WWC1 upregulation accelerates hyperuricemia by reduction of renal uric acid excretion through Hippo signaling pathway.

Hyperuricemia (HUA) is a metabolic disorder characterized by elevated serum uric acid (UA), primarily attributed to the hepatic overproduction and renal underexcretion of UA. Despite the elucidation of molecular pathways associated with this underexcretion, the etiology of HUA remains largely unknown. In our study, using by Uox knockout rats, HUA mouse and cell line models, we discovered that the increased WWC1 levels were associated with decreased renal UA excretion. Additionally, using by knockdown and overexpression approaches, we found that WWC1 inhibited UA excretion in renal tubular epithelial cells. Mechanistically, WWC1 activated the Hippo pathway, leading to phosphorylation and subsequent degradation of the downstream transcription factor YAP1, thereby impairing the ABCG2 and OAT3 expression through transcriptional regulation. Consequently, this reduction leaded to a decrease in UA excretion in renal tubular epithelial cells. In conclusion, our study has elucidated the role of upregulated WWC1 in renal tubular epithelial cells inhibiting the excretion of UA in the kidneys and causing HUA.

Deciphering the molecular regulatory of RAB32/GPRC5A axis in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a significant public health problem characterized by persistent airflow limitation. Despite previous research into the pathogenesis of COPD, a comprehensive understanding of the cell-type-specific mechanisms in COPD remains lacking. Recent studies have implicated Rab GTPases in regulating chronic immune response and inflammation via multiple pathways. In this study, the molecular regulating mechanism of RAB32 in COPD was investigated by multiple bioinformatics mining and experimental verification. METHODS: We collected lung tissue surgical specimens from Zhongshan Hospital, Fudan University, and RT-qPCR and western blotting were used to detect the expression of Rabs in COPD lung tissues. Four COPD microarray datasets from the Gene Expression Omnibus (GEO) were analyzed. COPD-related epithelial cell scRNA-seq data was obtained from the GSE173896 dataset. Weighted gene co-expression network analysis (WGCNA), mfuzz cluster, and Spearman correlation analysis were combined to obtain the regulatory network of RAB32 in COPD. The slingshot algorithm was used to identify the regulatory molecule, and the co-localization of RAB32 and GPRC5A was observed with immunofluorescence. RESULTS: WGCNA identified 771 key module genes significantly associated with the occurrence of COPD, including five Rab genes. RAB32 was up-regulated in lung tissues from subjects with COPD as contrast to those without COPD on both mRNA and protein levels. Integrating the results of WGCNA, Mfuzz clusters, and Spearman analysis, nine potential interacting genes with RAB32 were identified. Among these genes, GPRC5A exhibited a similar molecular expression pattern to RAB32. Co-expression density analysis at the cell level demonstrated that the co-expression density of RAB32 and GPRC5A was higher in type I alveolar epithelial cells (AT1s) than in type II alveolar epithelial cells (AT2s). The immunofluorescence also confirmed the co-localization of RAB32 and GPRC5A, and the Pearson correlation analysis found the relationship between RAB32 and GPRC5A was significantly stronger in the COPD lungs (r = 0.65) compared to the non-COPD lungs (r = 0.33). CONCLUSIONS: Our study marked endeavor to delineate the molecular regulatory axis of RAB32 in COPD by employing diverse methods and identifying GPRC5A as a potential interacting molecule with RAB32. These findings offered novel perspectives on the mechanism of COPD.

The correlation between serum angiopoietin-2 levels and acute kidney injury (AKI): a meta-analysis.

INTRODUCTION: The correlation between serum angiopoietin-2 levels and acute kidney injury (AKI) is a topic of significant clinical interest. This meta-analysis aims to provide a comprehensive evaluation of this relationship. CONTENT: A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane databases up to October 11, 2023. The included studies were evaluated using the Newcastle-Ottawa Scale (NOS) and Methodological Index for Non-Randomized Studies (MINORS). Weighted mean differences (WMD) and odds ratios (OR) were calculated using random-effects models. Sensitivity analysis, funnel plots, and Egger's test were used to assess the robustness and publication bias of the findings. Subgroup analyses were performed to explore potential variations between adults and children. SUMMARY: Eighteen studies encompassing a total of 7,453 participants were included. The analysis revealed a significant elevation in serum angiopoietin-2 levels in patients with AKI compared to those without (WMD: 4.85; 95 % CI: 0.75 to 0.27; I²=93.2 %, p<0.001). Subgroup analysis indicated significantly higher angiopoietin-2 levels in adults with AKI (WMD: 5.17; 95 % CI: 3.51 to 6.83; I²=82.6 %, p<0.001), but not in children. Additionally, high serum angiopoietin-2 levels were associated with an increased risk of AKI (OR: 1.58; 95 % CI: 1.39 to 1.8; I²=89.1 %, p<0.001). Sensitivity analysis validated the robustness of these results, showing no substantial change in the overall effect size upon the exclusion of individual studies. OUTLOOK: This meta-analysis supports a significant association between elevated serum angiopoietin-2 levels and increased risk of AKI. The observed differential association between adults and children highlights the need for further targeted research to understand these age-specific variations.

Near-edge x-ray absorption fine structure spectra and specific dissociation of small peptoid molecules.

In this study, the total ion yield near-edge x-ray absorption fine structure spectra of four similar peptoid molecules, which differ in the numbers and positions of methyl groups, were investigated experimentally and theoretically. At each excitation energy, the intensity and branching ratio of each ionic product were measured. At a few resonant excitation energies, a specific dissociation of the C-CO bond at the nitrogen and oxygen K-edges and of the N-CO bond at the carbon K-edge was dominant, which correlated well with the predicted destination antibonding orbitals of the core electron excitation. These specific dissociation mechanisms of small peptoid molecules could provide insights into similar phenomena that occur in peptide molecules.

Glucose-Triggered Release of trans-N-p-Coumaroyltyramine from Zeolitic Imidazolate Framework-8 (ZIF8) Modified with Dioscorea opposita Thunb Polysaccharide.

A Dioscorea opposita Thunb polysaccharide (DOP)-modified ZIF8 material was developed in this study, which can be used as a "smart" glucose-responsive carrier to control the slow release of drugs. The 3-aminophenylboronic acid (APBA) functionalized carboxylated long-chain polymer poly(ethylene glycol) (PEG) segments, which were first modified on the surface of ZIF8 nanoparticles with a hydrogen bond and then chemically cross-linked with DOP through a borate ester bond, leading to the drugs loaded on ZIF8 being "closed" in PBS but being "open" via taking off the DOP coating in high concentrations of glucose; thus, leakage can be prevented in the drug loaded and a glucose-triggered release can effectively result. Moreover, the materials showed good biocompatibility and the released trans-N-p-coumaroyltyramine (NCT) could work synergistically with the DOP to improve insulin resistance and promote glucose consumption in insulin-resistant HepG2 cells.

Fibroblast growth factor 10 attenuates chronic obstructive pulmonary disease by protecting against glycocalyx impairment and endothelial apoptosis.

BACKGROUND: The defects and imbalance in lung repair and structural maintenance contribute to the pathogenesis of chronic obstructive pulmonary diseases (COPD), yet the molecular mechanisms that regulate lung repair process are so far incompletely understood. We hypothesized that cigarette smoking causes glycocalyx impairment and endothelial apoptosis in COPD, which could be repaired by the stimulation of fibroblast growth factor 10 (FGF10)/FGF receptor 1 (FGFR1) signaling. METHODS: We used immunostaining (immunohistochemical [IHC] and immunofluorescence [IF]) and enzyme-linked immunosorbent assay (ELISA) to detect the levels of glycocalyx components and endothelial apoptosis in animal models and in patients with COPD. We used the murine emphysema model and in vitro studies to determine the protective and reparative role of FGF10/FGFR1. RESULTS: Exposure to cigarette smoke caused endothelial glycocalyx impairment and emphysematous changes in murine models and human specimens. Pretreatment of FGF10 attenuated the development of emphysema and the shedding of glycocalyx components induced by CSE in vivo. However, FGF10 did not attenuate the emphysema induced by endothelial-specific killing peptide CGSPGWVRC-GG-D(KLAKLAK)2. Mechanistically, FGF10 alleviated smoke-induced endothelial apoptosis and glycocalyx repair through FGFR1/ERK/SOX9/HS6ST1 signaling in vitro. FGF10 was shown to repair pulmonary glycocalyx injury and endothelial apoptosis, and attenuate smoke-induced COPD through FGFR1 signaling. CONCLUSIONS: Our results suggest that FGF10 may serve as a potential therapeutic strategy against COPD via endothelial repair and glycocalyx reconstitution.

Research on application of a new bottom trap technology to catch particles rich in nutrients in a large shallow lake.

The resuspension and sedimentation of particulate matter and the release of nutrients from sediment are important factors affecting the eutrophication of shallow lakes. The capture and removal of particles rich in nitrogen, phosphorus, and other nutrients at the bottom of lakes is of great significance for improving the management and eutrophication status of lakes. This study investigated the feasibility of applying lake bottom trap technology in seven different locations in Lake Chaohu, which is the fifth largest freshwater lake in China. The results showed that the trap in the western part of Lake Chaohu had the highest sedimentation rate and could capture most of the nutrients. The sedimentation rates were higher in spring and summer than in autumn and winter. The bottom trap effectively collected and preserved chlorophyll a, organic matter, total nitrogen, and total phosphorus. The trap per meter length (15-20 m wide) could catch 20.7-27.6 m3 of particles rich in nutrients with a water content of 50-70%, organic matter content of 281.9-375.8 kg, total nitrogen content of 24.5-32.6 kg, and total phosphorus content of 10.5-14 kg. The proposed bottom trap had little impact on the benthic organism system of the lake. The bottom trap technology used in this study could solve the problem of nitrogen, phosphorus, and algae accumulation in lakes and reservoirs, broaden the utility of lake hydrodynamics in environmental pollution control, and provide new ideas and strategies for the control and management of cumulative pollution in shallow lakes and reservoirs.

Noble Gas in a Ring.

We have designed a new type of molecule with a noble gas (Ng = Kr and Xe) atom in a six-membered ring. Their structures and stability have been studied by density functional theory and by correlated electronic structure calculations. The results showed that the six-membered ring is planar with very short Ng-O and Ng-N polar covalent bonds. The calculated energy barriers for all the unimolecular dissociation pathways are higher than 20 and 35 kcal/mol for Ng = Kr and Xe, respectively. The current study suggests that these molecules and their derivatives might be synthesized and observable at cryogenic conditions.

Different concentrations of C5a affect human dental pulp mesenchymal stem cells differentiation.

BACKGROUND: During the process of deep decay, when decay approaches the pulp, an immune response is triggered inside the pulp, which activates the complement cascade. The effect of complement component 5a (C5a) on the differentiation of dental pulp mesenchymal stem cells (DPSCs) is related to dentin reparation. The aim of the present study was to stimulate DPSCs with different concentrations of C5a and evaluate the differentiation of odontoblasts using dentin sialoprotein (DSP). METHODS: DPSCs were divided into the following six groups: (i) Control; (ii) DPSCs treated with 50 ng/ml C5a; (iii) DPSCs treated with 100 ng/ml C5a; (iv) DPSCs treated with 200 ng/ml C5a; (v) DPSCs treated with 300 ng/ml C5a; and (vi) DPSCs treated with 400 ng/ml C5a. Flow cytometry and multilineage differentiation potential were used to identify DPSCs. Mineralization induction, Real-time PCR and Western blot were conducted to evaluate the differentiation of odontoblast in the 6 groups. RESULT: DPSCs can express mesenchymal stem cell markers, including CD105, CD90, CD73 and, a less common marker, mesenchymal stromal cell antigen-1. In addition, DPSCs can differentiate into adipocytes, neurocytes, chondrocytes and odontoblasts. All six groups formed mineralized nodules after 28 days of culture. Reverse transcription-quantitative PCR and western blotting indicated that the high concentration C5a groups expressed higher DSP levels and promoted DPSC differentiation, whereas the low concentration C5a groups displayed an inhibitory effect. CONCLUSION: In this study, the increasing concentration of C5a, which accompanies the immune process in the dental pulp, has demonstrated an enhancing effect on odontoblast differentiation at higher C5a concentrations in vitro.

Blind Spots of Traditional Microbiological Tests for Severe Community-Acquired Pneumonia in Adults and Availability of Nonculture Techniques: A Nationwide Survey of Physicians in China.

BACKGROUND: In China, no national survey has been conducted to evaluate physicians' attitudes and compliance with guidelines in the management of adult patients with community-acquired pneumonia (CAP). Therefore, this study aimed to evaluate physicians' awareness of the use of microbiological tests in the management of severe CAP (SCAP) and to investigate the availability of nonculture tests in China. METHODS: A nationwide electronic questionnaire survey was conducted among Chinese physicians between March and July 2018, which assessed their viewpoints concerning the issues in the management of SCAP. RESULTS: A total of 6333 physicians completed this survey, evenly covering all career stages. Among these, 3208 (50.6%) and 1936 (30.6%) had blind spots in the application of blood and sputum cultures in the management of SCAP, respectively. Nonteaching hospital, nonrespirologists, and junior career stage were independently associated with misunderstandings. Regarding nonculture methods, 52.7% of the facilities had no access to polymerase chain reaction-based pathogen detection tests. The accessibility of urinary antigen tests for Streptococcus pneumoniae (42.5%) and Legionella pneumophila (38.5%) was also low. The main barriers were inland and remote region, lower hospital level, and nonteaching hospital. CONCLUSIONS: Insufficient use of sputum and blood cultures, together with low accessibility of major nonculture techniques, were noticeable barriers to achieving microbiological diagnosis of SCAP in China. To help curb the overuse of broad-spectrum antibiotics, further measures should be taken to raise awareness among nonspecialists and promote rapid nonculture tests, especially in nonteaching hospitals and developing regions.

Performance of brief ICF-sleep disorders and obesity core set in obstructive sleep apnea patients.

BACKGROUND: Clinical questionnaires are mainly applied as screening tools for identification of the Obstructive sleep apnea (OSA) patients. Little attention has been paid to assess the body functions and health status of the patients. International Classification of Functioning, Disability and Health (ICF) was designed for better understanding and describing functioning and disability of patients. This study adopted the Brief ICF-Sleep Disorders and Obesity Core Set to evaluate the impairment of functioning and health status of OSA patients. METHODS: Five hundred ninety-two participants were enrolled in this cross-sectional study. Data were collected using Brief ICF-Sleep Disorders and Obesity Core Set Polysomnography was performed and basic characteristics of the patients were recorded. RESULTS: The scores for the component Body Functions and Code b130, b134, b140, b440, b530, s330, d160, d240, d450 of the two core sets were significantly different among the patients divided by apnea-hypopnea index (AHI) or oxygen saturation (SaO2) nadir, but the frequency of code s330, d160, d240, d450 was low. The Body Functions component of the both sets were closely related to neck circumference (NC), body mass index (BMI), apnea-hypopnea index (AHI) of the OSA patients. Body Functions of the Brief ICF-Sleep Disorders performed better with a threshold of 4 with sensitivity, specificity and area under the receiver operating characteristic curve (AUC) as 0.62, 0.74, 0.68(AHI ≥ 5), 0.69, 0.63, 0.66 (AHI ≥ 15), 0.75, 0.56, 0.66 (AHI ≥ 30), 0.56, 0.70, 0.63 (SaO2 nadir≤90%), 0.67, 0.66, 0.66 (SaO2 nadir<85%), 0.71, 0.59, 0.65 (SaO2 nadir<80%), separately. CONCLUSION: The Body Functions component of both two sets could be an evaluation tool of impairment of body functions for OSA patients. The Brief ICF-Sleep Disorders Body Functions component performed better with a threshold of 4 and might provide a new insight for physicians to assess OSA patients.

Evidence and evolution of Criegee intermediates, hydroperoxides and secondary organic aerosols formed via ozonolysis of α-pinene.

α-Pinene, the most abundant monoterpene in the atmosphere, accounts for more than 50% of global monoterpene emission. Though its reaction with ozone has been generally perceived as a major source of secondary organic aerosols (SOAs), direct evidence of its reaction intermediates (RI) and their evolution remain lacking. Here we study the ozonolysis of α-pinene between 180 and 298 K using a long-path, temperature-variable aerosol cooling chamber coupled to a rapid-scan time-resolved Fourier transform infrared spectrometer. The spectroscopic signatures of large Criegee intermediates (CIs) and hydroperoxides (HPs) were found for the first time. The aerosol size evolution during the reaction was also measured. In contrast to a previous perception, we show that temperature plays a determinant role in the ozonolysis kinetics. Finally, we show that the formation of HPs is an energetically favorable pathway to dissipate CIs. This study provides new insights into the ozonolysis of α-pinene and its contribution to SOA formation.

Predictors of acute cardiovascular events following acute exacerbation period for patients with COPD: a nested case-control study.

BACKGROUND: It has been noted that there is an increase in the incidence of acute cardiovascular events (CVEs) in patients with chronic obstructive pulmonary disease (COPD) during an acute exacerbation (AE), thereby causing increased inpatient mortality. Thus, we have tried to identify predictors of acute CVEs in patients with AECOPD via a nested case-control study. METHODS: A total of 496 cases hospitalized for AECOPD were included in this study, and followed-up for up to 6 months after discharge. Acute CVEs in the AE period were defined as a new or worsening acute coronary syndrome (ACS), arrhythmia, or left ventricular disfunction (LVD). Predictors of CVEs were selected from several variables, including baseline characteristics and treatments in the stable period as well as symptoms, laboratory tests, complications and treatments in the AE period. RESULTS: Thirty cases (6.05%) had acute CVEs, namely 2 had ACS, 13 had LVD and 19 experienced some form of arrhythmia. Four deaths were observed in the CVE group, with significantly increased death risk compared with the non-CVE group (P = 0.001, OR = 5.81). Moreover, patients who had CVEs were more prone to have re-exacerbation within 3 months. Multivariate analysis showed that previous LVD history (P = 0.004, OR = 5.06), 20% increase in heart rate (HR) (P = 0.003, OR = 10.19), electrolyte disturbance (P = 0.01, OR = 4.24) and diuretics (P = 0.002, OR = 6.37) were independent predictors of CVEs. In addition, usage of theophylline, fluoroquinolone and inhaled beta agonists in the AE period were not statistically associated with acute CVEs. CONCLUSIONS: Our preliminary study indicates that patients hospitalized for AECOPD with previous LVD history or increased HR need close observation and diuretics should be cautiously used with regular electrolyte monitoring. These findings need to be confirmed in a large cohort.

Elevated serum procalcitonin level in patients with chronic kidney disease without infection: A case-control study.

BACKGROUND: Inflammation is a necessary component of chronic kidney disease (CKD) that can be attributed to an accumulation of toxins and a reduced clearance of proinflammatory cytokines. Procalcitonin (PCT) is a widely applied biomarker in the diagnosis of infection, and considering the presence of pre-existing inflammation in CKD patients, the PCT level could be high in such a population; however, no reference value for PCT in CKD patients has been available to date. METHODS: During the present study period, 361 CKD patients and 119 healthy controls were included. The PCT level and other biochemistry parameters were assayed by using a COBAS system. Statistical analysis was conducted to compare the differences in PCT levels and other biochemistry parameters between the two groups, and linear regression was used to assess the correlation between two variables. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of PCT and the optimal cutoff value to differentiate between CKD patients and healthy controls. RESULTS: The PCT level in CKD patients was significantly higher than that in healthy controls, and among the CKD patients, the PCT level was increased with advanced clinical stage. Moreover, PCT was moderately correlated with CysC. The optimal off-value was 0.075 with a sensitivity of 94.7% and specificity of 90.8%. CONCLUSION: The PCT level was significantly higher in CKD patients than in healthy controls, and the reference value for CKD patients should be adjusted to avoid unnecessary antibiotic treatments which may pose a negative impact on residual renal function.

Theoretical Prediction on the New Types of Noble Gas Containing Anions OBONgO- and OCNNgO- (Ng = He, Ar, Kr and Xe).

The fluorine-less noble gas containing anions OBONgO- and OCNNgO- have been studied by correlated electronic structure calculation and density functional theory. The obtained energetics indicates that for Ng = Kr and Xe, these anions should be kinetically stable at low temperature. The molecular structures and electron density distribution suggests that these anions are stabilized by ion-induced dipole interactions with charges concentrated on the electronegative OBO and OCN groups. The current study shows that in addition to the fluoride ion, polyatomic groups with strong electronic affinities can also form stable noble gas containing anions of the type Y-…NgO.

Mediated Drug Release from Nanovehicles by Black Phosphorus Quantum Dots for Efficient Therapy of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is an intractable disease involving a sticky mucus layer and nanoagents with mucus-penetrating capability offer a new way to deliver drugs. However, drug release from nanovehicles requires optimization to enhance the therapeutic effects of COPD therapy. Herein, black phosphorus quantum dots (BPQDs) are combined with PEGylated chitosan nanospheres containing the antibiotic amikacin (termed PEG@CS/BPQDs-AM NPs). As a drug-delivery system, the hydrophilicity of PEG and positive charge of CS facilitate the penetration of nanovehicles through the mucus layer. The nanovehicles then adhere to the mucous membrane. Furthermore, the BPQDs degrade rapidly into nontoxic PO43- and acidic H+ , thereby promoting the dissociation of PEGylated CS nanospheres, accelerating the release of AM, decreasing the vitality of biofilms for ease of eradication. Our results reveal that drug delivery mediated by BPQDs is a feasible and desirable strategy for precision medicine and promising for the clinical therapy of COPD.

The creative thinking cognitive process influenced by acute stress in humans: an electroencephalography study.

This study examined the underlying neural mechanism of acute stress affecting creative thinking. Twenty-six male participants underwent the Alternative Uses Test before and after acute stress test (Montreal Imaging Stress Task). Compared to before stress, stressed participants responded with higher salivary cortisol and salivary alpha-amylase. The electroencephalogram results indicated a general decrease in upper-frequency alpha power after stress, compared with that of before stress. The decrease in upper-frequency alpha power observed in the first stage after exposure to stress was related to memory and attention. Additionally, stress also reduced the differences between individuals with different creative abilities. In summary, these findings indicated that acute stress impaired creative thinking and primarily affected the earlier phase of the process of creative cognition. This study provides some practical implications for educational practice and corporate innovation in that a more relaxed environment promotes creative output. Lay Summary Acute stress impaired creative thinking performance and mainly affects the earlier phase of the process of creative cognition. Additionally, stress seems to reduce the differences between individuals with different creative abilities.

Attentional blink affected by acute stress in women: The role of affective stimuli and attentional resources.

The role of attentional resources and affective stimuli on temporal selective attention in the rapid serial visual presentation (RSVP) paradigm under acute stress was explored among women. Seventy-three female undergraduates were randomly assigned to the Trier Social Stress Test (TSST) group or control group. We found that when the first target was negative, stress increased its accuracy. Stress promoted the recognition of neutral target two (T2) only at lag2, and there was no interaction with theemotionality of target one (T1). In addition, the accumulated effect of stress enhanced temporal selective attention, predominately 20-40 min after the TSST task; cortisol concentration during this time period could significantly predict AB task performance. In summary, when attentional resources were severely insufficient, individuals under stress were more able to focus on the current target; that is, stress facilitated selective attention. A novel result was that participants were exempt from the affective influence of previous targets, which may have been caused by activation of the autonomic nervous system and gender differences.

Development of a Nomogram to Predict the Risk of 30-Day Re-Exacerbation for Patients Hospitalized for Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Acute exacerbation (AE) is the main cause of increased disability and mortality for patients with Chronic Obstructive Pulmonary Disease (COPD). Short-term re-exacerbation after discharge is common for in-hospital patients with AECOPD. Thus, we aimed to design a scoring system to effectively predict the 30-day re-exacerbation using simple and easily accessible variables. We retrospectively enrolled 686 cases hospitalized for AECOPD in two Chinese hospitals from 2005 to 2017. A variety of parameters were collected like demographics, clinical manifestations and treatments in stable and AE period. The optimal subset of covariates in the multivariate logistic analysis was identified by the smallest Akaike Information Criterion (AIC) and was further used to develop a practical and reliable nomogram to predict the 30-day re-exacerbation. The efficacy of the nomogram was internally validated by concordance index (C-index) and a calibration plot. The incidence of 30-day re-exacerbation was 15.8%. Based on the smallest AIC, eight easily-accessible parameters were included in the nomogram, including sex, COPD assessment test (CAT) scores, AE with respiratory failure in the previous year, new purulent sputum, new cardiovascular events, combined antibiotic therapy, theophylline therapy for AE and ICU admission. Our nomogram revealed good discriminative ability with the C-index of 0.702. The calibration curve showed good agreement between nomogram-predicted probability and actual observation. Incorporating eight common variables, a nomogram for 30-day re-exacerbation after discharge with high predictive performance was constructed for patients with AECOPD, which was helpful in predicting individualized risk of re-exacerbation and offering individualized post-discharge support.

Central Lymph Node Status has Significant Prognostic Value in the Clinically Node-Negative Tall-Cell Variant of Papillary Thyroid Cancer Regardless of T-Staging and Radioactive Iodine Administration: First Evidence From a Population-Based Study.

BACKGROUND: The prognostic value of central lymph node (CLN) status in papillary thyroid cancer (PTC) remains controversial. This study aimed to provide the first evidence on this issue for the aggressive tall-cell variant (TCV) subtype. METHODS: The study identified TCV patients from the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method, log-rank test, and multivariate Cox regression models were used for analysis. RESULTS: Of the 744 patients included, 404 were recorded as N0, which were pathologically or only clinically confirmed. Overall survival (OS) and cancer-specific survival (CSS) did not differ significantly between the N0 and pN1a patients (p > 0.05). To investigate the reason, the N0 patients were subdivided according to the number of examined lymph nodes (ELN). The patients with a N0 diagnosis confirmed by two or more ELNs (N0-e2+) showed significantly better outcomes than the pN1a patients and their N0 counterparts without ELN (N0-e0) (p < 0.05), whereas the N0-e0 and pN1a groups demonstrated comparable outcomes in both the log-rank and multivariate analyses (p > 0.05). Moreover, the subgroup analyses showed that even among the patients with early T-staging (T1-T2) or receipt of radioactive iodine (RAI) therapy, the N0-e0 patients still demonstrated compromised OS compared with the N0-e2+ group (p < 0.05). CONCLUSION: The cN0 patients without ELN (N0-e0) had outcomes similar to those of the pN1a patients, but showed a poorer OS than the N0-e2+ group regardless of T-staging and RAI administration, suggesting that occult CLN metastases might act as a negative prognosticator in cN0 TCV. Therefore, prophylactic central neck dissection might be considered for biopsy-proven cN0 TCV patients. Prospective studies are expected to further validate our conclusions.