The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes, the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease (IBD). In the past few years, with the advances in the understanding of microbiome, its metabolites and further application of next generation sequencing, analysis of dynamic alteration of gut micro-environment was realized, which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis status. The subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential therapy. In this review, we will summarize the recent knowledge about multi-dimensional dysbiosis, the inter-action between fungus and bacteria under inflamed mucosa, and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD. Type 2 diabetes mellitus (T2DM), a worldwide epidemic, has caused tremendous economic and social burden, but the pathogenesis remains uncertain. Nowadays, the impact of unrhythmic circadian clock caused by irregular sleep and unhealthy diet on T2DM has started to be increasingly studied. However, the contribution of the endogenous circadian clock system to the development of T2DM has not yet been satisfactorily explored. It is now becoming clear that the gut microbiota and the circadian clock interact with each other to regulate the host metabolism. Considering all these above, we review the literature related to the gut microbiota, circadian clock, and T2DM to elucidate the idea that the gut microbiota is closely tied to the regulation of the circadian clock in the development of T2DM, which provides potential for gut microbiota-directed therapies to ameliorate the effects of circadian disruptions linked to the occurrence and development of T2DM.Historically, breast cancer has been regarded as an immunogenic „cold” tumor hence it has not experienced the explosion of immunotherapy. However, the discovery of immune checkpoint inhibitors has made immunotherapy becoming an emerging new treatment modality for breast cancer. This review discusses the immune system, immune features of breast cancer, and the programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) inhibitors used in the treatment of breast cancer. High T lymphocyte infiltration and mutation burden were observed in triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2) breast cancer. Increasing breast cancer immunogenicity and modulating the tumor microenvironment has been reported to improve the therapeutic efficacy of immunotherapy. Recent clinical trials involving PD-1/PD-L1 inhibitors monotherapy in breast cancer has revealed little efficacy and this highlights the need to develop combinations of PD-1/PD-L1 inhibitors with chemotherapy, molecularly targeted therapies, and other immunotherapies to maximize the clinical efficacy. In conclusion, the development of a new combined regimen involving PD-1/PD-L1 inhibitors and the exploration as potential biomarkers is important in breast cancer immunotherapy.BACKGROUND Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line uric-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk subgroups, and specify the safety of different ULT. METHODS We searched PubMed, Embase, the Cochrane Library, Wanfang, CQVIP, and China National Knowledge Infrastructure (CNKI) Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into subgroups analysis based on blinding status and patients’ history of CV dise incidence of cardiovascular events, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.BACKGROUND Squamous cell carcinoma (SCC) is the most common malignant tumor of the nail unit. No guidelines currently exist regarding the role of imaging in this specific location. OBJECTIVE To investigate the utility of routine imaging in SCC of the nail apparatus. METHODS A multi-institutional retrospective review of patients treated for nail unit SCC was performed. Data were collected on patient characteristics, tumor qualities, treatment, and radiographic imaging. A change in treatment was defined as more aggressive treatment (amputation) rather than local excision or Mohs micrographic surgery (MMS). RESULTS One hundred seven patients with nail unit SCC were identified. Approximately 44/107 (41.1%) of patients were imaged and 63/107 (58.9%) were not. Mohs micrographic surgery was the most common primary treatment (66.4%). Mohs micrographic surgery was more commonly performed in nonimaged patients, and amputation was more commonly performed in imaged patients (p less then .001). Bony changes were identified in 13/44 (29.5%) of imaged patients. In 8/44 (18.2%), imaging findings caused a change in treatment. In 99/107 (92.5%) of the cohort, imaging was either not performed or did not change management. CONCLUSION In select cases, imaging may help guide patient management. Sufficient evidence does not yet exist to support routine imaging for patients with nail unit SCC.OBJECTIVES Speech-in-noise (SIN) perception is essential for everyday communication. In most communication situations, the listener requires the ability to process simultaneous complex auditory signals to understand the target speech or target sound. As the listening situation becomes more difficult, the ability to distinguish between speech and noise becomes dependent on recruiting additional cognitive resources, such as working memory (WM). Previous studies have explored correlations between WM and SIN perception in musicians and nonmusicians, with mixed findings. However, no study to date has examined the speech perception abilities of musicians and nonmusicians with similar WM capacity. The objectives of this study were to investigate (1) whether musical experience results in improved listening in adverse listening situations, and (2) whether the benefit of musical experience can be separated from the effect of greater WM capacity. DESIGN Forty-nine young musicians and nonmusicians were assigned to subgrohave heightened basic auditory abilities, the effect on SIN performance may be more subtle. Our results also show that regardless of prior music training, listeners with high WM capacity are able to perform significantly better on speech-in-noise tasks.Uterine artery myogenic tone (MT) develops during pregnancy in hemochorial placentates such as rats and humans. The physiological reason for its appearance is not clear, and we reasoned that it may be a late pregnancy (LP) event in preparation for controlling hemorrhage during parturition. We also hypothesized that gestational increases in RhoA-induced vascular smooth muscle (VSM) calcium sensitivity are contributory and occur under the tonic influence of nitric oxide (NO). Second-order pre-placental radial arteries from early-pregnant (day 12, n = 5), mid-pregnant (day 16, n = 5) and LP (day 20, n = 20) rats were used in combination with arteriography, VSM calcium measurements, pharmacological RHO/Rho-associated protein kinase (ROCK) and nitric oxide synthase (NOS) inhibition, and Western blotting. A subgroup of LP animals (LP + LN; n = 5) treated with L-NAME from gestational days 10 to 20 were used to determine the effects of NOS inhibition on MT and RhoA expression. MT was evident throughout pregnancy, but its expression in pressurized vessels was masked by endothelial NO-induced vasodilation during early gestation. RhoA protein expression was upregulated in LP and attenuated by in vivo NOS inhibition (as was MT). In vitro RHO/ROCK inhibition decreased MT in a concentration-dependent manner without reducing VSM calcium. In summary, pressure-dependent uterine artery tone increases with gestational age due to a combination of RhoA-mediated increases in VSM calcium sensitivity and a loss of endothelial NO influence. © 2020 S. Karger AG, Basel.Effortful control (EC) or self-regulation refers to the ability to regulate behavior, emotion, and cognition. It has been identified as a contributor to both adaptive and adverse outcomes in children, adolescents, and adults and this across many domains. As such, it could be considered as a transdiagnostic dimension underlying internalizing (e.g., mood and anxiety disorders) and externalizing (e.g., substance use disorders, ADHD) psychopathology. We aimed to examine the role of EC throughout the adult psychopathological spectrum by means of a literature search of studies published between 2008 and 2018. Overall, the results point to the role of EC in the development of a broad spectrum of psychiatric diagnosis, reflecting the transdiagnostic characteristic of this construct. This role may be both directly causal or as a mediator factor influencing outcomes of a specific disorder. Early assessment of EC and early interventions to improve EC might help to avoid or decrease the risk of developing psychopathology. © 2020 S. Karger AG, Basel.INTRODUCTION Although biomechanically corrected intraocular pressure (bIOP) is available, the effectiveness of intraocular pressure correction in keratoconus and forme fruste keratoconus (FFK) eyes has not been investigated. OBJECTIVE Evaluation of bIOP measurements in eyes with keratoconus and FFK. METHODS Forty-two eyes in 21 patients with keratoconus in one eye and FFK in the fellow eye were examined (KC/FFK group; 24.62 ± 8.6 years; 16 males, 5 females). The control group consisted of 62 eyes in 31 unaffected subjects (26.26 ± 3.64 years; 15 males; 16 females). The bIOP was determined using a Scheimpflug-based tonometer after measuring the IOP with a conventional non-contact tonometer (NIOP). The agreement between NIOP and bIOP values was examined using the Bland-Altman plot. The difference between NIOP and bIOP (bIOP correction amount) was compared between keratoconus and FFK eyes. RESULTS In the control group, there were no significant differences between right and left eyes both in NIOP and bIOP values (p = 0.975 and p = 0.224, respectively). In the KC/FFK group, NIOP values were significantly lower in keratoconus eyes (9.93 ± 1.96 mmHg) than in FFK eyes (12.23 ± 3.03 mmHg, p = 0.0003). There was no significant difference in bIOP values between right and left eyes of the KC/FFK group (p = 0.168). The bIOP correction amount in keratoconus eyes (3.58 ± 2.12 mmHg) was significantly increased compared to FFK eyes (1.80 ± 3.32 mmHg, p = 0.011). CONCLUSIONS For eyes with keratoconus and FFK, the bIOP method is effective to adjust IOP measurements based on corneal biomechanical properties. © 2020 S. Karger AG, Basel.