Acidic Pepsin Affects Laryngeal Carcinoma Cell Growth and Invasion Through Glycolysis.

OBJECTIVE: The pathogenic mechanism underlying the effects of acidic pepsin in laryngeal cancer remains unclear. This study investigated whether acidic pepsin influences Glut-1 expression and glycolytic activity in laryngeal carcinoma cells and whether it plays a role in the growth and migration of these cells through glycolysis. STUDY DESIGN: In vitro study. SETTING: A university-affiliated hospital. METHODS: Laryngeal carcinoma TU 212 and TU 686 cells were treated with acidic pepsin and 2-deoxy-d-glucose (2-DG), then transfected with Glut-1 small interfering RNA (siRNA). Glucose uptake was detected by a radioimmunoassay counter, lactate secretion was detected by a lactic acid kit, and Glut-1 expression was detected by western blotting. Cell viability, migration and invasion, and clonal formation were assessed using the Cell Counting Kit-8, Transwell chamber, and clonal formation assays, respectively. RESULTS: Acidic pepsin significantly increased Glut-1 expression in laryngeal carcinoma cells compared with the control group (P < .01). It also significantly enhanced 18F-fluorodeoxyglucose (Cin/Cout) uptake, lactate secretion, cell viability, migration, invasion, and clonal formation in laryngeal carcinoma cells compared with the control group (P < .01). The glycolytic inhibitor 2-DG and Glut-1 siRNA significantly reversed the effects of acidic pepsin on laryngeal carcinoma cells (P < .01). CONCLUSION: Acidic pepsin enhances the growth and migration of laryngeal carcinoma cells by upregulating Glut-1, thus promoting glycolysis.

Thalassospira aquimaris sp. nov. and Winogradskyella marincola sp. nov. two marine bacteria isolated from an agar-degrading co-culture.

Two novel Gram-stain-negative, aerobic, and non-motile strains, designated FZY0004T and YYF002T, were isolated from an agar-degrading co-culture, which was obtained from seawater of the intertidal zone of Yancheng City, the Yellow Sea of China. Strain FZY0004T optimally grew at 28 °C, pH 7.0, and 2-6% NaCl, while strain YYF002T optimally grew at 28 °C, pH 7.5, and 2-4% NaCl. Strain FZY0004T possessed Q-9 as the major respiratory quinone, and its major fatty acids (> 10%) were summed feature 8 (C18:1 ω7c), C16:0, and summed feature 3 (C16:1 ω7c/C16:1 ω6c). The polar lipids identified in strain FZY0004T were phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and several unidentified phospholipids (PL) and lipids (L). On the other hand, strain YYF002T had MK-6 as the predominant respiratory quinone and its major fatty acids consisted of iso-C15:0, iso-C15:1 G, and iso-C15:0 3-OH. The polar lipids identified in strain YYF002T were aminolipid (AL), PE, and several unidentified lipids. Strain FZY0004T shared 99.5% 16S rRNA gene sequence similarity and 90.1% average nucleotide identity (ANI) with T. povalilytica Zumi 95T, and strain YYF002T shared 99.2% 16S rRNA gene sequence similarity and 88.2% ANI with W. poriferorum JCM 12885T. The genomic DNA G + C contents of strains FZY0004T and YYF002T were 54.5% and 33.5%, respectively. The phylogenetic, phenotypic, and physiological characteristics permitted the distinction of the two strains from their neighbors, and we thus propose the names Thalassospira aquimaris sp. nov. (type strain FZY0004T = JCM 35895T = MCCC 1K08380T) and Winogradskyella marincola sp. nov. (type strain YYF002T = JCM 35950T = MCCC 1K08382T).

Comparison of learning curves and related postoperative indicators between endoscopic and robotic thyroidectomy: a systematic review and meta-analysis.

BACKGROUD: Endoscopic thyroidectomy (ET) and robotic thyroidectomy (RT) yield similar perioperative outcomes. This study investigated how the learning curve (LC) affects perioperative outcomes between ET and RT, identifying factors that influence the LC. MATERIALS AND METHODS: Two researchers individually searched PubMed, EMBASE, Web of Science, and Cochrane Library for relevant studies published until February 2024. The Newcastle-Ottawa Scale assessed study quality. Random effects model was used to compute the odds ratio and weighted mean difference (WMD). Poisson regression comparison of the number of surgeries (NLC) was required for ET and RT to reach the stable stage of the LC. Heterogeneity was measured using Cochran's Q. Publication bias was tested using funnel plots, and sensitivity analysis assessed findings robustness. Subgroup analysis was done by operation type and patient characteristics. RESULTS: This meta-analysis involved 33 studies. The drainage volume of ET was higher than that of RT (WMD=-17.56 [30.22, -4.49]). After reaching the NLC, the operation time of ET and RT was shortened (ET: WMD=28.15[18.04, 38.26]; RT: WMD=38.53[29.20, 47.86]). Other perioperative outcomes also improved to varying degrees. Notably, RT showed more refined central lymph node resection(5.67 vs. 4.71), less intraoperative bleeding (16.56 mL vs. 42.30 mL), and incidence of transient recurrent laryngeal nerve injury(24.59 vs. 26.77). The NLC of RT was smaller than that of ET(Incidence-rate ratios [IRR]=0.64[0.57, 0.72]). CUSUM analysis (ET: IRR=0.84[0.72, 0.99]; RT: IRR=0.55[0.44, 0.69]) or a smaller number of respondents (ET: IRR=0.26[0.15, 0.46]; RT: IRR=0.51[0.41, 0.63]) was associated with smaller NLC. In RT, transoral approach (IRR=2.73[1.96, 4.50]; IRR=2.48[1.61, 3.84]) and retroauricular approach (RAA) (IRR=2.13[1.26, 3.60]; IRR=1.78[1.04, 3.05]) had smaller NLC compared to bilateral axillo-breast and transaxillary approach (TAA). In ET, the NLC of RAA was smaller than that of TAA (IRR=1.61[1.04, 2.51]), breast approach(IRR=1.67[1.06, 2.64]), and subclavian approach(IRR=1.80[1.03, 3.14]). CONCLUSIONS: Rich surgical experience can improve surgical results of ET and RT. After reaching the NLC, the perioperative outcomes of RT are better than those of ET. Study subjects, surgical approaches, and analysis methods can affect NLC.

Association of sudden sensorineural hearing loss with meteorological factors: a time series study in Hefei, China, and a literature review.

Air pollution can cause disease and has become a major global environmental problem. It is currently believed that air pollution may be related to the progression of SSNHL. As a rapidly developing city in recent years, Hefei has serious air pollution. In order to explore the correlation between meteorological variables and SSNHL admissions, we conducted this study. This study investigated the short-term associations between SSNHL patients admitted to the hospital and Hefei climatic variables. The daily data on SSNHL-related hospital admissions and meteorological variables containing mean temperature (T-mean; °C), diurnal temperature range (DTR; °C), atmospheric pressure (AP; Hp), and relative humidity (RH; %), from 2014 to 2021 (2558 days), were collected. A time-series analysis integrating distributed lag non-linear models and generalized linear models was used. PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Literature published up to August 2023 was reviewed to explore the potential impact mechanisms of meteorological factors on SSNHL. The mechanisms were determined in detail, focusing on wind speed, air pressure, temperature, humidity, and air pollutants. Using a median of 50.00% as a baseline, the effect of exceedingly low T-mean in the single-day hysteresis effect model began at a lag of 8 days (RR = 1.032, 95% CI: 1.001 ~ 1.064). High DTR affected the admission rate for SSNHL on lag 0 day. The significance of the effect was the greatest on that day (RR = 1.054, 95% CI: 1.007 ~ 1.104) and then gradually decreased. High and exceedingly high RH affected the admission rate SSNHL on lag 0 day, and these effects lasted for 8 and 7 days, respectively. There were significant associations between all grades of AP and SSNHL. This is the first study to assess the effect of meteorological variables on SSNHL-related admissions in China using a time-series approach. Long-term exposures to high DTR, RH values, low T-mean values, and all AP grades enhance the incidence of SSNHL in residents. Limiting exposure to extremes of ambient temperature and humidity may reduce the number of SSNHL-related hospital visits in the region. It is advisable to maintain a suitable living environment temperature and avoid extreme temperature fluctuations and high humidity. During periods of high air pollution, it is recommended to stay indoors and refrain from outdoor exercise.

Trends and cross-country inequalities in the global burden of osteoarthritis, 1990-2019: A population-based study.

OBJECTIVE: To evaluate the trends and cross-country inequalities of global osteoarthritis (OA) burden over the last 30 years, and further predicted its changes to 2035. METHODS: The estimates and 95 % uncertainty intervals (UIs) for incidence, prevalence, and disability-adjusted life-years (DALYs) of OA were extracted from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. We described OA epidemiology at global, regional, and national levels, analyzed 1990-2019 trends in OA burden from overall, local, and multi-dimension scopes, decomposed OA burden according to population size, age structure, and epidemiologic changes, quantified cross-country inequalities in OA burden using standard health equity methods recommended by World Health Organization, and predicted changes of OA burden to 2035. RESULTS: GBD 2019 estimated 527,811,871 (95 % UIs: 478,667,549 to 584,793,491) prevalent cases, 41,467,542 (95 % UIs: 36,875,471 to 46,438,409) incident cases and 18,948,965 (95 % UIs: 9,571,298 to 37,659,660) DALYs cases of OA worldwide in 2019, with the highest cases in East Asia and highest age-standardized rate (ASR) in high-income North America. The global burden of OA increased overall from 1990 to 2019 with the fastest growth observed in the first decade of the 21st century. Decomposition analysis revealed that OA knee (62.78 %), women (60.47 %), and middle sociodemographic index (SDI) quintile (32.35 %) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging. A significant increase in SDI-related inequalities was detected, and the gap in DALYs between the highest SDI country and the lowest SDI country increased from 179.5 [95 % confidence interval (CI): 149.3-209.8] per 100,000 in 1990 to 341.9 (95 % CI: 309.5-374.4) per 100,000 in 2019. Notably, although the ASR of incidence, prevalence, and DALYs of OA was predicted to decrease annually from 2020 to 2035, the case number of these metrics was predicted to keeping increasing, with predicted values of 52,870,737 [95 % credible interval (Crl): 39,330,063 to 66,411,411], 727,532,373 (95 % Crl: 542,765,783 to 912,298,962), and 25,986,983 (95 % Crl: 19,216,928 to 32,757,038) in 2035, respectively. CONCLUSIONS: As a major public health issue, the global burden of OA showed an overall increasing trend from 1990 to 2019, which was primarily driven by population growth and aging. Countries with high SDI shouldered disproportionately high OA burden, and the SDI-related inequalities across countries exacerbated over time. This study highlighted great challenges in the control and management of OA, including both growing case number and distributive inequalities worldwide, which may be instructive for better making public health policy and reasonably allocating medical source.

[Noise exposure-induced stress response and its measurement methods].

Noise, as an unavoidable stress (pressure) source in the modern life, affects animals in many ways, both behaviorally and physiologically. Behavioral changes may be driven by changes in hormone secretion in animals. When animals face with noise stress, the neuroendocrine systems, mainly the hypothalamic-pituitary-adrenal (HPA) axis, are activated, which promotes the secretion and release of stress hormones, and then leads to a series of behavioral changes. The behavioral changes can be easily observed, but the changes in physiological indicators such as hormone levels need to be accurately measured. Currently, many studies have measured the variations of stress hormone levels in animals under different noise conditions. Taking glucocorticoid as an example, this paper summarizes the different measurement methods of stress hormones, especially the non-invasive measurement methods, and compares the advantages and shortcomings of them. It provides a variety of measurement choices for the study of related issues, and also helps us to further understand the sources of animal stress, in order to provide a better habitat for animals.

GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy.

BACKGROUND: Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. METHODS: C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. RESULTS: CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. CONCLUSIONS: Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

Potential of semen coicis in enhancing the anti-tumor effects of PD-1 inhibitor on A549 cell lines by blocking the PI3K-AKT-mTOR pathway.

BACKGROUND: The objective of this research was to investigate how the combination of semen coicis extract and PD-1 inhibitors can potentially work together to enhance the anti-tumor effects, with a focus on understanding the underlying mechanism. METHODS: We obtained the active components and specific targets of semen coicis in the treatment of NSCLC from various databases, namely TCMSP, GeneCard, and OMIM. By utilizing the STRING database and Cytoscape software, we established a protein interaction network (PPI) for the active ingredient of semen coicis and the target genes related to NSCLC. To explore the potential pathways involved, we conducted gene ontology (GO) and biological pathway (KEGG) enrichment analyses, which were further supported by molecular docking technology. Additionally, we conducted cyto-inhibition experiments to verify the inhibitory effects of semen coicis alone or in combination with a PD-1 inhibitor on A549 cells, along with examining the associated pathways. Furthermore, we investigated the synergistic mechanism of these two drugs through cytokine release experiments and the PD-L1 expression study on A549 cells. RESULTS: Semen coicis contains two main active components, Omaine and (S)-4-Nonanolide. Its primary targets include PIK3R1, PIK3CD, PIK3CA, AKT2, and mTOR. Molecular docking experiments confirmed that these ingredients and targets form stable bonds. In vitro experiments showed that semen coicis demonstrates inhibitory effects against A549 cells, and this effect was further enhanced when combined with PD-1 inhibitors. PCR and WB analysis confirmed that the inhibition of the PI3K-AKT-mTOR pathway may contribute to this effect. Additionally, semen coicis was observed to decrease the levels of IFN-γ, IL-6, and TNF-α, promoting the recovery of the human anti-tumor immune response. And semen coicis could inhibit the induced expression of PD­L1 of A549 cells stimulated by IFN­Î³ as well. CONCLUSION: Semen coicis not only has the ability to kill tumor cells directly but also alleviates the immunosuppression found in the tumor microenvironment. Additionally, it collaboratively enhances the effectiveness of PD-1 inhibitors against tumors by blocking the activation of PI3K-AKT-mTOR.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities.

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

Injectable Nano-Micro Composites with Anti-bacterial and Osteogenic Capabilities for Minimally Invasive Treatment of Osteomyelitis.

The effective management of osteomyelitis remains extremely challenging due to the difficulty associated with treating bone defects, the high probability of recurrence, the requirement of secondary surgery or multiple surgeries, and the difficulty in eradicating infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Hence, smart biodegradable biomaterials that provide effective and precise local anti-infection effects and can promote the repair of bone defects are actively being developed. Here, a novel nano-micro composite is fabricated by combining calcium phosphate (CaP) nanosheets with drug-loaded GelMA microspheres via microfluidic technology. The microspheres are covalently linked with vancomycin (Van) through an oligonucleotide (oligo) linker using an EDC/NHS carboxyl activator. Accordingly, a smart nano-micro composite called "CaP@MS-Oligo-Van" is synthesized. The porous CaP@MS-Oligo-Van composites can target and capture bacteria. They can also release Van in response to the presence of bacterial micrococcal nuclease and Ca2+, exerting additional antibacterial effects and inhibiting the inflammatory response. Finally, the released CaP nanosheets can promote bone tissue repair. Overall, the findings show that a rapid, targeted drug release system based on CaP@MS-Oligo-Van can effectively target bone tissue infections. Hence, this agent holds potential in the clinical treatment of osteomyelitis caused by MRSA.

The role of radiotherapy in tumor immunity and the potential of PET/CT in detecting the expression of PD-1/PD-L1.

Upregulation of PD-1/PD-L1 allows cancer cells to escape from host immune systems by functionally inactivating T-cell immune surveillance. Clinical blockade strategies have resulted in an increased prevalence of patients with late-stage cancers. However, many cancer patients had limited or no response to current immunotherapeutic strategies. Therefore, how to improve the sensitivity of immunotherapy has become the focus of attention of many scholars. Radiotherapy plays a role in the recruitment of T cells in the tumor microenvironment, increases CD4 + and CD8 + T cells, and increases PD-L1 expression, resulting in the synergistically enhanced antitumor effect of irradiation and PD-L1 blockade. Radiotherapy can cause changes in tumor metabolism, especially glucose metabolism. Tumor glycolysis and tumor immune evasion are interdependent, glycolytic activity enhances PD-L1 expression on tumor cells and thus promotes anti-PD-L1 immunotherapy response. Therefore, the mechanism of radiotherapy affecting tumor immunity may be partly through intervention of tumor glucose metabolism. Furthermore, some authors had found that the uptake of 2'-deoxy-2'-[18F]fluoro-D-glucose(18F-FDG) was correlated with PD-1/PD-L1 expression. Positron emission tomography/computed tomography (PET/CT) is a non-invasive detection method for PD-1/PD-L1 expression and has several potential advantages over immunohistochemical (IHC), PET/CT can dynamically reflect the expression of PD-1/PD-L1 inside the tumor and further guide clinical treatment.

Molybdenum Nanodots for Acute Lung Injury Therapy.

Acute respiratory disease syndrome (ARDS) is a common critical disease with high morbidity and mortality rates, yet specific and effective treatments for it are currently lacking. ARDS was especially apparent and rampant during the COVID-19 pandemic. Excess reactive oxygen species (ROS) production and an uncontrolled inflammatory response play a critical role in the disease progression of ARDS. Herein, we developed molybdenum nanodots (MNDs) as a functional nanomaterial with ultrasmall size, good biocompatibility, and excellent ROS scavenging ability for the treatment of acute lung injury (ALI). MNDs, which were administered intratracheally, significantly ameliorated lung oxidative stress, inflammatory response, protein permeability, and histological severity in ALI mice without inducing any safety issues. Importantly, transcriptomics analysis indicated that MNDs protected lung tissues by inhibiting the activation of the Nod-like receptor protein 3 (NLRP3)-dependent pyroptotic pathway. This work presents a promising therapeutic agent for patients suffering from ARDS.

Marixanthotalea marina gen. nov., sp. nov., a bacterium in the family Flavobacteriaceae isolated from seawater.

A Gram-stain-negative, yellow-pigmented, non-motile, rod-shaped, catalase-positive, strictly aerobic marine bacterium, designated XHP0103T, was isolated from seawater collected from the southern Yellow Sea, PR China (34° 45' 53″ N 119° 25' 30″ E). Strain XHP0103T grew optimally at 28 °C, pH 7.5 and in 1.0-3.0 % (w/v) sea salt. MK-6 was the major respiratory quinone. The major cellular fatty acids (>10%) were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The polar lipid profile contained phosphatidylethanolamine, an unidentified aminolipid, an unidentified glycolipid and an unidentified lipid. Results of 16S rRNA gene sequence analysis indicated that strain XHP0103T displayed highest sequence similarity to Aestuariibaculum marinum IP7T (94.1 %). However, the phylogenetic trees based on 16S rRNA gene sequences suggested that strain XHP0103T clustered with Tamlana crocina HST1-43T (93.4 % sequence similarity) and Aestuariivivens insulae AH-MY3T (93.5 %). Genome sequencing revealed that strain XHP0103T comprised 3 134 388 bp with 2770 protein-coding genes, and the DNA G+C content was 35.5 %. The average nucleotide identity and digital DNA-DNA hybridization values between strain XHP0103T and T. crocina HST1-43T were 73.6 and 17.3 %, respectively. Based on phylogenetic, phenotypic, genomic and chemotaxonomic evidence, strain XHP0103T represents a novel genus in the family Flavobacteriaceae, for which the name Marixanthotalea marina gen. nov., sp. nov. is proposed. The type strain is XHP0103T (=MCCC 1K06060T=JCM 34682T).

Surgical treatment of mixed cervical spondylosis with spontaneous cerebrospinal fluid leakage: A case report.

BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leaks associated with cervical spondylosis are rare. To our knowledge, only a few cases have been reported in which treatment is challenging and varies from case to case. Here, we review the literature and describe the surgical treatment of a 70-year-old woman who presented with a CSF leak due to a cervical spine spur. CASE SUMMARY: A 70-year-old female patient who was treated for a cerebral infarction, presented with complains of weakness in the right lower extremity and a feeling of stepping on cotton. The patient underwent regular neck massage and presented with neck and right shoulder pain radiating to the right upper extremity one-month ago. Magnetic resonance imaging showed a strip of leaking cerebrospinal fluid posterior to the C1-4 vertebrae, and computed tomography showed a "sickle-shaped" disc prolapse with calcification in C4/5. We chose to perform an anterior cervical discectomy. When the prolapsed C4/5 disc was scraped, clear fluid leakage was observed, and exploration revealed a 1 mm diameter rupture in the anterior aspect of the dura mater, which was compressed continuously with cotton patties, with no significant cerebrospinal fluid leakage after 1 h. CONCLUSION: Three months after surgery, the patient was asymptomatic and follow-up imaging demonstrated complete resolution.

A global assessment of incidence trends of autoimmune diseases from 1990 to 2019 and predicted changes to 2040.

AIM: To analyze the global incidence trends for four autoimmune diseases (ADs) including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis from 1990 to 2019, and further predict their changes to 2040 at global, regional, and national levels. METHODS: The estimates and 95% uncertainty intervals (UIs) for case number and agestandardized incidence rate (ASIR) of RA, IBD, MS and psoriasis were derived from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Estimated annual percentage change (EAPC) was utilized to quantify the global incidence trends for RA, IBD, MS and psoriasis from 1990 to 2019. Furthermore, a log-linear age-period-cohort model was adopted to predict the new case number and incidence rates for these four ADs through 2040. RESULTS: From 1990 to 2019, the global ASIR rose significantly for RA (EAPC = 0.30%, 95% CI: 0.26 to 0.34) whereas declined significantly for IBD (EAPC = -0.60%, 95% CI: -0.72 to - 0.48), MS (EAPC = -0.19%, 95% CI: -0.24 to -0.13) and psoriasis (EAPC = -0.77%, 95% CI: -0.78 to -0.76). From 2020 to 2040, the global ASIR of RA, IBD, and psoriasis was predicted to decrease whereas the global ASIR of MS was predicted to increase, with continuous increasing case number of all these diseases. Furthermore, the predicted incidence trends of these four ADs varied significantly across 195 countries and territories, with a prominent higher burden in high-income North America and Western Europe. CONCLUSIONS: There are strong heterogeneities in the global incidence trends (1990-2019) and predicted changes (2020-2040) of ADs across the world, highlighting prominent challenges in the control of ADs, including both growing case number and distributive disparities of these diseases worldwide, which may be instructive for better public health policy establishment and healthcare resource allocation.

A general method for endowing hydrophobic nanoparticles with water dispersion abilities.

Inorganic nanoparticles with long-chain ligands are usually hydrophobic. However, simple and practical methods for converting hydrophobic nanoparticles to hydrophilic nanoparticles are still lacking. Herein, we developed a general method involving using dimercaptosuccinic acid (DMSA) for endowing hydrophobic nanoparticles with water dispersion abilities. By mixing a tetrahydrofuran solution of DMSA with a cyclohexane solution of hydrophobic nanoparticles, the long-chain ligands were replaced with DMSA, with the replacement due to the strong and broad-spectrum coordination abilities of sulphydryls and carboxyls. Four representative kinds of hydrophobic nanoparticles, namely Ag, NaGdF4, TiO2, and ZnS nanoparticles, were selected for verifying the performance of this DMSA-based modification method. Meanwhile, this method can also widen the applications of hydrophobic nanoparticles and facilitate their being subjected to further graft modifications. We hope that our research will increase the chances for applications of nanomaterials to be made.

Predictive validation of existing bleeding and thromboembolic scores in elderly patients with comorbid atrial fibrillation and acute coronary syndrome.

BACKGROUND: The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients. METHODS: A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared. RESULTS: During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar. CONCLUSIONS: The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.

Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy.

OBJECTIVE: To investigate the role of H+ /K+ ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells. STUDY DESIGN: Translation research. SETTING: Affiliated Hospital of University. METHODS: Immunohistochemistry was used to detect pepsin, H+ /K+ ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+ /K+ -ATPase distribution of VCL cells were investigated. RESULTS: The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+ /K+ -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification. CONCLUSION: Pepsin and H+ /K+ -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+ /K+ -ATPase.

Effectiveness of the recurrent laryngeal nerve monitoring during endoscopic thyroid surgery: systematic review and meta-analysis.

BACKGROUND: Thyroid disease is a common endocrine disorder, and thyroid surgeries and postoperative complications have increased recently. This study aimed to explore the effectiveness of intraoperative nerve monitoring (IONM) in endoscopic thyroid surgery using subgroup analysis and determine confounding factors. MATERIALS AND METHODS: Two researchers individually searched for relevant studies published till November 2022 in the PubMed, Embase, Web of Science and Cochrane Library databases. Eventually, eight studies met the inclusion criteria. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. The odds ratio or risk difference were calculated using fixed-effects models. The weighted mean difference of continuous variables was calculated. Subgroup analysis was performed according to the disease type. RESULTS: Eight eligible papers included 915 patients and 1242 exposed nerves. The frequencies of transient, permanent and total recurrent laryngeal nerve (RLN) palsy were 2.64, 0.19 and 2.83%, respectively, in the IONM group and 6.15, 0.75 and 6.90%, respectively, in the conventional exposure group. In addition, analysis of the secondary outcome indicators for the average total length of surgery, localisation time of the RLN, recognition rate of the superior laryngeal nerve and length of incision revealed that IONM reduced the localisation time of the RLN and increased the identification rate of the superior laryngeal nerve. Subgroup analysis showed that IONM significantly reduced the incidence of RLN palsy in patients with malignancies. CONCLUSIONS: The use of IONM significantly reduced the incidence of transient RLN palsy during endoscopic thyroid surgery, but it did not significantly reduce the incidence of permanent RLN palsy. However, the reduction in the total RLN palsy was statistically significant. In addition, IONM can effectively reduce the location time of the RLN and increase the recognition rate of the superior laryngeal nerve. Therefore, the application of IONM for malignant tumours is recommended.