Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.

Objective: To evaluate the efficacy of neoadjuvant chemotherapy (NACT) in the treatment of locally advanced olfactory neuroblastoma (ONB), and to explore the factors related to the efficacy of NACT. Methods: A total of 25 patients with ONB who underwent NACT in Beijing TongRen Hospital from April 2017 to July 2022 were retrospectively analyzed. There were 16 males and 9 females, with an average age of 44.9 years (ranged 26-72 years). There were 22 cases of Kadish stage C and 3 cases of stage D. After multiple disciplinary team(MDT) discussion, all patients were treated sequentially with NACT-surgery-radiotherapy. Among them, 17 cases were treated with taxol, cis-platinum and etoposide (TEP), 4 cases with taxol, nedaplatin and ifosfamide (TPI), 3 cases with TP, while 1 case with EP. SPSS 25.0 software was used for statistical analysis, and survival analyses were calculated based on the Kaplan-Meier method. Results: The overall response rate of NACT was 32% (8/25). Subsequently, 21 patients underwent extended endoscopic surgery and 4 patients underwent combined cranial-nasal approach. Three patients with stage D disease underwent cervical lymph node dissection. All patients received postoperative radiotherapy. The mean follow-up time was 44.2 months (ranged 6-67 months). The 5-year overall survival rate was 100.0%, and the 5-year disease-free survival rates was 94.4%. Before NACT, Ki-67 index was 60% (50%, 90%), while Ki-67 index was 20% (3%, 30%) after chemotherapy [M (Q₁, Q₃)]. The change of Ki-67 before and after NACT was statistically significant (Z=-24.24, P<0.05). The effects of age, gender, history of surgery, Hyams grade, Ki-67 index and chemotherapy regimen to NACT were analyzed. Ki-67 index≥25% and high Hyams grade were related to the efficacy of NACT (all P<0.05). Conclusions: NACT could reduce Ki-67 index in ONBs. High Ki-67 index and Hyams grade are clinical indicators sensitive to the efficacy of NACT. NACT-surgery-radiotherapy is effective for patients with locally advanced ONB.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Neoadjuvant Therapy/methods* ; Retrospective Studies ; Esthesioneuroblastoma, Olfactory/etiology* ; Ki-67 Antigen ; Paclitaxel ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Nasal Cavity ; Nose Neoplasms/therapy* ; Neoplasm Staging

Objective: To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. Method: The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR(2)) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR(2) rate was analyzed. Results: 68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR(2). All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR(2) compared with non-KIT D816 group (23.1% vs 57.1%, χ(2)=7.559, P=0.006), and patients with longer CR(1) duration achieved significantly higher CR(2) than those with CR(1) duration less than 12 months (74.1% vs 31.9%, χ(2)=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR(1) duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. Conclusion: KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.
Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Humans ; Leukemia, Myeloid, Acute/therapy* ; Prognosis ; Retrospective Studies ; Salvage Therapy

Objective To study the tolerability and safety of single and multiple doses of Picika oral solution in healthy volunteers.Methods A single center, randomized, single -blind, placebo -controlled, dose -escalation study was designed.50 patients were given single dose, and 10 cases were given multiple doses.All of them had half male and fe-male.Single -dose group: 20 mL(4 subjects), 40 mL(6 subjects), 60 mL(10 subjects; 2 using placebo), 90 mL(10 subjects; 2 using place-bo), 120 mL (10 subjects ; 2 using placebo), 160 mL (10 subjects; 2 using placebo); multiple doses group: 10 subjects(2 using placebo), 40 mL? times-1 , tid, continuous medication for 10 days.Results Of the sixty healthy subjects enrolled , 58 finally completed the trial, and two shed.One case (female) of adverse event in single -dose 160 mL group was reported: her ctivated partial thromboplastin time (APTT) was ab-normal with clinical significance.It may not be associated with the medi-cation.In multiple doses group, one case of abdominal pain (female) was reported, may not be associated with the medication.Conclusion Single and multiple doses of Picika oral solution are safe and well tolera -ted in healthy subjects.

OBJECTIVETo assess complete remission (CR), the overall survival (OS), event-free survival (EFS) and adverse events of newly diagnosed acute promyelocytic leukemia (APL) with homoharringtonine (HHT) plus ATRA, to evaluate the therapeutic effect by comparing HHT plus ATRA with daunorubicin plus ATRA as induction regimen (HA with DA as post-remission regimen).

METHODS115 APL patients (54 in HHT group, 61 in DNR group) after long-term follow-up were enrolled in the analyses of clinical feature, chromosome karyotype, molecular biology, OS and EFS.

RESULTSThe overall CR of 115 patients was 100%, the median interval to achieve hematological CR was 32 (22 - 43) days, the overall median OS was within 0.23 - 77.34 months, median EFS was within 0.23 - 77.34 months. 3-year OS rate was 93%, 5-year OS rate 93%, 3-year EFS rate 85% and 5-year RFS rate 75% respectively. Converting to PML-RARα PCR-negative after the induction therapy in the HHT and DNR group was 31.3% and 15.5% respectively, at the end of 1 consolidation course was 68.6% and 77.6% respectively, while the remaining 4 patients tested PML-RARα PCR-negative at the end of 2 consolidation courses in the DNR group. While both groups obtained the identical molecular biology relapse rate (9.8% and 8.6%, respectively). Survival analysis indicated that no significant difference was found on OS and EFS between the HHT group and the DNR group (P = 0.206 and 0.506). 5-year OS rate was 87% for the HHT group while 98% for the DNR group, 5-years EFS rate was 80% for the HHT group while 71% for the DNR group. And the risk group was not the factor affecting OS and EFS (P = 0.615 and 0.416). Grade 2 fever in the HHT group was less than in the DNR group during induction therapy. And no difference was found in terms of liver dysfunction, renal dysfunction, cardiac dysfunction, and hematologic toxicity between two groups.

CONCLUSIONOur study demonstrated comparable therapeutic effect of HHT or DNR on APL. HHT was also well tolerated and didn't cause serious adverse events.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Harringtonines ; administration & dosage ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Prognosis ; Treatment Outcome ; Tretinoin ; administration & dosage ; Young Adult

Objective To determine independent factors correlated with clinical effects of DK crush and classical crush technique with drug-eluting stents on bifurcation lesions.Methods 311 patients with bifurcation lesions were randomized to classical(C,n=156)or double kissing(DK)crush(n=155)stent implantation group.The primary endpoints included major adverse cardiac events(MACE).Results Final kissing balloon inflation(FKBI)success rate was 76%in C and 100%in DK groups(P＜0.001).Dkcrush procedure was characterized by lower unsatisfactory FKBI rate(27.6%VS.6.3%,P＜0.01).Clinical follow-up was available in 100%and angiographic follow-up in 82%patients.The overall restenosi srate was 32.3%in C and 20.3%in DK groups(P=0.01).respectively.Cumulative 8-month MACE was 35.9%in without-FKBI and 19.7%in with-FKBI sub-groups,and 11.4%in DK group(P=0.02).The incidence of stent thrombosis was 3.2%in C group (5.1%without VS.1.7%with FKBI)and 1.3%in Dkgroup(P＞0.05).The predictive factors of MACE included minimal side branch stent lumen diameter and lack of DK crush technique.Conclusion DK crush technique is an alternative of double stenting techniquesin terms of improvement of restenosis and clinical outcomes.

OBJECTIVETo investigate the clinical and lab features of sibling brother and sister both with Duchenne muscular dystrophy (DMD).

METHODSWe conducted comprehensive clinical and lab investigations including the test of serum enzymes, electromyography (EMG), electrocardiography, color Doppler echocardiography, HE staining of skeletal muscles, immunohistochemical study of dystrophin and utrophin, multiple ligation probe amplification (MLPA) on exon 1-79 of dystrophin gene, and short tandem repeat-poly- merase chain reaction of CA repeats located in dystrophin gene.

RESULTSThese two patients were confirmed to suffer from DMD. They were characterized by typical features of DMD including typical clinical manifestations, increased serum enzymes, EMG presenting myogenic impairment, HE staining presentation belonging to DMD, negative dystrophin in brother, and inconstantly positive on the sarcolemma of sister. Furthermore, no deletion or duplication was found in the 1-79 exons of dystrophin gene. The suffering brother and sister carried the same maternal X chromosome.

CONCLUSIONSCarriers of DMD gene show typical clinical and laboratory manifestations of DMD. Comprehensive examinations should be performed for such carriers.

Dystrophin ; genetics ; Female ; Genetic Linkage ; Heterozygote ; Humans ; Male ; Muscular Dystrophy, Duchenne ; genetics ; metabolism ; physiopathology ; Siblings

OBJECTIVETo construct the eukaryotic expression vector of human microdystrophin gene and observe its expression in rat mesenchymal stem cells (rMSCs) in vitro.

METHODSThe plasmid PBSK-MICRO containing human microdystrophin cDNA was digested by restriction endonuclease, and the resultant microdystrophin fragment was inserted into the NotI site of pcDNA3.1(+) to prepare the eukaryotic expression vector-pcDNA3.1(+)/ microdystrophin, which was identified by endonuclease digestion and sequencing. The recombinant plasmid was transfected into rMSCs via lipofectamine, and after G418 selection, the expression of microdystrophin was detected by RT-PCR and indirect immunofluorescence assay.

RESULTSMicrodystrophin gene fragment was correctly inserted into the plasmid pcDNA3.1(+), as conformed by sequencing and digestion with Not I and Hind III. The total mRNA of the transfected rMSCs was extracted and microdystrophin mRNA expression was found in the cells by RT-PCR. Indirect immunofluorescence assay for the protein expression of microdystrophin showed bright red fluorescence in the transfected rMSCs.

CONCLUSIONEukaryotic expression plasmid pcDNA3.1(+)/microdystrophin has been constructed successfully and microdystrophin can be expressed in transfected rMSCs in vitro, which may facilitate further research of Duchenne muscular dystrophy treatment by genetically modified allogeneic stem cell transplantation.

Animals ; Base Sequence ; Cells, Cultured ; Dystrophin ; biosynthesis ; genetics ; Fluorescent Antibody Technique, Indirect ; Gene Expression ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Molecular Sequence Data ; Peptide Fragments ; biosynthesis ; genetics ; Plasmids ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection

OBJECTIVETo evaluate the prognostic value of plasma brain natriuretic peptide (BNP) and C-reactive protein (CRP) in patients with acute coronary syndromes (ACS) underwent percutaneous coronary intervention (PCI).

METHODSPatients with ACS underwent PCI in our hospital from December 2004 to September 2005 were included in this study. Plasma BNP (n = 189) and CRP (n = 141) were measured at a median of (34.2 +/- 16.3) hours from symptom onset, total mortality and the risk for major adverse cardiac events (MACE, including death, recurrent MI, recurrent angina, heart failure, readmission for any reason) at 30 days and at 3 months was analyzed.

RESULTSPatients were divided into 4 groups according to their BNP levels (BNP 100 ng/L to 300 ng/L to 600 ng/L) and the 3-month mortality was 0%, 1.4%, 7.7%, 48.3% and 3-month incidence of MACE was 7.9%, 17.1%, 57.7%, 79.3% respectively. Multivariate logistic regression analyses showed that the plasma BNP level predicted 30-day (r = 0.8515, P < 0.01) and 3-month (r = 0.9201, P < 0.01) mortality and 30-day (r = 0.7066, P < 0.01) and 3-month (r = 0.7090, P < 0.01) incidence of MACE independent of other known prognostic factors such as age, gender, family heredity, hypercholesterolemia diabetes, hypertension, smoking and LVEF. Patients were divided into 3 groups according to their CRP levels (CRP 8.0 mg/L to 32.0 mg/L) and 3-month mortality was 2.7%, 7.7% and 28.6% and 3-month incidence of MACE was 28.4%, 41.0% and 60.7% respectively. CRP predicted 30-day (r = 0.5882, P = 0.0044) and 3-month (r = 0.5235, P = 0.0038) mortality independent of traditional risk factors, and predicted 30-day (r = 0.2705, P = 0.0380) and 3-month (r = 0.2290, P = 0.0429) incidence of MACE after adjustment for patient age. CRP lost its predictive value after BNP was introduced into the model, while BNP was still an independent predictor for mortality and incidence of MACE at 30 days and 3 months in ACS patients underwent PCI.

CONCLUSIONBoth plasma BNP and CRP are good predictors for early mortality and MACE incidence in ACS patients underwent PCI.

Acute Coronary Syndrome ; blood ; diagnosis ; therapy ; Adult ; Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; C-Reactive Protein ; metabolism ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Predictive Value of Tests ; Prognosis

OBJECTIVETo detect the disease-causing point mutations in the dystrophin gene of Duchenne muscular dystrophy (DMD) patients.

METHODSThe approach of denaturing high performance liquid chromatography (DHPLC) coupling with sequencing was used to screen the point mutations of 79 exons and the untranslated regions of dystrophin gene without large deletions/duplications, which was in 6 unrelated DMD probands from 6 DMD families.

RESULTSFive disease-causing mutations, 697-698insGT, C616T, G1255T, C4279T, and C2302T, were ides created the new stop codons in downstream sites of mutations, respectively. In addition to the disease-causing point mutations, a point mutation T5586+61A in intron 39 was also found at patient 3, and a missense mutation A694T in exon 8 was detected at patient 5. Four point mutations, C2168+13T, 5740-13dupG, G5234A and C5280T, were also detected at patient 6 whose causative point mutation was unavailable. Seven point mutations have not been reported previously. Bi-directional PCR amplification of specific alleles (Bi-PASA) method was established to distinguish the haplotypes of heterozygote or homozygote in a single PCR reaction.

CONCLUSIONVia automated DHPLC screening or detecting the subexonic mutations in dystrophin gene is feasible to clinical laboratories, and also is a superior method in terms of sensitivity and efficiency.

Base Sequence ; Chromatography, High Pressure Liquid ; DNA Mutational Analysis ; Dystrophin ; genetics ; Gene Duplication ; Humans ; Male ; Muscular Dystrophy, Duchenne ; genetics ; Point Mutation ; Polymerase Chain Reaction ; Sequence Deletion