Objective:To observe the ameliorative effects of exogenous miR-146a-5p on lipopolysaccharide (LPS)-induced embryonic resorption and fetal mouse dysplasiamice, and to preliminarily investigate its mechanism of action.Methods:1) After 36 healthy adult female mice were mated with male mice, uterine tissues were collected from females on day (D) 0 (D0/not pregnant), D0.5 (the day of embryo observed), D4.5, D7.5, D9.5 and D13.5 of gestation, and the expression levels of miR-146a-5p and its target gene TRAF6 protein in uterine tissues of mice at different gestation periods were detected by real-time fluorescent quantitative PCR (qPCR) and Western blotting. 2) The mice on D7.5 of pregnancy were treated with intraperitoneal injection of saline (control, COL group), intraperitoneal injection of 250 μg/kg LPS (named LPS250 group), LPS combined with tail vein injection of 10 nmol miR-146a-5p unrelated sequence (negative control, NC, named LPS250+NC group), or LPS combined with tail vein injection of 10 nmol miR-146a-5p agonist (miR-146a-5p agomir, named LPS250+miR-146a-5p agomir group). The total number of embryos and the number of absorbed embryos in the uterus of pregnant mice were measured and statistically analyzed on D8.5, and the expression levels of TNFα mRNA and TRAF6 protein in uterine tissues were detected by qPCR and Western blotting. 3) Then we reduced the dosage of LPS to 50 μg/kg and treated the same groups, named LPS50+NC group, LPS50+miR-146a-5p agomir group, respectively. The total number of fetal mice/embryos, the number of absorbed embryos, the number of surviving fetal mice, the weight of surviving fetal mice and the weight of the placenta were measured and statistically analyzed on D16.5. 4) Primary mouse bone marrow-derived macrophages (BMDM) were isolated and cultured. Mouse BMDM was inducted to M1 polarization by LPS stimulation, and then was transient transfected miR-146a-5p mimics or their NC fragments. The expression levels of TNFα mRNA and pSTAT1 protein were detected by qPCR and Western blotting. Results:The expression level of miR-146a-5p was significantly higher in the implantation sites of D7.5, D9.5 and D13.5 pregnant mice than in the non-implantation sites ( P=0.013, P=0.012, P=0.003), and the protein expression level of TRAF6 was significantly lower in the implantation site of D13.5 pregnant mice than in the non-implantation site ( P=0.012). After intraperitoneal injection of 250 μg/kg of LPS into D7.5 pregnant mice, the embryo absorption rate of the LPS group on D8.5 was 43.13%±3.31%, which was significantly higher than that of COL group (0%, P=0.002), while the embryo absorption rate of the LPS250+miR-146a-5p agomir group (13.50%±0.87%) was significantly lower than that of the LPS250+NC group (59.33%±4.04%, P=0.001). After intraperitoneal injection of 50 μg/kg of LPS combined with tail vein injection of NC or miR-146a-5p agomir to D7.5 pregnant mice, the fetal mouse weight [(0.29±0.09) g] and placental weight [(0.06±0.02) g] of surviving fetal mice in the LPS50+NC group on D16.5 and the LPS50+miR-146a-5p agomir group were statistically significant [(0.46±0.06) g, P<0.001; (0.07±0.02) g, P=0.021], and the differences in the number of absorbed embryos and embryo uptake rate between the two groups were not statistically significant (all P>0.05). The expression levels of both pSTAT1 protein and TNFα mRNA were significantly downregulated in BMDM transfected with miR-146a-5p mimics compared with those transfected with NC ( P=0.012, P=0.039). Conclusion:miR-146a-5p expression levels were significantly increased at the maternal-fetal interface during the late stage of mouse embryo implantation and placental development. Exogenous miR-146a-5p could effectively improve LPS-induced mouse embryo resorption and fetal mouse dysplasia. miR-146a-5p could inhibit the M1 polarization activity of mouse macrophages, suggesting that miR-146a-5p may inhibit the M1 polarization activity of mouse macrophages by suppressing M1 polarization of mouse maternal-fetal interface macrophages to safeguard the normal establishment and maintenance of pregnancy.

Objective:To observe the ameliorative effects of exogenous miR-146a-5p on lipopolysaccharide (LPS)-induced embryonic resorption and fetal mouse dysplasiamice, and to preliminarily investigate its mechanism of action.Methods:1) After 36 healthy adult female mice were mated with male mice, uterine tissues were collected from females on day (D) 0 (D0/not pregnant), D0.5 (the day of embryo observed), D4.5, D7.5, D9.5 and D13.5 of gestation, and the expression levels of miR-146a-5p and its target gene TRAF6 protein in uterine tissues of mice at different gestation periods were detected by real-time fluorescent quantitative PCR (qPCR) and Western blotting. 2) The mice on D7.5 of pregnancy were treated with intraperitoneal injection of saline (control, COL group), intraperitoneal injection of 250 μg/kg LPS (named LPS250 group), LPS combined with tail vein injection of 10 nmol miR-146a-5p unrelated sequence (negative control, NC, named LPS250+NC group), or LPS combined with tail vein injection of 10 nmol miR-146a-5p agonist (miR-146a-5p agomir, named LPS250+miR-146a-5p agomir group). The total number of embryos and the number of absorbed embryos in the uterus of pregnant mice were measured and statistically analyzed on D8.5, and the expression levels of TNFα mRNA and TRAF6 protein in uterine tissues were detected by qPCR and Western blotting. 3) Then we reduced the dosage of LPS to 50 μg/kg and treated the same groups, named LPS50+NC group, LPS50+miR-146a-5p agomir group, respectively. The total number of fetal mice/embryos, the number of absorbed embryos, the number of surviving fetal mice, the weight of surviving fetal mice and the weight of the placenta were measured and statistically analyzed on D16.5. 4) Primary mouse bone marrow-derived macrophages (BMDM) were isolated and cultured. Mouse BMDM was inducted to M1 polarization by LPS stimulation, and then was transient transfected miR-146a-5p mimics or their NC fragments. The expression levels of TNFα mRNA and pSTAT1 protein were detected by qPCR and Western blotting. Results:The expression level of miR-146a-5p was significantly higher in the implantation sites of D7.5, D9.5 and D13.5 pregnant mice than in the non-implantation sites ( P=0.013, P=0.012, P=0.003), and the protein expression level of TRAF6 was significantly lower in the implantation site of D13.5 pregnant mice than in the non-implantation site ( P=0.012). After intraperitoneal injection of 250 μg/kg of LPS into D7.5 pregnant mice, the embryo absorption rate of the LPS group on D8.5 was 43.13%±3.31%, which was significantly higher than that of COL group (0%, P=0.002), while the embryo absorption rate of the LPS250+miR-146a-5p agomir group (13.50%±0.87%) was significantly lower than that of the LPS250+NC group (59.33%±4.04%, P=0.001). After intraperitoneal injection of 50 μg/kg of LPS combined with tail vein injection of NC or miR-146a-5p agomir to D7.5 pregnant mice, the fetal mouse weight [(0.29±0.09) g] and placental weight [(0.06±0.02) g] of surviving fetal mice in the LPS50+NC group on D16.5 and the LPS50+miR-146a-5p agomir group were statistically significant [(0.46±0.06) g, P<0.001; (0.07±0.02) g, P=0.021], and the differences in the number of absorbed embryos and embryo uptake rate between the two groups were not statistically significant (all P>0.05). The expression levels of both pSTAT1 protein and TNFα mRNA were significantly downregulated in BMDM transfected with miR-146a-5p mimics compared with those transfected with NC ( P=0.012, P=0.039). Conclusion:miR-146a-5p expression levels were significantly increased at the maternal-fetal interface during the late stage of mouse embryo implantation and placental development. Exogenous miR-146a-5p could effectively improve LPS-induced mouse embryo resorption and fetal mouse dysplasia. miR-146a-5p could inhibit the M1 polarization activity of mouse macrophages, suggesting that miR-146a-5p may inhibit the M1 polarization activity of mouse macrophages by suppressing M1 polarization of mouse maternal-fetal interface macrophages to safeguard the normal establishment and maintenance of pregnancy.

Objectives:To screen out genes potentially involved in the dysregulation of immune microhomeostasis at the maternal-fetal interface of recurrent miscarriage (RM) patients, and to identify novel biomarkers of RM by bioinformatic analysis.Methods:The dataset GSE165004 of endometrial tissues from RM patients ( n=24) and normal women as the control ( n=24) was downloaded from the GEO database, and differentially expressed genes (DEGs) and immune-related modules were analyzed by using the R language's Limma package, along with CIBERSORT immune infiltration and Weighted Gene Co-expression Network Analysis (WGCNA). The functional associations of these core genes were evaluated through Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). Finally, we used the decidual tissue dataset GSE161969 to further validate the diagnostic value of these key genes. Results:Differential analysis identified 580 DEGs, and 3 271 immune-related modular genes were selected by WGCNA analysis. FGF2, ANO1, and LAPTM5 were subsequently identified as key genes through machine learning techniques. GSVA analysis further revealed critical roles of FGF2, ANO1 and LAPTM5 in immune infiltration and macrophage pathways. Conclusion:FGF2, ANO1 and LAPTM5 might participate in the immuno-related pathogenesis of RM, and present potential biomarkers for the early diagnosis and treatment of RM.

Objectives:To screen out genes potentially involved in the dysregulation of immune microhomeostasis at the maternal-fetal interface of recurrent miscarriage (RM) patients, and to identify novel biomarkers of RM by bioinformatic analysis.Methods:The dataset GSE165004 of endometrial tissues from RM patients ( n=24) and normal women as the control ( n=24) was downloaded from the GEO database, and differentially expressed genes (DEGs) and immune-related modules were analyzed by using the R language's Limma package, along with CIBERSORT immune infiltration and Weighted Gene Co-expression Network Analysis (WGCNA). The functional associations of these core genes were evaluated through Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). Finally, we used the decidual tissue dataset GSE161969 to further validate the diagnostic value of these key genes. Results:Differential analysis identified 580 DEGs, and 3 271 immune-related modular genes were selected by WGCNA analysis. FGF2, ANO1, and LAPTM5 were subsequently identified as key genes through machine learning techniques. GSVA analysis further revealed critical roles of FGF2, ANO1 and LAPTM5 in immune infiltration and macrophage pathways. Conclusion:FGF2, ANO1 and LAPTM5 might participate in the immuno-related pathogenesis of RM, and present potential biomarkers for the early diagnosis and treatment of RM.

Background: Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations. Methods: Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Results: In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P<0.001). Most of the guidelines advocated systolic BP targets <130 mm Hg (12 guidelines, 60%) and diastolic BP targets <80 mm Hg (14 guidelines, 70%) in DM patients. Approximately half of the guidelines supported systolic BP thresholds >140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients. Conclusion The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.

Background: Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations. Methods: Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Results: In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P<0.001). Most of the guidelines advocated systolic BP targets <130 mm Hg (12 guidelines, 60%) and diastolic BP targets <80 mm Hg (14 guidelines, 70%) in DM patients. Approximately half of the guidelines supported systolic BP thresholds >140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients. Conclusion The lower official BP targets (<130/80 mm Hg) in patients with DM are advocated by most of the guidelines, but they contain conflicting recommendations on the official BP thresholds. Moreover, the gaps regarding the lower limit of official BP targets and the ABPM/HBPM targets and thresholds need to be considered by future study.

Objective : To study the anatomical characteristics of the root and root canal system of the mandibular second permanent molar in the Uygur people and provide a reference for clinical practice. Methods : A total of 125 mandibular second permanent molars were extracted from Uygur patients in hospitals in the Xinjiang Uygur Autonomous Region. Three-dimensional reconstruction was performed after micro-CT scanning. The number of root canals, the root canal type (Weine classification and Fan′s C-shaped canal classification) and the occurrence of lateral accessory canals were observed. Results : A sex difference was not detected in the root number or root form (χ2 = 1.277, P = 0.259). The incidence of 2-rooted molars was 70.4% (n = 88); type 2-1 canals were most common in the mesial root, with an incidence of 29.5%, followed by type 1-1 and 2-2 canals (each with an incidence of 26.1%), and the distal root mostly had a type 1-1 canal (96.6%). The incidence of single-rooted molars was 28.8%, and the frequency of C-shaped (n = 28) and non-C-shaped (n = 8) single-rooted molars was 22.4% and 6.4%, respectively. A three-rooted molar was detected in one case. The incidence of accessory canals was 65.2%. Conclusion Uygur mandibular second molars are mainly composed of two roots, and the incidence of a single root and root canal fusion is low (including C-shaped canals). Two-rooted molars frequently have two mesial canals and one distal canal.

Objective To explore the application effect of PDCA cycles on the normal limb position of stroke patients with hemiplegia. Methods The stroke patients with hemiplegia (128 cases) were selected as study subjects. Patients(62 cases)during January to September 2014 were set as the control group,and received routine nursing care. Patients(66 cases)during October 2014 to July 2015 were set as the experimental group,and used PDCA cycles management on the normal limb position additionally. The application effect of PDCA cycles on the normal limb position was evaluated through comparing two groups with qualification rates of normal limb position and incidence of complications. Results The qualification rates of normal limb position in the control group was 38.71%(24/62), which was higher than that of the control group, which was 75.76% (50/66) (χ2=16.504, P<0.01). The complications occurred in the control group were strephenopodia (11 cases), foot drop (16 cases), dislocation of shoulder (9 cases), omodynia (27 cases) and myospasm (34 cases), and they were 3 cases, 7 cases, 2 cases, 15 cases and 18 cases in the experimental group respectively. The incidence of complications was lower than those of the control group (χ2=4.001-8.961, P < 0.05), and the difference was statistically significant between two groups. Conclusions PDCA cycles management could improve the qualification rates of normal limb position and reduce the incidence of complications, which was beneficial to the recovery of limb function.

Objective To evaluate the value of transperineal targeted biopsy with real-time fusion images of transrectal ultrasound (TRUS)and multiparametric magnetic resonance imaging (mpMRI)for the diagnosis of prostate cancer (PCa).Methods Clinical and imaging data of 62 consecutive patients suspected of PCa at the mpMRI scan and PSA>4.0 μg/L were retrospectively analyzed.Targeted biopsies (TB)were carried out for each cancer-suspicious lesion,and followed a systematic 12-core biopsy (SB) protocol.Pathological findings of TB and SB were analyzed.Results The age of the patients was (68.38± 6.57)years (range 5 1 -79 years).The preoperative PSA value was (10.21 ±5.57)μg/L (range 4.5 -30.1μg/L).Preoperative prostate volume was (34.05±9.86)ml (range 19-64 ml).The PCa patients detected by SB and/or TB were 34 (54.8%).Cancer-detected rates of SB and TB cores were 7.53% and 26.2%, respectively (P <0.001).The positive core length of SB and TB cores were (3.71 ±2.77)mm (range 1 -14 mm)and (5.00±3.04)mm (range 2-1 7 mm),respectively (P =0.016).The positive core percent of SB and TB cores were (28.77 ± 20.13 )% (range 7 - 100%)and (35.76 ± 1 8.73 )% (range 1 1 % - 100%), respectively (P =0.048).Moreover,clinically cores detected by the SB and TB for final diagnosis of PCa were 19 cores (2.6%)and 48 cores (1 8.5%),respectively (P < 0.001 ).Conclusions Transperineal TB using real-time TRUS and mpMRI fusion imaging can improve sampling quality and elevate clinically detection rate of PCa when application combined with SB.