Circular RNA circ-3626 promotes bone formation by modulating the miR-338-3p/Runx2 axis.

OBJECTIVE: Disorders of bone homeostasis are the key factors leading to metabolic bone disease, such as senile osteoporosis, which is characterized by age-related bone loss. Bone marrow stromal cells (BMSCs) possess high osteogenic capacity which has been regarded as a practical approach to preventing bone loss. Previous studies have shown that the osteogenic differentiation ability of BMSCs is significantly decreased in senile osteoporosis. Recently, circular RNAs (circRNAs) have been regarded as critical regulators in controlling the osteogenic differentiation of BMSCs by sponging microRNAs (miRNAs). Our study aimed to discover new and critical osteogenesis-related circRNAs that can promote bone formation in senile osteoporosis. METHODS: We detected the dysregulated circRNAs of BMSCs upon osteogenic differentiation induction and identified the critical osteogenic circRNA (circ-3626). The relationship between circ-3626 and osteoporosis was further verified in clinical bone samples and aged mice by qPCR. Moreover, circ-3626 AAV was constructed to examine the osteogenic effect of circ-3626 on bone formation via using Micro-CT, double calcein labeling, and the three-point bending tests. Bioinformatics analysis, Luciferase report gene assays, FISH, RNA pull-down, qPCR, Western Blots, and alizarin red staining assay explore the effects and mechanisms of circ-3626 on osteogenic differentiation of BMSCs. RESULTS: Circ-3626 was identified as a pivotal osteogenesis-related circRNA via RNA sequencing. The results of alizarin red staining, Western blots, and qPCR assays suggest that overexpressing circ-3626 dramatically accelerates the osteogenic capability of BMSCs. Furthermore, the bone repair capability of aging mice could be significantly improved by circ-3626 AAV treatment. Micro RNA miR-338-3p was identified as the downstream target of circ-3626. Overexpression of circ-3626 increases the expression of Runx2 by sponging miR-338-3p, thereby promoting the osteogenic differentiation of BMSCs by upregulating the expression of osteogenic genes. In addition, Western blots, and qPCR assays suggest circ-3626 AAV treatment promote the expression of Runx2 and osteogenic marker genes. CONCLUSION: Thus, we demonstrate that circ-3626 plays a pivotal role in promoting bone formation through the miR-338-3p/Runx2 axis and may provide new strategies for preventing and treating the bone loss of senile osteoporosis.

Population attributable fractions of adverse childhood experiences for emotional problems and self-harming behaviors among middle school students in China.

The population attributable fractions of health outcomes attributed to adverse childhood experiences (ACEs) among Chinese middle school students is unknown. Of all the 22,868 middle school students, 29.8 % had exposure to four or more ACEs. Findings showed a graded relationship between ACE scores and those adverse outcomes. The PAFs of six outcomes attributed to experiencing ≥ 4 ACEs ranged from 23.1 % to 44.2 %. The results emphasized the significance of preventive interventions to alleviate the negative legacies of ACEs.

Endoscopic Release Superficial Rather Than Deep to the Transverse Carpal Ligament for Carpal Tunnel Syndrome Improves Immediate Postoperative Transient Symptomatic Exacerbation With Fewer Absences From Work.

PURPOSE: To determine the endoscopic release superficially rather than deep to the transverse carpal ligament to reduce the incidence of transient symptomatic exacerbation and postoperative absence from work in patients with carpal tunnel syndrome. METHODS: From January 2012 to January 2018, patients with idiopathic carpal tunnel syndrome who underwent one-portal endoscopic release superficial to the transverse carpal ligament (ERSTCL) were analyzed. For comparison, a cohort treated with the conventional Chow endoscopic release between February 2008 and October 2013 were included. Transient worsening of symptoms, discrimination sensation, and days off work were assessed. The minimal clinically important difference was calculated for discrimination sensation. Severity of symptom and functional status also were assessed using the Levine-Katz Questionnaire. Significance was set at P < .05. RESULTS: There was a significant difference between the ERSTCL group and the control group regarding the incidence of symptomatic exacerbation 1 week after surgery (2% vs 9%; P = .003) but no difference in other time intervals within the initial 3 months. There was a significant difference in 2-point discrimination 1 week (mean change = -0.13, 95% confidence interval [CI] -0.30 to 0.04, P = .01) and 2 weeks after surgery (mean change = -0.18, 95% CI -0.36 to -0.01, P = .033). Postoperative 1 and 2 weeks, 28% and 35% patients in ERSTCL group achieved a minimal clinically important difference, respectively. Compared with control group, the difference in frequencies was statistically significant (28% vs 45%; P = .027; 35% vs 57%; P = .015). The difference between the 2 groups in postoperative absence from work was statistically significant (95% CI 1.083-4.724; P = .002), with an average reduction in sick leave of 3 days in ERSTCL group. At a mean follow-up of 3 years, no significant difference was found between the groups regarding symptom and function statuses. CONCLUSIONS: Endoscopic release superficial rather than deep to transverse carpal ligament for carpal tunnel syndrome improves immediate postoperative transient symptomatic exacerbation, which allows the patients to return to work earlier. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Comparison of characteristics between neuropathic pain and non-neuropathic pain in patients with diabetic carpal tunnel syndrome: A cross-sectional study.

Background: The aim of the study was to compare the clinical characteristics of diabetic carpal tunnel syndrome between patients with neuropathic pain (NeuP) and non-NeuP. Methods: We enrolled 276 patients with diabetic carpal tunnel syndrome. Pain symptoms were evaluated using a visual analog scale. Douleur Neuropathique 4, the Neuropathic Pain Symptoms Inventory questionnaire, and the body map were used to assess neuropathic symptoms. Baseline information, clinical manifestations, electrophysiological test results, and psychological status were compared between the neuropathic pain (NeuP) and non-NeuP to identify the risk factor for NeuP occurrence. Results: Results showed that the degree of pain was more severe in NeuP patients than in nociceptive pain patients (p = 0.025). The frequencies of light touch and pinprick were more pronounced in the NeuP group than in the non-NeuP group (light touch: p = 0.001; pinprick: p = 0.004). There were 48 and 27 NeuP patients with extramedian and proximal spread, respectively, whereas in the non-NeuP group, there were 11 and 9 patients, respectively (p = 0.03). Electrophysiological results showed that patients in the NeuP group exhibited greater sensory nerve conduction velocity impairment compared with the non-NeuP group (p = 0.033). Pain Catastrophizing Scale total scores of the NeuP group were significantly higher than those of the non-NeuP group (p = 0.006). Conclusion: Of the 276 diabetic carpal tunnel syndrome patients studied, the majority had NeuP. Furthermore, light touch, electrophysiological test results, and psychological factors were found to be related to NeuP occurrence in patients with diabetic carpal tunnel syndrome.

Activated carbon modified with nano manganese dioxide triggered electron transport pathway changes for boosted anaerobic treatment of dyeing wastewater.

Herein, an expanded granular sludge bed (EGSB) reactor with activated carbon (AC)-nano manganese dioxide (MnO2) added was employed for azo dye wastewater treatment to investigate its effectiveness at decolorizing of azo dyes and removing COD. The results showed that the treatment of azo dye wastewater with the AC-MnO2 modified EGSB reactor gave an 83% average decolorization efficiency, which was more efficient than the pure AC modified EGSB reactor. Moreover, the COD removal and changes in the intermediate products were controlled by AC-MnO2. Additionally, there was a sharp increase in the sludge conductivity, while there was a significant decrease in the coenzyme F420 concentration with long-term operation. Moreover, electrochemical analysis showed that the addition of AC-MnO2 can enhance electron transfer in anaerobic system. The AC-MnO2 can act as redox mediator; in the presence of the Mn4+/Mn2+ cycle, accelerating the electron transfer between the microbial cells and dyes, thereby promoting the decolorization of azo dyes. This caused a decrease in the methanogenic activity. Furthermore, high-throughput sequencing showed that the relative abundances of Pseudomonas and Desulfovibrio were significantly high among the acidogenic bacteria community, while Methanobacterium and Methanosaeta had very low abundances from among the methanogenic archaea community.

Core-shell ZVI@carbon composites reduce phosphate inhibition of ZVI dissolution and enhance methane production in an anaerobic sewage treatment.

Inhibitory effects of phosphate on zero-valent iron (ZVI) dissolution have been studied mainly focusing on a single chemical system. Little is known about inhibitory effects and the mechanism of phosphate on ZVI dissolution within a bioreactor during long-term operation. This study demonstrates the feasibility of achieving energy recovery from phosphate-containing domestic sewage using an efficient anaerobic reactor with micro-sized or nano-sized ZVI addition. The results indicate that the chemical oxygen demand (COD) removal and methane production are enhanced by ZVI addition. A maximum COD removal efficiency of 89% and methane content of 60% was achieved. However, the strengthening effect of ZVI on methane production is weakened by the presence of phosphate in domestic sewage. Analyzing the variations of Fe2+ ions and phosphate concentrations and characterizing the micro-morphology of corroded ZVI proved that the generated Fe2+ ions reacts with phosphate and forms a passivation layer on the ZVI surface, inhibiting further dissolution of ZVI. As an improved alternative, we chose the double layered core-shell structured ZVI@carbon composite as an excellent candidate to reduce the inhibitory effects of phosphate on ZVI dissolution. In this way, the direct formation of precipitates on the ZVI surface can be avoided due to the protective carbon layer which adjusts the ion transfer. Adding ZVI@carbon composites accelerate the methane content by 16%. To our knowledge, this is the first report on adding ZVI@carbon composites to promote the anaerobic metabolism in studies, which are focusing on reducing the inhibition of ZVI by phosphate.

The psychological symptoms of patients with mild symptoms of coronavirus disease (2019) in China: A cross-sectional study.

AIMS: To determine psychological symptoms of patients with mild symptoms of coronavirus disease 2019 in China and to explore the influencing factors. DESIGN: A cross-sectional study. METHODS: A convenience sample of 296 mild coronavirus disease 2019 patients were recruited from a Fangcang hospital in Wuhan, Hubei Province, from 3-5 March, 2020. Participants were assessed using a sociodemographic and clinical characteristics questionnaire, and Symptom Check List 90. The binary logistic regression was utilized to explore the influencing factors of psychological symptoms of patients with mild symptoms of coronavirus disease 2019. RESULTS: In total, 296 of 299 patients with mild symptoms of coronavirus disease 2019 participated in the study (response rate: 99.0%). The findings revealed that 12.8% patients with mild symptoms have mental health problems; the most common psychological symptoms are phobic anxiety (58.4%), paranoid ideation (50.7%) and psychoticism (40.2%). Female patients [OR = 3.587, 95% CI (1.694-7.598)] and those having physical symptoms currently [OR = 2.813, 95% CI (1.210-6.539)] are at higher risk, while those in the middle duration of hospitalization [OR = 0.278, 95% CI (0.121-0.639)] protect against mental-health problems. CONCLUSIONS: The minority of patients with mild symptoms of coronavirus disease 2019 were still suffering from psychological symptoms. Healthcare providers are recommended to pay particular attention to screening these high-risk groups (women, those in the initial stages of hospitalization and those with physical symptoms currently) and implement targeted psychological care as required. IMPACT: This study found that most patients of coronavirus disease 2019 in Fangcang hospital exhibited normal mental health at par with the general Chinese norm and the minority of them were suffering from psychological symptoms. The findings can provide a reference for healthcare providers to screen high-risk psychological symptoms groups and implement targeted psychological intervention for patients with coronavirus disease 2019.

The relationship between resilience, anxiety and depression among patients with mild symptoms of COVID-19 in China: A cross-sectional study.

AIMS AND OBJECTIVES: To explore the role of resilience in anxiety and depression and to clarify their relationships among patients with mild symptoms of coronavirus disease 2019 (COVID-19) in Wuhan, China. BACKGROUND: The outbreak of COVID-19 has negatively affected some individuals, but resilience plays a decisive role in the response of individuals under pressure and can help them deal with pressure more effectively. DESIGN: The cross-sectional descriptive correlational survey was reported in line with the STROBE guidelines. SUBJECT AND SETTING: In total, 296 patients from FangCang Hospital in Wuhan, Hubei, China, with mild symptoms of COVID-19 were recruited. METHODS: Participants were recruited through convenience sampling. The data collected included their demographic information, the Connor-Davidson Resilience Scale and Hospital Anxiety and Depression Scale. RESULTS: A small number of patients in this study had above threshold anxiety (subthreshold anxiety and major anxiety) and depression (subthreshold depression and major depression). The mean total resilience score of the participants was slightly below the normal level of ordinary Chinese adults. Resilience was inversely associated with and was a protective factor for both anxiety and depression in our samples. Risk factors for anxiety include being female and having colleagues with COVID-19, while a risk factor for depression was having family members with COVID-19. CONCLUSIONS: This study shows that after taking the general demographics into consideration, higher levels of resilience were associated with lower anxiety and depression among mild COVID-19 patients in Wuhan, China. RELEVANCE TO CLINICAL PRACTICE: Health professionals, especially clinical nurses, need to be aware of the psychological status of COVID-19 patients and promote resilience to improve their mental health.

[Relationship between changes of serum soluble Fas levels and delayed encephalopathy after acute carbon monoxide poisoning].

OBJECTIVE: By explore the role of serum soluble Fas (sFas) in occurrence and progression of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect serum sFas levels in 40 patients with DEACMP in acute stage and convalescent stage, with 36 healthy elderly subjects as the control group. RESULTS: Serum sFas levels of the patients with DEACMP in both the acute and convalescent stages showed no significant difference from those in the control group (P=0.737 and 0.137, respectively), nor was any significant difference found between the patients in acute and exacerbation stages (P=0.059). CONCLUSION: Serum sFas is not involved in the occurrence and progression of DEACMP.

Osteopontin is involved in urotensin II-induced migration of rat aortic adventitial fibroblasts.

Recent studies suggest that both osteopontin and urotensin II (UII) play critical roles in vascular remodeling. We previously showed that UII could stimulate the migration of aortic adventitial fibroblasts. In this study, we examined whether osteopontin is involved in UII-induced migration of rat aortic adventitial fibroblasts and examined the effects and mechanisms of UII on osteopontin expression in adventitial fibroblasts. Migration of adventitial fibroblasts induced by UII could be inhibited significantly by osteopontin antisense oligonucleotide (P<0.01) but not sense or mismatch oligonucleotides (P>0.05). Moreover, UII dose- and time-dependently promoted osteopontin mRNA expression and protein secretion in the cells, with maximal effect at 10(-8)mol/l at 3h for mRNA expression or at 12h for protein secretion (both P<0.01). Furthermore, the UII effects were significantly inhibited by its receptor antagonist SB710411 (10(-6)mol/l), and Ca(2+) channel blocker nicardipine (10(-5)mol/l), protein kinase C (PKC) inhibitor H7 (10(-5)mol/l), calcineurin inhibitor cyclosporine A (10(-5)mol/l), mitogen-activated protein kinase (MAPK) inhibitor PD98059 (10(-5)mol/l) and Rho kinase inhibitor Y-27632 (10(-5)mol/l). Thus, osteopontin is involved in the UII-induced migration of adventitial fibroblasts, and UII could upregulate osteopontin gene expression and protein synthesis in rat aortic adventitial fibroblasts by activating its receptor and the Ca(2+) channel, PKC, calcineurin, MAPK and Rho kinase signal transduction pathways.

Transforming growth factor-ß1 involved in urotensin II-induced phenotypic differentiation of adventitial fibroblasts from rat aorta.

BACKGROUND: Urotensin II (UII) is a new vasoconstrictive peptide that may activate the adventitial fibroblasts. Transforming growth factor-ß1 (TGF-ß1) is an important factor that could induce the phenotypical transdifferentiation of adventitial fibroblasts. This study aimed to explore whether TGF-ß1 is involved in UII-induced phenotypic differentiation of adventitial fibroblasts from rat aorta. METHODS: Adventitial fibroblasts were prepared by the explant culture method. TGF-ß1 protein secretion from the cells was determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression of α-smooth nuscle actin (α-SM-actin), the marker of phenotypic differentiation from fibroblasts to myofibroblasts, were determined using real-time quantitative RT-PCR (real-time RT-PCR) and Western blotting, respectively. RESULTS: UII stimulated the secretion of TGF-ß1 in cultured adventitial fibroblasts in a time-dependent manner. The secretion reached a peak at 24 hours, was higher by 69.8% (P < 0.01), than the control group. This effect was also concentration dependent. Maximal stimulation was reached at 10(-8) mol/L of UII (P < 0.01), which was increased by 59.9%, compared with in the control group (P < 0.01). The secretion of TGF-ß1 induced by UII was significantly blocked by SB-710411 (10(-7) mol/L), a specific antagonist of UII receptor. In addition, both UII (10(-8) mol/L) and TGF-ß1 significantly stimulated α-SM-actin mRNA and protein expression. Moreover, the α-SM-actin induced by UII was inhibited by the specific neutralizing antibody (20 µg/ml) of TGF-ß1, while the α-SM-actin expression stimulated by TGF-ß1 (20 ng/ml) was inhibited by SB-710411 (10(-7) mol/L), the UII receptor antagonist. CONCLUSION: This study suggests that UII could induce TGF-ß1 secretion in adventitial fibroblasts via UT activation, and TGF-ß1 might be involved in phenotypic differentiation from adventitial fibroblasts into myofibroblasts induced by UII, and TGF-ß1 signaling might be one of the important pathways by which UII is involved in vascular fibrosis.

Urotensin II is an autocrine/paracrine growth factor for aortic adventitia of rat.

Urotensin II (UII) is a potent vasoconstrictive peptide; however, its significance in vascular adventitia has not been clearly elucidated. In this study, rat aortic adventitia showed mRNA expression and immunoreactivity of UII and its receptor (UT). Moreover, radioligand-binding assay showed that maximum binding capacity (Bmax) of [(125)I]-UII was higher in adventitia than in media (28.60+/-1.94 vs. 20.21+/-1.11 fmol/mg, P<0.01), with no difference in binding affinity (dissociation constant [Kd] 4.27+/-0.49 vs. 4.60+/-0.40 nM, P>0.05). Furthermore, in cultured adventitial fibroblasts, UII stimulated DNA synthesis, collagen synthesis and secretion in a concentration-dependent manner. These effects were inhibited by the UII receptor antagonist urantide (10(-6) mol/l), Ca(2+) channel blocker nicardipine (10(-5) mol/l), protein kinase C inhibitor H7 (10(-6) mol/l), and mitogen-activated protein kinase inhibitor PD98059 (10(-6) mol/l) but not the phosphatidyl inositol-3 kinase inhibitor wortmannin (10(-7) mol/l). UII may act as an autocrine/paracrine factor through its receptor and the Ca(2+) channel, protein kinase C, and mitogen-activated protein kinase signal transduction pathways, in the pathogenesis of vascular remodeling by activating vascular adventitia.

Urotensin II induces phenotypic differentiation, migration, and collagen synthesis of adventitial fibroblasts from rat aorta.

BACKGROUND: Urotensin II is a new potent vasoconstrictor. Nevertheless, little is known about its effects on the activation of adventitial fibroblasts. OBJECTIVE: To explore the effects of urotensin II on phenotypic differentiation, migration, and collagen I synthesis of rat aortic adventitial fibroblasts. METHODS: Growth-arrested adventitial fibroblasts were incubated in serum-free medium with urotensin II and some inhibitors of signal transduction pathways. The alpha-smooth muscle-actin expression, collagen I synthesis and migration of adventitial fibroblasts induced by urotensin II were evaluated by western blot, enzyme-linked immunosorbant assay, and the transwell technique, respectively. RESULTS: Urotensin II induced the [alpha]-smooth muscle-actin expression in a dose-dependent and time-dependent manner, with maximal effect at a concentration of 10(-8) mol/l at 24 h (79.9%); it also caused a dose-dependent increase in collagen I synthesis, with maximal effect at a concentration of 10(-7) mol/l (42.6%). The Ca2+ channel blocker nicardipine (10(-5) mol/l), protein kinase C inhibitor H7 (10(-5) mol/l), Rho protein kinase inhibitor Y-27632 (10(-5) mol/l), calcineurin inhibitor cyclosporine A (10(-5) mol/l), and mitogen-activated protein kinase inhibitor PD98059 (10(-5) mol/l) inhibited urotensin II-induced increases in [alpha]-smooth muscle-actin expression and collagen synthesis. Meanwhile, urotensin II stimulated the migration of adventitial fibroblasts dose dependently, with maximal effect at a concentration of 10(-8) mol/l, which was 5.7-fold greater than that of the control. This effect could also be inhibited by PD98059, H7, cyclosporine A, and Y-27632 but not nicardipine. CONCLUSION: Urotensin II may stimulate adventitial fibroblasts phenotypic conversion, migration, and collagen I synthesis through the protein kinase C, mitogen-activated protein kinase, calcineurin, Rho kinase, and/or Ca2+ signal transduction pathways, contributing to the development of vascular remodeling through adventitial fibroblasts activation.

Urotensin II accelerates cardiac fibrosis and hypertrophy of rats induced by isoproterenol.

AIM: To study whether urotensin II (UII), a potent vasoconstrictive peptide, is involved in the development of cardiac hypertrophy and fibrogenesis of rats induced by isoproterenol (ISO). METHODS: Thirty male Wistar rats were randomly divided into 3 groups. Group 1 was the healthy control group, group 2 was the ISO group, and group 3 was the ISO+UII group. In groups 2 and 3, ISO (5 mg x kg(-1) x d(-1)) was given (sc) once daily for 7 d. Group 3 was also given UII in the first day [3 nmol/kg (5 microg/kg), iv], followed by sc (1.5 microg/kg) twice daily. Group 1 received 0.9% saline. UII receptor (UT) mRNA expression was determined by RT-PCR. The contents of UII and angiotensin II (Ang II) were determined by radioimmunoassay. In vitro, the effects of UII on DNA/collagen synthesis of cardiac fibroblasts were determined by [3H]thymidine/[3H]proline incorporation. RESULTS: The ratio of heart weight/body weight, plasma lactate dehydrogenase activity, myocardial malondialdehyde and hydroxyproline concentration increased significantly in the ISO group, as well as UT mRNA expression, plasma and cardiac UII and ventricular Ang II, compared with the control group (P< 0.01). ISO induced significant myocardial fibrogenesis. Moreover, UII+ISO co-treatment significantly increased the changes of biochemical markers of injury and the degree of cardiac hypertrophy and fibrosis. In vitro, 5 x 10(-9 )-5 x 10(-7 ) mol/L UII stimulated [3H]thymidine/[3H] proline incorporation into cardiac fibroblasts in a dose-dependent manner (P< 0.01). CONCLUSION: These results suggest that UII was involved in the development of cardiac fibrosis and hypertrophy by synergistic effects with ISO.