The Effects of MicroRNAs in the Development of Heart Failure.

PURPOSE OF REVIEW: Heart failure is a severe clinical syndrome with complex and unclarified mechanisms, and it poses a serious threat to human health. MicroRNA, a non-coding RNA, can directly bind to target genes and regulate their expression. The important role of microRNAs in the development of HF has become a hot topic of research in recent years. This paper summarizes and prospects the mechanisms of microRNAs in regulating cardiac remodeling during heart failure to provide reference ideas for further research and clinical treatment. RECENT FINDINGS: With extensive research, more target genes for microRNAs have been clarified. By modulating various molecules, microRNAs affect the contractile function of the myocardium and alter the process of myocardial hypertrophy, myocyte loss, and fibrosis, thereby interfering with the process of cardiac remodeling and exerting an important effect in the process of heart failure. Based on the above mechanism, microRNAs have promising applications in the diagnosis and treatment of heart failure. MicroRNAs form a complex post-transcriptional control mechanism of gene expression, and the increase or decrease of their content during heart failure largely alters the course of cardiac remodeling. By continuously identifying their target genes, it is expected to achieve more precise diagnosis and treatment of this important topic of heart failure.

Chemoselective Reactions of Isocyanates with Secondary Amides: One-Pot Construction of 2,3-Dialkyl-Substituted Quinazolinones.

A facile method for the preparation of 2,3-dialkyl-substituted quinazolinones from readily available N-arylamides and commercial isocyanates was developed. This one-pot procedure involves the chemoselective activation of the secondary amide with Tf2O/2-Br-Pyr, the sequential addition of isocyanate, and cyclization. The mild reaction is general for a wide range of substrates and can be run on a gram scale.

Isolation and genetic analysis of a nidovirus from crucian carp (Carassius auratus).

A nidovirus was isolated from crucian carp (Carassius auratus). The complete genome of the crucian carp nidovirus (CCNV) is 25,971 nt long and has five open reading frames, encoding the polyprotein 1ab (pp1ab), spike glycoprotein (S), membrane protein (M), and nucleocapsid protein (N). CCNV has the highest similarity to Chinook salmon nidovirus (CSNV). However, the CCNV HB93 pp1ab protein sequence has three long fragment deletions compared with the CSNV. Phylogenetic analysis based on the complete genome sequence showed that CCNV HB93 clusters with CSNV, indicating that CCNV represents a second species in the new genus Oncotshavirus within the new family Tobaniviridae in the order Nidovirales.

Effect of supervised exercise training on cardiovascular function in patients with intermittent claudication: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to determine the effect of supervised exercise training (SET) on cardiovascular function in patients with intermittent claudication (IC). A systematic search in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases was conducted. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), rate pressure product (RPP), cardiac output (CO), peak oxygen consumption (VO2peak), and heart rate variability (HRV). Secondary outcomes were maximum walking distance (MWD) and pain-free walking distance (PFWD). Outcomes were reported as weighted mean difference (WMD) between the SET group and the control group and synthesized by using the random-effects model. Seventeen RCTs with a total of 936 patients were included in this review. SET resulted in significant improvements of SBP (WMD = - 7.40, 95% CI - 10.69 ~ - 4.11, p < 0.001, I2 = 15.2%), DBP (WMD = - 1.92, 95% CI - 3.82 ~ - 0.02, p = 0.048, I2 = 0.0%), HR (WMD = - 3.38, 95% CI - 6.30 ~ - 0.46, p = 0.023, I2 = 0.0%), RPP (WMD = - 1072.82, 95% CI - 1977.05 ~ - 168.59, p = 0.020, I2 = 42.7%), and VO2peak with plantar flexion ergometer exercise (WMD = 5.57, 95% CI 1.66 ~ 9.49, p = 0.005, I2 = 62.4%), whereas CO and HRV remained statistically unaltered. SET also improved MWD (WMD = 139.04, 95% CI 48.64 ~ 229.44, p = 0.003, I2 = 79.3%) and PFWD (WMD = 40.02, 95% CI 23.85 ~ 56.18, p < 0.001, I2 = 0.0%). In conclusion, SET is effective in improving cardiovascular function in patients with IC, which was confirmed on outcomes of cardiovascular function associated with exercise ability. The findings hold out that the standard therapy of SET can improve not only walking distance but also cardiovascular function in patients with IC.

A systematic review and meta-analysis of cold exposure and cardiovascular disease outcomes.

Background: Cold exposure has been considered an essential risk factor for the global disease burden, while its role in cardiovascular diseases is still underappreciated. The increase in frequency and duration of extreme cold weather events like cold spells makes it an urgent task to evaluate the effects of ambient cold on different types of cardiovascular disease and to understand the factors contributing to the population's vulnerability. Methods: In the present systematic review and meta-analysis, we searched PubMed, Scopus, and Cochrane. We included original research that explored the association between cold exposure (low temperature and cold spell) and cardiovascular disease outcomes (mortality and morbidity). We did a random-effects meta-analysis to pool the relative risk (RR) of the association between a 1°C decrease in temperature or cold spells and cardiovascular disease outcomes. Results: In total, we included 159 studies in the meta-analysis. As a result, every 1°C decrease in temperature increased cardiovascular disease-related mortality by 1.6% (RR 1.016; [95% CI 1.015-1.018]) and morbidity by 1.2% (RR 1.012; [95% CI 1.010-1.014]). The most pronounced effects of low temperatures were observed in the mortality of coronary heart disease (RR 1.015; [95% CI 1.011-1.019]) and the morbidity of aortic aneurysm and dissection (RR 1.026; [95% CI 1.021-1.031]), while the effects were not significant in hypertensive disease outcomes. Notably, we identified climate zone, country income level and age as crucial influential factors in the impact of ambient cold exposure on cardiovascular disease. Moreover, the impact of cold spells on cardiovascular disease outcomes is significant, which increased mortality by 32.4% (RR 1.324; [95% CI 1.2341.421]) and morbidity by 13.8% (RR 1.138; [95% CI 1.015-1.276]). Conclusion: Cold exposure could be a critical risk factor for cardiovascular diseases, and the cold effect varies between disease types and climate zones. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022347247.

The Peripheral Circulating Exosomal microRNAs Related to Central Inflammation in Chronic Heart Failure.

Sympathetic hyperactivity plays an important role in the progression of chronic heart failure (CHF). It is reported that inflammation in the rostral ventrolateral medulla (RVLM), a key region for sympathetic control, excites the activity of neurons and leads to an increase in sympathetic outflow. Exosome, as the carrier of microRNAs (miRNAs), has the function of crossing the blood-brain barrier. The present study was designed to investigate the effect of exosomal miRNAs on central inflammation via peripheral-central interaction in CHF. The miRNA microarray detection was performed to compare the difference between circulating exosomes and the RVLM in CHF rats. It was shown that the expression of miR-214-3p was significantly up-regulated, whereas let-7g-5p and let-7i-5p were significantly down-regulated in circulating exosomes and the RVLM. Further studies in PC12 cells revealed that miR-214-3p enhanced the inflammatory response, while let-7g-5p and let-7i-5p reduced the neuroinflammation. The direct interaction between the miRNA and its inflammatory target gene (miR-214-3p, Traf3; let-7g-5p, Smad2; and let-7i-5p, Mapk6) was confirmed by the dual-luciferase reporter assay. These results suggest that the circulating exosomes participate in the enhancement of inflammatory response in the RVLM through their packaged miRNAs, which may further contribute to sympathetic hyperactivity in CHF.

Resveratrol inhibits autophagy and promotes apoptosis in uveal melanoma cells via miR-512-3P/DUSPl axis / 中国药理学通报

Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L

Role of TGF-β/Smad signaling pathway in pulmonary fibrosis after rheumatoid arthritis in mice / 中国药理学通报

Aim To investigate the role of TGF-β/Smad signaling pathway in rheumatoid arthritis (RA) - associated postinterstitial pulmonary fibrosis in mice. Methods The mouse model of RA was constructed by subcutaneous administration of complete Freund's adjuvant (CFA) and chicken II collagen (Col-II) to the tail root of mice. The blank group was given the same amount of distilled water, and the control group was given the same amount of glacial acetic acid (solvent). The degree of toe swelling (joint swelling degree and arthritis index) was monitored to evaluate the mouse modeling. The pathological changes of mouse lung tissues were observed by HE and Masson staining. The expression of TGF-β in lung tissues were observed by immunohistochemical staining. The level of hydroxyproline in lung tissues was measured by chemiluminescence method. The expressions of Smad2, Smad3 and phosphorylated p-Smad2 and phosphorylated p-Smad3 in lung tissues were detected by Western blot. Results Compared with blank group and solvent group, the joint swelling and arthritis index of model group significantly increased. Twenty-one days after administration, HE staining showed inflammatory changes in lung interstitium of the model group, Masson staining showed collagen fiber deposition and obvious fibrosis in lung interstitium of the model group, and immunohistochemical staining showed that the expression of TGF-β in cytoplasm of lung interstitial cells of the model group increased, which was brown and yellow. Meanwhile, hydroxyproline was significantly raised in lung tissue homogenate of the model group. Further WB analysis showed that compared with blank group and solvent group, the expression of p-Smad2 and pSmad3 in lung tissues of the model group was significantly up-regulated (P < 0. 05, P < 0. 01). Conclusions RA can give rise to pulmonary fibrosis, and the expressions of p-Smad2 and p-Smad3 are up-regulated, which is be pivotal in pulmonary fibrosis and RA-related post-interstitial pulmonary fibrosis.

Paeonol inhibits rheumatoid arthritis through formyl peptide receptors / 中国药理学通报

Aim To investigate the pharmacological effects of paeonol as a formyl peptide receptor activator on rheumatoid arthritis (HA).Methods The target rlataset was obtained from the high throughput Gene Expression Database ( GEO) , and multiple data sets were combined by USING R language to explore three groups of macrophage differentially expressed genes ( DEGs) in untreated,lipopolysaccharide (LPS) treat¬ment and paeonol and LPS treatment, and their enrich-ment pathway was analyzed.Protein-protein interaction (PPI) networks were constructed in the STRING data¬base anrl visualized in Cytoscape software.The inhibi¬tor}' effect of Hub gene formyl peptide receptor ( FPR) on RA inflammation was validated by TNF-cx stimula¬tion of fibroblast synovial cells ( FLS).Results Through bioinformatics analysis, 169 differential genes ( DEGs) related to inflammation and 275 DEGs related to the mechanism of paeonol action were obtained.Combined analysis of the two groups of DEGs showed that FPR played a key role in the anti-inflammatory mechanism of paeonol.Further studies on the mecha¬nism of paeonol showed that paeonol activated FPR, and the inhibitory effect of paeonol on FLS inflamma¬tion was rescued by TRP-ARg-TRP-TRP-TRP-TRP- TRP-TRP-NH2 (WRW4).Conclusion Paeonol can inhibit the inflammatory development of RA through the FPR pathway.

Dopamine-Induced Formation of Ultrasmall Few-Layer MoS2 Homogeneously Embedded in N-Doped Carbon Framework for Enhanced Lithium-Ion Storage.

Molybdenum disulfide with a layered structure and high theoretical capacity is attracting extensive attention for high-performance lithium-ion batteries. In this study, a simple and scalable method by freeze-drying of (NH4)2MoS4 and dopamine mixed solutions along with subsequent calcination is developed to realize the self-assembly of hierarchical MoS2/carbon composite nanosheets via the effect of dopamine-induced morphology transformation, in which ultrasmall few-layer MoS2 nanosheets were homogeneously embedded into a N-doped carbon framework (denoted as MoS2@N-CF). The embedded ultrasmall MoS2 nanosheets (∼5 nm in length) in the composites consist of less than five layers with an expanded interlayer spacing of the (002) plane. When tested as anode materials for rechargeable Li-ion batteries, the obtained MoS2@N-CF nanosheets exhibit outstanding electrochemical performance in terms of high specific capacity (839.2 mAh g-1 at 1 A g-1), high initial Coulombic efficiency (85.2%), and superior rate performance (702.1 mAh g-1 at 4 A g-1). Such intriguing electrochemical performance was attributed to the synergistic effect of uniform dispersion of few-layer MoS2 into the carbon framework, expanded interlayer spacing, and enhanced electronic conductivity in the unique hierarchical architecture. This work provides a simple and effective strategy for the uniform integration of MoS2 with carbonaceous materials to significantly boost their electrochemical performance.

Effect of cardiopulmonary resuscitation on hippocampal brain after cardiac arrest in rats and its mechanism / 中国药理学通报

Aim To investigate the protective effect of cardiopulmonary resuscitation (CPR) on hippocampal brain tissues of rats after cardiac arrest and its mechanism. Methods Forty SD rats were randomly divided into control group, ischemia group, cardiopulmonary resuscitation group and Edaravone treatment group. The rats in ischemia group were subjected to cardiac arrest by suffocation for 10 min. In resuscitation group, cardiac arrest/cardiopulmonary resuscitation (CA/CPR) was performed, after 3 min of cardiac arrest, cardiopulmonary resuscitation was performed for 7 min. After 10 min, the rats in each group were sacrificed, venous blood was taken to detect oxidative stress indicators, and the pathology of rat hippocampal brain tissues were examined by HE staining and electron microscopy, and the expressions of Nrf2 and Keapl gene and proteins were detected by real-time fluorescent quantitative PCR and Western blot. Results Compared with control group, the serum oxidative stress level of the ischemic model group rats increased, the Nissl body of the hippocampal nerve cells decreased significantly, the mitochondrial cristae were destroyed significantly, and the expressions of Nrf2 and Keapl genes and proteins in the hippocampal tissues increased. Compared with ischemic group, the serum oxidative stress level of resuscitation group rats decreased. Compared with ischemic group, the serum oxidative stress level of the rats in cardiopulmonary resuscitation group decreased, the neuronal cells in the hippocampus increased, the mitochondrial cristae damage was alleviated, and the expressions of Nrf2 and Keapl genes and proteins in the hippocampus decreased. Conclusions CPR has protective effect on hippocampal tissues of rats, and its mechanism is related to the alleviation of Nrf2/Keapl pathway of oxidative stress injury.

Effects of 5-aza-2'-deoxycytidine on proliferation of SPC-Al cells and expression of SFRPl and MGMT methylated proteins in lung cancer / 中国药理学通报

Aim To observe the effect of methylation inhibitors of 5-aza-2'-deoxycytidine (5-Aza-CdR) on SPC-Al - lung cancer cell proliferation, cell scratches and apoptosis, to explore the influence of secretion curl associated protein 1 (SFRPl) and 06-methylguanine-DNA-methyltransferase (MGMT) gene promoter region in which DNA methylation mRNA and protein expression and meaning. Methods The effects of 5-Aza-CdR at different concentrations on the proliferation of human lung cancer SPC-A 1 cells were determined by CCK-8 assay. The effect of 5-Aza-CdR on the migration ability of SPC-A 1 cells was determined by scratch assay. The apoptosis of lung cancer SPC-A 1 cells was detected by Hoechst 33258 staining after treatment with 5-Aza-CdR for 24 h. mRNA and protein expressions of SFRPl and MGMT in SPC-Al cells were detected by RT-PCR and Western blot. Results 5-Aza-CdR could reduce the proliferation of SPC-A 1 cells by concentration gradient,and IC50 was 21.2 jjimol • L

Clinical observation on deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle for trigeminal neuralgia of wind and heat / 中国针灸

OBJECTIVE@#To compare the clinical therapeutic effect between deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle and conventional acupuncture in patients with trigeminal neuralgia (TN) of wind and heat, and explore its mechanism.@*METHODS@#A total of 60 patients with TN of wind and heat were randomized into an observation group (30 cases) and a control group (30 cases). In the observation group, deep needling with round sharp needle was applied at Xiaguan (ST 7), and tapping with plum-blossom needle was applied at Yangbai (GB 14), Quanliao (SI 18), Dicang (ST 4), Sibai (ST 2), etc. of affected side. In the control group, conventional acupuncture was applied at the same acupoints selected in the observation group. The treatment was given once a day, 5 times a week for 4 weeks in the both groups. Before and after treatment, the scores of short-form McGill pain questionnaire (SF-MPQ), TCM syndrome, patient global impression of change (PGIC) and comprehensive symptom were observed, the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vasoactive intestinal peptide (VIP) and β-endorphin (β-EP) were detected, and the adverse reaction was observed in the both groups.@*RESULTS@#After treatment, the scores of PRI, PPI, VAS, TCM syndrome, PGIC and comprehensive symptom and the serum levels of IL-6, TNF-α and VIP were decreased compared before treatment in the both groups (@*CONCLUSION@#Deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle can effectively treat the trigeminal neuralgia of wind and heat and relieve pain, its therapeutic effect is superior to conventional acupuncture. The mechanism may be related to the regulation of serum IL-6, TNF-α, VIP and β-EP.

Paeonol suppresses fibroblast synovitis by increasing MANF expression / 中国药理学通报

Aim To investigate the possible mechanism of paeonol inhibiting the inflammatory response of fibroblast synovial cells (RA-FLSS) in rheumatoid arthritis. Methods CCK-8 assay was used to detect Paeonol's inhibitory level on the abnormal proliferation of arthritis human fibroblast synovial cells (RA-FLSs). The levels of endoplasmic reticulum stress-related proteins MANF and ATF6 were detected by Western blot. Cell localization of transcription factor p65 and Mesencephalic Astrocyte Derived Neurotrophic Factor (MANF) was detected by immunofluorescence. RT-qPCR detected the changes of p65 target genes. Results Paeonol could significantly inhibit the abnormal proliferation of RA-FLSS cells. Paeonol activates ATF6 and increases the expression of MANF. Paeonol promoted the nuclear transfer of MANF protein and inhibited the transcriptional activity of p65. Conclusion Paeonol promotes the expression of MANF and nuclear transfer through the endoplasmic reticulum stress pathway and affects the progression of RA by inhibiting the transcriptional activity of p65.

Effects of Different Routes in PMSC Transfusion on the Levels of Hematopoietic Regulatory Factors in Aplastic Anemia Rats / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of different routes in placental mesenchymal stem cells (PMSC) on serum expression levels of IL-4, IL-17, TNF-α and IFN-γ in aplastic anemia (AA) rats.@*METHODS@#The rat model of aplastic anemia (AA rats) was established by 5-fluorouracil combined with busulfan. The rats was divided into four groups: control, experimental, PMSC-injected into the tail vein, and PMSC-injected into the medullary cavity. The general state of rats in each group was observed in detail before and after treatment. The serum levels of interleukin-4 (IL-4) , interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA) at week 1, 3 and 5 after treatment.@*RESULTS@#The serum levels of TNF-α, IFN-γ and IL-17 in the experimental group were significantly higher than those in the control group, while the level of IL-4 was significantly decreased (P＜0.05). The levels of TNF-α, IFN-γ and IL-17 gradually decreased after treatment while the level of IL-4 increased. By the fifth week, the above indexes were closed to the control group (P＞0.05), and the levels of TNF-α, IFN-γ and IL-17 in the group with PMSCs injected via the medullary cavity decrease more significantly than those group with PMSC injected via the tail vein, but level of IL-4 was not significantly different between two groups.@*CONCLUSION@#The level of serum hematopoietic negative regulators increase significantly, and the level of hematopoietic promoting factors decreases significantly in aplastic anemia rats. PMSC can down-regulate the level of hematopoietic negative regulators and up-regulate the level of hematopoietic promoting factors in the rats with aplastic anemia, and the inhibition of hematopoietic negative regulators by intramedullary injection is more significant than that by caudal vein injection.

Diagnostic value of optic disc retinal nerve fiber layer thickness for diabetic peripheral neuropathy / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#To investigate the value of optic disc retinal nerve fiber layer (RNFL) thickness in the diagnosis of diabetic peripheral neuropathy (DPN).@*METHODS@#Ninety patients with type 2 diabetes, including 60 patients without DPN (NDPN group) and 30 patients with DPN (DPN group), and 30 healthy participants (normal group) were enrolled. Optical coherence tomography (OCT) was used to measure the four quadrants and the overall average RNFL thickness of the optic disc. The receiver operator characteristic curve was drawn and the area under the curve (AUC) was calculated to evaluate the diagnostic value of RNFL thickness in the optic disc area for DPN.@*RESULTS@#The RNFL thickness of the DPN group was thinner than those of the normal and NDPN groups in the overall average ((101.07± 12.40) µm vs. (111.07±6.99) µm and (109.25±6.90) µm), superior quadrant ((123.00±19.04) µm vs. (138.93±14.16) µm and (134.47±14.34) µm), and inferior quadrant ((129.37±17.50) µm vs. (143.60±12.22) µm and (144.48±14.10) µm), and the differences were statistically significant. The diagnostic efficiencies of the overall average, superior quadrant, and inferior quadrant RNFL thicknesses, and a combined index of superior and inferior quadrant RNFL thicknesses were similar, and the AUCs were 0.739 (95% confidence interval (CI) 0.635-0.826), 0.683 (95% CI 0.576-0.778), 0.755 (95% CI 0.652-0.840), and 0.773 (95% CI 0.672-0.854), respectively. The diagnostic sensitivity of RNFL thickness in the superior quadrant reached 93.33%.@*CONCLUSIONS@#The thickness of the RNFL in the optic disc can be used as a diagnostic method for DPN.

Effect of fertilization combination of nitrogen, phosphorus, and potassium on yield and quality of Salvia miltiorrhiza / 中草药

Objective: To study the effect of fertilization combination of nitrogen, phosphorus, and potassium on the yield and quality of Salvia miltiorrhiza in order to explore the optimal N, P, and K ratios and dosages in middle south of Shandong, and provide theoretical guidance for precision fertilization. Methods: Based on “3414” randomized block design, 14 fertilization combination treatments of N, P and K were designed to determine the yield, growth, and bioactive components of S. miltiorrhiza. The effects of different fertilization treatments on the yield and quality of S. miltiorrhiza were analyzed, and a fertilizer effect model of S. miltiorrhiza in middle south of Shandong was established by stepwise regression analysis. The maximum yield of fertilized S. miltiorrhiza and the best amount of economic fertilization were estimated. Results: Nitrogen, phosphorus, and potassium deficiency treatments reduced the yields by 27.29%, 22.09%, and 23.83%, respectively, and the optimal treatment for increasing yield was N2P2K2 with a yield of 16 740 kg/hm2. Single factor fertilizer effect analysis showed that the yield of S. miltiorrhiza showed a trend of increasing first and then decreasing with the increase in the application amount of these fertilizers. The main nutrient elements limiting yield and benefit of S. miltiorrhiza in middle south of Shandong were as follow: N > K > P. The analysis of the interaction between the two factors showed that the nitrogen, phosphorus, and potassium fertilizers promoted each other at a certain application amounts, the interaction effect were as follow: NP > NK > PK. Through the effects of fertilization combination of nitrogen, phosphorus, and potassium on growth, nitrogen significantly promoted the material accumulation in roots of S. miltiorrhiza. Potassium had a certain role in promoting the plant width and root width. The effect of fertilization on the content of active ingredients showed that potassium promoted the accumulation of phenolic acids and tanshinones, while potassium had the adverse effect. Conclusion: The quadratic function fitting result between the amount of fertilizer applied and the yield of S. miltiorrhiza is in line with the law of diminishing returns, which can better reflect the relationship between the amount of fertilizer and yield. The best fertilizer scheme in middle south of Shandong should be N 195.63 kg∙/hm2, P2O5 116.64 kg/hm2, and K2O 153.84 kg/hm2 estimated by ternary quadratic function fitting.

Relationship Between the Change of Microbial Diversity and Gastrointestinal Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the change of microbial diversity and its relation with gastrointestinal (GI) graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#Fecal samples were collected at the time point of 2 weeks before transplantation (pre-transplant group), 1 month after transplantation (post-tranplant group) and onset of GI GVHD in 65 hematonosis patients, which were also collected in 26 donors and 10 healthy subjects (control group). 16S rRNA was extracted from fecal microbiotas whose V4 variable region was amplified. The amplification products were sequenced in Illumina HiSeq 2500 platform, and the sequencing results were analyzed and compared.@*RESULTS@#The microbial diversity was 5.70（3.74, 10.60）in pre-transplant group, 7.30（4.89, 11.41）in control group, and the differences between them were not statistically significant. The microbial diversity was 3.88（2.39, 6.49）in post-transplant group, lower than that in control group and pre-transplant group. After transplantation, the microbial diversity was 4.24（2.47, 7.16）in the patients without GI GVHD, while the microbial diverosity was 2.90 (1.48, 5.64) in patients subsequently suffered from GI GVHD, but the differences between them were not statistically significant. The microbial diversity was 2.13（1.76, 3.75）onset of GI GVHD, which was lower than that without GI GVHD.@*CONCLUSION@#Intestinal microbial diversity decreases after allo-HSCT, and is associated with with Gl GVHD.

An analysis of GNAS and THRA gene mutations in children with congenital hypothyroidism / 中国当代儿科杂志

OBJECTIVE@#To preliminarily investigate the relationship between stimulatory G protein α subunit (GNAS) and thyroid hormone receptor α (THRA) gene mutations and clinical phenotypes in children with congenital hypothyroidism (CH).@*METHODS@#A total of 70 children with CH diagnosed by neonatal screening were enrolled. Their peripheral blood samples were collected to extract genomic DNA. GNAS and THRA genes were screened for mutations using next-generation sequencing. Bioinformatics software was used to analyze the pathogenicity of gene mutations.@*RESULTS@#Of the 70 children with CH, nine missense mutations (three known mutations and six novel mutations) in the GNAS gene were detected in three patients (4%), and one gene polymorphism, c.508A>G(p.I170V), in the THRA gene was detected in four patients. The analysis results of bioinformatics software and ACMG/AMP guidelines showed that the two GNAS gene mutations [c.301C>T(p.R101C) and c.334G>A(p.E112K)] were more likely to be pathogenic. Three children with GNAS gene mutations showed different degrees of hypothyroidism.@*CONCLUSIONS@#GNAS gene mutations are related to the development of CH, and children with CH have different clinical manifestations. THRA gene mutations may not be associated with CH.

Clinical significance of expression of MnSOD/SIRT3 in pernicious placenta previa combined with placenta implantation / 医学研究生学报

Objective Dangerous placenta previa(PPP) combined with placenta implantation seriously threatens maternal life safety. This paper aim to explore the changes of MnSOD and SIRT3,the expression of SIRT3 in maternal placenta PPP combined with placenta implantation, and the relationship between trophoblast invasion and placental implantation. Methods 90 cases with placenta implantation of pernicious placenta previa were collected from January 2014 to June 2018 in Anhui Maternal and Child Health Hospital. According to the depth of placental villus invading uterine myometrium, 30 cases of placenta adhesion, 30 cases of placental implantation, and 30 cases of placenta penetration, 30 cases of normal control group．Immunohistochemical SP and Western blot were used to detect the expression of MnSOD and SIRT3 in placental tissues of the study group and the control group, then compared and analyzed. Results Compared with the control group, the expression of MnSOD and SIRT3 in the placental implantation group were increased. With the increasing of placental implantation degree, the level of MnSOD and SIRT3 decreased significantly (P<0.05). Western blot showed that , the relative protein expressions of MnSOD/β-actin and SIRT3/β-actin in the control group were (0.39±0.05) and (0.41±0.08), which were higher than those in the adhesion group[(0.35±0.04), (0.32±0.02)], the implantion group[(0.28±0.02), (0.20±0.03)], and the penetration group[(0.23±0.01), (0.17±0.02)]. The difference was statistically significant(P<0.05). Conclusion The expressions of MnSOD and SIRT3 incytoplasm or nucleus of invasive trophoblasts and placental tissues of pregnant women with placental implantation is significantly decreased, both of which are involved in the occurrence and development of placental implantation, but the specific pathogenesis still needs to be further explored.