Peiella sedimenti gen. nov., sp. nov., a novel taxon within the family Caulobacteraceae isolated from sediment of a river.

A Gram-stain-negative bacterium, designated XZ-24T, was isolated from sediment of a river in Mianyang city, Sichuan province, PR China. Cells (1.0-2.0 µm long and 0.4-0.5 µm in width) were strictly aerobic, non-spore-forming, rod shaped, prosthecate and motile by means of a polar flagellum. Growth occurred at 10-37 °C (optimum, 30 °C), at pH 5.0-9.0 (optimum pH 7.0) and with 0-3.0 % (w/v) NaCl (optimum 1.0 % NaCl). The results of phylogenetic analysis based on genomes and 16S rRNA gene sequences indicated that XZ-24T formed a distinct phyletic branch within the family Caulobacteraceae and was most closely related to members of the genera Brevundimonas, Caulobacter and Phenylobacterium with 95.3-96.5 % 16S rRNA gene sequence similarities. The average amino acid identities (AAI) between XZ-24T and species of the family Caulobacteraceae were 47.0-64.5 %, which were below the genus boundary (70 %). The predominant cellular fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0, C18 : 1ω7c 11-methyl and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), the isoprenoid quinone was Q-10, and the major polar lipids were 1,2-di-O-acyl-3-O-α-d-glucopyranuronosyl glycerol; 1,2-di-O-acyl-3-O-[d-glucopyranosyl-(1→4)-α-d glucopyranuronosyl] glycerol and phosphatidylglycerol. The genome size of XZ-24T was 2.64 Mb with a DNA G+C content of 68.9 %. On the basis of the evidence presented in this study, strain XZ-24T represents a novel species of a novel genus in the family Caulobacteraceae, for which the name Peiella sedimenti gen. nov., sp. nov. (Type strain XZ-24T=CCTCC AB 20 23 094T=KCTC 8038T) is proposed.

Assessing the Influence of B-US, CDFI, SE, and Patient Age on Predicting Molecular Subtypes in Breast Lesions Using Deep Learning Algorithms.

OBJECTIVES: Our study aims to investigate the impact of B-mode ultrasound (B-US) imaging, color Doppler flow imaging (CDFI), strain elastography (SE), and patient age on the prediction of molecular subtypes in breast lesions. METHODS: Totally 2272 multimodal ultrasound imaging was collected from 198 patients. The ResNet-18 network was employed to predict four molecular subtypes from B-US imaging, CDFI, and SE of patients with different ages. All the images were split into training and testing datasets by the ratio of 80%:20%. The predictive performance on testing dataset was evaluated through 5 metrics including mean accuracy, precision, recall, F1-scores, and confusion matrix. RESULTS: Based on B-US imaging, the test mean accuracy is 74.50%, the precision is 74.84%, the recall is 72.48%, and the F1-scores is 0.73. By combining B-US imaging with CDFI, the results were increased to 85.41%, 85.03%, 85.05%, and 0.84, respectively. With the integration of B-US imaging and SE, the results were changed to 75.64%, 74.69%, 73.86%, and 0.74, respectively. Using images from patients under 40 years old, the results were 90.48%, 90.88%, 88.47%, and 0.89. When images from patients who are above 40 years old, they were changed to 81.96%, 83.12%, 80.5%, and 0.81, respectively. CONCLUSION: Multimodal ultrasound imaging can be used to accurately predict the molecular subtypes of breast lesions. In addition to B-US imaging, CDFI rather than SE contribute further to improve predictive performance. The predictive performance is notably better for patients under 40 years old compared with those who are 40 years old and above.

Nucleoside-diphosphate kinase of uropathogenic Escherichia coli inhibits caspase-1-dependent pyroptosis facilitating urinary tract infection.

Uropathogenic Escherichia coli (UPEC) is the most common causative agent of urinary tract infection (UTI). UPEC invades bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol, and establishes biofilm-like intracellular bacterial communities (IBCs). Nucleoside-diphosphate kinase (NDK) is secreted by pathogenic bacteria to enhance virulence. However, whether NDK is involved in UPEC pathogenesis remains unclear. Here, we find that the lack of ndk impairs the colonization of UPEC CFT073 in mouse bladders and kidneys owing to the impaired ability of UPEC to form IBCs. Furthermore, we demonstrate that NDK inhibits caspase-1-dependent pyroptosis by consuming extracellular ATP, preventing superficial BEC exfoliation, and promoting IBC formation. UPEC utilizes the reactive oxygen species (ROS) sensor OxyR to indirectly activate the regulator integration host factor, which then directly activates ndk expression in response to intracellular ROS. Here, we reveal a signaling transduction pathway that UPEC employs to inhibit superficial BEC exfoliation, thus facilitating acute UTI.

Nano vitamin E improved the antioxidant capacity of broiler chickens.

Vitamin E (VE) is a potent nutritional antioxidant that is critical in alleviating poultry oxidative stress. However, the hydrophobic nature and limited stability of VE restrict its effective utilization. Nanotechnology offers a promising approach to enhance the bioavailability of lipophilic vitamins. The objective of this experiment was to investigate the effects of different sources and addition levels of VE on the growth performance, antioxidant capacity, VE absorption site, and pharmacokinetics of Arbor Acres (AA) broilers. Three hundred and eighty-four 1-d-old AA chicks were randomly allocated into four groups supplemented with 30 and 75 IU/kg VE as regular or nano. The results showed that dietary VE sources had no significant impact on broiler growth performance. However, chickens fed 30 IU/kg VE had a higher average daily gain at 22 to 42 d and 1 to 42 d, and lower feed conversion ratio at 22 to 42 d than 75 IU/kg VE (P < 0.05). Under normal feeding conditions, broilers fed nano VE (NVE) displayed significantly higher superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) enzyme activities and lower malonic dialdehyde (MDA) concentration (P < 0.05). Similarly, NVE had a higher antioxidant effect in the dexamethasone-constructed oxidative stress model. It was found that nanosizing technology had no significant effect on the absorption of VE in the intestinal tract by examining the concentration of VE in the intestinal tract (P > 0.05). However, compared to broilers perfused with regular VE (RVE), the NVE group displayed notably higher absorption rates at 11.5 and 14.5 h (P < 0.05). Additionally, broilers perfused with NVE showed a significant increase in the area under the concentration versus time curve from zero to infinity (AUC0-∞), mean residence time (MRT0-∞), elimination half-life (t1/2z), and peak concentration (Cmax) of VE in plasma (P < 0.05). In summary, nanotechnology provides more effective absorption and persistence of VE in the blood circulation for broilers, which is conducive to the function of VE and further improves the antioxidant performance of broilers.

With the rapid development of intensive farming, factors such as high temperature, harmful gases, high-fat and high-protein diets, and changes in feeding methods have become causes of oxidative stress in animals. Studies have shown that oxidative stress decreases livestock feed intake and slows growth in animals, thereby affecting the quality of livestock products. Antioxidants and micronutrients are commonly added to animal feed to reduce the effects of oxidative stress. Since the progress in nanotechnology, nanovitamins have gained extensive recognition due to their novel qualities, including a high level of adsorption capacity and low toxicity. Therefore, the present study compared the effects of dietary supplementation with different sources of vitamin E (regular, RVE vs. nano, NVE) and varying inclusion levels on the growth performance, antioxidant capacity, VE absorption sites, and pharmacokinetics in AA broilers. The results indicated that supplementing broiler diets with NVE provides superior antioxidant benefits compared to RVE. This improvement is attributed to the enhanced absorption efficiency and extended half-life of NVE, both contributing to increased antioxidant performance of broilers.

Active Components of Pueraria lobata through the MAPK/ERK Signaling Pathway Alleviate Iron Overload in Alcoholic Liver Disease.

OBJECTIVE: To delve into the primary active ingredients and mechanism of Pueraria lobata for alleviating iron overload in alcoholic liver disease. METHODS: Pueraria lobata's potential targets and signaling pathways in treating alcohol-induced iron overloads were predicted using network pharmacology analysis. Then, animal experiments were used to validate the predictions of network pharmacology. The impact of puerarin or genistein on alcohol-induced iron accumulation, liver injury, oxidative stress, and apoptosis was assessed using morphological examination, biochemical index test, and immunofluorescence. Key proteins implicated in linked pathways were identified using RT-qPCR, western blot analysis, and immunohistochemistry. RESULTS: Network pharmacological predictions combined with animal experiments suggest that the model group compared to the control group, exhibited activation of the MAPK/ERK signaling pathway, suppression of hepcidin expression, and aggravated iron overload, liver damage, oxidative stress, and hepatocyte death. Puerarin and genistein, the active compounds in Pueraria lobata, effectively mitigated the aforementioned alcohol-induced effects. No statistically significant disparities were seen in the effects above between the two groups receiving drug therapy. CONCLUSION: This study preliminarily demonstrated that puerarin and genistein in Pueraria lobata may increase hepcidin production to alleviate alcohol-induced iron overload by inhibiting the MAPK/ERK signaling pathway.

Preoperative glucose-to-lymphocyte ratio predicts survival in cancer.

Background: Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. Methods: We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. Results: The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Conclusion: Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients.

Ascorbic acid induces ferroptosis via STAT3/GPX4 signaling in oropharyngeal cancer.

Ferroptosis is recognized as a new type of regulated cell death initiated by iron-dependent accumulation of lipid peroxidation. Recent studies have shown that the administration of ascorbic acid (AA) preferentially kills tumor cells by impairing iron metabolism and exerting pro-oxidant effects. Despite mounting evidence indicating the anticancer potential of AA, the underlying molecular mechanisms remain unknown. In this study, we demonstrated that AA decreased cell viability and Ki67 expression, along with its accumulation in the G0/G1 phase in FaDu and SCC-154 cell lines. Furthermore, AA exposure induced morphological changes in mitochondria associated with ferroptosis. AA-induced ferroptosis is accompanied by depletion of glutathione (GSH) and increased levels of ferrous ions (Fe2+), reactive oxygen species (ROS), and malondialdehyde (MDA). However, these ferroptotic effects were ameliorated by deferoxamine and N-acetylcysteine. Network pharmacology results showed that signal transducer and activator of transcription 3 (STAT3) is a key target of AA against oropharyngeal cancer. AA markedly downregulates the relative mRNA expression of STAT3 and glutathione peroxidase 4 (GPX4). Immunoblotting indicated that the protein levels of p-STAT3, STAT3, and GPX4 in FaDu and SCC-154 cells decreased significantly in response to AA treatment. Mechanistically, a chromatin immunoprecipitation assay confirmed that AA exposure reduced STAT3 expression in the GPX4 promoter region. Additionally, AA-induced inhibition of cell growth and ferroptosis was suppressed by STAT3 and GPX4 overexpression, respectively. In summary, AA inhibited oropharyngeal cancer cell growth in vitro by regulating STAT3/GPX4-mediated ferroptosis, which may provide a novel theoretical basis for the clinical treatment of oropharyngeal cancer with AA.

Ascorbic acid acts as an anticancer agent by inducing ferroptosis, reducing the viability of SCC-154 and FaDu cells.Ascorbic acid-mediated ferroptosis acts through STAT3/GPX4 pathway.The induction of ferroptosis has a significant potential for cancer therapy.

A new nomogram prediction model for pulmonary embolism in older hospitalized patients.

Purpose: Diagnosing pulmonary embolism (PE) in older adults is relatively difficult because of the atypical clinical symptoms of PE in older adults accompanied by multiple complications. This study aimed to establish a nomogram model to better predict the occurrence of PE in older adults. Methods: Data were collected from older patients (≥65 years old) with suspected PE who were hospitalized between January 2012 and July 2021 and received confirmatory tests (computed tomographic pulmonary angiography or ventilation/perfusion scanning). The PE group and non-PE (control) group were compared using univariable and multivariable analyses to identify independent risk factors. A nomogram prediction model was constructed with independent risk factors and verified internally. The effectiveness of the nomogram model, Wells score, and revised Geneva score was assessed using the area under the receiver operating characteristic curve (AUC). Results: In total, 447 eligible older patients (290 PE patients and 157 non-PE patients) were enrolled. Logistic regression analysis revealed nine independent risk factors: smoking, inflammation, dyspnea, syncope, mean corpuscular hemoglobin concentration, indirect bilirubin, uric acid, left atrial diameter, and internal diameter of the pulmonary artery. The AUC, sensitivity, and specificity of the nomogram prediction model were 0.763 (95 % confidence interval, 0.721-0.802), 74.48 %, and 67.52 %, respectively. The nomogram showed superior AUC compared to the Wells score (0.763 vs. 0.539, P < 0.0001) and the revised Geneva score (0.763 vs. 0.605, P < 0.0001). Conclusions: This novel nomogram may be a useful tool to better recognize PE in hospitalized older adults.

Harnessing Sulforaphane Potential as a Chemosensitizing Agent: A Comprehensive Review.

Recent advances in oncological research have highlighted the potential of naturally derived compounds in cancer prevention and treatment. Notably, sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables including broccoli and cabbage, has exhibited potent chemosensitizing capabilities across diverse cancer types of bone, brain, breast, lung, skin, etc. Chemosensitization refers to the enhancement of cancer cell sensitivity to chemotherapy agents, counteracting the chemoresistance often developed by tumor cells. Mechanistically, SFN orchestrates this sensitization by modulating an array of cellular signaling pathways (e.g., Akt/mTOR, NF-κB, Wnt/ß-catenin), and regulating the expression and activity of pivotal genes, proteins, and enzymes (e.g., p53, p21, survivin, Bcl-2, caspases). When combined with conventional chemotherapeutic agents, SFN synergistically inhibits cancer cell proliferation, invasion, migration, and metastasis while potentiating drug-induced apoptosis. This positions SFN as a potential adjunct in cancer therapy to augment the efficacy of standard treatments. Ongoing preclinical and clinical investigations aim to further delineate the therapeutic potential of SFN in oncology. This review illuminates the multifaceted role of this phytochemical, emphasizing its potential to enhance the therapeutic efficacy of anti-cancer agents, suggesting its prospective contributions to cancer chemosensitization and management.

Red blood cell distribution width is associated with sarcopenia risk in early-stage non-small cell lung cancer.

BACKGROUND: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. METHODS: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. RESULTS: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. CONCLUSION: RDW is associated with sarcopenia risk in early-stage NSCLC.

Flavobacterium sedimenticola sp. nov., isolated from sediment.

A novel yellow-pigmented bacterial strain, designated YZ-48T, was isolated from the sediment of the Yangtze River, PR China. Cells were Gram-stain-negative, non-motile, rod-shaped, strictly aerobic, catalase-positive and oxidase-positive. The strain grew optimally on R2A medium at 37 °C, pH 7.0 and with 1.0 % (w/v) NaCl. Strain YZ-48T showed the closest 16S rRNA gene sequence similarity to Flavobacterium solisilvae SE-s27T (96.4 %) and F. dankookense DSM 25687T (96.2 %). The phylogenetic trees based on 16S rRNA gene sequences showed that strain YZ-48T belonged to the genus Flavobacterium but formed a distinct phylogenetic lineage. The obtained average nucleotide identity and digital DNA-DNA hybridization values between YZ-48T and the two closest strains were 75.0 and 74.5 % and 19.6 and 19.0 %, respectively. The sole respiratory quinone was MK-6. The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and three unidentified polar lipids. The major cellular fatty acids were iso-C16 : 0, iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3-OH, iso-C15 : 0 3-OH and iso-C16 : 0 3-OH. The DNA G+C content was 40.2 mol%. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic data, strain YZ-48T represents a novel species of the genus Flavobacterium, for which the name Flavobacterium sedimenticola sp. nov. is proposed, with strain YZ-48T (=KCTC 82329T=CCTC AB 2023061T=MCCC 1K08804T) as the type strain.

Empedobacter sedimenti sp. nov., isolated from sediment of East Taihu Lake.

A Gram-reaction-negative, strictly aerobic, pale yellow, non-gliding, rod-shaped bacterium, designated DT-LB-19T, was isolated from the sediment of East Taihu Lake in Jiangsu Province, PR China. Strain DT-LB-19T showed the highest 16S rRNA gene sequence similarities to members of the genera Algoriella, Chishuiella and Empedobacter (94.84-95.77 %) in the family Weeksellaceae. In phylogenetic trees based on genomes, strain DT-LB-19T clustered within the genus Empedobacter but formed a separate subclade with a high bootstrap value. The average nucleotide identity and digital DNA-DNA hybridization values between DT-LB-19T and the closely related type strains were in the range of 82.5-86.9 % and 25.8-32.3 %, respectively. The major cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 1 ω5c, C16 : 0, summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B), summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and iso-C15 : 03-OH. The predominant menaquinone was menaquinone-6. The polar lipid profile consisted of phosphatidylethanolamine, one glycolipid, two aminophospholipids and five unidentified lipids. The DNA G+C content was 31.8 mol%. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic results, we propose that strain DT-LB-19T represents a novel species of the genus Empedobacter, for which the name Empedobacter sedimenti sp. nov. is proposed, with strain DT-LB-19T (=KCTC 82330T=CCTCC AB 2023026T= JSACC 11448T) as the type strain.

Feasibility and accuracy of a task-autonomous robot for zygomatic implant placement.

STATEMENT OF PROBLEM: Zygomatic implants (ZIs) should be placed accurately as planned preoperatively to minimize complications and maximize the use of the remaining bone. Current digital techniques such as static guides and dynamic navigation are affected by human error; therefore, new techniques are required to improve the accuracy of ZI placement. PURPOSE: The purpose of this clinical study was to assess the feasibility and accuracy of a task-autonomous robot for ZI placement. MATERIAL AND METHODS: Patients indicated for ZI placement were enrolled, and an appropriate surgical positioning piece was selected based on the presence of natural teeth in the maxilla. Preoperative cone beam computed tomography (CBCT) scanning was performed with the surgical positioning piece, and virtual implant design and socket preparation procedures were initiated. Implant socket preparation and placement were automatically performed by the robot according to the preoperative plan under the supervision of the surgeon. Postoperative CBCT scanning was performed to evaluate deviations between the virtual and actual implants. All quantitative data were expressed as standardized descriptive statistics (mean, standard deviation, minimum, maximum, and 95% confidence interval [CI]). The Shapiro-Wilk test was used to assess the normal distribution of all variables (α=.05). RESULTS: Six participants were enrolled, and 8 ZIs were inserted. No intraoperative or postoperative complications were observed. Robotic ZI placement showed a global coronal deviation of 0.97 mm (95% CI: 0.55 to 1.39 mm), a global apical deviation of 1.27 mm (95% CI: 0.71 to 1.83 mm), and an angular deviation of 1.48 degrees (95% CI: 0.97 to 2.00 degrees). CONCLUSIONS: Task-autonomous robots can be used for ZI placement with satisfactory accuracy. Robotic ZI surgery can be an alternative to static guidance and dynamic navigation to improve the accuracy of implant placement.

Vibrio chanodichtyis sp. nov., isolated from the intestine of swordfish Chanodichthys dabryi.

A Gram-stain-negative, facultatively anaerobic, motile, curved-rod-shaped flagellated bacterium, designated DSL-7T, was isolated from the intestine of Chanodichthys dabryi in the Yangtze river, PR China. The strain grew optimally in tryptone soy broth medium at 37 °C, pH 7.0 and with 1 % (w/v) NaCl. Strain DSL-7T showed less than 96.2 % 16S rRNA gene sequence similarity to type strains of the genus Vibrio. Phylogenetic analysis based on genomes indicated that strain DSL-7T belonged to the genus Vibrio and formed a subclade with Vibrio mimicus NCTC 11435T, Vibrio metoecus OP3HT, Vibrio cholerae ATCC 14035T, Vibrio albensis ATCC14547T, Vibrio paracholerae OP3HEDC-792T and Vibrio tarriae 2521-89T. The average nucleotide identity (ANI) and in digital DNA-DNA hybridization (dDDH) values between DSL-7T and closely related type strains were below the accepted threshold to delineate a new species of 95 and 70 %, respectively. The major cellular fatty acids were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), C16 : 0, summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and C14 : 0. The genomic DNA G+C content was 47.6 mol%. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic data, strain DSL-7T represents a novel species of the genus Vibrio, for which the name Vibrio chanodichtyis sp. nov. is proposed, with strain DSL-7T (=KCTC 92851T=CCTCC AB 2022396T) as the type strain.

LINC02454 promotes thyroid carcinoma progression via upregulating HMGA2 through CREB1.

Thyroid carcinoma (THCA) is the most common malignancy in the endocrine system. Long intergenic non-coding RNA 2454 (LINC02454) exhibits an HMGA2-like expression pattern, but their relationship and roles in THCA are largely unknown. The present purpose was to delineate the roles of LINC02454 in THCA progression and its molecular mechanisms. We collected THCA tissues from patients and monitored patient survival. THCA cell colony formation, migration, and invasion were evaluated. Metastasis was evaluated by examining EMT markers through Western blotting. Gene interaction was determined with ChIP, RIP, RNA pull-down, and luciferase activity assays. A mouse model of a subcutaneous tumor was used to determine the activity of LINC02454 knockdown in vivo. We found that LINC02454 was highly expressed in THCA, and its upregulation was associated with poor survival. The knockdown of LINC02454 repressed colony formation, migration, and invasion. Moreover, loss of LINC02454 inhibited tumor growth and metastasis in mice. HMGA2 promoted LINC02454 transcription via binding to the LINC02454 promoter, and silencing of HMGA2 suppressed malignant behaviors through downregulation of LINC02454. HMGA2 was a novel functional target of LINC02454 in THCA cells, and knockdown of LINC02454-mediated anti-tumor effects was reversed by HMGA2 overexpression. Mechanically, LINC02454 promoted CREB1 phosphorylation and nuclear translocation, and CREB1 was subsequently bound to the HMGA2 promoter to facilitate its expression. LINC02454 cis-regulates HMGA2 transcription via facilitating CREB1 phosphorylation and nuclear translocation, and, in turn, HMGA2 promotes LINC02454 expression, thus accelerating thyroid carcinoma progression. Our results support therapeutic targets of LINC02454 and HMGA2 for THCA.

Ultrasound-guided anterior quadratus lumborum block at the L2 level for postsurgical analgesia in patients undergoing laparoscopic gynaecological surgery: a single-centre, randomised, double-blinded trial at a university-affiliated hospital in China.

OBJECTIVE: This study aimed to investigate the analgesic effect of an ultrasound-guided anterior quadratus lumborum block (QLB) at the L2 level on postoperative pain after laparoscopic gynaecological surgery. DESIGN: Prospective single-centre randomised double-blind trial. SETTING: University-affiliated hospital. PARTICIPANTS: Sixty patients aged between 18 and 65 years scheduled for laparoscopic gynaecological surgery. INTERVENTIONS: Before surgery, bilateral anterior QLB was performed with 20 mL of 0.375% ropivacaine injected on each side in the QLB group, whereas equal amount of saline was administered in the placebo group. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the cumulative morphine dose in the first 24 hours, and the secondary endpoints were morphine consumption at each time interval, area under the curve (AUC) of the numeric rating scale (NRS) for pain, maximum pain intensity, incidence of moderate-to-severe pain (NRS>3), sedation score, adverse events, and time to home-readiness. RESULTS: Cumulative morphine consumption in the first 24 hours after surgery was significantly lower in the QLB group than in the placebo group (mean difference, 14.2; 95% CI 6.3 to 22.1; p<0.001). The AUCs of NRS pain intensity scores, including visceral and incisional pain at rest and on movement, were significantly lower in the QLB group than in the placebo group (all p<0.001). The time to home-readiness was significantly shorter in the QLB group than in the placebo group (p<0.05). CONCLUSION: Ultrasound-guided anterior QLB at the L2 level significantly reduced morphine consumption and relieved visceral and incision pain intensity after laparoscopic gynaecological surgery, which was beneficial for enhanced recovery. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR-IOR-17011960).

Serum hyaluronic acid and procollagen III, N-terminal propeptide levels are highly associated with disease severity and predict the progression of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving global emergency and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. In order to early identify severe and critical patients, we retrospectively analyze the clinical characteristics and risk indicators of severe disease in patients with corona virus disease 2019 (COVID-19). Methods: A total of 420 confirmed COVID-19 patients were included in the study. According to the "Diagnosis and Treatment of novel coronavirus Pneumonia (10th Edition)", the cases were divided into mild group (n = 243) and severe group (n =177). Laboratory parameters were analyzed in combination with clinical data. Results: Male patients over 46 years who have smoking habits were more likely to suffer from severe COVID-19. Critically ill patients had lower lymphocyte counts and red blood cell counts, and higher white blood cell counts (P<0.05). Expectedly, serum inflammatory factors (NLR, PLR, LMR, CLR, PCT, CRP), coagulation markers (APTT, PT, TT, FIB, D-Dimer), Myocardial damage markers (hs-TNT, LDH) were significantly increased (P<0.05) in severe COVID-19 patients. Surprisedly, those patients showed obviously elevated levels of common tumor markers (ProGRP, CYFRA21-1, SCC, NSE) (P<0.05). In this case, the levels of tumor marker reflected more the condition of inflammation than the growth of tumor. More importantly, HA and PIIIN-P were highly associated with COVID-19 severity. The AUC of the ROC curve for the diagnosis of severe COVID-19 by HA and PIIIN-P was 0.826. Meanwhile, HA was positively correlated with myocardial damage markers (hs-TNT, LDH). PIIIN-P was positively correlated with myocardial damage markers (hs-TNT, LDH) and inflammatory factors (NLR, PLR, LMR, CLR, ProGRP, SCC, PCT, CRP). On the contrary, PIIIN-P was negatively correlated with pulmonary function indexes (oxygenation index and oxygen saturation of hemoglobin). Conclusion: HA and PIIIN-P are highly associated with disease severity and progression of COVID-19 and can be used as new markers for the prediction of severe COVID-19.

Repeated pulmonary nodules as the primary symptom of familial hemophagocytic lymphohistiocytosis in adults: a case report and review.

Pulmonary nodules are usually considered to be associated with malignant tumors and benign lesions, such as granuloma, pulmonary lymph nodes, fibrosis, and inflammatory lesions. Clinical cases of pulmonary nodules associated with hemophagocytic lymphohistiocytosis have rarely been reported. Therefore, when patients develop pulmonary nodules, the possibility of developing hemophagocytic lymphohistiocytosis is often not considered. We report the first case of familial hemophagocytic lymphohistiocytosis with recurrent pulmonary nodules as the first symptom. Our findings will hopefully provide new ideas for the diagnosis and treatment of pulmonary nodules in the future.

Conditional knockout of ITGB4 in bronchial epithelial cells directs bronchopulmonary dysplasia.

Neonatal respiratory system disease is closely associated with embryonic lung development. Our group found that integrin ß4 (ITGB4) is downregulated in the airway epithelium of asthma patients. Asthma is the most common chronic respiratory illness in childhood. Therefore, we suspect whether the deletion of ITGB4 would affect fetal lung development. In this study, we characterized the role of ITGB4 deficiency in bronchopulmonary dysplasia (BPD). ITGB4 was conditionally knocked out in CCSP-rtTA, Tet-O-Cre and ITGB4f/f triple transgenic mice. Lung tissues at different developmental stages were collected for experimental detection and transcriptome sequencing. The effects of ITGB4 deficiency on lung branching morphogenesis were observed by fetal mouse lung explant culture. Deleting ITGB4 from the airway epithelial cells results in enlargement of alveolar airspaces, inhibition of branching, the abnormal structure of epithelium cells and the impairment of cilia growth during lung development. Scanning electron microscopy showed that the airway epithelial cilia of the ß4ccsp.cre group appear to be sparse, shortened and lodging. Lung-development-relevant factors such as SftpC and SOX2 significantly decreased both mRNA and protein levels. KEGG pathway analysis indicated that multiple ontogenesis-regulating-relevant pathways converge to FAK. Accordingly, ITGB4 deletion decreased phospho-FAK, phospho-GSK3ß and SOX2 levels, and the correspondingly contrary consequence was detected after treatment with GSK3ß agonist (wortmannin). Airway branching defect of ß4ccsp.cre mice lung explants was also partly recovered after wortmannin treatment. Airway epithelial-specific deletion of ITGB4 contributes to lung developmental defect, which could be achieved through the FAK/GSK3ß/SOX2 signal pathway.

Preoperative small airway dysfunction is associated with skeletal muscle loss in early-stage non-small cell lung cancer.

BACKGROUND: Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. METHODS: There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. RESULTS: This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5 ± 8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p = 0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p = 0.046; for FEF50%, r = -0.142, p = 0.008; and for FEF25-75%, r=-0.124, p = 0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p > 0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p = 0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P = 0.041) were associated with postoperative complications. CONCLUSION: Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.