Hyperglycemia-depleted glutamine contributes to the pathogenesis of diabetic corneal endothelial dysfunction.

Diabetic mellitus (DM) causes various complications, including the corneal endothelial dysfunction that leads to corneal edema and vision loss, especially in the DM patients with intraocular surgeries. However, the pathogenic mechanism of hyperglycemia-caused corneal endothelial dysfunction remains incomplete understood. Here we firstly screened and identified the glutamine contents of aqueous humor (AH) were significantly reduced in the type 2 diabetic patients and type 1 and type 2 diabetic mice. To explore the potential therapeutic effects of glutamine (Gln) supplement on the protection of diabetic corneal endothelial dysfunction, we performed the anterior chamber perfusion with the addition of L-alanyl-L-glutamine (Ala-Gln), and confirmed that Ala-Gln supplement not only accelerated the resolution of corneal edema and recovery of corneal thickness, but also preserved the regular arrangement and barrier-pump function of cornea. Mechanistically, we revealed that the supplements of Ala-Gln protect corneal endothelial cells (CECs) from the deleterious effects of high glucose-induced oxidative stress, mitochondrial dysfunction, and cell apoptosis. Overall, these results indicate the Gln depletion plays an important role in the diabetic corneal endothelial dysfunction, while the Ala-Gln supplement during intraocular surgery provide an effective prevention strategy through regulating the redox homeostasis and mitochondrial function of corneal endothelium.

[Analysis of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein deficiency and High molecular weight kininogen deficiency].

OBJECTIVE: To analyze the laboratory phenotype and genetic variants of two consanguineous Chinese pedigrees affected with Hereditary prokallikrein (PK) and High molecular weight kininogen (HMWK) deficiency and explore their molecular pathogenesis. METHODS: A PK deficiency pedigree (10 individuals from 4 generations) and a HMWK deficiency pedigree (6 individuals from 3 generations) which were admitted to the First Affiliated Hospital of Wenzhou Medical University on December 3, 2021 and June 16, 2022, respectively were selected as the study subjects. Clinical data of the two pedigrees were collected, and the related coagulation indexes of the probands and their family members were determined. Genomic DNA of the two pedigrees was extracted from peripheral blood samples. All of the exons and flanking sequences of the KLKB1 and KNG1 genes of the probands were analyzed by direct sequencing. And the corresponding sites were sequenced among other family members. Bioinformatic software was used to analyze the conservation of variation sites and the effect of variant on the protein function. RESULTS: The plasma PK activity of proband 1, a 29-year-old female, and her brother were extremely low (< 1.0%). Proband 2 was a 66-year-old male with extremely low plasma HMWK activity (< 1.0%). Genetic sequencing revealed that the proband 1 and her brother had both harbored a homozygous c.417_418insCATTCTTA (p.Arg140Hisfs*3) insertional variant in exon 5 of the KLKB1 gene. Proband 2 had harbored a homozygous c.460C>A (p.Pro154Thr) missense variant in exon 4 of the KNG1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively rated as pathogenic (PVS1+PM2_Supporting+PM4) and likely pathogenic (PS4+PM2_Supporting+PP3+PP4). CONCLUSION: The c.417_418insCATTCTTA (p.Arg140Hisfs*3) variant of the KLKB1 gene and the c.460C>A (p.Pro154Thr) variant of the KNG1 gene probably underlay the decreased PK and HMWK activities in the two pedigrees, respectively.

[Analysis of three Chinese pedigrees affected with Hereditary factor â ¦ deficiency due to compound heterozygous variants of F7 gene].

OBJECTIVE: To analyze the types of genetic variants and clinical characteristics of three Chinese pedigrees affected with Hereditary coagulation factor Ⅶ (FⅦ) deficiency. METHODS: Three pedigrees who had visited the First Affiliated Hospital of Wenzhou Medical University between December 2021 and October 2022 were selected as the study subjects. Prothrombin time (PT), activated partial thromboplastin time (APTT) and FⅦ activity (FⅦ:C) were measured in the three probands and their pedigree members. All exons and their flanking sequences were analyzed by direct sequencing, and candidate variants were verified by reverse sequencing. The corresponding variant loci in the family members were also analyzed. ClustalX-2.1-win was used to analyze the conservation of the variant loci. Varcards and Spcards online software was used to predict the pathogenicity of the variants. Pymol software was used to analyze the changes in protein structure and molecular forces. RESULTS: Three cases of hereditary FⅦ deficiency were found to have decreased FⅦ:C, prolonged PT and normal APTT. Genetic analysis identified a total of four genetic variants, and all three probands had harbored compound heterozygous variants of the F7 gene, including p.Cys389Gly and p.His408Gln in proband 1, p.Cys389Gly and IVS6+1G>T in proband 2, and IVS6+1G>T and IVS1a+5G>A in proband 3. Conservation analysis showed that both the p.Cys389 and p.His408 loci are highly conserved among orthologous species. Analysis with Varcards and Spcards software showed that these variants were pathogenic. Protein modeling analysis showed that the p.Cys389Gly and p.His408Gln variants may result in altered protein structures and changes in hydrogen bonds. CONCLUSION: The clinical manifestations of the three FⅦ-deficient probands may be attributed to the compound heterozygous variants of p.Cys389Gly/p.His408Gln, p.Cys389Gly/IVS6+1G>T and IVS6+1G>T/IVS1a+5G>A of the F7 gene. The combination of the three compound heterozygous variants was unreported previously.

Using Chicken Embryos to Identify the Key Determinants of Nanoparticles for the Crossing of Air-Blood Barriers.

Fine particulates (FPs) are a major class of airborne pollutants. In mammals, FPs may reach the alveoli through the respiratory system, cross the air-blood barrier, spread into other organs, and induce hazardous effects. Although birds have much higher respiratory risks to FPs than mammals, the biological fate of inhaled FPs in birds has rarely been explored. Herein, we attempted to disclose the key properties that dictate the lung penetration of nanoparticles (NPs) by visualizing a library of 27 fluorescent nanoparticles (FNPs) in chicken embryos. The FNP library was prepared by combinational chemistry to tune their compositions, morphologies, sizes, and surface charges. These NPs were injected into the lungs of chicken embryos for dynamic imaging of their distributions by IVIS Spectrum. FNPs with diameters <16 nm could cross the air-blood barrier in 20 min, spread into the blood, and accumulate in the yolk sac. In contrast, large FNPs (>30 nm) were mainly retained in the lungs and rarely detected in other tissues/organs. In addition to size, surface charge was the secondary determinant for NPs to cross the air-blood barrier. Compared to cationic and anionic particles, neutrally charged FNPs showed the fastest lung penetration. A predictive model was therefore developed to rank the lung penetration capability of FNPs by in silico analysis. The in silico predictions could be well validated in chicks by oropharyngeal exposure to six FNPs. Overall, our study discovered the key properties of NPs that are responsible for their lung penetration and established a predictive model that will greatly facilitate respiratory risk assessments of nanoproducts.

Aircraft-Based AirCore Sampling for Estimates of N2O and CH4 Emissions.

Airborne measurements offer an effective way to quantify urban emissions of greenhouse gases (GHGs). However, it may be challenging due to the requirement of high measurement precision and sufficiently enhanced signals. We developed a new active AirCore system based on the previous unmanned aerial vehicle (UAV) version, which is capable of sampling atmospheric air for several hours aboard a lightweight aircraft for postflight simultaneous and continuous measurements of N2O, CH4, CO2, and CO. We performed 13 flights over the urban areas of Groningen, Utrecht, and Rotterdam and evaluated the aircraft-based AirCore measurements against in situ continuous CH4 measurements. One flight was selected for each of the three urban areas to quantify the emissions of N2O and CH4. Compared to the Dutch inventory, the estimated N2O emissions (364 ± 143 kg h-1) from the Rotterdam area are ∼3 times larger, whereas those for Groningen (95 ± 90 kg h-1) and Utrecht (32 ± 16 kg h-1) are not significantly different. The estimated CH4 emissions for all three urban areas (Groningen: 2534 ± 1774 kg CH4 hr-1, Utrecht: 1440 ± 628 kg CH4 hr-1, and Rotterdam: 2419 ± 922 kg CH4 hr-1) are not significantly different from the Dutch inventory. The innovative aircraft-based active AirCore sampling system provides a robust means of high-precision and continuous measurements of multiple gas species, which is useful for quantifying GHG emissions from urban areas.

Profiles of depressive symptoms and influential factors among people living with HIV in China.

BACKGROUND: Depressive symptoms are highly prevalent among people living with HIV (PLWH). We leveraged Latent Profile Analysis (LPA) to identify profiles of depressive symptoms among PLWHs. We also investigated differences in psychological factors of interest, demographic characteristics, and HIV-related factors across patients' profiles. METHODS: A cross-sectional study was conducted at one hospital and two designated prison facilities in Hunan province, China. A total sample of 533 PLWHs (320 recruited from the hospital, 213 recruited from prisons) completed the survey. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9). Family function, resilience, childhood trauma, demographic characteristics, and HIV-related factors were also evaluated. We conducted LPA and multinomial logistic regression analyses to: 1) identify distinct profiles for depressive symptoms; 2) identify demographic characteristics, and HIV-related, and psychological factors predicting PLWHs' likelihood to express a specific profile. RESULTS: We identified three distinct profiles of depressive symptoms among PLWHs: severe symptoms (11.8%), moderate symptoms (40.5%), and low/no symptoms (47.7%). Moderate/ severe family dysfunction, low resilience, experiencing emotional abuse and neglect were more likely to fall in the "severe symptoms" rather than the "low/no symptoms" profile. In addition, severe family dysfunction, low resilience, and experiencing emotional neglect indicated a higher likelihood of being classified in the "moderate symptoms" profile, compared to the "low/no symptoms" profile. CONCLUSION: Identifying profiles of depressive symptoms among PLWHs using the PHQ-9 items allows for understanding of the distinct paths of development of depressive symptoms and for developing tailored prevention and intervention programs for PLWHs.

Differences in Gut Microbiota between Healthy Individuals and Patients with Perianal Abscess before and after Surgery.

Surgery is the most important treatment for perianal abscesses. However, the gut microbiota of patients with perianal abscess and the effects of perianal abscess on the gut microbiota after surgery are unknown. In this study, significant changes in interleukin 6 and tumor necrosis factor-α in the blood of healthy subjects, patients with perianal abscesses, and patients after perianal abscess surgery were identified. 16S rRNA gene sequencing technology was used to detect the changes in the gut microbiota among 30 healthy individuals and 30 patients with perianal abscess before and after surgery. Venn diagrams and alpha diversity analyses indicated differences in the abundance and uniformity of gut microbiota between the healthy individuals and patients with perianal abscesses before and after surgery. Beta diversity analysis indicated that the grouping effects among the control, abscess, and surgery groups were good. The classification and compositional analysis showed significant differences in the gut microbiota between healthy individuals and patients with perianal abscesses before and after surgery. LEfSe analysis, random forest analysis, and ROC curve analysis showed that Klebsiella (AUC = 0.7467) and Bilophila (AUC = 0.72) could be potential biomarkers for the diagnosis of perianal abscess. The functional prediction results showed that the differential microbiota is significantly enriched in the pathways related to nutrition and drug metabolism. This study may have important implications for the clinical management and prognostic assessment of patients with perianal abscesses.

Associations Between Family Function and Non-suicidal Self-injury Among Chinese Urban Adolescents with and Without Parental Migration.

The study aims to explore the effect of family function on non-suicidal self-injury (NSSI) among Chinese urban adolescents with and without parental migration. Between April 21st to May 12th, 2021, adolescents were recruited from Shenzhen city of Guangdong province, China (n = 124,357). Of all the participants, 22,855 (18.4%) were left-behind children (LBC). Family function, NSSI, depression, and socio-demographic characteristics were assessed using a series of self-reported questionnaires. Urban LBC had a higher NSSI frequency, while a lower level of family function than non-LBC. After controlling for confounders, parental migration was significantly associated with NSSI, and family dysfunction was a robust risk factor for NSSI as well. The protective effect of family function on NSSI of LBC was stronger than non-LBC. This implies that children with higher levels of family function tend to exhibit a lower frequency of NSSI, especially in those with parental migration. In practice, adolescents' NSSI prevention and intervention strategies should focus on improving family function.

Golgi-localized calcium/manganese transporters FgGdt1 and FgPmr1 regulate fungal development and virulence by maintaining Ca2+ and Mn2+ homeostasis in Fusarium graminearum.

Calcium and manganese transporters play important roles in regulating Ca2+ and Mn2+ homeostasis in cells, which is necessary for the normal physiological activities of eukaryotes. Gdt1 and Pmr1 function as calcium/manganese transporters in the Golgi apparatus. However, the functions of Gdt1 and Pmr1 have not been previously characterized in the plant pathogenic fungus Fusarium graminearum. Here, we identified and characterized the biological functions of FgGdt1 and FgPmr1 in F. graminearum. Our study shows that FgGdt1 and FgPmr1 are both localized to the cis- and medial-Golgi. Disruption of FgGdt1 or FgPmr1 in F. graminearum caused serious defects in vegetative growth, conidiation, sexual development and significantly decreased virulence in wheat but increased deoxynivalenol (DON) production. Importantly, FgGdt1 is involved in Ca2+ and Mn2+ homeostasis and the severe phenotypic defects of the ΔFggdt1 mutant were largely due to loss of FgGdt1 function in Mn2+ transportation. FgGdt1-mCherry colocalizes with FgPmr1-GFP at the Golgi, and FgGDT1 exerts its biological function upstream of FgPMR1. Taken together, our results collectively demonstrate that the cis- and medial-Golgi-localized proteins FgGdt1 and FgPmr1 regulate Ca2+ and Mn2+ homeostasis of the Golgi apparatus, and this function is important in modulating the growth, development, DON biosynthesis and pathogenicity of F. graminearum.

Mouse 4T1 Breast Cancer Cell-Derived Exosomes Induce Proinflammatory Cytokine Production in Macrophages via miR-183.

Tumor-associated macrophages (TAMs) play a critical role in the tumor inflammatory microenvironment and facilitate tumor growth and metastasis. Most types of tumors aberrantly express microRNAs (miRNAs), which can be transferred between cells by exosomes and can regulate gene expression in recipient cells, but it remains unclear whether tumor-derived miRNAs are transferred by exosomes and regulate the TAM phenotype. We report that mouse 4T1 breast cancer cell-derived exosomes enhanced TAM expression of IL-1ß, IL-6, and TNF-α and that inhibition of 4T1-cell exosome secretion through short hairpin RNA-mediated Rab27a/b depletion repressed tumor growth and metastasis and markedly downregulated IL-1ß, IL-6, and TNF-α in a 4T1 breast tumor model. Furthermore, miRNA expression profiling revealed that three miRNAs (miR-100-5p, miR-183-5p, and miR-125b-1-3p) were considerably more abundant in 4T1 cell exosomes than in mouse bone marrow-derived macrophages, indicating potential exosome-mediated transfer of the miRNAs, and, notably, miR-183-5p was found to be transferred from 4T1 cells to macrophages through exosomes. Moreover, PPP2CA was verified as an miR-183-5p target gene, and PPP2CA downregulation enhanced NF-κB signaling and promoted macrophage expression of IL-1ß, IL-6, and TNF-α. Lastly, when miR-183-5p was downregulated in exosomes through miR-183-5p sponge expression in 4T1 cells, these 4T1-derived exosomes triggered diminished p65 phosphorylation and IL-1ß, IL-6, and TNF-α secretion, and the miRNA downregulation also led to repression of tumor growth and metastasis in the 4T1 breast tumor model in vivo. Thus, miR-183-5p expressed in tumor cells was transferred to macrophages by exosomes and promoted the secretion of proinflammatory cytokines by inhibiting PPP2CA expression, which contributed to tumor progression in a breast cancer model.

Influences of light and humidity on carbonyl sulfide-based estimates of photosynthesis.

Understanding climate controls on gross primary productivity (GPP) is crucial for accurate projections of the future land carbon cycle. Major uncertainties exist due to the challenge in separating GPP and respiration from observations of the carbon dioxide (CO2) flux. Carbonyl sulfide (COS) has a dominant vegetative sink, and plant COS uptake is used to infer GPP through the leaf relative uptake (LRU) ratio of COS to CO2 fluxes. However, little is known about variations of LRU under changing environmental conditions and in different phenological stages. We present COS and CO2 fluxes and LRU of Scots pine branches measured in a boreal forest in Finland during the spring recovery and summer. We find that the diurnal dynamics of COS uptake is mainly controlled by stomatal conductance, but the leaf internal conductance could significantly limit the COS uptake during the daytime and early in the season. LRU varies with light due to the differential light responses of COS and CO2 uptake, and with vapor pressure deficit (VPD) in the peak growing season, indicating a humidity-induced stomatal control. Our COS-based GPP estimates show that it is essential to incorporate the variability of LRU with environmental variables for accurate estimation of GPP on ecosystem, regional, and global scales.

The effectiveness of combining e-learning, peer teaching, and flipped classroom for delivering a physiology laboratory course to nursing students.

The Internet and 5G era makes e-learning a vital part of modern education, and extensive evidence has shown that peer teaching and flipped classroom contribute to increased success in medical teaching. However, the applicability of these pedagogies in laboratory courses remains largely unexplored. This study aimed to evaluate the academic performance, proficiency in procedural skills, and perception of nursing students in physiology laboratory classes delivered with nontraditional classroom (NTC) pedagogies comprising the combination of e-learning, peer teaching, and flipped classroom. Each class was subdivided into two equal halves by successive student identification (ID) number and randomly assigned to the control or NTC group. Compared to the control class, NTC teaching significantly enhanced mean score of six preclass tests (67.77 ± 9.83 vs. 62.94 ± 9.70), with "B" graders increased obviously, suggesting that preclass e-learning was more effective than textbook-based preview, especially for general grasp of the topic. Similarly, average scores on postclass quizzes in the NTC group were improved (79.40 ± 9.12 vs. 74.43 ± 8.88). Lesser time cost and higher success rates were observed in trachea, artery, and heart catheterizations in the NTC group, although no disparities were found in ureteral intubation. The majority (∼74%) of students supported the reform and shared positive experiences with NTC methodology. They reported that virtual experiments and self-paced procedural skill videos affected pre- and in-class learning outcomes most, respectively. These findings indicated that NTC pedagogy was workable to improve students' subject scores and proficiency in complicated and direct-viewing procedural skills and was favorable to students.

Valence and arousal ratings for 11,310 simplified Chinese words.

This study reports valence and arousal ratings for 11,310 simplified Chinese words, including 9774 two-character words, 949 three-character words, and 587 four-character words. These affective ratings are validated through comparisons with prior ratings of smaller word samples. All but four words included in this study are from the MEgastudy of Lexical Decision in Simplified CHinese (MELD-SCH) database. As age-of-acquisition ratings and concreteness ratings have recently become available for large portions of words in the MELD-SCH, the affective ratings not only further enrich the database as a valuable research tool, but also allow us to gain insight into a range of psycholinguistic constructs based on normative ratings of a large set of Chinese words. Cross-language comparisons of the valence ratings between Chinese words and English words appear to indicate cultural and sociopolitical influences reflected in affect representations.

MicroRNA-3613-3p functions as a tumor suppressor and represents a novel therapeutic target in breast cancer.

BACKGROUND: MicroRNAs have been reported to participate in tumorigenesis, treatment resistance, and tumor metastasis. Novel microRNAs need to be identified and investigated to guide the clinical prognosis or therapy for breast cancer. METHOD: The copy number variations (CNVs) of MIR3613 from Cancer Genome Atlas (TCGA) or Cancer Cell Line Encyclopedia (CCLE) were analyzed, and its correlation with breast cancer subtypes or prognosis was investigated. The expression level of miR-3613-3p in tumor tissues or serum of breast cancer patients was detected using in situ hybridization and qPCR. Gain-of-function studies were performed to determine the regulatory role of miR-3613-3p on proliferation, apoptosis, and tumor sphere formation of human breast cancer cells MDA-MB-231 or MCF-7. The effects of miR-3613-3p on tumor growth or metastasis in an immunocompromised mouse model of MDA-MB-231-luciferase were explored by intratumor injection of miR-3613-3p analogue. The target genes, interactive lncRNAs, and related signaling pathways of miR-3613-3p were identified by bioinformatic prediction and 3'-UTR assays. RESULTS: We found that MIR3613 was frequently deleted in breast cancer genome and its deletion was correlated with the molecular typing, and an unfavorable prognosis in estrogen receptor-positive patients. MiR-3613-3p level was also dramatically lower in tumor tissues or serum of breast cancer patients. Gain-of-function studies revealed that miR-3613-3p could suppress proliferation and sphere formation and promote apoptosis in vitro and impeded tumor growth and metastasis in vivo. Additionally, miR-3613-3p might regulate cell cycle by targeting SMS, PAFAH1B2, or PDK3 to restrain tumor progression. CONCLUSION: Our findings indicate a suppressive role of miR-3613-3p in breast cancer progression, which may provide an innovative marker or treatment for breast cancer patients.

CircHYBID regulates hyaluronan metabolism in chondrocytes via hsa-miR-29b-3p/TGF-ß1 axis.

BACKGROUND: Hyaluronan (HA) metabolism by chondrocytes is important for cartilage development and homeostasis. However, information about the function of circular RNAs (circRNAs) in HA metabolism is limited. We therefore profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis (OA). METHODS: CircHYBID function in HA metabolism in chondrocytes was investigated using gain-of-function experiments, and circHYBID mechanism was confirmed via bioinformatics analysis and luciferase assays. The expression of circHYBID-hsa-miR-29b-3p-transforming growth factor (TGF)-ß1 axis was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. CircHYBID, TGF-ß1, and HA levels in cartilage samples were evaluated using qRT-PCR and pathological examination. Enzyme-linked immunosorbent assay was used to assess HA accumulation in chondrocyte supernatant. RESULTS: CircHYBID expression was significantly downregulated in damaged cartilage samples compared with that in the corresponding intact cartilage samples. CircHYBID expression was positively correlated with alcian blue score. Interleukin-1ß stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis showed that circHYBID upregulated TGF-ß1 expression by sponging hsa-miR-29b-3p. CONCLUSIONS: Our results describe a novel HA-related circRNA that could promote HA synthesis and accumulation. The circHYBID-hsa-miR-29b-3p-TGF-ß1 axis may play a powerful regulatory role in HA metabolism and OA progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.

Association between alcohol consumption and oesophageal microbiota in oesophageal squamous cell carcinoma.

BACKGROUND: Microbiota has been reported to play a role in cancer patients. Nevertheless, little is known about the association between alcohol consumption and resultant changes in the diversity and composition of oesophageal microbiota in oesophageal squamous cell carcinoma (ESCC). METHODS: We performed a hospital-based retrospective study of 120 patients with pathologically diagnosed primary ESCC. The relevant information for all study participants were collected through a detailed questionnaire. The differences in adjacent tissues between non-drinkers and drinkers were explored using 16S rRNA gene sequencing. Raw sequencing data were imported into QIIME 2 to analyse the diversity and abundance of microbiota. Linear discriminant analysis effect size (LEfSe) and unconditional logistic regression were performed to determine the bacterial taxa that were associated with drinking. RESULTS: The Shannon diversity index and Bray-Curtis distance of oesophageal microbiota were significantly different among drinkers(P < 0.05). The alcohol-related bacteria were primarily from the orders Clostridiales, Gemellales and Pasteurellales, family Clostridiaceae, Lanchnospiraceae, Helicobacteraceae, Alcaligenaceae, Bacteroidaceae, Pasteurellaceae and Gemellaceae; genus Clostridium, Helicobacter, Catonella, Bacteroides, Bacillus, Moraxella, and Bulleidia; and species B. moorei and longum (genus Bifidobacterium). In addition, the diversity and abundance of these microbiota were observed to be affected by the age, residential districts of the patients, and sampling seasons. Moreover, the higher the frequency and years of alcohol consumption, the lower was the relative abundance of genus Catonella that was observed. CONCLUSION: Alcohol consumption is associated with alterations in both the diversity and composition the of the oesophageal microbiota in ESCC patients.

Health-related quality of life and treatment modality among esophageal squamous cell carcinoma survivors: A prospective study using time to deterioration model analysis.

BACKGROUND AND OBJECTIVES: This study aimed to analyze the association between health-related quality of life and treatment modality among esophageal squamous cell carcinoma (ESCC) survivors. METHODS: Patients completed the EORTC QLQ-C30 and EORTC QLQ-OES18 at baseline and follow-up. A time to deterioration model analysis was performed to compare longitudinal EORTC QLQ-C30/QLQ-OES18 data between surgery alone and surgery with adjuvant chemotherapy. RESULTS: For EORTC QLQ-C30 scale, compared with surgery alone, significant delays in time to deterioration in role functioning (16.05 months vs. 15.00 months; p = .045), cognitive functioning (20.80 months vs. 16.26 months; p = .017), social functioning (19.09 months vs. 12.35 months; p = .001), and dyspnea (18.53 months vs. 14.62 months; p = .011) were observed for surgery with adjuvant chemotherapy. For QLQ-OES18 scale, compared with surgery alone, significant delays in time to deterioration in dysphagia (13.75 months vs. 8.16 months; p = .005), choking when swallowing (20.67 months vs. 15.08 months; p = .001), and dry mouth (21.78 months vs. 17.28 months; p = .039) were observed for surgery with adjuvant chemotherapy. CONCLUSIONS: Patients who received postoperative chemotherapy had significant delay in time to deterioration in multiple ESCC-related symptoms, functions of EORTC QLQ-C30 and EORTC QLQ-OES18.

Serum exosomal microRNA-766-3p expression is associated with poor prognosis of esophageal squamous cell carcinoma.

The aim was to analyze the association between exosomal microRNA (miR)-766-3p expression levels in serum and the prognosis of esophageal squamous cell carcinoma (ESCC). The serum global exosomal miRNA expression of ESCC patients was measured by microRNA microarray. Quantitative real-time PCR was used to analyze the expression levels of candidate miRNAs in both serum and tissues from ESCC patients. Wilcoxon tests were applied to evaluate clinical characteristics and their association with serum levels of exosomal miR-766-3p. A Cox regression model was used to identify prognostic factors. The effects of miR-766-3p expression on cell migration and invasion were examined using Transwell assays, and CCK-8 assays were carried out to measure cell proliferation. The TNM stage was associated with high serum exosomal miR-766-3p levels of ESCC patients (P = .030). Higher serum exosomal miR-766-3p expression levels were associated with poor prognosis (for overall survival, hazard ratio [HR] [95% confidence interval (CI)], 2.21 [1.00, 4.87]; for disease-free survival, HR [95% CI], 2.15 [1.01, 4.59]). However, we found no association between the expression of miR-766-3p in tissue and ESCC prognosis. In vitro results showed that miR-766-3p promotes cell migration and invasion, but not cell proliferation. By using dual-luciferase reporter assay, HOXA13 was confirmed as a direct target gene of miR-766-3p. The ESCC patients with highly expressed serum exosomal miR-766-3p had a significantly worse survival. Therefore, serum exosomal miR-766-3p could serve as a prognostic marker for the assessment of ESCC.

An immunosuppressive peptide from the horsefly inhibits inflammation by repressing macrophage maturation and phagocytosis.

Ectoparasites repress host immune responses while they obtain nutrition from their hosts. Understanding the immunosuppressive mechanisms between ectoparasites and their hosts will provide new strategies to develop potential immunosuppressive drugs against immune disorder diseases. Previously, we have discovered that a small peptide, immunoregulin HA, from the horsefly (Hybomitra atriperoides) may play an immunosuppressive role in rat splenocytes. However, the targeting cells and detailed mechanisms of immunoregulin HA in immunosuppressive reactions are not well defined. Here, we show that immunoregulin HA reduces the secretion of proinflammatory cytokines upon lipopolysaccharide (LPS) stimulation. Interestingly, we discover that the major cytokines repressed by immunoregulin HA are secreted by macrophages, rather than by T cells. Furthermore, immunoregulin HA inhibits macrophage maturation and phagocytosis. Mechanically, the activations of c-JUN N-terminal kinase and extracellular signal-regulated kinase upon LPS stimulation are decreased by immunoregulin HA. Consistently, immunoregulin HA treatment exhibits an anti-inflammatory activity in a mouse model of adjuvant-induced paw inflammation. Taken together, our data reveal that immunoregulin HA conducts the anti-inflammatory activity by blocking macrophage functions.

Sex differences in antihypertensive drug use and blood pressure control.

BACKGROUND: Hypertension is the most important modifiable cardiovascular risk factor. Epidemiological studies have shown the benefits of lowering blood pressure (BP), but BP control is a major challenge. Furthermore, there are significant sex differences in antihypertensive drug use and BP control. This study examined sex differences in antihypertensive drug use and BP control, with the aim of reducing the complications of hypertension and improving quality of life. METHODS: The study was performed in our outpatient hypertension clinic, and included 1529 patients without secondary hypertension or comorbidities. The study, investigated BP control rates and patterns of antihypertensive drug use in male and female. All data were collected using structured questionnaires and patient measurements. RESULTS: The study included 713 males and 816 females in this study. Fewer females had hypertension in the younger age group (16.2% vs 11.6%; p>0.05), but this difference disappeared in middle-aged (47.8% vs 49.9 %; p<0.05) and elderly age groups (36.0% vs 38.5%; p<0.05). BP control rates differed between males and females (35.6% in male, 31.9% in female, p<0.01). There was an overall difference in BP control rates between males and females (35.6% in males, 31.9% in females, p<0.01). In this aged 18-44 years, angiotensin converting enzyme inhibitors (ACEIs) showed the best control rate in males, while calcium channel blockers (CCBs) were least effective (61.5% with ACEIs, 28.6% with CCBs; p<0.05). In this aged 45-64 years, diuretics (DUs) showed the best control rate in females, while CCBs were least effective (47.5% with DUs, 28.3% with CCBs; p<0.05). CONCLUSIONS: Sex plays an important role in BP control. In those aged 18-44 years, males using ACEIs showed best control rates. In those aged 45-64 years, females using DUs showed best control rates. Our study provides a basis with the selection of antihypertensive drugs according to sex and age.