Xanthene, cyanine, oxazine and BODIPY: the four pillars of the fluorophore empire for super-resolution bioimaging.

In the realm of biological research, the invention of super-resolution microscopy (SRM) has enabled the visualization of ultrafine sub-cellular structures and their functions in live cells at the nano-scale level, beyond the diffraction limit, which has opened up a new window for advanced biomedical studies to unravel the complex unknown details of physiological disorders at the sub-cellular level with unprecedented resolution and clarity. However, most of the SRM techniques are highly reliant on the personalized special photophysical features of the fluorophores. In recent times, there has been an unprecedented surge in the development of robust new fluorophore systems with personalized features for various super-resolution imaging techniques. To date, xanthene, cyanine, oxazine and BODIPY cores have been authoritatively utilized as the basic fluorophore units in most of the small-molecule-based organic fluorescent probe designing strategies for SRM owing to their excellent photophysical characteristics and easy synthetic acquiescence. Since the future of next-generation SRM studies will be decided by the availability of advanced fluorescent probes and these four fluorescent building blocks will play an important role in progressive new fluorophore design, there is an urgent need to review the recent advancements in designing fluorophores for different SRM methods based on these fluorescent dye cores. This review article not only includes a comprehensive discussion about the recent developments in designing fluorescent probes for various SRM techniques based on these four important fluorophore building blocks with special emphasis on their effective integration into live cell super-resolution bio-imaging applications but also critically evaluates the background of each of the fluorescent dye cores to highlight their merits and demerits towards developing newer fluorescent probes for SRM.

Associations Between Physical Activity, Tinnitus, and Tinnitus Severity.

OBJECTIVES: To examine the associations between physical activity and tinnitus development and physical activity and tinnitus severity in a large representative sample of US adults. DESIGN: Data were obtained from 3826 eligible participants (20 to 69 years) in the National Health and Nutrition Examination Survey between 2015 and 2016. Physical activity was assessed using a Global Physical Activity Questionnaire. We used multivariable logistic regression to test the associations of physical activity (without physical activity, with physical activity) and amount of physical activity (min/week, in quartiles) with tinnitus symptoms. Adults with depressive symptoms were excluded, and the models were controlled for relevant sociodemographic, lifestyle, and health-related covariates. A restricted cubic spline was used to explore the dose-response relationship between the amount of physical activity and tinnitus. RESULTS: Overall, 12.8% of the population who engaged in physical activity reported tinnitus, compared with 18.5% of the population who did not ( p = 0.005). Subgroup analysis based on the amount of physical activity showed that participants who performed physical activity (150 to 300, 310 to 540, and 550 to 4800 min/week) had lower risks of tinnitus than those with no physical activity (odds ratio = 0.72, 0.56, and 0.62, respectively), after adjusting for covariates. However, no correlation was observed between physical activity and tinnitus severity in the present study. The dose-response analysis showed a nonlinear relationship (P for nonlinearity = 0.04) between the amount of physical activity and the risk of tinnitus. CONCLUSIONS: Physical activity may be associated with a reduced risk of tinnitus. Further research using a longitudinal design is required to confirm these findings and clarify the direction of causation.

Transcutaneous electrical acupoint stimulation for suspected laryngopharyngeal reflux disease.

PURPOSE: To determine the efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with proton pump inhibitor (PPI) therapy on symptoms and signs of patients with suspected laryngopharyngeal reflux disease (LPRD). METHODS: This was a prospective randomized controlled study. Seventy patients with reflux symptom index (RSI) > 13 and reflux finding score (RFS) > 7 were recruited and received PPI alone (control group) or TEAS combined with PPI (experimental group) for 12 weeks. Patients in the experimental group received TEAS at Tiantu (RN22), Renying (ST9), and Neiguan (PC6) once a day, five times a week. RSI, RFS, throat pain visual analog score (VAS), and LPR-health-related quality-of-life (LPR-HRQL) scores were evaluated at baseline and after 4 and 12 weeks. RESULTS: The decreases in total RSI and RFS, along with several subscores, were significantly higher in the experimental group than in the control group after 12 weeks (P < 0.05). The throat pain VAS and LPR-HRQL scores decreased significantly at 4 and 12 weeks after treatment in both groups, with significant differences between the groups (P < 0.001). No severe adverse events occurred, and the rates of adverse events were similar between the two groups. CONCLUSION: Compared with PPI alone, TEAS combined with PPI showed a significantly greater improvement in symptoms, signs, and quality of life in the treatment of LPRD without increasing the occurrence of adverse effects. Therefore, TEAS could serve as a useful and safe treatment method for LPRD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100046755.

Identification of Molecular Targets for Predicting Colon Adenocarcinoma.

BACKGROUND Colon adenocarcinoma mostly happens at the junction of the rectum and is a common gastrointestinal malignancy. Accumulated evidence has indicated that colon adenocarcinoma develops by genetic alterations and is a complicated disease. The aim of this study was to screen differentially expressed miRNAs (DEMs) and genes with diagnostic and prognostic potentials in colon adenocarcinoma. MATERIAL AND METHODS In this study we screened DEMs and their target genes (DEGs) between 100 colon adenocarcinoma and normal samples in The Cancer Genome Atlas (TCGA) database by using the DEseq toolkit in Bioconductor. Then Go enrichment and KEGG pathway analysis were performed on the selected differential genes by use of the DAVID online tool. A regulation network of miRNA-gene was constructed and analyzed by Cytoscape. Finally, we performed ROC analysis of 8 miRNAs and ROC curves were drawn. RESULTS A total of 159 DEMs and 1921 DEGs were screened, and 1881 pairs of miRNA-target genes with significant negative correlations were also obtained. A regulatory network of miRNA-gene, including 60 cancer-related genes and 47 miRNAs, was successfully constructed. In addition, 5 clusters with several miRNAs regulating a set of target genes simultaneously were identified through cluster analysis. There were 8 miRNAs involved in these 5 clusters, and these miRNAs could serve as molecular biomarkers to distinguish colon adenocarcinoma and normal samples indicated by ROC analysis. CONCLUSIONS The identified 8 miRNAs were closely associated with colon adenocarcinoma, which may have great clinical value as diagnostic and prognostic biomarkers and provide new ideas for targeted therapy.

[Observation of the long-term clinical efficacy of "Fuyang Guben" acupuncture-moxibustion therapy on perennial allergic rhinitis and its effects on the total IgE and IL-4 in the serum].

OBJECTIVE: To investigate the long-term clinical efficacy and safety of "Fuyang Guben" (supporting yang and consolidating root) acupuncture-moxibustion therapy on perennial allergic rhinitis (PAR), and to explore its functioning mechanism. METHODS: The patients with PAR were randomly divided into acupuncture + western medicine group (n=30) and western medicine group (n=30). In the western medicine group, fluticasone propionate nasal spray was administered, one spray in each nostril in one treatment, once a day, for 6 weeks. On the basis of the western medicine group, fuyangguben acupuncture-moxibustion therapy was supplemented. Acupuncture was applied to Shangxing (GV23), Yintang (GV24+), and bilateral Yingxiang (LI20), Shangyingxiang (EX-HN8), Sibai (ST2), Hegu (LI4) and Chize (LU5); warm needling was applied at Dazhui (GV14). The patients of this group received 30 min of acupuncture-moxibustion therapy 3 times weekly during the first 4 weeks and twice a week in the last 2 weeks, totally for 6 weeks. Before treatment, after treatment, in week 10, 18 and 30 of follow-up visits, the reflective total nasal symptom score (rTNSS), the total non-nasal symptom score (TNNSS), the total ophthalmic symptom score (TOSS), and the score of the rhinitis quality of life (RQLQ) scale were compared in the patients of the two groups separately. Using ELISA, the serum concentrations of total immunoglobulin E (IgE) and interleukin-4 (IL-4) were detected before and after treatment. RESULTS: After treatment, the rTNSS, TNNSS, TOSS, as well as RQLQ score were lower in comparison with those before treatment in each group (P<0.05).The rTNSS, TNNSS, TOSS and the score of RQLQ in the week 10, 18 and 30 of follow-up visits were reduced when compared with those before treatment in each group (P<0.05), and these scores in the acupuncture + western medicine group were remarkably lower than those of the western medicine group (P<0.05). After treatment, the serum contents of total IgE and IL-4 were significantly decreased when compared with those before treatment in the acupuncture + western medicine group (P<0.05), and these indicators in the acupuncture + western medicine group were lower than those of the western medicine group (P<0.05). CONCLUSION: On the base of treatment with fluticasone propionate nasal spray, "Fuyang Guben" acupuncture-moxibustion therapy is safe and effective on PAR, presenting a remarkably long-term efficacy. The functioning mechanism may be related to the down-regulation of total IgE and IL-4 in serum.

State of the art: non-invasive electrical stimulation for the treatment of chronic tinnitus.

Subjective tinnitus is the perception of sound in the absence of external stimulation. Neuromodulation is a novel method with promising properties for application in tinnitus management. This study sought to review the types of non-invasive electrical stimulation in tinnitus to provide the foothold for further research. PubMed, EMBASE, and Cochrane databases were searched for studies on the modulation of tinnitus by non-invasive electrical stimulation. Among the four forms of non-invasive electrical modulation, transcranial direct current stimulation, transcranial random noise stimulation, and transauricular vagus nerve stimulation yielded promising results, whereas the effect of transcranial alternating current stimulation in the treatment of tinnitus has not been confirmed. Non-invasive electrical stimulation can effectively suppress tinnitus perception in some patients. However, the heterogeneity in parameter settings leads to scattered and poorly replicated findings. Further high-quality studies are needed to identify optimal parameters to develop more acceptable protocols for tinnitus modulation.

Trial of transcutaneous electrical acupoint stimulation in laryngopharyngeal reflux disease: study protocol for a randomized controlled trial.

BACKGROUND: Patients with persistent globus sensation, throat clearing, chronic cough, hoarseness, and other throat symptoms account for a large proportion of patients in ears, nose, and throat clinics. Laryngopharyngeal reflux disease (LPRD) is increasingly valued by otolaryngologists. Transcutaneous electrical acupoint stimulation (TEAS) is possibly a new method for the treatment of LPRD. This trial aims to determine whether TEAS combined with proton pump inhibitor (PPI) is better than PPI alone in the treatment of LPRD. METHODS: This prospective randomized controlled trial will be implemented in a tertiary hospital in China. Seventy patients diagnosed with LPRD will be randomly assigned to the TEAS + PPI group (intervention group) or PPI group (control group), at a ratio of 1:1. In addition to using PPI, the intervention group will receive TEAS at four groups of acupoints, and each group will be treated for 15 min, once for 60 min, five times a week, for 12 weeks, 60 times. The main outcome will be changes in the Reflux Symptom Index scores at 4, 12, and 24 weeks after treatment. The secondary outcomes will include changes in the reflux finding score, Laryngopharyngeal Reflux-Health-related Quality of Life score, and throat pain visual analog scale score. DISCUSSION: This trial will explore the feasibility of TEAS combined with PPI for the treatment of LPRD and provide potential evidence for its effectiveness and safety. The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046755 . Registered on May 28, 2021.

Characteristics of tinnitus and factors influencing its severity.

Background and Objectives: There is a wealth of information regarding the treatment methods for tinnitus; however, the treatment available is unsatisfactory because of the following reasons: first, tinnitus has various etiologies and second, it has distinct heterogeneity among different individuals. Numerous studies have focused on understanding the causes of tinnitus severity, but the conclusions have been inconsistent. The purpose of the present study was to define factors that differentially influence subjectively perceived tinnitus severity. Methods: Clinical data of patients with chronic tinnitus who visited our outpatient clinic from April 2020 to April 2021 were collected. Tinnitus Handicap Inventory (THI) and Tinnitus Evaluation Questionnaire (TEQ) were used to evaluate tinnitus severity among patients, and the independent factors influencing the severity of tinnitus were investigated by performing univariate and multivariate stepwise regression analyses. Results: Eleven variables were associated with THI and TEQ scores, of which nine were identical. Multiple regression analyses results revealed that five variables had a significantly unique predictive effect on tinnitus severity based on THI and the TEQ scores. Three factors including Self-Rating Scale of Sleep (SRSS), change in loudness, and Self-Rating Anxiety Scale (SAS) were identical. Conclusion: Sleep status, anxiety level, and change in loudness in patients with chronic tinnitus were significantly correlated with severity of tinnitus. Follow-up studies should investigate the causal relationship between these factors and tinnitus severity.

Effect of acupuncture therapy combined with fluticasone propionate in the treatment of persistent allergic rhinitis: study protocol for a randomized controlled trial.

BACKGROUND: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory response. Persistent allergic rhinitis (PAR) is a subtype of AR, but the treatment of PAR is still a problem. Acupuncture is used as an alternative therapy for AR in clinical practice. The aim of this study is to evaluate the effectiveness of acupuncture therapy combined with fluticasone propionate nasal spray in comparison to fluticasone propionate nasal spray alone in the relief of symptoms for PAR. METHODS: This study is a multicenter, single-blind, randomized controlled trial. A total of 260 eligible patients will be randomly assigned into the treatment group or the control group. The treatment group will receive the nasal fluticasone propionate combined with acupuncture, and the control group will receive fluticasone propionate nasal spray alone for 6 weeks. The primary outcome is the change in the Reflective Total Nasal Symptom Score (rTNSS) from baseline to the end of treatment, and the Total Non Nasal Symptom Score (TNNSS), reflective total ocular symptom score (rTOSS), Rhinitis Quality of Life Questionnaire (RQLQ), use of antiallergic drugs, and the Rhinitis Control Assessment Test (RCAT) are used as secondary outcomes. The participants will be followed up for another 24 weeks after treatment. DISCUSSION: This clinical trial will be able to provide high level evidence on the acupuncture therapy combined with fluticasone propionate nasal spray in the treatment of PAR. TRIAL REGISTRATION: ISRCTN Registry, ID: ISRCTN44040506 . Registered on 22 July 2020.

Opioids contribute to fracture risk: a meta-analysis of 8 cohort studies.

OBJECTIVE: To evaluate the association between chronic opioid use for non-cancer pain and fracture risk by conducting a meta-analysis of cohort studies. METHODS: Cohort studies were identified by searching PubMed and EMBASE from their inception to July 2014. A fracture was considered an endpoint. The information was extracted by two authors independently. When the heterogeneity was significant, a random-effects model was used to calculate the overall pooled risk estimates. RESULTS: Eight cohort studies were included in the final meta-analysis. On the basis of the Newcastle-Ottawa Scale (NOS), six studies were considered to be of high quality. The overall combined relative risk for the use of opioids and fractures was 1.88 (95% confidence interval [CI] 1.51-2.34). A subgroup analysis revealed the sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed. CONCLUSIONS: This meta-analysis of cohort studies demonstrates that opioids significantly increase the risk of fractures.