Objective To investigate the effects of estrogen ( E2) on the resistance to anoikis and a possible role of extracellular signal-regulated kinse ( ERK)-focal adhesion kinse ( FAK) signaling in the effect of estrogen to under-stand its underlying mechanism .Methods Poly-Hema-coated culture of human breast cancer cell line MCF-7 was used to induce anoikis .Cells were treated with E2 and/or pretreated with MEK or FAK inhibitors .Western blot was used to assess the phosphorylation of ERK and FAK , trypan blue staining and cell counting were employed to evaluate cell viability , and Hoechst staining was used to check apoptosis .Results Suspension culture greatly re-duced cell survival (P<0.01), and exposure of MCF-7 cells to E2 (10 nmol/L) led to a significantly increased resistance to anoikis and survival ( P<0.05 ) as compared to DMSO .Meanwhile , E2 induced increased phospho-rylation of both ERK and FAK .Pharmacological inhibition of MEK with U 0126 ( 10 μmol/L ) reduced E2-in-creased cell survival by 57.48%(P<0.01) and E2-decreased anoikis;Treatment with FAK inhibitor (10μmol/L) attenuated E2-enhanced cell survival by 53.59% ( P<0.01 ) and E2-reduced apoptosis .Conclusions E2 con-tributes to the enhanced cell viability and increased resistance to anoikis in MCF-7 breast cancer cells , and ERK-FAK signaling may be involved in the E 2-stimulated survival during suspension culture of MCF-7 cells.

Objective To detect the expression levels of high mobility group box chromosomal protein 1 (HMGB1) and Th17 cells transcription factors, related cytokines in peripheral blood of rheumatoid arthritis (RA) patients and analyze the relations between HMGB1 and CRP, ESR, RF in RA patients. The other aim of this study is to identify the expression level of HMGBI and the relationship between HMGB1 and Th17 in RA patients. Methods The mRNA levels of HMGB1, RORyt, interleukin (IL)-17 in the peripheral blood mononuclear cells (PBMC) were determined by quantitative real-time PCR (QRT-PCR) from 80 patients with rheumatoid arthritis,including 32 RA patients in stable phase and 48 patients in active phase, and 50 healthy volunteers. The concentration of HMGB1, IL-23, IL-17 in plasma were detected by enzyme linked immunosorbent assay (ELISA), one-way ANOVA and Spearman's correleation were adopted for statistical analysis.Results The mRNAs of HMGBI, RORyt and IL-17 in RA patients were higher than that in healthy control group (P<0.05), especially in active RA patients [ HMGB 1 (0.424±0.262) pg/ml, RORγt (0.34±0.25) pg/ml,IL-17 (1.42±0.38) pg/ml,P<0.01 ] when compared with patients with stable disease. The concentration of HMGB1, IL-23 and IL-17 in the plasma of RA patients was higher than that of the healthy control group (P< 0.05), and was positively correlated with the expression levels of HMGB1, Th 17-associated factors and the level of CRP, ESR, RF in RA patients' plasma(P<0.05). Conclusion The HMGB1 and Thl7 cells levels are higher in active RA patients than those in patients with stable disease, arid there is significant positive correlation between them. Detection of peripheral HMGB1 and Thl7 cell-specific transcription factors or related cytokines can help to understand the development and progress of rheumatoid arthritis and provide clues for new treatment targets for RA.

Objective:To discover the clinical features of nocturnal enuresis (NE) in adults and to detect factors that correlated with the symptom severity.Methods:This cross-sectional study recruited NE subjects from September 2017 through December 2020. All patients had experienced enuresis at least once per week and with a symptom duration of 3 months or longer. Followed by documentation of history and medical records, three-day bladder diary was adopted to assess their voiding pattern, and urodynamic parameters were obtained to evaluate lower urinary tract function.Results:A total of 106 NE patients (43 male and 63 female) were identified. There is no statistical difference regarding the average age (men: 57.8±15.6 vs. women: 56.1±14.0, P>0.05) and BMI (men: 23.9±3.4 vs. women: 23.3±4.3, P>0.05) between men and women. Comorbidities are extremely common in NE patients (n=85, 80.2%), with the incidence rate higher in men compared to women [88.4% (38/43)vs. 74.6% (47/63), P<0.05]. Hypertension (n=58, 54.7%), hyperlipemia (n=41, 38.7%), diabetes mellitus (n=38, 35.8%), coronary heart disease (n=22, 20.8%) were the most frequently reported conditions. On bladder diaries, subjects were frequently manifested nocturnal polyuria (NP, 47/106, 44.3%), reduced nocturnal bladder capacity (NBC, 74/106, 69.8%), or combination of both(33/106, 31.3%). Urodynamic studies suggested that the incidence of reduce bladder compliance, detrusor overactivity (DO), stress incontinence, bladder outlet obstruction(BOO), detrusor underactivity(DU)and detrusor hyperreflexia with impaired contractility(DHIC)was 27.4%(29/106), 39.6%(42/106), 17.9%(19/106), 9.4%(10/106), 25.5%(27/106)and 15.1%(16/106), respectively. Women were more likely to suffer from stress urinary incontinence [2.3%(1/43) men vs. 28.6% (18/63) women, P<0.01], while men were prone to have bladder outlet obstruction [ 23.3%(10/43) men vs. 0 women, P<0.01]. Correlation analysis demonstrated that obesity( r=0.63, P<0.01), systemic comorbidities( r=0.40, P<0.01), presence of NP( r=0.50, P<0.01) and NP+ NBC( r=0.47, P<0.01), post-void residual( r=0.53, P<0.01), reduced compliance( r=0.21, P=0.04), DU( r=0.28, P<0.01), stress incontinence( r=0.42, P<0.01)and DHIC ( r=0.35, P<0.01)are positively correlated with NE severity. Whereas, reduced Q max( r=-0.35, P<0.01), low capacity( r=0.21, P=0.03), and reduced bladder sensation( r=-0.21, P=0.03) correlate negatively with NE severity. Conclusions:The presence of NE is not only a sign of bladder dysfunction, but also an implication of obesity, systematic chronic diseases, urine production malfunctioning. Therefore, a thorough history regarding the lower urinary tract function and systemic comorbidities should be taken carefully, so that, an integrated and personalized treatment can be carried out.

Objective:To investigate the safety and effectiveness of tension adjustment technique using anatomical landmarks during retropubic midurethral synthetic sling.Methods:The data of 36 consecutive female patients with urinary incontinence, who had underwent retropubic midurethral synthetic sling procedure from January to August 2019 were analyzed retrospectively. The mean age was (60.83±7.93) years old and the body mass index was (24.43±2.44) kg/m 2. Among the recruited subjects, 36 had positive stress test and Marshall-Marchetti test. 20 (55.6%) were pure stress urinary incontinence, and 16 (44.4%) were mixed urinary incontinence. The severity of incontinence was classified into mild (5 cases, 13.9%), moderate (14 cases, 38.9%), severe (13 cases, 36.1%) and very severe (4 cases, 11.1%) using one-hour pad tests. Urodynamics were performed in 17 cases, with 5 (29.4%) presented detrusor overactivity, 3 (17.7%) possessed intrinsic sphincter deficiency. For each case, the tension of the sling was adjusted based on the anatomical landmarks, i. e. using an angled clamp attached closely to the pubic symphysis ventrally and the tip parallel to the edge of hymen dorsally. All patients were catheter-free right after the procedure. The subjective and objective effectiveness, and safety (the rate of urinary retension after surgery and postvoid residual volume 3 months later) were evaluated.The subjective cure rate was was defined as complete leakage free or very mild leakage during excessive bladder filling and fierce cough. The subjective effectiveness was defined as over 50% improvement of the leakage symptom. The objective cure rate was defined as a negative stress test. Results:For all 36 patients, the median hospital stays was 8 (5-95)h. No bladder perforation or transfusion cases. All patients were catheter-free right after the procedure, with no incidence of urinary retention. 27 patients completed a 3-month follow-up, with 22 had post-void residual data, 23 had subjective effectiveness data and 23 had objective effectiveness data. The median post-void residual was 7.5 (5-64) ml, subjective cure rate was 91.3% (21/23), and objective cure rate was 95.7% (22/23). 8.7% (2/23) reported difficult urination alleviated without the necessity of clinical interference. No urethra erosion or vagina extrusion was found. At 2-year follow-up, 34 patients completed assessment by phone. The subjective cure rate was 91.2% (31/34), with only 2.9% (1/34) reported difficult urination. Besides, at 3-month follow-up, there was no difference regarding the subjective cure rate [100.0%(12/12) vs. 81.8%(9/11)]or objective cure rate [91.7%(11/12) vs. 100.0%(11/11)] between patients with stress and mixed incontinence. No difference was noted among patients with mild, moderate, severe and very severe leakage[75.0% (3/4) vs. 100.0%(6/6) vs. 90.0%(9/10) vs. 100.0%(3/3)]. Of the 12 cases with urodynamic records, the presence of detrusor overactivity [66.7%(2/3) vs. 88.9%(8/9)] or intrinsic sphincter deficiency [0(0/1) vs. 90.9%(10/11)] did not significantly affected the cure rate of the procedure. At 2-year follow-up, there was no difference regarding the subjective cure rate between patients with stress and mixed incontinence [94.7%(18/19) vs. 86.7%(13/15)]. No difference was also noted among patients with mild, moderate, severe and very severe leakage[80.0%(4/5) vs. 100.0%(13/13) vs. 83.3%(10/12) vs. 100.0%(4/4)]. Of the 16 cases with urodynamic records, the presence of detrusor overactivity [60.0%(3/5) vs. 90.9%(10/11)]or intrinsic sphincter deficiency [66.7%(2/3) vs. 84.6%(11/13)]did not significantly affected the cure rate of the procedure.Conclusions:Tension adjustment using anatomic landmarks during sling procedure is safe and feasible for urinary incontinence, with minimum complications and residual volume, and high subjective/objective cure rate.

Objective To explore the efficacy of retropubic midurethral synthetic sling(RMUS)in relieving urgency and urge urinary incontinence(UUI)symptoms in patients with mixed urinary incontinence(MUI).Methods Clinical data of 44 female MUI patients treated with RMUS during Jan.2018 and Dec.2020 in Shanghai Renji Hospital were retrospectively analyzed.All patients had positive results in stress test and Marshall-Marchetti test before operation,and 27 of them completed ICIQ-FLUTS-LF questionnaire.Urodynamic(UDS)tests suggested that 9 patients(20.5％)presented detrusor overactivity(DO).During RMUS procedure,the tension of the sling was adjusted based on the anatomical landmarks.The postoperative efficacy and improvement of urinary incontinence were analyzed.Results The patients aged(58.59±9.08)years,with a body mass index of 24.71±2.77.Among the 40 patients who completed telephone interview 2 years after surgery,the subjective cure rate was 85.0％(34/40).Among the 27 patients with records of questionnaires before and after surgery,there were significant differences in the incidence of urine leakage[100％(27/27)vs.18.5％(5/27)],stress urinary incontinence(SUI)[100％(27/27)vs.18.5％(5/27)]and UUI[70.4％(19/27)vs.29.6％(8/27)](P＜0.05).However,no statistical differences were found regarding nocturia voiding episode(≥1 times),urgency,dysuria,hesitancy,strain to void,intermittent stream and enuresis(P＞0.05).Based on preoperative UDS test,there were significant differences regarding the subjective cure rate in patients with or without preoperative DO[55.6％(5/9)vs.93.5％(29/31)],incidence of SUI[66.7％(4/6)vs.4.8％(1/21)],and UUI[66.7％(4/6)vs.19.0％(4/21)](P＜0.05),while there was no statistical difference regarding urgency[66.7％(4/6)vs.33.3％(7/21)](P＞0.05).Conclusion RMUS is effective in treating MUI patients with positive stress test and Marshall-Marchetti test results,which can relieve SUI and UUI symptoms,but has no effects on urgency symptoms.DO on preoperative urodynamics results in poorer subjective outcomes.

Objective To screen and verify the genes that play key role in the occurrence and development of esophageal cancer by u-sing bioinformatics and real-time fluorescence quantitative PCR(qRT-PCR)methods to find new markers for diagnosis of esophageal cancer(ESCA).Methods Using the TCGA database and Wayne plot analysis,the cross genes between the differentially expressed genes of ESCA and the genes which have the most significant impacts on disease-free survival(DFS)rate in esophageal cancer patients were preliminarily identified.Following conducting protein-protein interaction(PPI)network analysis on the overlapping genes,GO and KEGG functional analysis was performed to screen the potential key genes as the diagnostic markers of esophageal cancer.qRT-PCR was used to quantitatively analyze the expression of mRNA of the key gene in peripheral blood.Statistical analysis was con-ducted based on the clinico-pathological characteristics of the patients to determine its potential value as a new diagnostic marker for e-sophageal cancer.Results After overlapping of differentially expressed genes of ESCA and disease-free survival genes in the TCGA database,39 upregulated genes and 20 downregulated genes were found to be differentially expressed,all of which affected disease-free survival rate.After conducting PPI network analysis,15 upregulated genes with core interactions were identified,and the downregulat-ed genes did not form any interaction network.Further enrichment analysis of these 15 core interacting genes through GO and KEGG,revealed that fibronectin 1(FN1)may be a potential biomarker for ESCA diagnosis.The qRT-PCR results showed that compared with the healthy control group,the mRNA expression level of FN1 in the peripheral blood of esophageal cancer patients was significantly ele-vated.After analyzing the clinical characteristics of patients,it was found that the patients with poor differentiation and high clinico-pathological staging had significantly increased peripheral blood FN1 mRNA levels.The model with FN1 mRNA expression levels can distinguish esophageal cancer patients from healthy individuals.Conclusion FN1 mRNA may be a potential non-invasive diagnostic biomarker for esophageal cancer.

[Objective] To explore the application of pelvic floor ultrasonography in the treatment of mixed urinary incontinence (MUI) by transvaginal retropubic midurethral synthetic sling (RMUS), in order to understand the relationship between the morphological changes of pelvic floor structures and the efficacy of RMUS. [Methods] Clinical data of 44 female MUI patients undergoing RMUS during Jan.2018 and Dec.2020 were retrospectively analyzed.Urodynamics detected detrusor overactivity (DO) in 9 cases (20.5%). During RMUS procedure, the tension of the sling was adjusted based on the anatomical landmarks. The changes of ultrasonic parameters before and after operation, the relationship between the ultrasonic results, surgical efficacy and urodynamic results were analyzed. [Results] The patients averaged (58.59±9.08) years, with the body mass index being 24.71±2.77.The subjective cure rate was 91.3% (21/23) 3 months after surgery, and 85.0% (34/40) 2 years after surgery.Pelvic floor ultrasonography showed significant differences in posterior urethravesical angel at rest and during Valsalva, bladder neck descent distance and the rate of urethral funneling during Valsalva (P<0.05). According to the group analysis of the preoperative ultrasonic results, there was no statistical significance in the subjective cure rate between the funneling group and the non-funneling group during Valsalva, and the bladder neck non downward group/mild downward group/moderate downward group/severe downward group during Valsalva 3 months and 2 years after surgery (P>0.05). At 3-month follow-up, all pre-RMUS urethral funneling during Valsalva disappeared in patients without preoperative DO.Comparatively, 50.0% (3/6) urethral funneling still presented in DO patients, who had a lower cure rate (55.6%, 5/9) at the 2-year follow-up. [Conclusion] RMUS can reduce the posterior urethravesical angel at rest and during Valsalva, reduce bladder neck descent distance and the rate of urethral funneling during Valsalva in MUI patients, which can enhance urinary continence.There seems to be a correlation between DO and urethral funneling during Valsalva, while RMUS may potentially reverse the two markers.