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 describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.
Child ; Female ; Male ; Humans ; High-Throughput Nucleotide Sequencing ; Neoplasm, Residual/genetics* ; Retrospective Studies ; Genomics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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 investigate the regulatory mechanisms of piwi-interacting RNA (piRNA) in bisphenol A (BPA)-induced prostate cancer cell invasion and migration. Methods: The Cancer Genome Atlas (TCGA) data was used to analyze and screen for piRNAs with significantly increased expression in prostate cancer tissues. PC-3 cells were treated with different concentrations of BPA for 12, 24, and 48 h, respectively, and the 20% inhibitory concentration (IC₂₀) was measured using a CCK-8 assay. The expression levels of piRNAs before and after BPA treatment were determined by reverse transcription-quantitative PCR. Target genes regulated by BPA and associated with prostate cancer were screened in the Comparative Toxicogenomics Database (CTD). Dual-luciferase reporter gene assay was performed to verify the relationship between piRNA and target genes, and the expression change of the piRNA target gene was detected by Western blotting. Cell migration and invasion assays were used to determine the effects of piRNA on the malignant phenotype of prostate cancer cells. Results: After treatment of PC-3 cells with 160 μmol/L BPA, the expression of piR-sno48 was most significantly increased (P<0.05). Transfection of piR-sno48 antagomir resulted in decreased expression of endogenous piR-sno48 and a significant increase in the expression of its target gene GSTP1 (P<0.05). However, the expression of GSTP1 did not change significantly in BPA-treated PC-3 cells after transfection with piR-sno48 antagomir (P>0.05). The dual-luciferase reporter gene confirmed that piR-sno48 inhibited the expression of GSTP1 by forming an inversely complementary sequence with the 3'-UTR of GSTP1. The Transwell assay results showed that treatment with BPA significantly increased the invasion and migration ability of prostate cancer cells (P<0.01), whereas piR-sno48 antagonists significantly inhibited the effects above (P<0.01). Conclusion: BPA promotes the invasion and migration of prostate cancer cells by upregulating the expression of piR-sno48 and suppressing the expression of GSTP1. Interfering with the expression of endogenous piR-sno48 may inhibit the malignant phenotype of prostate cancer cells caused by BPA.
Male ; Humans ; Prostate ; Piwi-Interacting RNA ; Antagomirs ; Prostatic Neoplasms/genetics*

Objective: To investigate the regulatory mechanisms of piwi-interacting RNA (piRNA) in bisphenol A (BPA)-induced prostate cancer cell invasion and migration. Methods: The Cancer Genome Atlas (TCGA) data was used to analyze and screen for piRNAs with significantly increased expression in prostate cancer tissues. PC-3 cells were treated with different concentrations of BPA for 12, 24, and 48 h, respectively, and the 20% inhibitory concentration (IC₂₀) was measured using a CCK-8 assay. The expression levels of piRNAs before and after BPA treatment were determined by reverse transcription-quantitative PCR. Target genes regulated by BPA and associated with prostate cancer were screened in the Comparative Toxicogenomics Database (CTD). Dual-luciferase reporter gene assay was performed to verify the relationship between piRNA and target genes, and the expression change of the piRNA target gene was detected by Western blotting. Cell migration and invasion assays were used to determine the effects of piRNA on the malignant phenotype of prostate cancer cells. Results: After treatment of PC-3 cells with 160 μmol/L BPA, the expression of piR-sno48 was most significantly increased (P<0.05). Transfection of piR-sno48 antagomir resulted in decreased expression of endogenous piR-sno48 and a significant increase in the expression of its target gene GSTP1 (P<0.05). However, the expression of GSTP1 did not change significantly in BPA-treated PC-3 cells after transfection with piR-sno48 antagomir (P>0.05). The dual-luciferase reporter gene confirmed that piR-sno48 inhibited the expression of GSTP1 by forming an inversely complementary sequence with the 3'-UTR of GSTP1. The Transwell assay results showed that treatment with BPA significantly increased the invasion and migration ability of prostate cancer cells (P<0.01), whereas piR-sno48 antagonists significantly inhibited the effects above (P<0.01). Conclusion: BPA promotes the invasion and migration of prostate cancer cells by upregulating the expression of piR-sno48 and suppressing the expression of GSTP1. Interfering with the expression of endogenous piR-sno48 may inhibit the malignant phenotype of prostate cancer cells caused by BPA.
Male ; Humans ; Prostate ; Piwi-Interacting RNA ; Antagomirs ; Prostatic Neoplasms/genetics*

Myelodysplastic syndromes (MDS) are a subset of myeloid malignancies defined by clonality of immature hematopoietic stem cells that leads to faulty blood cell development. These syndromes can lead to an increased risk of infection and may transform into acute myeloid leukemia, making it critical to determine effective treatments for the condition. While hypomethylating agents such as azacitidine and decitabine, as well as stem cell transplants, have been delineated as favored treatments for MDS, not all patients are physiologically receptive to these treatments. However, black raspberries (BRBs) have been shown to exert hypomethylating effects in various malignancies, with minimal adverse effects and thus a broader range of potential candidacies. This study aimed to investigate the potential of BRBs to exert such effects on MDS using Addition of Sex Combs Like/Tet Methylcytosine Dioxygenase 2 (Asxl1/Tet2) double knockout mice (Vav-cre Asxl1fl/fl Tet2fl/fl ), which typically manifest symptoms around 25 weeks of age, mirroring genetic mutations found in humans with MDS. Following a 12-week dietary supplementation of Vav-cre Asxl1fl/fl Tet2fl/fl mice with 5% BRBs, we observed both hyper- and hypomethylation at multiple transcription start sites and intragenic locations linked to critical pathways, including hematopoiesis. This methylation profile may have implications for delaying the onset of MDS, prompting a need for in-depth investigation. Our results emphasize the importance of exploring whether an extended BRB intervention can effectively alter MDS risk and elucidate the relationship between BRB-induced methylation changes, thus further unlocking the potential benefits of BRBs for MDS patients.

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cytarabine/therapeutic use* ; Daunorubicin/therapeutic use* ; Female ; Homoharringtonine/therapeutic use* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/genetics* ; Male ; Middle Aged ; Nuclear Proteins ; Prognosis ; Remission Induction ; Retrospective Studies ; Young Adult

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Cytarabine/therapeutic use* ; Hematopoietic Stem Cell Transplantation ; Humans ; Idarubicin/therapeutic use* ; Leukemia, Myeloid, Acute/drug therapy* ; Neutropenia ; Prospective Studies ; Recurrence ; Retrospective Studies

OBJECTIVE: To investigate the efficacy and safety of arsenic trioxide combined with ATRA and chemo- therapy for treatment of relapsed acute promyelocytic leukemia (APL) patients. METHODS: The clinic data of 25 patients with relapse APL treated in our hospital from 1996 to 2013 were collected and analyzed. Among the 25 patients, 15 patients suffered first-time hematological relapse (HR), and the other 10 patients showed first-time molecular relapse (MR). The patients with first-time replase were treated with ATO+ATRA+Anthracycline re-induction chemotherapy. The clinical features, complete remission (CR) rate, overall survival (OS), disease-free survival (DFS) and adverse events after re-induction therapy were analyzed. RESULTS: Fourteen of 15 hematological relapsed patients achieved the second-time hematological complete remission (CR2) after re-induction therapy except one patient died of bleeding complication during the re-induction. 8 of 14 patient showed molecular complete remission (CRm) after two cycles of therapy with this regimen. Totally, eleven out of the 14 HR patients were alive without disease till the last follow-up, and 3 of the 14 HR patients died because of bleeding complications. All of the 10 molecular relapsed patients received the second CRm after treated by the regimen. Among these 10 patients, 6 patients suffered only once relapse and continued with the molecular CR2 status, and for the other 4 patients with more than two-relapses, only 1 survived untill 89.3 months after achieved second-time CRm, and other 3 patients died because of bleeding complications. CONCLUSION For relapsed APL patients, the treatment with ATO+ATRA+chemotherapy regimen after relapse still shows encouraging efficacy, no matter whether or not the application of ATO in the previous regimens. In addition, patients with more than two molecular relapses show a poor prognosis.

Objective: To analyze the epidemic characteristics of enterovirus infection in Yueqing city from 2010 to 2018, and to provide reference for the prevention and control of hand, foot and mouth disease (HFMD) caused by enterovirus. Methods: Clinical data of HFMD cases caused by enterovirus infection during 2010 to 2018 were derived from the disease monitoring information report management system of Yueqing city. Descriptive epidemiological study was performed to analyze the characteristics of enterovirus infection by season, age, gender and region and the features of pathogens. Results: There were 53 178 patients with HFMD in total, including 75 severe cases and six deaths. Enterovirus infection occurred in every month of the years and peaked from April to July. Most of the cases were scattered children and nursery children under five years old and the incidence was higher in males than in females. From 2010 to 2018, the characteristics of enterovirus in Yueqing city had changed significantly. Enterovirus 71 (EV71) was the predominant pathogen during 2010 to 2014, but its detection rate had gradually decreased since 2013. In recent years, the incidence of HFMD caused by non-EV71 and non-coxsackievirus A16 (non-CVA16) enteroviruses significantly increased. Conclusions Enterovirus infection in Yueqing city was featured by significant seasonality and population-specific variation. Etiological detection should be strengthened. Comprehensive prevention and control measures should be taken to prevent the outbreak of HFMD during April to July.