontline medical staff. We sought to investigate whether both diseases and their severity could be recognized by routine blood parameters. METHODS: Our retrospective study analysed the clinical data and first-time routine blood parameters of 80 influenza A patients and 123 COVID-19 patients. COVID-19 patients were divided into three groups according to treatment modalities and outcomes: outpatient group, inpatient without invasive mechanical ventilation (IMV) group, and inpatient with IMV group. We used the Mann-Whitney and Kruskal-Wallis tests to analyze the differences in routine blood parameters between the two or three groups. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) were used to assess the diagnostic accuracy. RESULTS: Compared with outpatient influenza A patients, outpatient COVID-19 patients had a higher neutrophil to lymphocyte ratio (NLR) (6.63 vs 3.55). ROC analysis showed that the NLR had a high diagnostic value for differentiating COVID-19 from influenza A (AUC = 0.739). The best cut-off point of the NLR was 6.48, the diagnostic sensitivity was 0.523, and the specificity was 0.925. The median platelet (PLT) count in the different COVID-19 groups was as follows: outpatient group (189×109/L), inpatient without IMV group (161×109/L), and inpatient with IMV group (94×109/L). Multivariate logistic regression analysis found a significant association between PLT and treatment modality and outcome in COVID-19 patients (p<0.001). CONCLUSIONS: NLR can be used as a potential biological indicator to distinguish COVID-19 and influenza A. Decreased PLT predicts the critical condition of COVID-19 patients and helps stratify the treatment of COVID-19 patients.

An Educational Intervention for Coronary Heart Disease Patients With Type D Personality: A Randomized Controlled Trial.

BACKGROUND: Type D personality, a newly specified personality type defined as the interaction of high levels of negative affectivity and social inhibition, is associated with poor health outcomes. Few interventional studies have been performed to improve health outcomes in this subpopulation. PURPOSE: This study was developed to examine the effects of an educational intervention on psychological health, health-promoting behaviors, and quality of life in coronary heart disease (CHD) patients with type D personality in China. METHODS: A randomized controlled trial was adopted. One hundred twenty-eight patients with CHD and type D personality were randomly assigned. The intervention group received the 12-week educational intervention in addition to usual care, whereas the control group received usual care only. Data on anxiety and depression, health-promoting behaviors, and quality of life were collected at baseline and at 1 and 3 months after enrollment. After controlling for the covariates, the generalized estimating equation model was used to examine the intervention effects. RESULTS: The mean age of the participants was 61.02 years, and more than 70% were male. Results of the generalized estimating equation analysis showed significantly greater improvements in anxiety, depression, and health-promoting behaviors in the intervention group than in the control group. In addition, quality of life, the domains of angina limitation, angina stability, and treatment satisfaction were found to have improved more significantly in the intervention group than the control group, whereas the posttest changes in angina frequency and disease perception were found to be similar in both groups. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The educational intervention was shown to be effective in improving psychological health, health-promoting behaviors, and certain domains of quality of life in patients with CHD and type D personality. Nurses should identify patients with this personality type and provide tailored care to improve their health outcomes in clinical practice.

Permeability Coefficient of Concrete under Complex Stress States.

Hydraulic structures are typically subjected to long-term hydraulic loading, and concrete-the main material of structures-may suffer from cracking damage and seepage failure, which can threaten the safety of hydraulic structures. In order to assess the safety of hydraulic concrete structures and realize the accurate analysis of the whole failure process of hydraulic concrete structures under the coupling effect of seepage and stress, it is vital to comprehend the variation law of concrete permeability coefficients under complex stress states. In this paper, several concrete samples were prepared, designed for loading conditions of confining pressures and seepage pressures in the first stage, and axial pressures in the later stage, to carry out the permeability experiment of concrete materials under multi-axial loading, followed by the relationships between the permeability coefficients and axial strain, and the confining and seepage pressures were revealed accordingly. In addition, during the application of axial pressure, the whole process of seepage-stress coupling was divided into four stages, describing the permeability variation law of each stage and analyzing the causes of its formation. The exponential relationship between the permeability coefficient and volume strain was established, which can serve as a scientific basis for the determination of permeability coefficients in the analysis of the whole failure process of concrete seepage-stress coupling. Finally, this relationship formula was applied to numerical simulation to verify the applicability of the above experimental results in the numerical simulation analysis of concrete seepage-stress coupling.

[Current Status of and Progress in Research on Obstructive Sleep Apnea and Comorbid Depressive Disorders].

Obstructive sleep apnea (OSA) and depressive disorders are common diseases in adults and they share in common many clinical symptoms, including sleep disturbance, fatigue, lack of concentration and cognitive function impairment. OSA and depressive disorders also share some common pathophysiological changes, including increased activity of the hypothalamic-pituitary-adrenal (HPA) axis, chronic low-grade inflammation, oxidative stress, and changes in gut microbiota and neurotransmitters, which may contribute to the comorbidity of OSA and depressive disorders. In the case of comorbid OSA and depressive disorders, OSA and depressive disorders may affect and exacerbate each other, thereby increasing the severity of diseases, entailing greater risk of cardiovascular and metabolic diseases, and causing greater difficulty in treatment. Herein, we summarized the latest research findings on the epidemiology, possible mechanisms, harms, and treatment of comorbid OSA and depressive disorders. This review may help improve clinicians' understanding of the comorbidity of OSA and depression disorders, thereby promoting early screening, prompt diagnosis and treatment, and improved prognosis. Further studies are needed for better understanding of the effect of the comorbidity of OSA and depressive disorders and treatment on cardiometabolic diseases.

[Effect of Objective Daytime Sleepiness on Heart Rate Variability in Patients With Obstructive Sleep Apnea].

Objective: Excessive daytime sleepiness (EDS) is associated with cardiovascular events in patients with obstructive sleep apnea (OSA). Our study explored the correlation between objective daytime sleepiness assessed with daytime multiple sleep latency tests (MSLT) and heart rate variability (HRV) in OSA patients. The results may provide insight into possible mechanisms underlying increased risk of cardiovascular events in patients with OSA. Methods: A retrospective analysis was conducted with the data of 139 patients with OSA and 35 patients with primary snoring. All subjects underwent polysomnography (PSG) and MSLT at West China Hospital between January 2019 and May 2022. We used mean sleep latency (MSL) to measure the severity of EDS and to categorize OSA patients into three groups, severe EDS, light EDS, and non-EDS, with MSL of less than 5 minutes, 5 to 10 minutes, and greater than 10 minutes as the respective defining criteria for classification. A comparison of sleep structure, clinical characteristics, and HRV parameters was performed in order to evaluate the difference between OSA subgroups with varying levels of objective EDS and the primary snoring group. In addition, we also analyzed the correlation between MSL and HRV parameters. Results: Severe EDS patients had higher values of standard deviation of all N-N intervals (SDNN), total spectral power (TOT), and low-frequency power (LF) as compared to non-EDS patients, which was indicative of sympathetic stimulation ( P<0.05). Additionally, high-frequency power (HF) was also higher in severe EDS patients, which indicated decreased parasympathetic drive. A significantly positive correlation was found between MSL and the values of SDNN, TOT, LF, and HF in OSA patients. Conclusion: OSA patients with objective EDS have elevated sympathetic drive and decreased parasympathetic drive. A positive correlation was found between this change in neural activity and the shortening of MSL.

[Clinical Characteristics of Obstructive Sleep Apnea and Comorbid Primary Aldosteronism].

Objective: To explore the characteristics of patients with obstructive sleep apnea (OSA) and comorbid primary aldosteronism (PA) and to explore the relevant factors affecting plasma aldosterone concentration. Methods: A total of 105 patients diagnosed with PA and admitted at West China Hospital, Sichuan University between January 2016 and December 2021 were retrospectively analyzed. The subjects were divided into a PA with comorbid snoring group (n=20) and a PA with comorbid OSA group (n=85) based on the results of polysomnography (PSG). The PA with comorbid OSA group was further divided into mild, moderate, and severe subgroups according to the apnea-hypopnea index (AHI). A total of 85 outpatients diagnosed with OSA were included as the control group. Demographic, clinical, biochemical, and PSG data were compared between the groups. Results: Compared with patients with only OSA, a significantly higher proportion of patients with OSA and comorbid PA had hypertension and elevated levels of systolic and diastolic blood pressure (P<0.05). In addition, patients with OSA and comorbid PA had significantly increased AHI and significantly decreased mean oxygen saturation and sleep efficiency (P<0.05). The more severe the OSA was, the higher levels of BMI, cholesterol, low-density lipoprotein, and uric acid the PA patients had. Linear regression analysis showed that the lowest oxygen saturation (ß=－0.222, P=0.045) was negatively correlated with plasma aldosterone concentration. Conclusion: Comorbidity with PA can aggravate the clinical manifestations of OSA, while OSA further disrupted the metabolism of lipids and uric acid in PA patients. Plasma aldosterone concentrations in patients with comorbid OSA and PA were affected by the lowest oxygen saturation level.

Insights on hematopoietic cell kinase: An oncogenic player in human cancer.

Hematopoietic cell kinase (Hck) is a member of the Src family and is expressed in hematopoietic cells. By regulating multiple signaling pathways, HCK can interact with multiple receptors to regulate signaling events involved in cell adhesion, proliferation, migration, invasion, apoptosis, and angiogenesis. However, aberrant expression of Hck in various hematopoietic cells and solid tumors plays a crucial role in tumor-related properties, including cell proliferation and epithelial-mesenchymal transition. In addition, Hck signaling regulates the function of immune cells such as macrophages, contributing to an immunosuppressive tumor microenvironment. The clinical success of various kinase inhibitors targeting the Src kinase family has validated the efficacy of targeting Src, and therapies with highly selective Hck kinase inhibitors are in clinical trials. This article reviews Hck inhibition as an emerging cancer treatment strategy, focusing on the expressions and functions of Hck in tumors and its impact on the tumor microenvironment. It also explores preclinical and clinical pharmacological strategies for Hck targeting to shed light on Hck-targeted tumor therapy.

Effects of Different Hamstring Eccentric Exercise Programs on Preventing Lower Extremity Injuries: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aims to investigate the effects and differences of various hamstring eccentric training protocols for the prevention of lower limb injuries, and we further propose a more refined hamstring eccentric training protocol for the prevention of lower limb injuries. A literature search for the effects of hamstring eccentric training on lower extremity sports injuries was conducted using the PubMed, Web of Science, and EMBASE databases, and the literature was searched covering the period from the date of the database's creation to 20 August 2022. A meta-analysis of the included literature was performed using R.4.21 for lower extremity injuries, injuries in various parts of the lower extremity, and subgroup analysis for exercise frequency, exercise cycle, and exercise population. A total of 23 randomized controlled trial (RCT) studies were found to be included in the meta-analysis, and 15 of these trials, totaling 14,721 patients, were determined to be included in the overall lower extremity injury prevention effect. The analysis showed that the implementation of a hamstring eccentric training program reduced lower extremity injuries by 28%, and it resulted in a 46% decrease in hamstring injury rate and a 34% decrease in knee injury rate. The subgroup analysis revealed that the frequency of exercise was most significant in the twice-a-week exercise group, that the exercise program was most effective in preventing injuries in the 21-30-week exercise period, and that the program was most effective in preventing injuries in elite athletes and amateur adult athletic populations, compared with adolescents.

MicroRNA miR-1275 coordinately regulates AEA/LPA signals via targeting FAAH in lipid metabolism reprogramming of gastric cancer.

Glycerophospholipid signal and fatty acid metabolism are closely related to the occurrence and progression of tumours, and metabolic reprogramming caused by hydrolytic enzymes plays an important role in gastric cancer (GC). Here, we performed whole transcriptome sequencing and combined qRT-PCR to screen out the significantly high expression of fatty acid amide hydrolase (FAAH) in GC tissues, which was further verified in both TCGA and Oncomine databases. Functional tests confirmed that FAAH played an oncogene role in GC, and silencing FAAH could delay tumour growth, inhibit tumour metastasis, and promote cell apoptosis both in vitro and in vivo. FAAH-mediated lipid metabolism reprogramming through coordinated regulation of arachidonoyl ethanolamide (AEA)/lysophosphatidic acid (LPA) signalling and activated the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) axis to promote GC progression. Luciferase reporter assay and immunofluorescence-fluorescence in situ hybridization (IF-FISH) were applied to validate the interactions of miR-1275/FAAH. Overexpression and knockdown of miR-1275 in vitro could indirectly modulate the above lipid signalling by targeting FAAH, thereby affecting GC progression. Our study indicates that deregulated FAAH is a key lipid signal and the miR-1275/FAAH/AEA/LPA axis can serve as a diagnostic biomarker for GC or as a target for therapy development.

Investigation of the Negative Emotions Exhibited in Patients with Coronary Heart Disease After PCI and Any Influencing Factors.

Purpose: To understand existing negative emotions in patients with coronary heart disease after percutaneous coronary stent implantation (PCI) and analyse its influencing factors. Methods: Patients with coronary heart disease after PCI in three tertiary hospitals in Changsha City from April to September 2018 were selected as the research subjects. The self-designed general information questionnaire assessed irritability, depression and anxiety (IDA) on a self-rating scale. It was used to examine patients' existing negative emotions with coronary heart disease after PCI and analyse the influencing factors. Results: 203 questionnaires were distributed, and 202 valid questionnaires were recovered, with an effective recovery rate of 99.5%. The IDA score of patients with coronary heart disease after PCI was 17.01±7.60 points, the incidence of negative emotions was 63.8%, and the incidences of depression, anxiety and irritability were 39.6%, 8.4% and 15.8%, respectively. Negative emotion was taken as the dependent variable and a patient's general data, such as lifestyle and disease, as the independent variables. A univariate analysis was conducted to obtain gender, age, educational level, marital status, work status, per capita monthly household income, sleep status, etc. Seven factors were identified as the influencing factors of negative emotions in patients with coronary heart disease after PCI, and the difference was statistically significant (P<0.05). Conclusion: Most patients with coronary heart disease after PCI tend to exhibit negative emotions such as anxiety and depression. Medical staff should attach great importance to evaluating any negative feelings in this group and take timely targeted intervention measures to prevent and mitigate the occurrence and development of these adverse emotions in patients with coronary heart disease after PCI.

A Nomogram Predicting the Overall Survival and Cancer-Specific Survival in Patients with Parathyroid Cancer: A Retrospective Study.

Purpose: This study aimed to explore a visual model for predicting the prognosis of patients with parathyroid carcinoma (PC) and analyze related biochemistries in different groups of stage. Methods: The training dataset of 342 patients with PC was obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and the validation dataset included 59 patients from The First Affiliated Hospital of Zhengzhou University. Univariate and multivariate Cox regression analyses were performed to evaluate significant independent prognostic factors. Based on those factors, nomograms and Web-based probability calculators were constructed to evaluate the overall survival (OS) and the cancer-specific survival (CSS) at 3, 5, and 8 years. The concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram in the training set and validation set. Moreover, biochemistries from the validation set were retrospectively analyzed in different groups of stage by Kruskal-Wallis test. Results: Age, marital status, tumor size, stage, lymph node status, and radiation were identified as prognostic factors of OS. In contrast, only tumor size and stage were predictive for CSS. The nomogram was developed based on these independent factors. The C-index, ROC curve, calibration curve, and DCA of the nomogram in both training and validation sets showed that the nomogram had good predictive value, stability, and clinical benefit in predicting 3-, 5-, and 8-year OS and CSS in PC patients. Among the 59 PC patients from our hospital, lower albumin (ALB) levels and higher postoperative parathyroid hormone (PTH) levels were found in patients with distant metastasis (Distant vs. Regional ALB levels: p = 0.037; Distant vs. Local ALB levels: p = 0.046; Distant vs. Regional postoperative PTH levels: p = 0.002; Distant vs. Local postoperative PTH: p = 0.002). Conclusion: The established nomogram application can provide accurate prognostics for patients with PC in the Chinese population, but it must be validated on prospectively collected real-world data.

Diagnostic value of procalcitonin for bacterial infections in patients undergoing hemodialysis: a systematic review and meta-analysis.

BACKGROUND: The diagnostic value of procalcitonin (PCT) in patients undergoing hemodialysis (HD) remains unclear. METHODS: We searched multiple databases (PubMed, EMBASE, and Cochrane Library) for studies published through August 2021 that evaluated the diagnostic performance of PCT in patients undergoing HD and having suspected bacterial infections. The bivariate fixed effects model was used to calculate pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (SROC) curves. RESULTS: We identified a total of 1799 studies, of which seven diagnostic studies comprised 1444 patients and 430 bacterial infection episodes. Bivariate pooled sensitivity and specificity for PCT were 0.90 (95% CI: 0.85-0.94) and 0.83 (95% CI: 0.56-0.95), respectively. Furthermore, pooled DOR, PLR, NLR, and area under the curve (AUC) were 47 (95% CI: 11-209), 5.4 (95% CI: 1.7-16.9), 0.12 (95% CI: 0.07-0.20), and 0.92 (95% CI: 0.90-0.94), respectively. We also compared the diagnostic accuracy of PCT and C-reactive protein (CRP), and our results showed that the diagnostic accuracy parameters for PCT were significantly higher than those for CRP. CONCLUSIONS: PCT is a useful marker for diagnosis of bacterial infections in patients undergoing HD at a cutoff value of 1.5 ng/ml.

[Characteristics of Sleep Electroencephalographic Power in Chronic Insomnia Patients].

OBJECTIVE: To study the sleep electroencephalogram (EEG) power features of patients with chronic insomnia. METHODS: Retrospective analysis was performed with patients who met the ICD-10 diagnostic criteria for chronic insomnia, using polysomnography (PSG) to examine the overnight sleep EEG. The sleep architectures and relative EEG power across five frequency bands during overnight sleep were compared to study the differences between the insomnia and control groups. Furthermore, the correlation between EEG power and various PSG measures was also analyzed. RESULTS: Forty-five subjects were enrolled in the study, including 25 chronic insomniacs (18 females, aged [36.2±10.7] years) and 20 controls (18 females, aged [36.1±7.6] years). Compared to those of the control group, insomnia patients had significantly lower value of delta power ([38.0±6.1] vs. [43.2±5.8], P<0.05) in the NREM1 stage, and increased value of beta power during total NREM, NREM1 and NREM2 (NREM sleep [5.4±2.3] vs. [3.8±1.4], NREM1 [11.3±3.5] vs. [8.7±2.8], and NREM2 [5.7±2.3] vs. [4.4±1.4], all P<0.05). For correlation analyses, in the insomnia group, a significantly positive correlation was found between the delta value during NREM sleep and the duration of NREM3 sleep ( r=0.527). The beta value during NREM sleep was found to be negatively correlated to the duration of NREM3 sleep ( r=－0.767). A positive correlation was found between the beta value during NREM sleep and the duration of NREM1 and NREM2 sleep ( r=0.486 and 0.589, respectively). CONCLUSION: The results suggest that patients with chronic insomnia have decreased low-frequency EEG power, but increased high-frequency EEG power during NREM sleep. The findings indicate that cortex arousal level is elevated in chronic insomniacs during NREM sleep.

Biogeography of the Respiratory Tract Microbiome in Patients With Malignant Tracheal Tumors.

BACKGROUND: This study aimed to characterize the bacterial microbiota in the oral cavity (OC), throat, trachea, and distal alveoli of patients with primary malignant tracheal tumors (PMTT), including squamous cell carcinoma (SCC) and salivary gland carcinoma patients (SGC), for comparison with a matched non-malignant tracheal tumor (NMTT) group. METHODS: Patients with pathological diagnosis of PMTT and NMTT were included in this study. Saliva, throat swab (TS), trachea protected specimen brush (PSB), and bronchoalveolar lavage fluid (BALF) samples were collected for 16S rRNA gene sequencing. The composition, diversity, and distribution of the microbiota were compared among biogeographic sampling sites and patient groups. The relationship between the genera-level taxon abundance and tracheal tumor types was also investigated to screen for candidate biomarkers. FINDINGS: The most represented phyla in the four sites were Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. In SCC patients, the relative abundance of Bacteroidetes and Firmicutes gradually decreased with increasing depth into the respiratory tract, while the relative abundance of Proteobacteria gradually increased. Bacterial communities at the four biogeographic sites formed two distinct clusters, with OC and TS samples comprising one cluster and PSB and BALF samples comprising the other group. Principal coordinate analysis showed that trachea microbiota in SCC patients were distinct from that of SGC or NMTT patients. In the trachea, AUCs generated by Prevotella and Alloprevotella showed that the abundance of these genera could distinguish SCC patients from both NMTT and SGC patients. INTERPRETATION: The structure of respiratory tract microbiota in PMTT patients is related to tumor type. Certain bacteria could potentially serve as markers of SCC, although verification with large-sample studies is necessary.