The responses of mesophilic and thermophilic anaerobic digestion of municipal sludge to periodic fluctuation disturbance of organic loading rate.

Fluctuation disturbance of organic loading rate (OLR) is common in actual anaerobic digestion (AD), but its effects on AD of municipal sludge gets little attention. This study investigated the responses of reactor performance and active microbial community in mesophilic and thermophilic AD of municipal sludge before, during and after OLR periodic fluctuation disturbance. The performance of both reactors were similar before and after disturbance although some parameter values changed during the disturbance, which indicated their enough buffer capacity to OLR periodic fluctuation. Different microbial community at RNA level was observed in the two reactors. When the OLR disturbance commenced, the microbial community changed greatly in thermophilic AD. Error and attack tolerance of the microbial network was analyzed in order to learn the response mechanisms to OLR disturbance. The results assisted that the thermophilic microbial community was more vulnerable, but the reactor performance of which could be maintained using the functional redundancy strategy under OLR fluctuation disturbance.

Survival nomogram for patients with bone metastatic renal cell carcinoma: A population-based study.

PURPOSE: Increased attention has been focused on the survival of renal cell carcinoma (RCC) patients with bone metastasis. This study proposed to establish and evaluate a nomogram for predicting the overall survival (OS) and cancer-specific survival (CSS) of RCC patients with bone metastasis. MATERIALS AND METHODS: RCC patients with bone metastasis between 2010 and 2015 were captured from the surveillance, epidemiology and end results (SEER) database. Univariate and multivariate cox regressions were performed to assess the effects of clinical variables on OS and CSS. The nomogram based on the Cox hazards regression model was developed. Concordance index (C-index) and calibration curve were performed to evaluate the accuracy of nomogram models, receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were conducted to assess the predict performance. RESULTS: A total of 2.471 eligible patients were enrolled in this study. The patients were assigned to primary (n=1.672) and validation (n=799) cohorts randomly. The 1-, 2-, and 3-year OS and CSS nomogram models were constructed based on age at diagnosis, sex, marital status, pathological grade, T-stage, N-stage, brain/liver/lung metastasis, surgery, radiotherapy and chemotherapy. The c for OS and CSS prediction was 0.730 (95% confidence interval [CI]: 0.719-0.741) and 0.714 (95%CI:0.702-0.726). The calibration curves showed significant agreement between nomogram models and actual observations. ROC and DCA indicated nomograms had better predict performance. CONCLUSIONS: The nomograms for predicting prognosis provided an accurate prediction of OS and CSS in RCC patients with bone metastasis, and contributed clinicians to optimize individualized treatment plans.

MLC1 Overexpression Inhibits Tumor Progression through PI3K/AKT Signal Pathway in Prostate Cancer.

Prostate cancer (PC) is a prevalent malignancy in males, characterized by high morbidity and mortality. Despite MLC1 being established as a key mediator in tumor progression, its role in PC remains unexplored. This study aims to validate MLC1's anti-tumor effects and uncover potential mechanisms. MLC1's clinical significance is assessed using data from The Cancer Genome Atlas and the Genotype-Tissue Expression databases. MLC1 expression is significantly reduced in PC samples compared with the adjacent normal tissues. MLC1 expression correlates negatively with tumor metastasis and positively with the survival of patients with PC. In vitro, up-regulating MLC1 effectively inhibits tumor progression by curtailing proliferation, infestation, and migration through the deactivation of the PI3K/AKT signaling pathway. Conversely, down-regulating MLC1 promotes PC progression, a phenomenon alleviated by the PI3K/AKT inhibitor, Gefitinib. Furthermore, the anti-tumor function of MLC1 is corroborated by a reduction in tumor volume compared with the negative control in vivo. This study confirms the anti-tumor effects of MLC1 via in vitro and in vivo experiments, demonstrating its potential mechanism of inhibiting the PI3K/AKT signaling pathway.

Succulent-Inspired Implicit Structural Change for Smart "ON/OFF" Switchable and Flexible EMI Shielding Coating.

Modern miniaturized intelligent electronics call for smart switchable and flexible electromagnetic interference (EMI) shielding material for highly precise applications. However, most switchable EMI shielding materials are based on an explicit structural change. Herein, we report a succulent-inspired smart switchable MXene (WR-MXene) coating film realized by inner implicit structural change, which benefits from the insertion of our reversible large-cavity yolk-shell biomicrospheres. The novel switchable yolk-shell biomicrospheres contain a soft N-isopropylacrylamide (PNIPAM) hydrogel core, an "ON/OFF" switchable cavity (over 30% volume fraction), and a porous polydopamine (p-PDA) shell. The yolk-shell biomicrospheres can be obtained by a facile two-step polymerization and a simple drying-dehydration treatment. Because of the "ON/OFF" switchable void space brought by the smart biomicrospheres and conductive framework of MXene, an optimized ultralight and flexible WR-MXene coating film (vWR-coating film) showed both large switchable change (over 60 dB) and extraordinary EMI shielding effectiveness, reaching 95 and over 50 dB in the whole X band (8.2-12.4 GHz). These novel reversible yolk-shell biomicrospheres and the succulent-inspired switchable coating films are promising for smart flexible wearable devices and many advanced multifunctional systems needing dynamic real-time response.

Involvement of basolateral amygdala-rostral anterior cingulate cortex in mechanical allodynia and anxiety-like behaviors and potential mechanisms of electroacupuncture.

AIMS: Chronic pain is highly associated with anxiety. Electroacupuncture (EA) is effective in relieving pain and anxiety. Currently, little is known about the neural mechanisms underlying the comorbidity of chronic pain and anxiety and the EA mechanism. This study investigated a potential neural circuit underlying the comorbid and EA mechanisms. METHODS: Spared nerve injury (SNI) surgery established the chronic neuropathic pain mouse model. The neural circuit was activated or inhibited using the chemogenetic method to explore the relationship between the neural circuit and mechanical allodynia and anxiety-like behaviors. EA combined with the chemogenetic method was used to explore whether the effects of EA were related to this neural circuit. RESULTS: EA attenuated mechanical allodynia and anxiety-like behaviors in SNI mice, which may be associated with the activity of CaMKII neurons in the basolateral amygdala (BLA). Inhibition of BLACaMKII-rACC induced mechanical allodynia and anxiety-like behaviors in sham mice. Activation of the BLACaMKII-rACC alleviated neuropathic pain and anxiety-like behaviors in SNI mice. The analgesic and anxiolytic effects of 2 Hz EA were antagonized by the inhibition of the BLACaMKII-rACC. CONCLUSION: BLACaMKII-rACC mediates mechanical allodynia and anxiety-like behaviors. The analgesic and anxiolytic effects of 2 Hz EA may be associated with the BLACaMKII-rACC.

High-Q Resonator-Inductor Using LiNbO3 Plate for Frequency Tuning in 1-5 GHz.

In this article, a new high quality factor ( Q ) inductor with piezoacoustic plate acoustic wave (PAW) resonators is presented. As indicated by the investigation of the acoustic wave propagation characteristics and transducer materials, the coupling coefficient ( k2 ) of the shear-horizontal plate (SH0) mode that propagates in the LiNbO3 plate increases to 55.7%, which leads to a wide inductive bandwidth of 29%. The longitudinal and transversal spurious modes are inhibited through novel edge reflector design and transducer engineering. The peak inductor quality factor ( [Formula: see text]) of the acoustic resonator-inductor is obtained as 347, and a large range of inductance values are achieved to be up to 49 nH by regulating the interdigital transducer (IDT) number of fingers (NF). It is noteworthy that a larger inductance is realized in a more miniaturized device. Furthermore, the wavelength-scaling-induced physics is investigated for frequency tuning in 1-5 GHz, which reveals the multifrequency ability on a single chip of the SH0 acoustic resonator-inductor.

High-Frequency and Spectrum-Clean Shear-Horizontal Acoustic Wave Resonators with AlN Overlay.

By bonding the sub-wavelength-thick lithium niobate (LiNbO3) layer to high-phase-velocity (vp) substrates, such as Si, the shear-horizontal (SH) modes no longer couple with the bulk modes leaking into substrates. As the propagation loss is no longer the major concern for these types of nonleaky SH wave devices, the YX-LiNbO3 with a low rotation angle providing ultra-large coupling coefficient (keff2) can be used. In addition, by overlaying a high-velocity layer such as AlN on top of LiNbO3/Si, the vp of the SH wave can be significantly enhanced at a small cost of keff2. By a careful design of the stack, both the wide-band spurious (Lamb wave) and near-band spurious (Rayleigh wave) are suppressed successfully. This paper focuses on the design of layered substrate not only to optimize its resonance characteristics-series frequency (fs), quality factor (Q), keff2, and temperature coefficient of frequency (TCF)-but also for eliminating the out-of-band spurious responses. The optimized substrate design demonstrates the minimal propagation loss, high fs of 3 GHz, large keff2 of 14.4% and a spurious-free response at 0-6 GHz. These novel nonleaky SH wave devices can potentially enable the low loss and wideband processing functions, which is promising for the 5G/6G radio frequency (RF) communication systems.

The non-contact-based determination of the membrane permeability to water and dimethyl sulfoxide of cells virtually trapped in a self-induced micro-vortex.

The cell-membrane permeabilities of a cell type toward water (Lp) and cryoprotective agents (Ps) provide crucial cellular information for achieving optimal cryopreservation in the biobanking industry. In this work, cell membrane permeability was successfully determined via directly visualizing the transient profile of the cell volume change in response to a sudden osmotic gradient instantaneously applied between the intracellular and extracellular environments. A new micro-vortex system was developed to virtually trap the cells of interest in flow-driven hydrodynamic circulation passively formed at the expansion region in a microfluidic channel, where trapped cells remain in suspension and flow with the streamline of the localized vortex, involving no physical contact between cells and the device structure; furthermore, this supports a pragmatic assumption of 100% sphericity and allows for the calculation of the active surface area of the cell membrane for estimating the actual cell volume from two-dimensional images. For an acute T-cell lymphoma cell line (Jurkat), moderately higher values (Lp = 0.34 µm min-1 atm-1 for a binary system, and Lp = 0.16 µm min-1 atm-1 and Ps = 0.55 × 10-3 cm min-1 for a ternary system) were measured than those obtained from prior methods utilizing contact-based cell-trapping techniques, manifesting the influence of physical contact on accuracy during the determination of cell membrane permeability.

Electro-Acupuncture for Bladder Pain Syndrome: A Protocol of a Randomized Controlled Trial and Study for Central Mechanism.

Objective: The efficacy of conventional treatments for treating bladder pain syndrome (BPS) remains unsatisfactory. Electro-acupuncture (EA) is one of the complementary treatments with great analgesic effect and minimal side effect, but evidence of the efficacy of EA on BPS is limited. Thus, this study aims to investigate the efficacy and safety of EA for treating BPS and study on central mechanism of patients with BPS. Methods/Design: The study is a randomized controlled and assessor-blinded design trial. A total of 84 participants will be randomly assigned to medication group (n=21), EA group (n=42) and sham electro-acupuncture (SA) group (n=21) in a 1:2:1 allocation ratio. This trial will include baseline period, 4-week treatment period and 4-week follow-up period. Participants in medication group will undergo treatment of amitriptyline for a period of 4 weeks. Participants in EA and SA groups will receive a 30 min EA or SA treatment for a total of 12 sessions over 4 weeks. The primary outcome is the Visual Analog Scale (VAS). The secondary outcomes include the O'Leary-Sant questionnaire, 24-hour voiding diary, Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and functional magnetic resonance imaging (fMRI). The VAS will be collected at baseline, week 2, week 4, and week 8 after randomization. The O'Leary-Sant questionnaire, HAMA and HAMD will be assessed at baseline, week 4 and week 8 after randomization. The 24-hour voiding diary will be assessed every single day. The fMRI data will be collected at baseline and week 4. Discussion: The results will provide evidence on the efficacy and safety of EA in the management of BPS and investigate the central mechanism of EA in treating patients with BPS. Trial Registration: ClinicalTrials.gov identifier: NCT05279963. Registered on 15 March 2022.

Current status of research on exosomes in general, and for the diagnosis and treatment of kidney cancer in particular.

Kidney cancer is a common urological tumour. Owing to its high prevalence and mortality rate, it is the third most malignant tumour of the urinary system, followed by prostate and bladder cancers. It exerts a high degree of malignancy, and most of the distant metastasis occurs at an early stage; it is insensitive to chemoradiotherapy and easily develops drug resistance. The current treatment for kidney cancer mainly includes surgery, interventional embolization and targeted therapy; however, the treatment efficacy is poor. In recent years, the role of exosomes as mediators of intercellular communication and information exchange in the tumour microenvironment in tumour pathogenesis has attracted much attention. Exosomes are rich in bioactive substances such as nucleic acids, proteins and lipids and are involved in angiogenesis, immune regulation, drug resistance, formation of pre-metastatic niche, invasion and metastasis. This article reviews the ongoing research and applications of exosomes for the diagnosis and treatment of kidney cancer.

LINC01451 drives epithelial-mesenchymal transition and progression in bladder cancer cells via LIN28/TGF-ß/Smad pathway.

BACKGROUND: The pathogenesis of bladder cancer (BLCa) is still unclear. Long non-coding RNAs (lncRNAs) participate in diverse biological processes across every branch of life, especially in cancer. Dysregulated lncRNAs in BLCa and their biological significance require further investigations. METHODS: Herein, a differential expression profile of lncRNAs in BLCa was conducted by microarray data. The expression level of lncRNA LINC01451 in 70 pairs of BLCa tissue samples and different BLCa cell lines were analyzed via real-time quantitative PCR. The CRISPR-CAS9 technique was employed to establish the LINC01451 stably transfected cell lines. Loss-of-function, as well as gain-of-function assays were carried out to evaluate the effects of LINC01451 on cell proliferation, migration, and invasion. Patient-derived xenograft (PDX) mouse models were adopted in the in vivo experiments. Western blot, biotinylated RNA probe pull-down assay, fluorescence in situ hybridization, and immunohistochemistry were utilized to assess the underlying molecular mechanisms of LINC01451 in BLCa. RESULTS: LINC01451 was identified a novel functional lncRNA, whose expression level in BLCa tissues was significantly higher compared with the normal tissues. Furthermore, it was found that LINC01451 directly docked LIN28A and LIN28B, and promoted the proliferation, invasion, and metastasis of BLCa. Mechanistically, LINC0145 was shown to depend on LIN28A and LIN28B, facilitated epithelial-mesenchymal transition (EMT) through activating the TGF-ß/Smad signaling pathway, which subsequently aggravated BLCa progression. CONCLUSIONS: We demonstrates that LINC01451 drives EMT-induced BLCa progression by activating the LIN28/TGF-ß/Smad signaling pathway. Promisingly, LINC01451 acts as a prognostic biomarker and a novel therapeutic target for BLCa.

Study on the relationship between sex hormone changes and erectile dysfunction in patients with chronic prostatitis/chronic pelvic pain syndrome.

BACKGROUND: To investigate the relationship between serum sex hormones and erectile dysfunction (ED), changes in erectile function and sex hormones were studied in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: A total of 171 patients with CP/CPPS who met the inclusion criteria from January 2016 to June 2019 were retrospectively analyzed. The level of patient's testosterone (TT), estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), premature ejaculation diagnostic tool (PEDT) score and international index of erectile function (IIEF-5) score were separately observed and compared. RESULTS: Among 171 eligible patients, 131 (76.61%) cases were diagnosed as ED and 40 (23.39%) cases were normal. Between the ED and No-ED groups, the PRL and PEDT score were statistically significant (P<0.01) based on the test results. ED-dependent and PEDT-dependent receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) were performed on different degrees of ED to determine the predictive performance and clinical applicability. The results showed that PRL can better predict the possibility of ED in CP/CPPS patients than PEDT. CONCLUSIONS: For CP/CPPS patients, the Prolactin level decreases as the degree of ED increases. Prolactin can be used as a predictor to better predict the possibility of ED in CP/CPPS patients.

Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index in Patients With Renal Cell Carcinoma Undergoing Laparoscopic Nephrectomy: A Multi-Institutional, Propensity Score Matching Cohort Study.

BACKGROUND: We conducted a multi-institutional clinical study to assess the prognostic value of the advanced lung cancer inflammatory index (ALI) and modified ALI (mALI) in patients with renal cell carcinoma (RCC). METHODS: We collected 440 patients who underwent laparoscopic nephrectomy at three centers from 2014 to 2019. ALI was defined as body mass index (BMI) × serum albumin (ALB)/neutrophil-to-lymphocyte ratio (NLR) and mALI as L3 muscle index × ALB/NLR. Kaplan-Meier curves, receiver operating characteristic (ROC) curves and Cox survival analysis were used to assess the effect of ALI and mALI on overall survival (OS). In addition, we performed 1:1 propensity score matching (PSM) for the high mALI and low mALI groups to further explore the impact of mALI on survival in RCC patients. RESULTS: The optimal cut-off values for ALI and mALI were 40.6 and 83.0, respectively. Based on the cut-off values, we divided the patients into high ALI and low ALI groups, high mALI and low mALI groups. ALI and mALI were significantly associated with the AJCC stage, Fuhrman grade, T stage, and M stage. Low ALI (p = 0.002) or low mALI (p < 0.001) was associated with poorer prognosis. ROC curves showed that mALI was a better predictor of OS than ALI. Multivariate Cox regression analysis showed that low mALI (aHR = 2.22; 95% CI 1.19-4.13, p = 0.012) was an independent risk factor for OS in RCC patients who underwent nephrectomy, while ALI (aHR = 1.40; 95% CI 0.73-2.66, p = 0.309) was not significantly associated. Furthermore, after PSM analysis, we found that mALI remained an independent risk factor for OS (aHR = 2.88; 95% CI 1.33-6.26, p = 0.007) in patients with RCC. CONCLUSIONS: For RCC patients undergoing laparoscopic nephrectomy, low ALI and low mALI were associated with poor prognosis, and preoperative mALI can be used as a potential independent prognostic indicator for RCC patients.

Inflammation induced by lipopolysaccharide advanced androgen receptor expression and epithelial-mesenchymal transition progress in prostatitis and prostate cancer.

BACKGROUND: To explore the mechanism of prostatic inflammation on prostate cancer (PCa) by comparing the changes of prostate epithelial cells and PCa cells in an inflammatory environment. METHODS: First, immunohistochemistry (IHC) was used to compare the level of expression of TNF-α, IL-1ß, IL-6, and TGF-ß between benign prostatic hyperplasia (BPH), prostatitis, and PCa. Then primary prostate epithelial cells were sampled from patients who were suspected of PCa and had histological prostatitis (HP) confirmed by pathological biopsy. Lipopolysaccharide (LPS) or BAY11-7082 were used to investigate the change of androgen receptor (AR) and AR-mediated transcription, epithelial-mesenchymal transition (EMT) in primary prostate epithelial cells, and lymph node carcinoma of the prostate (LNCap) cells. RESULTS: TNF-α, IL-1ß, IL-6, and TGF-ß were significantly increased in HP and PCa compared with those in BPH patients. The proliferation of primary prostate epithelial cells and LNCap cells got the inflection point at LPS 10 µg/mL. In an inflammatory environment with 10 µg/mL LPS, both primary prostate epithelial cell and LNCap cell viability increased, and AR, AR-mediated transcription, and EMT processes were significantly increased. Inhibitors of NF-κB with 10 nM BAY11-7082 decreased AR, AR-mediated transcription, and EMT processes. CONCLUSIONS: NF-κB regulates AR expression and EMT in prostatitis and PCa, and NF-κB inhibitors may have potential therapeutic value.

A high monocyte-to-lymphocyte ratio predicts poor prognosis in patients with radical cystectomy for bladder cancer.

BACKGROUND: At present, it is well known that many hemogram parameters were related to the prognosis of a variety of cancers. Among them, monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have attracted more and more attention. The purpose of this study was to investigate the prognostic value of MLR, NLR, PLR, especially MLR, in patients with bladder cancer (BC) treated with radical cystectomy (RC). METHODS: Between January 2009 and October 2018, 203 BC patients who underwent RC participated in the survey, and various clinical and hematological parameters were recorded. The optimal cutoff of MLR, NLR and PLR were determined by X-tile software, and Cox regression analysis was performed to investigated the effect of MLR, NLR and PLR on the overall survival (OS) and disease-free survival (DFS). RESULTS: The optimal cutoff values of MLR, NLR and PLR were 0.54, 4.10 and 164.63, respectively. Patients with high MLR (>0.54) predicted shorter OS [hazard ratio (HR): 2.30; 95% confidence interval (CI): 1.36-3.89; P=0.002] and DFS (HR: 2.13; 95% CI: 1.21-3.75; P=0.009) compared with patients with low MLR (≤0.54). Multivariate Cox regression analysis showed that only MLR was an independent risk factor for OS and DFS in MLR, NLR and PLR. In addition, receiver operating characteristic (ROC) analysis showed that at most time points, the area under the curve (AUC) of MLR was greater than that of NLR and PLR used to predict OS and DFS. CONCLUSIONS: Our results show that MLR can be independently used as a poor prognostic factor for OS and DFS in BC patients with RC. The prognosis of BC patients after RC can be predicted by measuring the level of MLR.

Rare Epididymal-Derived Myoepithelial Carcinoma: A Case Report and Review of Literature.

Myoepithelial carcinoma (MC), also known as malignant myoepithelial neoplasm, is more common in the parotid glands of the head and neck. The main clinical manifestation is the growth of a nonspecific, painless mass at the primary site. We report the first case of MC derived from the epididymis. The current reports of non-parotid MC are still rare, and epididymal-derived MC has not been reported previously. Simultaneously, we explore the role of EWSR1 fusion as a predicting marker and further reveal the origin of MC to provide new ideas for its diagnosis and treatment.

Cost-effectiveness analysis of two kinds of bladder cancer urinary diversion: Studer versus Bricker.

BACKGROUND: The purpose of our study was to evaluated the cost-effectiveness of two bladder cancer (BCa) urinary diversions: Studer and Bricker. METHODS: The study included 44 patients with Studer and 40 patients with Bricker. Collected and analyzed the patient's basic characteristics, health care costs, and prognosis survival. The quality-adjusted life-year (QALY) were calculated and verified by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30, Version 3, Chinese version). Cost-effectiveness depends on the incremental cost per QALY. The incremental cost-effectiveness ratio (ICER) was determined using the cost/QALY. RESULTS: We found the average total cost of the Studer group was $7,173.7±1,390.8, and the Bricker group was $6,545.2±1,458.4. There were significant differences in hospitalization time, total hospitalization expenses, bed cost, comprehensive medical service charge and drugs cost (all P<0.05). The hospitalization time, total hospitalization expenses, bed cost, comprehensive medical service charge, surgical treatment cost and drugs cost in Studer group were higher than those in Bricker group, while there was no significant difference in postoperative complications between the two groups (P=0.858). The ICER of Studer group and Bricker group were $8,535.6±2,027.6/QALY and $11,158.2±2,944.9/QALY, respectively. The ICER of Studer group over Bricker group was $2,514.0/QALY. CONCLUSIONS: We found the Studer group had higher hospitalization time, total hospitalization expenses, bed cost, comprehensive medical service charge, surgical treatment cost, and drugs cost than the Bricker group, but the Studer group had a higher ICER than the Bricker group.

A comparative study of mesophilic and thermophilic anaerobic digestion of municipal sludge with high-solids content: Reactor performance and microbial community.

This study involved a comparison between mesophilic (MAD) and thermophilic anaerobic digestion (TAD) of municipal sludge with high (10%) solids content; the reactor performance and the response of total and active microbial communities to changes in sludge properties were monitored. Both TAD and MAD were stably maintained. TAD performed better than MAD in biogas production and volatile total solids reduction upon feeding sludge 1. TAD was slightly inhibited by ammonia, whereas the performance of MAD was improved when sludge 2 was used as the feedstock. Alpha- and beta-diversity analyses revealed significant differences in the microbial community based on DNA and RNA datasets, indicating that not all microbes function in AD. The active microbial community diversity and composition in MAD and TAD were also driven by sludge properties. Moreover, MAD showed significantly higher richness and diversity of the active microbial community compared with TAD, regardless of changes in sludge properties.

Characterization of cis-regulatory elements conferring mercury-induced interleukin-4 gene expression in rat mast cells: a role for signal transducer and activator of transcription 6 and TATA box binding sites.

We have previously shown that oxidative stress is involved in the pathogenesis of a mercuric chloride (HgCl(2))-induced, T helper type 2 (Th2)-driven autoimmune syndrome in Brown Norway (BN) rats. In the context of the syndrome, the oxidative stress-induced mast cell response seems to determine the development of the early phase of vasculitis, while oxidative stress-mediated interleukin (IL)-4 production may contribute to the subsequent Th2-driven autoimmune response. However, the molecular basis of IL-4 gene transcription induced by HgCl(2) in mast cells remains unknown. In the present study, we dissect the critical regulatory mechanisms in the IL-4 gene promoter in the rat mast cell line RBL-2H3. Immunoprecipitation provided evidence that treatment with HgCl(2) increased phosphorylation of signal transducer and activator of transcription 6 (STAT6). Transient transfection reporter analyses with a series of 5' end deletions of the IL-4 promoter produced evidence that STAT6 and TATA box binding sites are important in HgCl(2)-induced IL-4 gene expression. Subsequent elimination of one or both sites by site-directed mutagenesis significantly inhibited IL-4 promoter activity. Our results provide evidence that STAT6 and TATA box regulatory elements play an important role in HgCl(2)-induced IL-4 transcription in rat mast cells.

[Combination of tolterodine and tamsulosin for benign prostatic hyperplasia].

OBJECTIVE: Overactive bladder may coexist with bladder outlet obstruction induced by benign prostatic hyperplasia (BPH). This study aimed to evaluate the efficacy of the combined use of tolterodine and tamsulosin in the treatment of BPH accompanied by overactive bladder. METHODS: We selected 53 cases of clinically diagnosed BPH, and randomly assigned them to a tamsulosin group (n = 25) to receive 0.2 mg of tamsulosin once a day and a tamsulosin + tolterodine group (n = 28) to be treated with 0.2 mg of tamsulosin once a day plus 2 mg of tolterodine twice a day, both for 12 weeks. Before and after the treatment, we obtained the International Prostate Symptoms Score (IPSS), quality of life (QOL) score and Qmax, and recorded the adverse events. RESULTS: All the patients accomplished the 12-week treatment. The tamsulosin group showed a significant decrease in IPSS and QOL from 21.50 +/- 5.42 and 4.58 +/- 0.94 before the treatment to 14.80 +/- 4.21 and 2.78 +/- 0.91 after it (P < 0.05), but a significant increase in Qmax from (12.20 +/- 6.60) ml/s to (16.40 +/- 5.13) ml/s (P < 0.05). In the tamsulosin + tolterodine group, IPSS and QOL were decreased from 20.90 +/- 5.15 and 4.61 +/- 0.86 at the baseline to 14.90 +/- 5.32 and 2.12 +/- 0.87 after the medication (P < 0.05), Qmax was increased from (13.30 +/- 7.80) ml/s to (16.70 +/- 6.32) ml/s (P < 0.05), and the score on the urinary storage phase symptoms was reduced from 10.12 +/- 3.10 to 4.77 +/- 0.75 (P < 0.05). CONCLUSION: Tamsulosin could quickly relieve BPH-induced lower urinary tract symptoms (LUTS) , while the combined use of tolterodine and tamsulosin could even better alleviate the LUTS and improve the QOL of BPH patients.