Chemokine CCL14 affected the clinical outcome and correlated with immune infiltrates in thyroid carcinoma.

BACKGROUND: As an important member of the chemokines, CCL14 plays a vital role in cancer progression. However, the role of CCL14 in THCA has not been investigated. This study aimed to reveal the clinical significance of CCL14 in THCA. MATERIAL AND METHODS: This study evaluated the expression and prognostic value of CCL14 in THCA. Also, the correlation between CCL14 and immune infiltrates was assessed. Enrichment analysis was finally performed to predict CCL14-associated pathways involved in THCA. RESULTS: The mRNA and protein expressions of CCL14 in THCA tissues were down-regulated compared with normal tissues. CCL14 high expression predicted favorable DFI and PFI but did not influence the DSS and OS. Further, CCL14 showed a good prediction performance on the PFI of patients. Enrichment analysis found that CCL14 was negatively correlated with migration-related pathways such as Notch signaling, ECM-receptor interaction, and cell adhesion molecules. Further, we found that CCL14 was negatively related to immune infiltrates and their gene markers. A negative relationship was also observed between CCL14 and immune checkpoint genes. These results implied the potential effect of CCL14 on the immune response and immune therapy in THCA. CONCLUSIONS: CCL14 high expression prolonged the DFI and PFI of THCA patients. It was negatively correlated with the migration-related pathways, suggesting that CCL14 might participate in the recurrence of THCA. Further, CCL14 was also shown to be important in immune response and immune therapy in THCA.

Sleep disorders and non-sleep circadian disorders predict depression: A systematic review and meta-analysis of longitudinal studies.

Patients with depression often suffer from sleep disorders and non-sleep circadian disorders. However, whether they precede and predict subsequent depression is unclear. We conducted a meta-analysis of studies on sleep disorders and non-sleep circadian disorders. We found insomnia, hypersomnia, short and long sleep duration, obstructive sleep apnea, restless legs syndrome and eveningness orientation at baseline all led to subsequent depression. Those with propensity to late meal patterns, heightened levels of cortisol in awakening response and low robustness of rest-activity rhythm at baseline had higher risks for later depression. Among insomnia subtypes, difficulty initiating sleep and difficulty maintaining sleep predicted future depression. Notably, persistent insomnia at baseline contributed to more than two-fold risk of incident depression compared to insomnia. Moreover, insomnia symptom numbers showed dose-dependent relationship with the incident depression. In conclusion, different types of sleep disorders and non-sleep circadian disorders were proven to be risk factors of subsequent depression, and mechanisms underlying the relationship between sleep disorders, non-sleep circadian disorders and subsequent depression should be further elucidated in the future.

Role of TREM-1 in the development of early brain injury after subarachnoid hemorrhage.

Triggering receptor expressed on myeloid cells-1 (TREM-1) was found to be induced in the context of subarachnoid hemorrhage (SAH) before. This study further investigates its role in the development of SAH-induced early brain injury (EBI). Firstly, rats were randomly divided into Sham and SAH groups for analysis of temporal patterns and cellular localization of TREM-1. Secondly, TREM-1 intervention was administrated to produce Sham, vehicle, antagonist and agonist groups, for analyzing TREM-1, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and NF-κB expressions at 24 h post-modeling, and EBI assessment at 24 h and 72 h. Thirdly, TLR4 inhibitor (TAK-242) was exploited to produce Sham, Sham+TAK-242, SAH, and SAH + TAK-242 groups to analyze the effects of TLR4 inhibition on TREM-1 induction and EBI evaluation at 72 h. Fourthly, the relationship of soluble TREM-1 (sTREM-1) levels in cerebrospinal fluid of SAH patients with Hunt-Hess grades were explored. The results showed that TREM-1 increased in the brain after experimental SAH (eSAH) early at 6 h and peaked at 48 h, which was found to be located in microglia and endothelial cells. TREM-1 inhibition attenuated EBI associated with TLR4/MyD88/NF-κB suppression, while enhancement had the opposite effects. Contrarily, TLR4 inhibition prevented TREM-1 induction and ameliorated EBI. In addition, sTREM-1 levels in SAH patients positively correlated with Hunt-Hess grades. Overall, the present study provides new evidence that TREM-1 increases dynamically in the brain after eSAH and it is located in microglia and endothelial cells, which may aggravate EBI by interacting with TLR4 pathway. And sTREM-1 in patients might act as a monitoring biomarker of EBI, providing new insights for future studies.

Synthesis of chiral pyrimidine-substituted diester D-A cyclopropanes via asymmetric cyclopropanation of phenyliodonium ylides.

A highly enantioselective cyclopropanation to synthesize pyrimidine-substituted diester D-A cyclopropanes is reported. Various N1-vinylpyrimidines react well with phenyliodonium ylides, delivering chiral cyclopropanes in up to 97% yield with up to 99% ee. Through simple [3+2] annulation with benzaldehyde or ethyl glyoxylate, different chiral pyrimidine nucleoside analogues with a sugar ring could be obtained.

The efficacy and safety of omega-3 fatty acids on depressive symptoms in perinatal women: a meta-analysis of randomized placebo-controlled trials.

Omega-3 fatty acids (FA), as a nutrient, has been proven effective in major depressive disorder (MDD), however, the results of monotherapy in perinatal depression (PND) remain unclear. To examine the efficacy and safety of omega-3 fatty acids (FA) monotherapy for perinatal depression (PND) compared with placebo. PubMed, Embase, PsycINFO, MEDLINE, Cochrane Library, and CINAHL were searched from inception up to November 2019. The reference lists of relevant review articles and included studies were also reviewed. Randomized placebo-controlled trials examining the efficacy and safety of omega-3 FA monotherapy in perinatal women with depressive symptoms were included. Pooled standard mean differences (SMD) were calculated and random-effects models were adopted for all analyses. Subgroups analyses and meta-regression were performed to quantify characteristics of the subjects and trials influencing the omega-3 response. In addition, meta-regression was conducted to identify the source of heterogeneity. The study protocol was registered at PROSPERO, CRD42020159542. Eight eligible randomized placebo-controlled trials were included involving 638 participants. There was a significant effect of omega-3 FA on perinatal depression. Omega-3 with higher ratio of EPA/DHA (≥1.5) had significant efficacy both in mild-to-moderate pregnant and postpartum depression with low incidence of side effects. Among the included trials reporting adverse effects, there was no significant difference in incidence of gastrointestinal and neurologic events between the omega-3 and placebo groups. There was no evidence of publication bias. Our findings suggested that omega-3 FA significantly improved depressive symptoms in perinatal women regardless of pregnant or postpartum and well-tolerated. Furthermore, the omega-3 response was linked to higher EPA proportion in omega-3 formula and mild- to-moderate depression.

[Effect of Individualized Low-protein Diet Intervention on Renal Function of Patients with Chronic Kidney Disease].

OBJECTIVE: To investigate whether individualized low-protein diet intervention for patients with chronic kidney disease(CKD)could improve the general condition,slow the deterioration of renal function,and delay the time of entering dialysis. METHODS: Forty CKD inpatients between July 2011 and July 2012 were randomly given with normal or individualized low-protein diet for six months according to random number table after signing informed consent. The levels of urine protein and biochemical indexes of renal function were measured at baseline and at the end of dietary intervention for six months, respectively. RESULTS: The baseline urine protein level,renal function,and biochemical indexes were not significantly different between these two groups. The diastolic blood pressure,protein intake,blood urea nitrogen,uric acid, potassium, phosphorus, C-reaction protein,24-hour urea nitrogen,and urine protein after six months were significantly lower than those at baseline,that is,(101.70 ± 15.78)mmHg vs.(91.75 ±15.52) mmHg,(63.87 ± 24.70)g/d vs.(50.02 ± 14.07)g/d,(20.01 ± 7.69)mmol/L vs.(15.11 ± 4.90) mmol/L,(362.75 ± 84.56)Μmol/L vs.(302.20 ± 8.48)Μmol/L,(5.22 ± 0.75)mmol/L vs.(4.79±0.36) mmol/L,(2.07 ± 0.68) mmol/L vs.(1.57 ± 0.41) mmol/L,1.19 [0.65,4.17] mg/L vs. 0.74 [0.38,1.33] mg/L,70.6 [8.70,101.18] mmol/L vs. 16.93 [3.23,72.27] mmol/L,1.00 [0.30,1.00] g/d vs. 0.15 [0,0.83] g/d (all P<0.05),among which albumin and hemoglobin were significantly higher [(0.34 ± 0.07)g/L vs.(0.37 ± 0.05)g/L, (99.38 ± 21.89)g/L vs.(126.35 ± 14.11)g/L,respectively] in the individualized low-protein diet group. The difference was statistically significant (P<0.05). The most relevant for urine protein producing was prealbumin (r=0.924, P<0.05). The differences of blood urea nitrogen, potassium, sodium, calcium, phosphorus, 24-hour urea nitrogen, urine specific gravity, urine protein, and hemoglobin in six months in the individualized low-protein diet group were significantly better than those in the normal low protein-diet group (P<0.05). CONCLUSIONS: Individualized low-protein diet intervention may have definite curative effectiveness in CKD patients. It can markedly improve the patients' condition,slow down the deterio-ration of renal function,and increase serum prealbumin levels that may reduce the generation of urine protein. It is worthy of wider clinical application.

Digital pH fluorescent sensing shown by small organic molecules.

A series of 2-(N-oxide pyridyl)-5-methoxythiazoles were synthesized and corresponding optical properties were also investigated. It is first found that a digital-type fluorescent responses in a sharp pH variation with dual-emission could be fulfilled based on a small fluorophore.