Objective : To analyze the expression and clinical significance of circ⁃RACGAP1 in bladder cancer tissues , and to explore the influence and mechanism of circ⁃RACGAP1 on the malignant biological behavior of bladder cancer cells. Methods : The expression of circ⁃RACGAP1 in bladder cancer tissues was explored through the TCGA database , and the relationship between the expression of circ⁃RACGAP1 and the clinicopathological features of bladder cancer patients was analyzed. The expression of circ⁃RACGAP1 in cell lines 5637 , T24 , J82 , RT⁃4 and UM⁃UC⁃3 was analyzed by quantitative real⁃time PCR (qPCR) . The circ⁃RACGAP1 knockdown plasmid was transfected into T24 cells by lipofection technology. Colony formation assay , scratch assay and Transwell assay were used to analyze the effects of knocking down circ⁃RACGAP1 on the proliferation , migration and invasion of T24 cells , respectively. The targeted binding between circ⁃RACGAP1 and miR⁃4324 was verified using deepBase , Circbank , CircInteractome , circRNABase databases and a fluorescent reporter system. The effect of knocking down circ⁃RACGAP1 on the expression of miR⁃4324 in T24 cells was detected by qPCR. Western blot was used to detect the effect of knocking down circ⁃RACGAP1 on the expression of recombinant rac⁃GTPase activating protein 1 (RACGAP1) protein and phosphatidylinositol⁃3 ⁃kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in T24 cells. Results circ⁃RACGAP1 was highly expressed in bladder cancer tissues (P < 0. 01) , and its expression increased with the clinical stage of the patients ( P < 0. 01) . The expression of circ⁃RACGAP1 in bladder cancer cell lines was significantly higher than that in normal human bladder epithelial cells ( all P < 0. 01) . Compared with the control group , the proliferation , migration and invasion abilities of T24 cells in the sh⁃circ⁃RAC⁃GAP1 group significantly decreased (all P < 0. 01) . circ⁃RACGAP1 could target and inhibit the expression of miR⁃4324 (P < 0. 01) . Compared with the control group , the expression level of RACGAP1 protein in T24 cells in the sh⁃circ⁃RACGAP1 group decreased (P < 0. 01) , and the expression levels of PI3K/AKT signaling pathway proteins phosphatidylinositol⁃3 ⁃kinase (p⁃PI3K) , phosphorylated protein kinase B (p⁃AKT) , nuclear factor kappa B (NF-κB) decreased (all P < 0. 01) . Conclusion circ⁃RACGAP1 is highly expressed in bladder cancer tissues and cell GAP1 plays a role by inhibiting the expression of miR⁃4324 and activating the PI3K/AKT signaling pathway.

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

Objective: To investigate the role of inflammatory biomarkers in the relationship between blood lead levels and blood pressure changes. Methods: A total of 9 910 people aged 18-79 years who participated in the China National Human Biomonitoring in 2017-2018 were included in this study. A self-made questionnaire was used to collect demographic characteristics, lifestyle and other information, and the data including height, weight and blood pressure were determined through physical examination. Blood and urinary samples were collected for the detection of blood lead and cadmium levels, urinary arsenic levels, white blood cells, neutrophils, lymphocytes, and hypersensitive C-reactive protein (hs-CRP). Weighted linear regression models were used to evaluate the associations between blood lead, inflammatory biomarkers and blood pressure. Mediation analysis was performed to investigate the role of inflammation in the relationship between blood lead levels and blood pressure changes. Results: The median (Q₁, Q₃) age of all participants was 45.4 (33.8, 58.4)years, including 4 984 males accounting for 50.3%. Multivariate logistic regression model analysis showed that after adjusting for age, gender, residence area, BMI, education level, smoking and drinking status, family history of hypertension, consumption frequency of rice, vegetables, and red meat, fasting blood glucose, total cholesterol, triglycerides, blood cadmium and urinary arsenic levels, there was a positive association between blood lead levels, inflammatory biomarkers and blood pressure (P<0.05). Each 2.71 μg/L (log-transformed) increase of the lead was associated with a 2.05 (95%CI: 0.58, 3.53) mmHg elevation in systolic blood pressure (SBP), 2.24 (95%CI: 1.34, 3.14) mmHg elevation in diastolic blood pressure (DBP), 0.25 (95%CI: 0.05, 0.46) mg/L elevation in hs-CRP, 0.16 (95%CI: 0.03, 0.29)×10⁹/L elevation in white blood cells, and 0.11 (95%CI: 0.02, 0.21)×10⁹/L elevation in lymphocytes, respectively. Mediation analysis showed that the levels of hs-CRP significantly mediated the association of blood lead with SBP, with a proportion about 3.88% (95%CI: 0.45%, 7.32%). The analysis also found that the levels of hs-CRP and neutrophils significantly mediated the association of blood lead with SBP, with a proportion about 4.10% (95%CI: 1.11%, 7.10%) and 2.42% (95%CI: 0.07%, 4.76%), respectively. Conclusion: This study suggests that inflammatory biomarkers could significantly mediate the association of blood lead levels and blood pressure changes.
Adult ; Male ; Humans ; Blood Pressure/physiology* ; C-Reactive Protein/analysis* ; Lead ; Arsenic/analysis* ; Cadmium ; Biomarkers ; Hypertension/epidemiology* ; China/epidemiology*

Objective:To explore the key points and implementation of establishing a whole-process clinical research management system.Methods:Based on the problems in practice, combined with project management experiences, this article analyzed the construction of the whole-process clinical research management system.Results:The establishment of the management system provides a comprehensive and sustainable safeguard for clinical research, as well as the improvement of efficiency and quality of clinical research.Conclusions:The establishment of an effective whole-process management system for clinical research project is a useful exploration of the research service model in China.

The chigger mite Leptotrombidium sialkotense is one of the 6 main vectors of scrub typhus in China. Before present study, L. sialkotense was found in some parts of Hunan province, China with a narrow geographical distribution. During field investigation 2016-2017, we found L. sialkotense in Jingha, southern Yunnan, China. Of 15 small mammal host species, L. sialkotense were collected from 6 species of the hosts. Rattus brunneusculus was a dominant host of L. sialkotense, from which 98.3% of the mites were collected. The chigger mite showed a relatively high infestation prevalence (PM=11.7%) and mean abundance (MA=0.5) in comparison with the rest 5 host species. These results reveal a certain host specificity of L. sialkotense to a rat R. brunneusculus. The mite L. sialkotense showed an aggregated distribution on the host (P<0.05). A positive correlation observed between L. sialkotense and the body length of hosts. There was a positive interspecific association between L. sialkotense and 2 other dominant vectors, L. deliense and L. scutellare.

Objective: To assess the feasibility and prognostic value of the minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in the newly diagnosed multiple myeloma (MM) patients of China. Methods: Clinical data of 106 consecutively newly diagnosed MM patients with MRD data were retrospectively analyzed in a single center in China from June 2013 to June 2015. Results: ① Of 106 patients, 48 (45.3%) achieved MRD negativity. The median time to MRD-negative was 3 months. More patients undergoing autologous stem cell transplantation (ASCT) achieved MRD negativity compared with non-ASCT patients (62.2% vs 36.2%, χ(2)=6.536, P=0.011). ② Of 48 patients in complete remission (CR), 7 (14.6%) was MRD positive, 5 of them showed disease progression (PD) during the follow-up, and 3 died. The median progression free survival (PFS) was 19 months, and the median overall survival (OS) was 28 months, both were significantly shorter than the CR patients with MRD-negative (P<0.05). ③At a median follow-up of 38 months, MRD-negative patients showed significantly superior outcomes compared with MRD positive ones, the PFS was not reach versus 17 months and the OS was not reach for both (P<0.001). Patients were grouped into 4 categories according to their MRD levels: 1% or higher, 0.1% to less than 1%, 0.01% to less than 0.1%, or negative. It showed that the outcomes (PFS and OS) tended to be improved along with the tumor depletion. ④ Multivariate prognostic analysis showed that MRD was a powerful independent prognostic factor for PFS[HR=0.133 (95% CI 0.062-0.288) , P<0.001] and OS[HR=0.156 (95% CI 0.050-0.484) , P=0.001]. According to MRD and cytogenetics, the patients were classified into 4 groups. High risk patients with MRD negative presented a significantly better outcome than high risk patients with MRD-positive, and a similar one to the standard risk patients with MRD-negative. Conclusions: MRD negativity by MFC was more popular in MM patients undergoing ASCT. MRD was an independent prognostic factor in MM. And the prognosis of MM patients can be stratified according to the level of MRD. MRD-negative patients with high risk cytogenetics presented a similar outcome to the standard risk ones. MRD by MFC should therefore be considered more widely applied in the clinic.
China ; Flow Cytometry ; Humans ; Multiple Myeloma ; Neoplasm, Residual ; Prognosis ; Retrospective Studies ; Treatment Outcome

Objective: To investigate the curative effect of hairy cell leukemia by clatabine. Methods: The clinical data of 24 patients with hairy cell leukemia treated by cladribine from November 2006 to October 2017 were analyzed retrospectively, then the curative effect and adverse drug reaction were analyzed. Results: ① A total of 24 patients including 22 male and 2 female, and the median age was 49.5 years (range 33 to 76) at diagnosis. There were 20 patients with of splenomegaly (4 patients with mild splenomegaly, 4 moderate splenomegaly, and 12 massive splenomegaly), 3 patients with enlargement of lymph nodes, and 1 patients who had undergone splenectomy. Five patients were pancytopenia, 15 were cytopenia in 2 lineages, and 4 patients were cytopenia only in one lineage. The median ratio of HCL cells detected by flow cytometry in bone marrow was 21.79% (0.69%-68.96%). BRAF mutation was detected in 15 patients by first generation or next generation sequencing technology. ② Among 24 patients, 20 were treated with cladribine alone (one course in 19 patients, 2 courses in 1 patient), and 4 patients were treated with cladribine combined with rituximab (one course in 3 patients, 2 courses in 1 patient). Excepting 5 patients whose follow-up time was not reaching 6 months, 19 patients were evaluated for efficacy in 6-12 months after treatment: 9 patients obtained CR, 9 obtained unconfirmed CR (Cru), the other 1 obtained PR, the CR/CRu rate was 94.7%, the overall response rate (ORR) was 100.0%. ③ All the 24 patients appeared 2-4 grade hematological adverse reactions after cladribine treatment, which were mainly grade 3/4 neutropenia (66.67%) and grade 3/4 thrombocytopenia (29.2%). All the adverse reactions were controlled or recovered spontaneously. ④ After the median follow-up time of 15 (3-133) months, no progression, recurrence or death occurred in the patients. Both median OS and PFS were not reached. Conclusion: This study suggests that treatment of HCL with cladribine has high response rate, controllable adverse reactions and the good prognosis.
Adult ; Aged ; Antineoplastic Agents/therapeutic use* ; Cladribine/therapeutic use* ; Female ; Humans ; Leukemia, Hairy Cell/drug therapy* ; Male ; Middle Aged ; Retrospective Studies ; Rituximab

Klinefelter syndrome (KS) is the set of symptoms that result from the presence of an extra X chromosome in males. Postnatal population-based KS screening will enable timely diagnosis of this common chromosomal disease, providing the opportunity for early intervention and therapy at the time point when they are most effective and may prevent later symptoms or complications. Therefore, through this study, we introduced a simple high-resolution melting (HRM) assay for KS screening and evaluated its clinical sensitivity and specificity in three medical centers using 1373 clinical blood samples. The HRM assay utilized a single primer pair to simultaneously amplify specific regions in zinc finger protein, X-linked (ZFX) and zinc finger protein, Y-linked (ZFY). In cases of KS, the ratios of ZFX/ZFY are altered compared to those in normal males. As a result, the specific melting profiles differ and can be differentiated during data analysis. This HRM assay displayed high analytical specificity over a wide range of template DNA amounts (5 ng-50 ng) and reproducibility, high resolution for detecting KS mosaicism, and high clinical sensitivity (100%) and specificity (98.1%). Moreover, the HRM assay was rapid (2 h per run), inexpensive (0.2 USD per sample), easy to perform and automatic, and compatible with both whole blood samples and dried blood spots. Therefore, this HRM assay is an ideal postnatal population-based KS screening tool that can be used for different age groups.
DNA/genetics* ; Dried Blood Spot Testing ; Humans ; Infant ; Infant, Newborn ; Karyotyping ; Klinefelter Syndrome/diagnosis* ; Kruppel-Like Transcription Factors/genetics* ; Male ; Mass Screening/methods* ; Polymerase Chain Reaction ; Reproducibility of Results ; Sensitivity and Specificity

Our study aims to investigate the roles that microRNA-214 (miR-214) plays in the epithelial mesenchymal transition (EMT) process and the development of interstitial cystitis (IC) in postmenopausal women by targeting Mitofusin 2 (Mfn2). IC bladder tissues and adjacent normal bladder tissues were collected from postmenopausal women. Immunohistochemistry (IHC) staining was conducted. The target relationship between miR-214 and Mfn2 was determined by a dual luciferase reporter gene assay. Adipose-derived mesenchymal stem cells (ADMSCs) were extracted from postmenopausal rats and assigned to the blank, mimics, miR-214 inhibitors, mimics negative control (NC), inhibitors NC, Mfn2 siRNA, miR-214 inhibitors and Mfn2 siRNA groups. Exosomes secreted by transfected ADMSCs were instilled into the bladders of postmenopausal rats. The expression of miR-214 and Mfn2 mRNA and EMT markers was assessed by qRT-PCR and western blotting. It was confirmed that Mfn2 was the target gene of miR-214 in IC. Compared with the normal bladder tissues, miR-214 decreased, but Mfn2 increased in IC bladder tissues. Compared with the blank group, the expression of miR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein increased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein decreased in the miR-214 mimics and Mfn2 groups. The expression of MiR-214 and the expression levels of N-cadherin, Fibronectin, Twist1, Snail and Vimentin mRNA and protein decreased, whereas the expression levels of Mfn2, E-cadherin and ZO-1 mRNA and protein increased in the miR-214 inhibitors group. Our findings indicate that the inhibition of miR-214 promotes the EMT process and contributes to bladder wall fibrosis by up-regulating Mfn2, thus leading to the occurrence of IC in postmenopausal women.
Animals ; Blotting, Western ; Cadherins ; Cystitis, Interstitial* ; Epithelial-Mesenchymal Transition ; Exosomes ; Female ; Fibronectins ; Fibrosis ; Genes, Reporter ; Humans ; Immunohistochemistry ; Luciferases ; Mesenchymal Stromal Cells ; Rats ; RNA, Messenger ; RNA, Small Interfering ; Snails ; Urinary Bladder ; Vimentin

Objective To evaluate the efficacy difference of different embolization agents in transcatheter embolization for treating massive hemoptysis caused by systemic pulmonary circulation shunt(SPS). Methods The clinical and imaging data in 98 patients with hemoptysis complicating SPS,including bronchodilator in 72 cases,pulmonary tuberculosis in 18 cases and lung carcinoma in 8 cases. All cases were treated with bronchial arterial embolization (BAE). According to different used embolization agents, the cases were divided into the gelfoam group and polyvinyl alcohol(PVA)grains embolization group. All cases were followed up at postoperative 1 d,1,3,6 months as well as 1,2 years. The data were analyzed by using Ridit test. Results Ninety-eight cases of massive hemoptysis were confirmed by DSA,among them,84 cases were complicating pulmonary artery fistula, 18 cases were pulmonary venous fistula and 2 cases were mixed fistula; 32 cases were simple BPS, 62 cases were pulmonary circulation fistula existed in the bronchial arteries and non-bronchial artery and 4 cases were simple non-BPS. The two groups had no complications such as embolism,paraplegia,esophagus-trachea fistula and skin ischemic necrosis. The follow up on postoperative 1 d, at postoperative 1, 3,6 months and at postoperative 1,2 years indicated that among 48 cases in the gelfoam group, 20 cases were cured, 18 cases were significantly effective,6 cases were effective and 4 cases were ineffective,the effective rate was 91.7 % ;among 50 cases in the PVA grain embolization group, 38 cases were cured, 8 cases were significantly effective,4 cases were effective and O case was ineffective, the effective rate was 100%. Moreove no severe complications such as ectopic embolism, paraplegia, esophagus-trachea fistula and skin ischemic necrosis occurred. The difference between the two groups had statistical significance by Ridit analysis. Conclusion Transcatheter embolization for treating massive hemoptysis caused by SPS is safe and reliable,has small trauma, using PVA grains embolization can reduce the long term recurrence rate of hemoptysis.