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BACKGROUND@#Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis (ALS) have previously been reported. This study aimed to examine the microbiota in the nasal cavity of ALS.@*METHODS@#Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled. High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid (rDNA) gene V3-V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa, predict function, and conduct correlation analysis between specific taxa and clinical features.@*RESULTS@#The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members. Genera Gaiella , Sphingomonas , Polaribacter _1, Lachnospiraceae _NK4A136_group, Klebsiella , and Alistipes were differentially enriched in ALS patients compared to controls. Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects (unweighted UniFrac P = 0.001), while Linear discriminant analysis Effect Size (LEfSe) analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level, whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients. Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised (ALSFRS-R; rs = 0.349, P = 0.020 and rs = 0.393, P = 0.008), while Prevotella -9 and Bacteroides operational taxonomic units (OTUs) were positively associated with lung function (FVC) in ALS patients ( rs = 0.304, P = 0.045, and rs = 0.300, P = 0.048, respectively). Prevotella -1 was positively correlated with white blood cell counts (WBC, rs = 0.347, P = 0.021), neutrophil percentage (Neu%, rs = 0.428, P = 0.004), and neutrophil-to-lymphocyte ratio (NLR, rs = 0.411, P = 0.006), but negatively correlated with lymphocyte percentage (Lym%, rs = -0.408, P = 0.006). In contrast, Streptococcus was negatively associated with Neu% ( rs = -0.445, P = 0.003) and NLR ( rs = -0.436, P = 0.003), while positively associated with Lym% ( rs = 0.437, P = 0.003). No significant differences in nasal microbiota richness and evenness were detected among the severe and mild ALS patients.@*CONCLUSIONS@#ALS is accompanied by altered nasal microbial community composition and diversity. The findings presented here highlight the need to understand how dysbiosis of nasal microbiota may contribute to the development of ALS.
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Humans , Amyotrophic Lateral Sclerosis/microbiology , Feces/microbiology , Microbiota/genetics , Gastrointestinal Microbiome/genetics , Bacteria/genetics , RNA, Ribosomal, 16S/geneticsABSTRACT
Objective:To compare the clinical curative effect of roxadustat and recombinant human erythropoietin (rhEPO) on non-dialysis stage 3 to 5 chronic kidney disease (CKD) combined with renal anemia (RA).Methods:A total of 108 patients with non-dialysis stage 3 to 5 CKD and RA admitted to Jiangbei Branch of Zhongda Hospital Affiliated to Southeast University were prospectively enrolled between January 2020 and October 2022. According to random number table method, they were divided into group A and group B, 54 cases in each group. The group A was treated with roxadustat and polysaccharide-iron complex (PIC) for 3 months, while group B was treated with rhEPO and PIC for 3 months. The clinical curative effect, levels of hemoglobin (Hb), red blood cell count (RBC), hematocrit (Hct), serum ferritin (SF), transferrin saturation (TSAT), transferrin (TRF), blood urea nitrogen (BUN), serum creatinine (Scr) and β2-microglobulin (β2-MG) before and after treatment, and the incidence of adverse reactions during treatment in the two groups were compared.Results:The total response rate of treatment in group A was significantly higher than that in group B: 87.04% (47/54) vs. 70.37% (38/54), and the difference was statistically significant ( P<0.05). After treatment, levels of RBC, Hb and Hct in group A were significantly higher than those in group B: (3.47 ± 0.59) × 10 12/L vs. (2.60 ± 0.51) × 10 12/L, (110.45 ± 12.97) g/L vs. (93.64 ± 10.58) g/L, 0.358 ± 0.054 vs. 0.303 ± 0.043, and the difference was statistically significant ( P<0.05). The levels of TSAT, SF and TRF in group A were significantly higher than those in group B: (35.17 ± 3.65)% vs. (29.82 ± 3.10)%, (286.74 ± 17.23) μg/L vs. (243.16 ± 15.49) μg/L, (2.76 ± 0.45) g/L vs. (2.40 ± 0.32) g/L, and the difference was statistically significant ( P<0.05). The levels of BUN, Scr and β2-MG in group A were significantly lower than those in group B: (3.98 ± 0.41) mmol/L vs. (4.36 ± 0.54) mmol/L, (62.57 ± 7.89) μmol/L vs. (80.34 ± 9.65) μmol/L, (1.50 ± 0.42) μg/L vs. (1.99 ± 0.58) μg/L, and the difference was statistically significant ( P<0.05). During treatment, incidence of adverse reactions in group A was significantly lower than that in group B: 11.11% (6/54) vs. 25.93% (14/54), and the difference was statistically significant ( P<0.05). Conclusions:Compared with rhEPO, roxadustat has better curative effect, which can effectively relieve anemia and improve iron metabolism in patients with non-dialysis stage 3 to 5 CKD and RA, with good safety.
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Objective To investigate the effect of low molecular weight heparin on lung Injury complicated by severe acute pancreatitis and explore its mechanism.Methods Ninety Wistar rats were randomly divided into 3 groups,namely sham operation (SO) group,acute necrotizing pancreatitis (ANP) group,low molecular weight heparin treatment (LH) group.4％ sodium taurocholate was injected into the pancreatic duct to induce ANP model.Subcutaneous low molecular weight heparin (10 U/100 g body weight) was injected in the LH group,the equivalent amount of normal saline was injected in the SO and ANP group.After 6,12,24 h,rats were sacrificed respectively,pancreas and lung tissues were harvested to observe the pathological changes and the pathological changes were scored;and the changes of TLR4 and VEGF protein expression in lung tissue was determined by immunohistochemical method.Serum and lung levels of IL-6,IL-l0,TNF-α were determined by ELASA method.Results The pancreas and lungs tissues were normal in SO group,diffuse hemorrhage,necrosis and a large number of inflammatory cells infiltration was observed in pancreas tissue in ANP group.Lung alveolar wall rupture,interstitial hyperemia,edema,a large number of infiltrating neutrophils could be seen in lung tissue in ANP group.The pancreas and lungs tissues injuries were significantly alleviated.The pancreas and lungs pathological scores of ANP group at 12 h were 6.34 ± 1.09,7.01 ± 1.16,and those were 5.48 ± 0.86,6.24 ± 0.86 in LH group,the values in LH group were significantly lower than those in ANP group (P ＜ 0.05),and there was a positive association between lung and pancreas scores (r =0.812,P ＜ 0.01).The expressions of TLR4,VEGF,IL-6,TNF-o,IL-10 in lung tissue of ANP group at 12 h were 0.68 ± 0.10,0.50 ± 0.11 and (2617.2 ± 485.3),(1603.1 ± 519.7),(608.3 ±137.5)pg/g,which were 0.61 ±0.09,0.41 ±0.06 and (2398.5 ±503.7),(1302.4±389.8),(753.2 ±100.0) pg/g in LH group,and the expressions of TLR4,VEGF,IL-6,TNF-α in LH group were significantly lower than those in ANP group,but the expression of IL-10 was significantly up-regulated,and the difference between the two groups was statistically significant (P ＜ 0.05).The serum levels of IL-6,TNF-α,IL-10 in ANP group at 12 h were (184.3 ± 45.7),(289.7 ± 60.4),(143.2 ± 30.4) μg/L,which were (143.8 ±31.8),(256.4 ±40.7),(189.3 ± 50.9)μg/L in LH group,and the levels of IL-6,TNF-α in LH group were significantly lower than those in ANP group,but the expression of IL 10 was significantly increased,and the difference was statistically significant (P ＜ 0.05).The expression of TLR4,VEGF in lung tissue was positively associated with the degree of lung injuries (r =0.524,0.503,P ＜ 0.05).Conclusions Low molecular weight heparin may improve lung injury complicated by ANP.The mechanism may involve inhibiting the expression of TLR4 and VEGF protein,IL-6,TNF-α,and up-regulation of the expression of IL-10.
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Objective To investigate the efficiency of levodopa in dopa responsive dystonia (DRD) patients and drugs safety in pregnancy cases confirmed by genetic detection.Methods The clinical characteristics of two patients were analyzed.Direct sequences were performed in guanosine triphosphate (GTP) cyclohydrolase Ⅰ (GCH1) gene and tyrosine hydroxylase (TH) gene mutation screening.Results Case 1 was a young man exhibiting writer's cramp and dystonia of lower legs with marked diurnal fluctuation.Writer's cramp could not be relieved by treatment of low dose levodopa/benserazide.After increasing dose,the symptom of writer's cramp appeared occasionally.Case 2 was a young woman who experienced gait disorder.The symptom disappeared completely by levodopa treatment.She used levodopa and benzhexol during pregnancy.By 38 gestational weeks,she gave birth to a healthy baby.Sequence analysis of GCH1 gene in case 1 revealed a mutation (c.230C ＞ G p.S77C) that is a novel pathogenic mutation.The confirmed mutation c.628delC (p.His210Thrfs* 5) found in case 2 had been reported previously.No mutations in TH gene were detected in two patients.Condnsions Most of DRD patients have dramatic response to levodopa,but patients exhibited writer' s cramp may respond to levodopa incompletely.The previous reports indicate that no adverse events have been reported in DRD pregnant women with the monotherapy of levodopa.
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Objective To investigate the clinical value of multi-slice spiral CT in the evaluation of esophageal variceal bleeding .Methods 50 cirrhosis patients with esophageal varices received multi-slice spiral CT and gastroscopy detection .The application value of multi-slice CT in the assessment of esophageal bleeding was evaluated according to the results of gastroscopy detection .Results CT angiography score had significantly positive correlation with the severity of endoscopic varices and endoscopic red color sign (r=0.762,0.687,all P<0.01).The sensitivity and specificity of CT angiography score in diagnosis of endoscopic red signs RC 3 were 76.92% and 92.50%. Conclusion The results of multi-slice CT and gastroscopy are positively correlated with the severity of esophageal varices,which can be used to predict the risk of esophageal bleeding .
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OBJECTIVE:To observe the clinical efficacy of reduced glutathione combined with Polyene Phosphatidylcholine for non-alcoholic fatty liver disease. METHODS: 60 patients with non-alcoholic fatty liver disease were randomly divided into trial group and control group: 30 patients in trial group were infused iv gtt with Polyene Phosphatidylcholine (10 mL) and reduced glutathione (1 200 mg) once daily for 1 months,and 30 in control group with Polyene Phosphatidylcholine (10 mL) once daily for 1 months. Parameters of liver function and blood lipid and color ultrasonic examination of two groups before and after treatment were compared for evaluation of therapeutic effects. RESULTS: In respect of the reduction of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and ?-GT,there were significant differences between the trial group and the control group in the effective rate (90.0% in trial group versus 63.3 % in control group,P0.05). CONCLUSION: Used concomitantly,reduced glutathione and Polyene Phosphatidylcholine showed satisfactory efficacy for non-alcoholic fatty liver disease.