OBJECTIVE: Previous studies have shown that insomnia is closely related to erectile dysfunction（ED）. However, the causal relationship between them is still unclear. Mendelian randomization (MR) provides a new method for studying the relationship between the two, and the theory of heart-kidney interaction in TCM provides a new idea for exploring the causal relationship between them. METHODS: Based on the statistical data collected by genome-wide association studies (GWAS), the causal relationship between insomnia and ED was discussed by MR. Inverse variance weighted (IVW) is the main analysis method, and weighted median (WME), simple mode (SM), weighted mode (WM) and MR Egger method were the supplementary analysis to evaluate the causal effect. MR-Egger intercept test, Cochran Q test and leave-one-out method were used in sensitivity analysis to verify the reliability of MR results. RESULTS: Thirty-nine SNPs significantly related to insomnia were finally included for MR analysis. The results of IVW method in MR analysis showed that insomnia had a significant causal relationship with the increased risk of ED (OR = 3.111，95% CI= 1.566－6.181，P=1.193×10－3). The results obtained by MR-Egger method, WME method, WM method and SM method were consistent with IVW method in the direction of effect. The sensitivity results suggested that the results of this study were robust. CONCLUSION Our study reveals the causal relationship between insomnia and ED, which provides a new basis for future clinical practice and prevention and treatment of ED.
Causality ; Sleep Initiation and Maintenance Disorders/genetics* ; Erectile Dysfunction/genetics* ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Humans ; Male ; Heart/physiology* ; Kidney/physiology* ; Polymorphism, Single Nucleotide ; Data Interpretation, Statistical

Objective: To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. Methods: The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized. Results: Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS) . Mean size of+8 clone in MDS patients[65% (15%-100%) ]was higher than that of AA patients[25% (4.8%-100%) , z=3.48, P=0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6% (20/36) ; 30-50%: 22.2% (8/36) ; ≥50%22.2% (8/36) ]and MDS patients[<30%:19.0% (4/21) ; 30%-<50%:19.0% (4/21) ; ≥50%61.9% (13/21) ] (P=0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (P=0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (P=0.002) . The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS (r(s)=0.109, P=0.125; r(s)=-0.022, P=0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (P=0.016, P=0.046, P=0.012, respectively) , but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8% (P=0.125) . Comparing with initial clone size (27.3%) , the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference (z=0.83, P=0.272) . Consistently, there was no significant change between initial clone size (72.5%) and 1-2 year clone size (70.5%) after IST in MDS patients. There was no significant difference in IST efficient rate between +8 clone size expansion and decline group of in AA patients at 0.5-<1, 1-2 and>2 years after IST. We found four dynamic evolution patterns of +8 clone, which were clone persistence (45%) , clone disappearance (30%) , clone emergence (10%) and clone recurrence (15%) . Conclusions: AA patients had a low clone burden, while MDS patients had a high burden of +8 clone. The +8 clone of AA patients didn't significantly expanded after IST, and the changes of +8 clone also had no effect on IST response.
Adolescent ; Adult ; Aged ; Anemia, Aplastic ; Bone Marrow ; Child ; Chromosomes, Human, Pair 8 ; Clonal Evolution ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Trisomy ; Young Adult

Objective: To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. Methods: The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized. Results: Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS) . Mean size of+8 clone in MDS patients[65% (15%-100%) ]was higher than that of AA patients[25% (4.8%-100%) , z=3.48, P=0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6% (20/36) ; 30-50%: 22.2% (8/36) ; ≥50%22.2% (8/36) ]and MDS patients[<30%:19.0% (4/21) ; 30%-<50%:19.0% (4/21) ; ≥50%61.9% (13/21) ] (P=0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (P=0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (P=0.002) . The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS (r_s=0.109, P=0.125; r_s=-0.022, P=0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (P=0.016, P=0.046, P=0.012, respectively) , but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8% (P=0.125) . Comparing with initial clone size (27.3%) , the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference (z=0.83, P=0.272) . Consistently, there was no significant change between initial clone size (72.5%) and 1-2 year clone size (70.5%) after IST in MDS patients. There was no significant difference in IST efficient rate between +8 clone size expansion and decline group of in AA patients at 0.5-<1, 1-2 and>2 years after IST. We found four dynamic evolution patterns of +8 clone, which were clone persistence (45%) , clone disappearance (30%) , clone emergence (10%) and clone recurrence (15%) . Conclusions AA patients had a low clone burden, while MDS patients had a high burden of +8 clone. The +8 clone of AA patients didn’t significantly expanded after IST, and the changes of +8 clone also had no effect on IST response.

OBJECTIVETo detect the expression of miRNA in de novo and complete response SAA patients and predict the targets of the miRNAs.

METHODSThe expression profiles of miRNA from bone marrow mononuclear cells of the SAA patients with de novo and CR were detected by miRNA microarray.

RESULTSTotally 35 up-regulated and 37 down-regulated miRNA were identified in CR SAA patients in comparison with de novo SAA patients. Furthermore, by predicting the targets of the differentlly expressed miRNA, it was found that some targets associated with T cell receptor signaling pathway and cell adhesion molecules.

CONCLUSIONSome miRNA may be involved in the pathogenesis of SAA.

Objective: To determine the valuable hemolytic characteristics in differential diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA) and hereditary spherocytosis (HS). Method: The clinical and hemolytic characteristics of 108 PNH patients, 127 AIHA patients and 172 HS patients diagnosed from January 1998 to April 2017 were compared. Results: ①Reticulocyte percentage (Ret%) of PNH patients [6.70% (0.14%-22.82%)] was significantly lower than that of AIHA [14.00%(0.10%-55.95%), P<0.001] and HS patients [11.83%(0.60%-57.39%), P<0.001]. The Ret% in PNH patients were significantly lower than those in AIHA and HS patients at the same levels of anemia, except for in mild anemia between PNH and AIHA patients. However, when comparing the Ret% between AIHA and HS patients, there was significant difference only in mild anemia [7.63%(1.87%-29.20%)% vs 11.20%(3.31%-22.44%), z=-2.165, P=0.030]. ②The level of TBIL in HS patients was significantly higher than that in AIHA and PNH patients [79.3 (11.2-244.0) μmol/L vs 57.6 (7.6-265.0) μmol/L, z=5.469, P<0.001; 79.3(11.2-244.0) μmol/L vs 26.2(4.6-217.7) μmol/L, z=-2.165, P<0.001], and the proportion of HS patients with TBIL more than 4 times the upper limit of normal (ULN) (64.1%) was significantly higher than that of AIHA (37.7%, χ(2)=19.896, P<0.001) and PNH patients (4.6%, P<0.001). ③The LDH level of PNH patients was significantly higher than that of AIHA and HS [1 500 (216-5 144) U/L vs 487 (29-3 516) U/L, z=-9.556, P<0.001; 1 500 (216-5 144) U/L vs 252 (132-663) U/L, z=-11.518, P<0.001], and the proportion of PNH patients with LDH more than 1 000 U/L (79.1%) was significantly higher than that of AIHA patients (13.0%, χ(2)=93.748, P<0.001) and HS patients (0, P<0.001). ④Splenomegaly occurred in 43.5% of PNH patients, including 16.0% with severe splenomegaly. In contrast, the occurrence of splenomegaly was 98.6% in AIHA patients and 100.0% in HS patients (P<0.001), and 63.0% of AIHA patients (P<0.001) and 90.4% of HS patients (P<0.001) were with severe splenomegaly. ⑤The prevalence of cholelithiasis in HS patients was up to 43.1%, significantly higher than that in AIHA patients (10.5%, P<0.001) and PNH patients (2.9%, P<0.001). Conclusion: The comprehensive assessment of the five hemolytic characteristics is simplified, practical and efficient, with great clinical significance, providing specific indicators for differential diagnosis and efficient approach for making further work-up.
Anemia, Hemolytic, Autoimmune ; Diagnosis, Differential ; Hemoglobinuria, Paroxysmal ; Hemolysis ; Humans ; Spherocytosis, Hereditary

In the present study, we carried out a phytochemical investigation of the ethanol extract of the aerial parts of Baeckea frutescens, which resulted in the isolation of two new flavonoid glycosides, myricetin 3-O-(5″-O-galloyl)-α-L-arabinofuranoside (1), 6-methylquercetin 7-O-β-D-glucopyranoside (2), one new methylchromone glycoside, 7-O-(4', 6'-digalloyl)-β-D-glucopyranosyl-5-hydroxy-2-methylchromone (3), together with three known compounds (4-6). The structures of these isolated compounds were established on the basis of 1D and 2D NMR techniques and chemical methods. The anti-inflammatory activities of the compounds 1-6 were evaluated for their inhibitory effects against cyclooxygenases-1 and -2 in vitro. Compounds 1-6 showed potent COX-1 and COX-2 inhibiting activities in vitro with IC values ranging from 1.95 to 5.54 μmol·L and ranging from 1.01 to 2.27 μmol·L, respectively.
Anti-Inflammatory Agents ; chemistry ; isolation & purification ; Cyclooxygenase 1 ; chemistry ; Cyclooxygenase 2 ; chemistry ; Cyclooxygenase Inhibitors ; chemistry ; isolation & purification ; Flavonoids ; chemistry ; isolation & purification ; Molecular Structure ; Myrtaceae ; chemistry ; Plant Components, Aerial ; chemistry ; Plant Extracts ; chemistry ; isolation & purification

OBJECTIVETo investigate the clinical characteristics and gene mutations of patients with Gilbert syndrome complicated with myeloproliferative neoplasms (MPN).

METHODSPeripheral blood samples from 1 patient with Gilbert syndrome complicated with MPN and his son were collected to analyse all exon mutations of UGT1A1 gene.

RESULTSThe patient with leukocytosis, thrombocythemia, mild anemia and positive JAK2/V617F mutation was initially diagnosed as MPN. The hyperbilirubinemia suggested concurrent disease. Further gene evaluation disclosed a insertion mutation in the (TA)TAA box, and a missense mutation(G→A) at 211 bp of exon 1, corresponding to the deficiency in the bilirubin-conjugating enzyme uridine-diphosphoglucuronosyl transferase1A1 (UGT1A1). His son only carried some polymorphism mutation without manifestation of this disease.

CONCLUSIONIt is a first report case of MPN complicated with Gilbert syndrome that can highlight the differential diagnosis for hyperbilirubinemia.

OBJECTIVETo explore the clinical characteristic, therapeutic efficacy and prognosis of patients with hepatitis-associated aplasitc anemia (HAAA).

METHODSthe clinical data and labrotatory examination results of 30 cases of HAAA were analyzed retrospectively, the 6-month response ratio and overall survival (OS) were assessed.

RESULTSHAAA most commonly occured in males, with the occurence rate of males and females was 4:1, the median onset age was 16 (4-43) years old, HAAA oriented focus on sever aplastic anemia (SAA)(4 cases,13%) and very sever aplastic anemia (VSAA)(22 cases,73%). Aplastic anemia (AA) could be seen on occurence of hepatitis (accompanied aplastic anemia) (7 cases,23%), or after the onset of hepatits (delayed aplastic anemia) (23 cases,77%), but more often occured in the latter. Statistical analysis showed that when compared with the patients of delayed aplastic anemia, patients accompanied aplastic anemia possesses lower levels of glutamic-pyruvic transaminase(ALT), aspertate aminotransferase (AST) and total bilirubin (TBIL)(P=0.042,0.012,0.001), and possessed a more obvious lymphoid cell disorder when AA occured, with more lower peripheral blood CD19B cells proportion (P=0.046) and more obvious imbalance of CD4/CD8ratio, but the difference was no statistical significant (P=0538). Factors affecting the 6-month respose were the severity of AA (P=0.044), the peak level of bilirubin of hepatitis (P=0.006) and the propotion of mature monocyte in bone marrow (P=0.034). The long-term follow-up showed that the 2-year OS of HAAA was 64.3±9.2%, the 6-month curative efficacy significantly affect the prognosis (P<0.001).

CONCLUSIONHAAA more often occur in young male, HAAA is mainly SAA and VSAA and mostly non-A-C hepatitis associated aplastic anemia, patients usually have a high incidence of early infection. Patients acompanied with aplastic anemia possess more obvious immunological derangement; the treatment efficacy for HAAA is poor, patients who haven't obtained 6-month response indicate a sinister prognosis, allogeneic hematopoietic stem cell transplantion is a better choice for these patients.

OBJECTIVETo explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload.

METHODSA single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload.

RESULTSAll patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period.

CONCLUSIONSAA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.

Anemia, Aplastic ; drug therapy ; Benzoates ; therapeutic use ; Blood Transfusion ; China ; Ferritins ; blood ; Humans ; Iron ; blood ; Iron Chelating Agents ; therapeutic use ; Iron Overload ; drug therapy ; Liver ; Prospective Studies ; Triazoles ; therapeutic use