A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer.

Bladder cancer (BLCA) is a common malignant tumor in urinary system all over the world. However, due to its high recurrence rate and complex causes, clinicians often have limited options for surgical and drug treatments. Recent researchs on the molecular mechanism of BLCA have reveals its biological progress and potential for early diagnosis. Serine hydroxymethyltransferase 1/2 (SHMT1/2) is a crucial enzyme in the one-carbon metabolism of tumor cells, and the expression levels of these isozymes have been found to be associated with the biological progression of various malignant tumors. However, the impact of SHMT1/2 on the biological progression of bladder cancer and its molecular regulation mechanism remain unclear. In this research utilizes BLCA clinical sample data, the TCGA database, and in vitro cell experiments to predict the expression levels of SHMT1/2 in BLCA. The findings indicate that SHMT1 remained unchanged, while SHMT2 expression is increased in BLCA, which was related to poor prognosis. Additionally, SHMT2 affects the growth, migration, and apoptosis of bladder cancer cells in vitro. It also influences the expression levels of E-cadherin and N-cadherin, ultimately impacting the malignant biological progression of bladder tumors. These results establish a correlation between SHMT2 and the malignant biological progression of BLCA, providing a theoretical basis for the early diagnosis and treatment of bladder cancer.

Efficacy, according to urodynamics, of OnabotulinumtoxinA compared with antimuscarinic drugs, for neurogenic detrusor overactivity: a systematic review and network meta-analysis.

To summarize the differences in urodynamic outcomes between oral antimuscarinic drugs and OnabotulinumtoxinA, and finding a therapy that maintains good urodynamics in neurogenic detrusor overactivity (NDO). We conducted a literature search of EMBASE and PubMed, with the language limited to English. In the analysis, all of the published randomized trials of OnabotulinumtoxinA or antimuscarinic drugs used to treat NDO were found and the results were finally obtained through Bayesian model analysis. A total of 12 RCTs and 2208 patients were included. OnabotulinumtoxinA 300U was superior to other drugs in terms of MCC, volume at IDC, and Pdetmax endpoints. OnabotulinumtoxinA 200U was more effective on the urodynamic endpoint of BC than other drugs or doses of OnabotulinumtoxinA. According to the MCC urodynamic results, oxybutynin, solifenacin 10 mg, and tolterodine 4 mg also had positive effects. OnabotulinumtoxinA 300U, 200U and 100U were better in improving the urodynamic results of NDO, and the current evidence also shows that selective injection of onabotulinumtoxinA can effectively improve the urodynamic results.

Integrative nomogram of intratumoral, peritumoral, and lymph node radiomic features for prediction of lymph node metastasis in cT1N0M0 lung adenocarcinomas.

Radiomics studies to predict lymph node (LN) metastasis has only focused on either primary tumor or LN alone. However, combining radiomics features from multiple sources may reflect multiple characteristic of the lesion thereby increasing the discriminative performance of the radiomic model. Therefore, the present study intends to evaluate the efficiency of integrative nomogram, created by combining clinical parameters and radiomics features extracted from gross tumor volume (GTV), peritumoral volume (PTV) and LN, for the preoperative prediction of LN metastasis in clinical cT1N0M0 adenocarcinoma. A primary cohort of 163 patients (training cohort, 113; and internal validation cohort, 50) and an external validation cohort of 53 patients with clinical stage cT1N0M0 were retrospectively included. Features were extracted from three regions of interests (ROIs): GTV; PTV (5.0 mm around the tumor) and LN on pre-operative contrast enhanced computed tomography (CT). LASSO logistic regression method was used to build radiomic signatures. Multivariable regression analysis was used to build a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. The discriminative performance of nomogram was validated both internally and externally. The radiomic signatures using the features of GTV, PTV and LN showed a good ability in predicting LN metastasis with an area under the curve (AUC) of 0.74 (95% CI 0.60-0.88), 0.72 (95% CI 0.57-0.87) and 0.64 (95% CI 0.48-0.80) respectively in external validation cohort. The integration of different signature together further increases the discriminatory ability: GTV + PTV (GPTV): AUC 0.75 (95% CI 0.61-0.89) and GPTV + LN: AUC 0.76 (95% CI 0.61-0.91) in external validation cohort. An integrative nomogram of clinical parameters and radiomic features demonstrated further increase in discriminatory ability with AUC of 0.79 (95% CI 0.66-0.93) in external validation cohort. The nomogram showed good calibration. Decision curve analysis demonstrated that the radiomic nomogram was clinically useful. The integration of information from clinical parameters along with CT radiomics information from GTV, PTV and LN was feasible and increases the predictive performance of the nomogram in predicting LN status in cT1N0M0 adenocarcinoma patients suggesting merit of information integration from multiple sources in building prediction model.

Prelamin A overexpression promotes detrusor calcification/aging in urinary incontinence via prelamin A accumulation.

Urinary incontinence (UI) is known as a distressing condition particularly among older adults, and negatively associated with health-related quality of life in both males and females. Prelamin A accumulation has been found in all progeroid laminopathies and is obviously linked to cell and organism aging. Therefore, this study was expected to investigate the effect of prelamin A on detrusor on UI. Prelamin A expression in clinical and animal samples was detected. To investigate the degree of prelamin A accumulation and detrusor calcification/aging, the detrusor cells were subcultured separately into low and high passage. The low-passage subculture cells were treated with transfection of overexpressed prelamin A plasmid, and transfection of overexpressed prelamin A plasmid and application of farnesyl transferase inhibitor (FTIs) H-9279, respectively. Zmpste24, Icmt and lamin A/C expression were detected to explore how prelamin A affected detrusor calcification/aging. Prelamin A was overexpressed in aged detrusor cells, indicating prelamin A expression was positively related to the age of subjects. The degree of prelamin A accumulation and detrusor calcification/aging was higher in aged rats and high passage subculture cells. Zmpste24, Icmt and lamin A/C were poorly expressed in cells transfected with overexpressed prelamin A, as well as cell proliferation activity decreased and calcium deposition and apoptotic rate increased. Furthermore, we also found that the effect of overexpressed prelamin A was lost when cells were treated with H-9279. These findings provide evidence that prelamin A overexpression impairs degradation of its farnesylated form, thus causing prelamin A accumulation which induces detrusor calcification/aging in UI.

MicroRNA-27a Suppresses Detrusor Fibrosis in Streptozotocin-Induced Diabetic Rats by Targeting PRKAA2 Through the TGF-ß1/Smad3 Signaling Pathway.

BACKGROUND/AIMS: We examined the effects of microRNA-27a (miR-27a) on detrusor fibrosis in streptozotocin (STZ)-induced diabetic rats. METHODS: Eighty healthy Sprague-Dawley (SD) rats were randomly allocated into control, diabetic, miR-27a mimics, mimics control, miR-27a inhibitors, inhibitors control, siRNA-PRKAA2 (siPRKAA2) and inhibitors + siPRKAA2 groups (the latter 7 groups were established as STZ-induced diabetic rat models and treated in different manners). Detrusor cell apoptosis in bladder tissues was determined through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining. Detrusor cells were assigned to the blank, miR-27a mimics, mimics control, miR-27a inhibitors, inhibitors control, siPRKAA2 and inhibitors + siPRKAA2 groups. Flow cytometry determined the cell cycle stage and apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting (WB) were used to assess the expression of miR-27a, PRKAA2, TGF-ß1, Smad3, p-Smad3, fibronectin (FN), connective tissue growth (CTGF), and collagen-I (COL-I) in tissues and cells. RESULTS: Compared with the control group, the diabetic, miR-27a mimics, and siPRKAA2 groups showed reduced weight and PRKAA2 expression, but elevated blood glucose, serum creatinine (sCr), blood urea nitrogen (BUN), cell apoptosis, and expression of TGF-ß1, Smad3, FN, COL-I, CTGF, and p-Smad3. The opposite trend was observed in the miR-27a inhibitors group. PRKAA2 is a target gene of miR-27a. Compared to the blank group, the miR-27a mimics and siPRKAA2 groups indicated markedly increased TGF-ß1, Smad3, FN, COL-I, CTGF and p-Smad3 expression; decreased PRKAA2 expression; and increased cell apoptosis. The miR-27a inhibitors group showed the opposite trend. CONCLUSION: These results indicate that miR-27a may contribute to detrusor fibrosis in STZ-induced diabetic rats by targeting PRKAA2 via the TGF-ß1/Smad3 signaling pathway.

Network meta-analysis of the efficacy and adverse effects of several treatments for advanced/metastatic prostate cancer.

This network meta-analysis was conducted to compare the efficacy and adverse effects of several treatments for advanced/metastatic prostate cancer (PC). The PubMed and Cochrane Library databases were searched for randomized controlled trials of treatments for advanced/metastatic PC. Eighteen studies covering 6,340 patients were included in this analysis. The calculated were odds ratios, 95% confidence intervals, and the surface under the cumulative ranking (SUCRA) curve. Pairwise meta-analysis showed that overall survival rates achieved with radiotherapy or endocrine therapy were lower than obtained with radiotherapy + endocrine therapy. The endocrine therapy includes estrogen therapy, luteinizing hormone-releasing hormone agonist (LHRH-A), anti-androgen therapy (ADT), ADT + LHRH-A and estrogen therapy + LHRH-A, and its SUCRA values indicated that for overall response rate, estrogen therapy + LHRH-A ranked the highest (92.6%); for overall survival rate, ADT ranked the highest (75.2%); for anemia, estrogen therapy ranked the highest (88.2%); and for diarrhea and hot flushes, ADT ranked the highest (diarrhea, 87.4%; hot flushes, 89.3%). Cluster analysis on the endocrine therapy showed that ADT + LHRH-A achieved the highest overall survival and overall response rates in the treatment of advanced/metastatic PC. Estrogen therapy and ADT had the lowest incidences of diarrhea and anemia. Thus, combined radiotherapy + endocrine therapy had higher overall survival rate, and among the endocrine therapy, in terms of overall response rate and overall survival rate, ADT + LHRH-A may be a better regimen in the treatment of advanced or metastatic PC.

MicroRNA-214 Affects Fibroblast Differentiation of Adipose-Derived Mesenchymal Stem Cells by Targeting Mitofusin-2 during Pelvic Floor Dysfunction in SD Rats with Birth Trauma.

BACKGROUND/AIMS: This study investigated whether microRNA-214 (miR-214) targets mitofusin-2 (Mfn2) in the process of fibroblast differentiation of adipose-derived mesenchymal stem cells (ADMSCs) during pelvic floor dysfunction (PFD) in Sprague Dawley (SD) rats with birth trauma. METHODS: The ADMSCs were isolated from 4-6 week male SD rats (n = 20) and were cultured and divided into the blank, miR-214 mimic negative control (NC), miR-214 mimic, miR-214 inhibitor NC, miR-214 inhibitor, empty vector, Mfn2 over-expression and miR-214 + Mfn2 over-expression groups. Fibroblast differentiation of ADMSCs was measured with immunocytochemistry and immunofluorescence methods. The expression of miR-214 and the mRNA and protein expression of Mfn2, FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ and Runx2 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. A dual-luciferase reporter assay was performed to confirm whether Mfn2 was the target gene of miR-214. RESULTS: During ADMSC differentiation into fibroblasts, miR-214 expression was up-regulated, but the expression of Mfn2 was down-regulated. Fibroblast differentiation of ADMSCs was promoted in the miR-214 mimic group but was inhibited in the miR-214 inhibitor and Mfn2 over-expression groups. The expression of Mfn2 was decreased, but the expression of FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ or Runx2 was increased in the miR-214 mimic group; the miR-214 inhibitor group and Mfn2 over-expression group exhibited the opposite results. Mfn2 was the target gene of miR-214. CONCLUSIONS: The study provided strong evidence that miR-214 could promote fibroblast differentiation of ADMSCs by down-regulating Mfn2 to improve PFD in SD rats with birth trauma.

Preoperative 3D and 4D-CT imaging using 640-Multislice CT (640-MSCT) in diagnosis of female urethral diverticulum.

OBJECTIVE: To determine the sensitivity and specificity of 640-Multislice CT (640-MSCT) in diagnosing the female UD. MATERIALS AND METHODS: We investigated 16 patients with symptomatic UDs preoperatively in our hospital from August 2010 to March 2016. The patients' average age was 38.8 years. All patients were performed 640-MSCT of pelvis; then, 3D and 4D images were reconstructed preoperatively. RESULTS: In 3D and 4D-CT images, out of 16 patients, thirteen patients had one ostium, two had 2 ostia and one had 3 ostia. Out of those thirteen patients, eight patients' ostia were located at 5 o'clock and five patients' at 7 o'clock. Patients with 2 ostia location were at 5 and 6 o'clock and 5 and 7 o'clock, respectively. Patients with 3 ostia location were at 5, 6 and 7 o'clock. The mean distance from the bladder neck to the ostia was 22.5 mm. The shape of UD was out-pouching in 11 patients (68.8%), U-shaped in four patients (25.0%) and circumferential in 1 patient (6.2%). The CT findings were confirmed by surgical findings. CONCLUSIONS: 640-MSCT is a useful tool in identifying UD's shape and ostium (including number, location) before operation. Preoperative 640-MSCT should be an adaptable modality for clinically suspected UD patients. ADVANCES IN KNOWLEDGE: Several imaging methods have been used to diagnose female UD. 640-MSCT may be more suitable to diagnose it for its higher sensitivity and specificity in diagnosis of female UD, especially in identifying UD's shape and number and location of ostium.

Chemical constituents from the leaves of Cyclocarya paliurus / 中成药

AIM To study the chemical constituents from the leaves of Cyclocarya paliurus (Batal.) lljinskaja.METHODS The ethyl acetate fraction of methanol extract from C.paliurus leaves was isolated and purified by silica,ODS and semi-preparative HPLC,then the structures of obtained compounds were identified by spectral data.RESULTS Eleven compounds were isolated and identified as (6S,7R,8R)-7α-[(β-glucopyranosyl) oxy] lyoniresinol (1),lyoniside (2),(-)-lyoniresinol 3 α-O-β-D-xylopyranoside (3),dihydrodehydrodiconiferyl alcohol 4'-O-β-D-glucoside (4),kaempferol-3-O-α-L-rhamnoside (5),kaempferol-3-O-α-L-(4"-Z-p-cumaroyl)-rhamnoside (6),naringenin (7),4'-hydroxywogonin (8),1-(3',4'-dihydroxyphenyl)-7-(4"-hydroxyphenyl)-4-hepten-3-one (9),grasshopper ketone (10),p-hydroxybenzoic acid (11).CONCLUSION Except for compounds 5,11,all the compounds are isolated from this plant for the first time.

Chemical constituents from the leaves of Cyclocarya paliurus / 中成药

AIM To study the chemical constituents from the leaves of Cyclocarya paliurus (Batal.) lljinskaja.METHODS The ethyl acetate fraction of methanol extract from C.paliurus leaves was isolated and purified by silica,ODS and semi-preparative HPLC,then the structures of obtained compounds were identified by spectral data.RESULTS Eleven compounds were isolated and identified as (6S,7R,8R)-7α-[(β-glucopyranosyl) oxy] lyoniresinol (1),lyoniside (2),(-)-lyoniresinol 3 α-O-β-D-xylopyranoside (3),dihydrodehydrodiconiferyl alcohol 4'-O-β-D-glucoside (4),kaempferol-3-O-α-L-rhamnoside (5),kaempferol-3-O-α-L-(4"-Z-p-cumaroyl)-rhamnoside (6),naringenin (7),4'-hydroxywogonin (8),1-(3',4'-dihydroxyphenyl)-7-(4"-hydroxyphenyl)-4-hepten-3-one (9),grasshopper ketone (10),p-hydroxybenzoic acid (11).CONCLUSION Except for compounds 5,11,all the compounds are isolated from this plant for the first time.