A Horizontal and Longitudinal Study on the Changes of Aging Thyroid Function in Elderly Male Population.

OBJECTIVES: There are few follow-up studies on thyroid function in the same group for many years. Therefore, the purpose of this study was to retrospectively analyze the changes of thyroid function in a group of people for 8 years and to explore the changes of thyroid function in elderly men with normal thyroid function with age. METHODS: Reviewing the records of elderly men who underwent physical examination in the Beijing Hospital physical examination center from 2013 to 2020, 354 subjects were included in the study. According to age, they are divided into 4 groups. The differences in thyrotropin (TSH), anti-triiodothyronine (rT3), free triiodothyronine (FT3), and free thyroid hormone (FT4) among different age groups in initial time (2013) were compared. Longitudinal comparison of changes of thyroid function in the same age group for 8 years was compared too. RESULTS: At the initial time, age was negatively correlated with FT3 (r = 0.349, p < 0.001), positively correlated with rT3 and TSH (r = 0.182, p < 0.001, r = 0.212, p < 0.001), but not correlated with FT4. The results of eight years of analysis show that, for TSH, during the whole follow-up period, the TSH of the >80 years group was higher than that of the <60 years and 60-69 years groups, and the difference was statistically significant. The 70-79 age group was higher than the <60 years group at different time points, except for the age group <60 years. The other three groups showed an increasing trend with age, especially in the group of ≥80 years. For FT3, in 2013, the age ≥80 years group was significantly lower than that of the 70-79 years, 60-69 years, and <60 years old groups (p < 0.05). The analysis results at different time points in each age group showed a downward trend and then an upward trend. For FT4, there was no significant difference in FT4 among different age groups in 2013. Still, during the follow-up period, the age group ≥80 was lower than other age groups in 2019 and lower than the <60 years groups in 2014, 2015, 2019, and 2020, and the difference was statistically significant. The change rule of FT4 with the increase of age was not clear. For rT3, during the whole follow-up period, the rT3 of the >80 years group was higher than that of the <60 years and 60-69 years groups, and the difference was statistically significant. The analysis results at different time points in each age group showed a trend of rising first, then falling, and finally rising. After 2017, the rT3 of the 70-79 years and ≥80 years groups increased with age. CONCLUSIONS: The thyroid function index of elderly men changes with age. In transverse analysis, the value of TSH is the highest, and FT3 is the lowest in the group ≥80 years old. There are differences between the changes in the longitudinal analysis and the results of the horizontal analysis. Therefore, the law of thyroid function changing with age in different individuals is not the same as that of the same individual with age, which should be paid more attention in medical research and clinical diagnosis and treatment.

Preschool children's asthma medication: parental knowledge, attitudes, practices, and adherence.

Introduction: As parents or legal guardians primarily care for children with asthma, understanding their knowledge, attitudes, and practices (KAP) barriers to treatment and medication adherence is of essential importance. This study aimed to analyze the KAP toward asthma medication and adherence among preschool-aged asthmatic children's parents and explore the factors influencing adherence. Methods: This cross-sectional study was conducted between February 2023 and April 2023. Parents of preschool children with asthma were asked to complete the questionnaire containing knowledge, attitude, practice dimensions, and demographic characteristics. The Morisky Medication Adherence Scale (MMAS) was used to investigate adherence. Results: A total of 632 valid questionnaires (154 male and 478 female) were included. Parents showed moderate knowledge (9.49 ± 2.86, 63.27%, possible range: 0-15) and moderate attitudes (26.18 ± 2.51, 74.80%, possible range: 7-35) towards asthma medication, while their practices (27.46 ± 5.26, 91.53%, possible range: 6-30) were proactive; however, medication adherence was low (4.84 ± 1.78, total score: 8). The attitude scores (OR = 1.10, 95% CI: 1.01-1.19, P=0.020), practice scores (OR = 1.16, 95%CI: 1.12-1.21, p < 0.001), and smoking (OR = 1.64, 95%CI: 1.14-2.37, p = 0.008) were associated with medication adherence. Discussion: Preschool-aged asthmatic children's parents showed moderate knowledge, attitudes, and proactive practice toward asthma medication. Continuous training and education programs should be provided for parents to improve asthma medication management in preschool children.

The impact of indirect notification of a cancer diagnosis and a risk model based on it to predict the prognosis of postoperative stage T3 esophageal cancer patients.

Chinese doctors are required to inform patients' direct relatives of a cancer diagnosis rather than the patients themselves. The disease may be hidden from patients by their family members, which could result in severe outcomes. We selected postoperative T3 esophageal cancer (EsC) patients hospitalized from June 2015 to December 2019 as research subjects. The patients were divided into a direct-notification group and an indirect-notification group. Several variables were used to evaluate both groups' 36-month progress-free survival (PFS). A risk prediction model of prognosis based on the risk score was established, which was assessed using the area under the curve (AUC) of the receiver operating characteristic curve. One hundred and thirteen patients were enrolled in the training group and forty-eight in the validation group. Cox multivariate regression analysis revealed that males, late stage, poor pathological differentiation, and indirect notification were independent worse risk factors for postoperative T3 stage EsC patients at 36-month PFS (hazard ratio (HR) = 0.454, 95% confidence interval (CI): 0.254-0.812, P = .008; HR = 1.560, 95% CI: 1.006-2.420, P = .047; HR = 0.595, 95% CI: 0.378-0.936, P = .025; HR = 2.686, 95% CI: 1.679-4.297, P < 0.001, respectively). The type of notification was the best correlation factor. The risk score was calculated as follows: risk score = 0.988 × cancer notification (indirect = 1, direct = 0)-0.790 × sex (female = 1, Male = 0) + 0.445 × stage (IIIB = 1, IIA + IIB = 0)-0.519 × pathological differentiation (moderately + well = 1, poorly = 0). The model had a sensitivity of 64.8% and specificity of 81.8%, with the AUC at 0.717 (95% CI: 0.614-0.810) in internal verification, and a sensitivity of 56.8% and specificity of 100%, with the AUC at 0.705 (95% CI: 0.651-0.849) in external validation. The model had good internal and external stability. The model showed a Brier score of 0.18. Indirect notification of a cancer diagnosis was an important negative predictor of postoperative EsC patients' PFS. The model displayed good accuracy and stability in the prediction of risk for cancer progression.

The role and mechanism of NADPH oxidase in the development and progression of thyroid carcinoma.

Thyroid cancer is the fastest increasing cancer in both men and women and is the most common endocrine cancer. Researchers have gradually intensified their research on the mechanism of thyroid cancer development. Within this realm, Oxidative stress is often believed to play a causal and contributory role in thyroid cancer development. NADPH oxidase is one of the important sources of reactive oxygen species for tumor cell growth and is involved in the biological processes of thyroid tumor cell proliferation, migration, invasion and epithelial-to-mesenchymal transition. However, the mechanism of NADPH oxidase in the pathogenesis of thyroid cancer is still not very clear at present. Clarifying the role and mechanism of NADPH oxidase in the pathogenesis of thyroid cancer will help to develop new strategies for the prevention and treatment of thyroid cancer as early as possible, and improve the survival rates of thyroid tumor patients. This article reviews the research progress on the mechanism of NADPH oxidase in thyroid cancer.

Evaluating treatment strategies for non-small cell lung cancer during COVID-19: A propensity score matching analysis.

We employed pandemic treatment strategies that we developed at the beginning of the coronavirus disease 2019 (COVID-19) pandemic, and it was not clear whether any adverse results were associated with our strategies. Therefore, we carried out a retrospective study to compare our pandemic treatment strategies with prepandemic protocols to determine whether the strategies used during the high-risk period of COVID-19 were appropriate. The observation period was September 2019 to February 2020. Patients hospitalized from December 2019 to February 2020 were included as an experimental group, and individuals hospitalized from September 2019 to November 2019 were included as a control group. All non-small cell lung cancer patients hospitalized during the observation period were included except for pediatric and obstetric patients, patients younger than 18 years old, and patients admitted only for routine follow-up examinations. Treatment strategies were evaluated based on the prognosis of the different treatment methods, including surgical and nonsurgical treatments and discontinuation of therapy. Survival curves were analyzed using the Kaplan-Meier method. Cox regression analysis was used for multivariate analysis of risk factors for progress-free survival. Propensity score matching was used for clinical characteristics to adjust for selection bias. Therapy discontinuation in the experimental group was significantly higher than in the control group (P < .001). The differences in cancer progression and the number of deaths between the 2 groups were not significant (P = .38 and .13, respectively). For late-stage patients, there were significant differences in nonsurgical treatment and discontinued therapy (P < .001 and < .001, respectively) between the 2 groups, while the cancer progression and death toll differences were not significant (P = .20 and .20, respectively). For early-stage patients, the differences in surgical treatment, discontinued therapy, cancer progression, and death toll were not significant (P = .24, 0.24, 0.61, and 0.49, respectively) between the 2 groups. Multivariate analysis revealed that temporary discontinuation of therapy did not predict poor progress-free survival independently (hazard ratio = 1.007, 95% confidence interval: 0.653-1.552, P = .98). For patients in geographical regions with a high risk for COVID-19 infections, temporarily suspending treatment for late-stage non-small cell lung cancer patients is not likely to significantly impact their prognosis if they can return to treatment within 3 months of discontinuation.

A novel prognostic model for malignant patients with Gram-negative bacteremia based on real-world research.

Gram-negative bacteremia (GNB) is a common complication in malignant patients. Identifying risk factors and developing a prognostic model for GNB might improve the survival rate. In this observational and real-world study, we retrospectively analyzed the risk factors and outcomes of GNB in malignant patients. Multivariable regression was used to identify risk factors for the incidence of GNB, while Cox regression analysis was performed to identify significant prognostic factors. A prognostic model was constructed based on Cox regression analysis and presented on a nomogram. ROC curves, calibration plots, and Kaplan-Meier analysis were used to estimate the model. It comprised 1004 malignant patients with Bloodstream infection (BSI) in the study cohort, 65.7% (N = 660) acquired GNB. Multivariate analysis showed gynecologic cancer, hepatobiliary cancer, and genitourinary cancer were independent risk factors related to the incidence of GNB. Cox regression analysis raised that shock, admission to ICU before infection, pulmonary infection, higher lymphocyte counts, and lower platelet counts were independent risk factors for overall survival (OS). The OS was significantly different between the two groups classified by optimal cut-off value (log-rank, p < 0.001). Above all, a nomogram was created based on the prognostic model, which was presented on a website freely. This real-world study was concentrated on the malignant patients with GNB and proved that shock, admission to ICU before infection, pulmonary infection, higher lymphocyte counts, and lower platelet counts were related to the death of these patients. And a prognostic model was constructed to estimate the risk score of mortality, further to reduce the risk of death.

Targeting NOX4 disrupts the resistance of papillary thyroid carcinoma to chemotherapeutic drugs and lenvatinib.

Advanced differentiated thyroid cancer cells are subjected to extreme nutritional starvation which contributes to develop resistance to treatments; however, the underlying mechanism remains unclear. Cells were subjected to serum deprivation by culture in medium containing 0.5% fetal bovine serum. A CCK8 assay, cell death Detection ELISAPLUS kit, and PI staining were conducted to determine cell viability, cell apoptosis, and cell cycle, respectively. NADPH oxidase 4 (NOX4) knockdown-stable cell lines were generated by lentivirus-mediated shRNA knockdown in BCPAP cells and TPC-1 cells. Etoposide and doxorubicin, two chemotherapeutic drugs, as well as lenvatinib were utilized to determine the effect of NOX4 on drug resistance. Lenvatinib-resistant BCPAP cells (LRBCs) were established to confirm this effect. The underlining mechanisms of NOX4 under starvation were explored using western blot. Finally, GLX351322, an inhibitor targeting NOX4, was used to inhibit NOX4-derived ROS in vitro and detect its effect on drug resistance of tumor cells in vivo. NOX4 is overexpressed under serum deprivation in BCPAP or TPC-1 cells. NOX4 knockdown impairs cell viability, increases cell apoptosis, extends G1 phase during cell cycle and modulates the level of energy-associated metabolites in starved cells. When the starved cells or LRBCs are treated with chemotherapeutic drugs or Lenvatinib, NOX4 knockdown inhibits cell viability and aggravates cell apoptosis depending on NOX4-derived ROS production. Mechanistically, starvation activates TGFß1/SMAD3 signal, which mediates NOX4 upregulation. The upregulated NOX4 then triggers ERKs and PI3K/AKT pathway to influence cell apoptosis. GLX351322, a NOX4-derived ROS inhibitor, has an inhibitory effect on cell growth in vitro and the growth of BCPAP-derived even LRBCs-derived xenografts in vivo. These findings highlight NOX4 and NOX4-derived ROS as a potential therapeutic target in resistance to PTC.

Identification of multiple transfer units and novel subtypes of tmexCD-toprJ gene clusters in clinical carbapenem-resistant Enterobacter cloacae and Klebsiella oxytoca.

OBJECTIVES: Tigecycline is a last-resort antibiotic used to treat lethal infections caused by carbapenem-resistant Enterobacterales; however, plasmid-borne tigecycline resistance tmexCD-toprJ gene clusters can confer tigecycline resistance. The aim of the study was to identify novel subtypes and the spread of tmexCD-toprJ. METHODS: Five non-duplicate isolates of different species, carrying tmexCD-toprJ gene clusters or novel subtypes, were isolated from patients across China between November 2018 and June 2019. WGS was performed using Illumina and Nanopore platforms. A phylogenetic tree was constructed using a dataset of 77 sequences carrying the tmexCD-toprJ gene clusters, 72 of which were downloaded from NCBI with a blastn identity cut-off of 95%. RESULTS: We detected six different transfer units and two novel subtypes (tmexC1D1.2-toprJ1 and tmexC2D2.2-toprJ2) of the tmexCD-toprJ gene clusters. Among the six transfer units, three were mediated by IS26, while the rest were presumably mediated by Tn5393, hypothetical integrases (xerD-hp clusters-umuC-integrases-tnfxB2-tmexC2D2-toprJ2-umuC) and hypothetical units (hp-hp-hp-tnfxB2-tmexC2D2.2-toprJ2-ΔTn5393-Tn6292). Moreover, two tmexCD-toprJ-like gene clusters co-located on the same plasmid with blaNDM in five isolates. Phylogenetic analysis revealed that tmexCD-toprJ gene clusters may have originated in Pseudomonas spp., being mainly distributed in Pseudomonas spp. and Klebsiella spp. (64/77). Most tmexCD-toprJ gene clusters in Enterobacterales were located on plasmids, indicating that the gene clusters have a high inter-species transfer risk after transfer to Enterobacterales. CONCLUSIONS: In summary, to the best of our knowledge, this is the first report of tmexCD-toprJ gene clusters being isolated from Enterobacter cloacae and Klebsiella oxytoca, revealing that these multiple transfer units should be further studied because of their clinical significance.

LINC01419 promotes cell proliferation and metastasis in hepatocellular carcinoma by enhancing NDRG1 promoter activity.

PURPOSE: Emerging evidence indicates that dysfunction of long non-coding RNAs (lncRNAs) plays an essential role in the initiation and progression of hepatocellular carcinoma (HCC). In this study we investigated the potential roles and molecular mechanisms involving LINC01419 in HCC. METHODS: The expression of LINC01419 in 40 pairs of HCC/normal tissues and 6 HCC cell lines was detected by qRT-PCR. MTS, EdU, colony formation, scratch wound-healing and transwell assays were performed to assess the role of LINC01419 in HCC cell (SMMC7721 and SK-Hep1) proliferation, migration and invasion in vitro. Artificial modulation of LINC01419 (up- and downregulation) was performed to explore the role of LINC01419 in tumor growth and metastasis in vivo. Interaction of LINC01419 with NDRG1 was assessed using qRT-PCR, RNA sequencing, Western blotting and immunohistochemistry. Physical interaction of LINC01419 with the NDRG1 promoter was assessed using a dual-luciferase reporter assay. RESULTS: We observed LINC01419 overexpression in primary HCC tissues and HCC cell lines and that this overexpression positively correlated with large tumor size, increased vascular invasion and advanced TNM stage in 40 HCC patients. Exogenous LINC01419 expression significantly promoted HCC cell proliferation, migration and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, we found that LINC01419 expression knockdown elicited opposite effects. Mechanistic investigations revealed that LINC01419 exerted its biological effects by regulating NDRG1. A dual-luciferase reporter assay revealed that LINC01419 interacts with a specific region within the NDRG1 promoter, resulting in its activation. CONCLUSIONS: From our data we conclude that LINC01419 acts clinically, functionally and mechanistically oncogenic in HCC. LINC01419 may, therefore, serve as a promising prognostic indicator and therapeutic target for HCC.

Decorated TiO2 Nanoparticles with La and Ag Elements to Improve Photocatalytic Activity Under Visible Light for the Degradation of MO.

Visible-light photocatalyst of TiO2/La/Ag nanocomposites were successfully synthesized via the conventional sol-gel method and reducing agent of Ag+. The photocatalytic activities were evaluated by methyl orange (MO) degradation. They have remarkable photocatalytic activities compared to TiO2-Anatase, which is thanks to the separation of electron-hole pairs by Ag nanoparticles and lanthanum. The products were characterized by a series of techniques such as X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), and Uv-vis. The results show that spherical nanocomposites have been prepared with the size 300 nm and Ag nanoparticles (~10 nm) are dispersed uniformly onto the surface of TiO2/La, which forms TiO2/La/Ag nanocomposites. TiO2/La/Ag nanocomposites have good absorption in the visible region (700 nm > λ > 400 nm). The reasons are as follows: (1) the efficient separation of photogenerated electrons and holes of the photocatalysts on the surface of TiO2/La/Ag nanocomposites and (2) a wide visible-light photoabsorption range (700 nm > λ > 400 nm). Therefore, this study may provide some new idea for the rational design and the facile synthesis of composite catalysts with a green, efficient pathway.

Synthesis and Characterization of α-ZrP@CHI Drug Deliver System.

This paper described the controlled synthesis and release properties of a new kind of multifunctional drug-release system which was prepared by encapsulation of zirconium bis-(monohydrogen orthophosphate) monohydrate (α-ZrP) with chitosan (CHI). As obtained the α-ZrP@CHI nanocomposites were found to possess the structural features of both α-ZrP and CHI. The release properties of the α-ZrP@CHI nanocomposites were evaluated using Gentamicin sulfate as the model drug. And α-ZrP@CHI composites showed a prolonged drug release time compared with α-ZrP, which can be attributed to the unique lamellar structure and the encapsulation with CHI. The controlled synthesis of α-ZrP@CHI nanocomposite thus provided a new opportunity for future development of delivery vehicles.

Synthesis and Characteristic of the NaYF4/Fe3O4@SiO2@Tb(DBM)3 . 2H2O/SiO2 Luminomagnetic Microspheres with Core-Shell Structure.

The structure and properties of the multifunctional nanoparticles were characterized by X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Photoluminescence spectra and Vibrating sample magnetometer (VSM). The experimental results show that the microsphere has the magnetic core and silica shell bonded with terbium complex. These multifunctional nanoparticles exhibit strong visible emission and up-conversion emission, which is based on the use of up-converting nanoparticles (UCNPs) of the NaYF4:Yb3+, Er3+/Tm3+ type that can be excited with 980 nm laser light to give a green and red luminescence, moreover, nanoparticles possess magnetism with a saturation magnetization of 18.48 emu/g and paramagnetism at room temperature.

Inorganic nanovehicle for potential targeted drug delivery to tumor cells, tumor optical imaging.

In this work, an inorganic multifunctional nanovehicle was tailored as a carrier to deliver anticancer drug for tumor optical imaging and therapy. The nanovehicle could be used as a dually targeted drug nanovehicle by bonded magnetical (passive) and folic acid (active) targeting capabilities. In addition, it was developed using rhodamine 6G (R6G) as a fluorescence reagent, and an α-zirconium phosphate nanoplatform (Zr(HPO4)2·H2O, abbreviated as α-ZrP) as the anticancer drug nanovehicle. The novel drug-release system was designed and fabricated by intercalation of α-ZrP with magnetic Fe3O4 nanoparticles and anticancer drug 5-fluorouracil (5-FU), followed by reacting with a folate acid-chitosan-rhodamine6G (FA-CHI-R6G) complex, and then α-ZrP intercalated with Fe3O4 nanoparticles and 5-fluorouracil (5-FU) was successfully encapsulated into chitosan (CHI). The resultant multifunctional drug delivery system was characterized by scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray analysis, photoluminescence spectra, magnetometry, fluorescence microscopy imaging studies and other characterization methods. Simultaneously, the drug release in vitro on the obtained nanocomposites that exhibited a sustained release behavior was carried out in buffer solution at 37 °C, which demonstrated clearly that the nanocomposites shown a sustained release behavior. Meanwhile, cell culture experiments also indicated that the drug-release system had the potential to be used as an dually targeted drug nanovehicle into the tumor cells.