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In this paper, a room with four inlets located at the ceiling in the centre of the room with an exhaust installed at the bottom sidewall was modelled and investigated. The air is supplied through the individual room air inlets filtered by a high-efficiency particulate air filter, and the air is removed from the room via the exhaust located at the bottom sidewall. It leads to two possible inlet arrangements with four inlets: 1 × 4 array and 2 × 2 array. In the modelling, an obstacle is built to represent a workbench located underneath the inlets. Both the array designs are compared on their air flow and ability to remove gaseous contaminants. This study also suggests that the behaviour of the air jet impingement on the surface of the obstacle must also be considered in determining the design of the inlet array in a clean room.Practical application: This paper is intended to provide a practical guide to building service engineers on the design arrangement of inlets for a Class 7 clean room. By using the same concept, the design arrangement concept can be extended to the sizing of a workbench (i.e. the obstacle) when there is a fixed inlet design. [ABSTRACT FROM PUBLISHER]

Two general protocols for the regioselective electrochemically enabled sulfonylation cyclization of N -alkenylacrylamides with sodium sulfinates or sulfonyl hydrazides were described. These methods were carried out under mild, chemical oxidant-free, and transition-metal-free conditions with a broad substrate scope and good functional group tolerance to provide sulfonyl-containing 4-pyrrolin-2-ones, which is readily scalable to the gram scale.

Renal tubulointerstitial fibrosis (TIF) is considered as the final convergent pathway of diabetic nephropathy (DN) without effective therapies currently. MiRNAs play a key role in fibrotic diseases and become promising therapeutic targets for kidney diseases, while miRNA clusters, formed by the cluster arrangement of miRNAs on chromosomes, can regulate diverse biological functions alone or synergistically. In this study, we developed clustered miR-23a/27a/26a-loaded skeletal muscle satellite cells-derived exosomes (Exos) engineered with RVG peptide, and investigated their therapeutic efficacy in a murine model of DN. Firstly, we showed that miR-23a-3p, miR-26a-5p and miR-27a-3p were markedly decreased in serum samples of DN patients using miRNA sequencing. Meanwhile, we confirmed that miR-23a-3p, miR-26a-5p and miR-27a-3p were primarily located in proximal renal tubules and highly negatively correlated with TIF in db/db mice at 20 weeks of age. We then engineered RVG-miR-23a/27a/26a cluster loaded Exos derived from muscle satellite cells, which not only enhanced the stability of miR-23a/27a/26a cluster, but also efficiently delivered more miR-23a/27a/26a cluster homing to the injured kidney. More importantly, administration of RVG-miR-23a/27a/26a-Exos (100 μg, i.v., once a week for 8 weeks) significantly ameliorated tubular injury and TIF in db/db mice at 20 weeks of age. We revealed that miR-23a/27a/26a-Exos enhanced antifibrotic effects by repressing miRNA cluster-targeting Lpp simultaneously, as well as miR-27a-3p-targeting Zbtb20 and miR-26a-5p-targeting Klhl42, respectively. Knockdown of Lpp by injection of AAV-Lpp-RNAi effectively ameliorated the progression of TIF in DN mice. Taken together, we established a novel kidney-targeting Exo-based delivery system by manipulating the miRNA-23a/27a/26a cluster to ameliorate TIF in DN, thus providing a promising therapeutic strategy for DN., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: The cadherin-4 gene (CDH4), a member of the cadherin family genes, encodes R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. The function of CDH4 in OSCC (oral squamous cell carcinoma) is unknown., Materials and Methods: We use the Cancer Genome Atlas (TCGA) database to find the expression of CDH4 in OSCC is more than normal tissue. Our tissue samples also confirmed that CDH4 gene was highly expressed in OSCC. The related cell function assay detected that CDH4 promotes the ability of cell proliferation, migration, self-renewal and invasion. Cell staining experiment confirmed that the change of CDH4 expression would change the cell mortality. The western blot of GPX4 (glutathione-dependent peroxidase-4), GSH (reduced glutathione) test assay and MDA(Malondialdehyde) test assay show that the expression of CDH4 may resist the sensitivity of ferropotosis in OSCC., Results: CDH4 was upregulated in OSCC samples and was correlation with poor survival of patients. High expression of CDH4 effectively promotes the proliferation, mobility of OSCC cells and reduce the sensitivity of OSCC cells to ferroptosis. CDH4 is positively correlated with EMT pathway genes, negatively correlated with fatty acid metabolism pathway genes and peroxisome pathway genes, and positively correlated with ferroptosis suppressor genes in OSCC., Conclusions: These results indicate that CDH4 may play a positive role in tumor progression and resistance ferroptosis and may be a potential therapeutic target for OSCC., (© 2023. The Author(s).)

Background: Compromised intestinal barrier integrity can be independently driven by hyperglycemia, and both hyperglycemia and intestinal barrier injury are associated with poor prognosis in critical illness. This study investigated the intestinal barrier biomarkers in critically ill patients, to explore the role of compromised intestinal barrier integrity on the prognosis of critically ill patients with pre-existing hyperglycemia., Methods: This was a retrospective observational study. The relationships between intestinal barrier biomarkers and glycated hemoglobin A1c (HbA1c), fasting blood glucose (FBG), indicators of clinical characteristics, disease severity, and prognosis in critically ill patients were investigated. Then the metrics mentioned above were compared between survivors and non-survivors, the risk factors of 90-day mortality were investigated by logistic regression analysis. Further, patients were divided into HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group, metrics mentioned above were compared between these two groups., Results: A total of 109 patients with critical illness were included in the study. D-lactate and lipopolysaccharide (LPS) were associated with sequential organ failure assessment (SOFA) score and 90-day mortality. LPS was an independent risk factor of 90-day mortality. DAO, NEU (neutrophil) proportion, temperature, lactate were lower in HbA1c ≥ 6.5% Group while D-lactate, LPS, indicators of disease severity and prognosis showed no statistical difference between HbA1c < 6.5% Group and HbA1c ≥ 6.5% Group., Conclusions: Intestinal barrier integrity is associated with the disease severity and prognosis in critical illness. Compromised intestinal barrier integrity might be responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia., (© 2022. The Author(s).)

The human ocular surface hosts a paucibacterial resident microbiome and virome. The factors contributing to homeostasis of this mucosal community are presently unknown. To determine the impact of ocular enucleation and prosthesis placement on the ocular surface microbiome, we sampled conjunctival swabs from 20 anophthalmic and 20 fellow-eye intact conjunctiva. DNA was extracted and subjected to quantitative 16S rDNA PCR, biome representational karyotyping (BRiSK), and quantitative PCR (qPCR) confirmation of specific organisms. 16S ribosomal qPCR revealed equivalent bacterial loads between conditions. Biome representational in silico karyotyping (BRiSK) demonstrated comparable bacterial fauna between anophthalmic and intact conjunctiva. Both torque teno virus and Merkel cell polyoma virus (MCPyV) were detected frequently in healthy and anophthalmic conjunctiva. By qPCR, MCPyV was detected in 19/20 anophthalmic samples compared with 5/20 fellow eyes. MCPyV copy number averaged 891 copies/ng in anophthalmic conjunctiva compared with 193 copies/ng in fellow eyes (p < 0.001). These results suggest that enucleation and prosthesis placement affect the ocular surface flora, particularly for the resident virome. As MCPyV has been shown to be the etiologic cause of Merkel cell carcinoma, understanding the mechanisms by which the ocular surface regulates this virus may have clinical importance., (© 2021. The Author(s).)

Tongue squamous cell carcinoma (TSCC) is one of the most common cancers in the oral cavity. Notch signaling is frequently dysregulated in cancer. However, the role of Notch2 in TSCC is not well understood. The aim of this study was to investigate the effect of abnormal expression of Notch2 in TSCC. The expression of Notch2 was tested in 47 pairs of tissues from tongue cancer and normal samples by using immunohistochemical staining. Tongue cancer cells were transfected with siRNA or plasmid. The proliferation of the cells was tested by the CCK8 assay and colony formation assay. Subcutaneous tumor model was established to observe tumor growth. Transwell assay was used to detect the changes of cell migration and invasion ability. A humanized anti-Notch2 antibody was used to TSCC cells. We found that Notch2 was upregulated in tongue carcinoma tissues. Knocking down the expression of Notch2 by siRNA in the TSCC cell lines decreased proliferation ability both in vitro and in vivo. In addition, migration and invasion abilities were inhibited by knockdown of Notch2 in the TSCC cells. However, overexpression of Notch2 increased tongue cancer cell proliferation, invasion and migration. The humanized anti-Notch2 antibody inhibited TSCC cell growth. The results indicated that Notch2 is an oncogene in tongue squamous cell carcinoma and may become the target of a new approach for treating TSCC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Radical prostatectomy is a standard surgical strategy for prostate cancer though with a few postoperative complications such as urinary incontinence, erectile dysfunction and vesicle urethral anastomotic stricture. Post-prostatectomy incontinence, as a common complication seriously affecting the patient's quality of life, is mainly diagnosed according to the clinical symptoms and the results of urodynamic and imaging examinations. Patients with post-prostatectomy incontinence may undergo corresponding anatomic and functional changes, which can be clearly and directly observed in imaging examination. This review focuses on the advances in the imaging studies of post-prostatectomy urinary incontinence from the perspectives of MRI, ultrasound and cystourethrography.

Our previous study demonstrated a close relationship between the NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). Its receptor gene, NOTCH1, and its downstream gene, HES1, contribute to the proliferation, invasion and metastasis of SACC. Accumulating evidence supports HEY1 as another effector of the signaling pathway. The purpose of this study was to explore the effects of the NOTCH1-HEY1 pathway on the proliferation, invasion and metastasis of SACC cells. Our results verified that HEY1 is a specific molecular target of the NOTCH signaling pathway in SACC cells and that its expression in carcinoma is much higher than that in paracarcinoma tissues. The expression of NOTCH1 and HEY1 are positively correlated in the salivary adenoid cystic carcinoma tissues. NOTCH1 is significantly related to the activation of HEY1 in SACC, and that HEY1 reciprocally regulates NOTCH1 expression in SACC. HEY1 promotes cell proliferation and spheroid formation and inhibits cell apoptosis in vitro . In addition, HEY1 enhances the tumorigenicity of SACC in vivo . Furthermore, HEY1 increases cell invasion and metastasis by driving the expression of epithelial-mesenchymal transition (EMT)-related genes and MMPs. The results of this study indicate that the NOTCH1-HEY1 pathway is specifically upregulated in SACC and promotes cell proliferation, self-renewal, invasion, metastasis and the expression of EMT-related genes and MMPs. Our findings suggest that a NOTCH1-HEY1 pathway inhibitor might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To investigate the effect of intraoperative lithotomy position (LP) with a head-down tilt (HDT) on the absorption of intraoperative irrigation fluid in patients undergoing bipolar plasmakinetic resection of the prostate (PKRP)., Methods: Eighty BPH patients underwent PKRP, 40 in a conventional 0-degree position (0° LP) and the other 40 in a －10-degree HDT position (－10° LP), with 0.9% saline containing 1% ethanol as intraoperative irrigation fluid. We determined the alcohol concentration in the exhaled breath of the patients with a digital alcohol detector at the start of the operation and every 10 minutes afterwards. Meanwhile we recorded the operation time, the volume of intraoperative intravenous crystalloid infusion and the weight of the resected prostatic tissue, monitored the mean arterial pressure (MAP) and heart rate (HR) at 5 minutes before surgery, 30 minutes after the start of surgery and the end of surgery, and measured the concentrations of Na+, K+, Cl－ and Ca2+ with an arterial blood gas analyzer at 5 minutes before surgery and 1 hour after the start of surgery., Results: There were no statistically significant differences in age, height, body weight and prostate volume, or in intraoperative MAP and HR between the 0° LP and －10° LP groups. Compared with the baseline, at 1 hour after the start of PKRP, the patients in the 0° LP group showed significantly decreased concentrations of K+ (［3.64 ± 0.29］ vs ［3.49 ± 0.22］ mmol/L, P = 0.002) and Ca2+ (［1.16 ± 0.03］ vs ［1.13 ± 0.04］ mmol/L, P = 0.001), increased concentration of Cl－ (［106.9 ± 2.2］ vs ［108.7 ± 2.3］ mmol/L, P = 0.006), but no significant difference in the concentration of Na+ (［139.7 ± 1.5］ vs ［139.4 ± 1.6］ mmol/L, P = 0.231), while those in the －10° LP group exhibited remarkably decreased concentration of Ca2+ (［1.14 ± 0.04］ vs ［1.13 ± 0.04］ mmol/L, P = 0.016) but no statistically significant differences in the concentrations of Na+ (［140.3 ± 1.8］ vs ［140.0 ± 2.0］ mmol/L, P = 0.156), K+ (［3.49 ± 0.36］ vs ［3.47 ± 0.34］ mmol/L, P = 0.506) and Cl－ (［108.2 ± 2.6］ vs ［109.1 ± 2.5］ mmol/L, P = 0.071). Over 1 500 ml of intraoperative irrigation fluid absorption was observed in 6 cases (15%) in the 0° LP group as compared with 4 cases (10%) in the －10°LP group, with no significant difference between the two groups., Conclusions: Lithotomy position with a 10-degree head-down tilt can reduce PKRP-induced decrease in the concentration of K+ and increase in that of Cl－ without affecting the levels of the other electrolytes.

Purpose: The Notch signaling pathway plays an oncogenic role in tongue squamous cell carcinoma. The aim of this study was to inhibit the proliferation and self-renewal of tongue cancer cells by applying Notch signaling pathway inhibitor FLI-06 (Selleck, USA) and to lay a foundation for the clinically targeted treatment of tongue cancer for the future., Methods: The mRNA expression level of Notch1 and the overall survival rate of patients with tongue cancer were examined by analyzing the TCGA database. Tongue cancer cells were treated with FLI-06. Cell proliferation, apoptosis, and stem cell self-renewal ability were tested in appropriate ways. A xenograft mouse model was established to observe tumor growth., Results: From the TCGA data, we demonstrated that patients with high expression of Notch1 had a poor prognosis. We observed that the Notch signaling pathway inhibitor FLI-06 can restrain the activation of the Notch signaling pathway, decrease cell proliferation and induce cell apoptosis in vitro. The xenograft experiment indicated that intraperitoneal injection of FLI-06 inhibited tumor growth and increased cell apoptosis. FLI-06 suppressed both the mRNA and protein expression of Notch receptor and Notch targeted genes. We also observed that FLI-06 suppressed the proliferation of tongue cancer stem cells., Conclusion: FLI-06 can block the proliferation and self-renewal of tongue cancer cells. It is inferred that this compound, which inhibits the Notch signaling pathway, may serve as a potential targeted drug for the treatment of tongue cancer in the clinic., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Gan et al.)

Many studies have shown that FZD2 is significantly associated with tumor development and tumor metastasis. The purpose of the present study was to gain insight into the role of FZD2 in the cell proliferation and invasion of tongue squamous cell carcinoma. According to TCGA-HNSC dataset, among the 10 Frizzled receptors, FZD2 exhibited the highest degree of differential expression between cancer tissues and normal tissues, and the overall survival of patients with higher FZD2 levels was shown to be significantly shorter compared with those with lower FZD2 levels. The upregulation of FZD2 in clinical tongue cancer tissues was validated by real-time PCR. Knockdown of FZD2 inhibited the proliferation, migration and invasion of CAL-27 and TCA-8113 cells, whereas overexpression of FZD2 led to the opposite results. Further analysis revealed that FZD2 is positively correlated with WNT3A, WNT5B, WNT7A and WNT2 and is negatively correlated with WNT4. These results indicated that FZD2 may act as an oncogene in tongue squamous cell carcinoma. Therefore, FZD2 may be a target for the diagnosis, prognosis and gene therapy of tongue cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aims: To examine the protective effects of caffeine in rats with diabetes mellitus (DM) by using urodynamics., Methods: Female Sprague-Dawley rats (n = 24) were divided into four groups: control group, DM group, DM + caffeine (5 mg/kg/day), and DM + caffeine (10 mg/kg/day). DM was induced by streptozotocin (STZ). Cystometric studies were conducted on all rats. After 8 weeks of treatment with caffeine, the urodynamic parameters, including bladder capacity, residual urine volume, voiding time, and peak voiding pressure, were measured., Results: DM rats had a higher bladder capacity and post-void residual urine volume (PVR), an increased voiding time and peak voiding pressure, and a markedly lower voiding efficiency than the control group rats. After treatment with caffeine, bladder capacity, post-void residual urine volume, and peak voiding pressure were significant lower than those in the DM group, but voiding efficiency was markedly higher., Conclusion: The results suggested that caffeine (5 or 10 mg/kg/day) may improve the bladder function at 8 weeks after STZ induction. Thus, this may represent a potential strategy to increase voiding efficiency in diabetes., (© 2018 Wiley Periodicals, Inc.)

Objectives: The present work evaluated preventive effect of curcumin on cisplatin-induced bladder cystopathy., Methods: Fifteen female rats were divided into (i) Control group administered with physiological saline solution for 5 days; (ii) Cis-P group injected with cisplatin (6 mg/kg); and (iii) Cis-Cur group given cisplatin (6 mg/kg) with curcumin for 5 consecutive days. The function of bladder was measured by means of urodynamic analysis. Furthermore, hematoxylin-eosin staining and Masson trichrome staining were performed for morphological analysis. The cell apoptosis was evaluated through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and flow cytometry. The expression of nerve growth factor (NGF), NF-E2-related factor 2, and hemeoxygenase-1 (HO-1) levels were measured through Western blotting., Results: Urodynamic assay and histopathological manifestations revealed that curcumin ameliorated the bladder dysfunction induced by cisplatin. The level of cisplatin-induced apoptosis in the bladder decreased following curcumin treatment. Also, the increased protein expression of NGF indicated that the curcumin could offer neuroprotection for bladder against cisplatin. Curcumin also activated NRF2, and elevated the expression of HO-1, but curcumin could not rescue cisplatin-induced apoptosis in the cell lines with knockdown of NRF2., Conclusions: Taken together, the results of this paper showed that curcumin could ameliorate cisplatin-induced cystopathy and inhibit the apoptosis of bladder cell in cisplatin-treated rats. This may be attributed to curcumin's broad biological functions, particularly antioxidant effect, and to its ability to activate the NRF2 protein., (© 2018 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.)

Background: Our previous study demonstrated a close relationship between NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). HES1 is a well-known target gene of NOTCH signaling pathway. The purpose of the present study was to further explore the molecular mechanism of HES1 in SACC., Methods: Comparative transcriptome analyses by RNA-Sequencing (RNA-Seq) were employed to reveal NOTCH1 downstream gene in SACC cells. Immunohistochemical staining was used to detect the expression of HES1 in clinical samples. After HES1-siRNA transfected into SACC LM cells, the cell proliferation and cell apoptosis were tested by suitable methods; animal model was established to detect the change of growth ability of tumor. Transwell and wound healing assays were used to evaluate cell metastasis and invasion., Results: We found that HES1 was strongly linked to NOTCH signaling pathway in SACC cells. The immunohistochemical results implied the high expression of HES1 in cancerous tissues. The growth of SACC LM cells transfected with HES1-siRNAs was significantly suppressed in vitro and tumorigenicity in vivo by inducing cell apoptosis. After HES1 expression was silenced, the SACC LM cell metastasis and invasion ability was suppressed., Conclusions: The results of this study demonstrate that HES1 is a specific downstream gene of NOTCH1 and that it contributes to SACC proliferation, apoptosis and metastasis. Our findings serve as evidence indicating that HES1 may be useful as a clinical target in the treatment of SACC.

Objectives: Notch1 regulates tumor biology in a complex, context-dependent manner. The roles of Notch1 in tongue cancer are still controversial. The aim of this study is to investigate the roles of Notch1 in tongue cancer., Materials and Methods: The expression of Notch1 was tested between tongue cancer and normal samples by using immunohistochemistry. Tongue cancer cells were transfected with siRNA or plasmid, respectively. Cell proliferation, apoptosis, migration and invasion ability were tested in appropriate ways. The subcutaneous tumor model was established to observe the tumor growth., Results: Notch1 was upregulated in tongue carcinoma tissues and the expression of Notch1 was related with tumor stage and differentiation. Overexpression of Notch1 could increase tongue cancer cells proliferation, invasion and migration. But inhibited the expression of Notch1 could decrease cells proliferation, invasion and migration and promote cell apoptosis in vitro and in vivo., Conclusion: Our results prove that the oncogenic role of Notch1 in tongue cancer and provide the direction of targeted therapy of tongue cancer.

Previous studies have reported that inhibitor of DNA binding 1 (ID1) exerts an oncogenic role in a number of tumors. In the present study, the role of ID1 in the growth, invasion and migration of salivary adenoid cystic carcinoma (SACC) cells was investigated. ID1 expression in clinical SACC samples was compared with that in normal salivary tissues using immunohistochemical staining, and the correlation between ID1 expression and clinical pathological characteristics was then determined. Subsequently, ID1 was overexpressed or silenced to investigate the effects of ID1 expression on SACC cell proliferation, invasion and migration. In addition, the gene expression levels of known ID1 target genes, including S100A9, CDKN2A and matrix metalloproteinase 1 (MMP1) was measured using reverse transcription‑quantitative polymerase chain reaction to elucidate the potential mechanisms of ID1 in SACC. The results of the present study indicated that the protein expression levels of ID1 were significantly increased in the SACC tissues compared with that in the normal salivary tissues (P<0.001), and a positive correlation between ID1 expression and tumor stage (P=0.001), tumor invasion (P=0.002) and metastasis (P=0.019) in SACC was observed. Knockdown of ID1 in SACC cells significantly inhibited cell growth, invasion and migration (all P<0.01), whereas overexpression of ID1 promoted cell proliferation, invasion and migration (all P<0.01). The gene expression level of MMP1 was significantly reduced following ID1 knockdown in SACC‑83 cells when compared with negative controls (P<0.05), whereas S100A9 and CDKN2A expression levels were significantly upregulated (both P<0.05). The results suggest that ID1 may regulate the growth, invasion and migration of SACC cells, and that MMP1, S100A9 and CDKN2A may serve as target genes of ID1 and mediate the effects of ID1 in SACC cells. Therefore, ID1 may present a potential target gene for the treatment of patients with SACC to inhibit cancer cell growth and metastasis.

Rcan2 increases food intake and plays an important role in the development of age- and diet- induced obesity in male mice. However, in females, wild-type mice grow almost at a similar rate as Rcan2-/- mice on normal chow diet from 6 weeks of age. Here we showed that the ability of Rcan2 to promote weight gain was attenuated by energy expenditure mediated by 17β-estradiol in female mice. Using ovariectomy-operated models, we found that 17β-estradiol deprivation did not alter food intake, but induced more weight gain in wild-type mice than Rcan2-/- mice. If wild-type mice ingested equally as Rcan2-/- mice, in the same ovarian state they exhibited similar weight changes, but the mice in ovariectomized groups were significantly heavier than the ovarian-intact mice, suggesting that body weight is not only regulated by Rcan2, but also by 17β-estradiol. Furthermore, we demonstrated that Rcan2 and 17β-estradiol independently regulated body weight even on high-fat diets. Therefore, our findings indicate that Rcan2 and 17β-estradiol regulate body weight through different mechanisms. Rcan2 increases food intake, whereas 17β-estradiol promotes energy expenditure. These findings provide novel insights into the sexual dimorphism of body weight regulation.

Objective: To assess the clinical efficacy of the saw palmetto fruit extract (SPFE) in the treatment of lower urinary tract symptoms (LUTS) in patients with type ⅢA prostatitis., Methods: This retrospective study included 54 cases of type ⅢA prostatitis treated in the Outpatient Department of our hospital from January to December 2015. The patients were aged 35.06 ± 5.85 years, with a mean disease course of 3.8 ± 2.1 years, and all received oral medication of SPFE Capsules at the dose of 320 mg qd for 12 weeks. We assessed the therapeutic effects by comparing the NIH-chronic prostatitis symptom indexes (NIH-CPSI), voiding diary, International Prostate Symptom Scores (IPSS), and results of urodynamic examination before and after treatment., Results: Compared with the baseline, both NIH-CPSI and IPSS were significantly decreased after medication (27.61 ± 3.76 vs 18.6 ± 5.34, P <0.01; 20.44 ± 4.51 vs 10.96±4.62, P <0.01), and urodynamic examination and voiding diary showed dramatic post-medication improvement in the average urinary flow rate (［8.05±1.42］ vs ［12.05±2.60］ ml/s, P <0.01 ), maximum urinary flow rate (［14.22±1.74］ vs ［21.32±4.51］ ml/s, P <0.01), residual urine volume (［46.15±16.57］ vs ［14.55±10.21］ ml, P <0.01), maximum urethral closure pressure (［76.52±3.53］ vs ［65.32±4.75］ cm H2O, P <0.01), mean urinary volume (［124.63±40.55］ vs ［285.93±58.68］ ml, P <0.01), urination frequency (16.96±4.17 vs 8.96±2.50, P <0.01), and nocturia frequency (8.94±3.23 vs 3.15±1.90, P <0.01). No apparent adverse reactions were observed in any of the patients., Conclusions: SPFE Capsules can safely and effectively improve LUTS and thus the quality of life of patients with type ⅢA prostatitis.

The cadherin-4 gene (CDH4) of the cadherin family encodes non-epithelial R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. In this study, we found higher expression of CDH4 mRNA in a salivary adenoid cystic carcinoma (SACC) cell line with low metastatic potential (SACC-83) than in a cell line with high metastatic potential (SACC-LM). By analyzing 67 samples of SACC tissues and 40 samples of paraneoplastic normal tissues, we found R-cad highly expressed in 100% of normal paraneoplastic tissue but only expressed in 64% of SACC tumor tissues (P<0.001). Knockdown of CDH4 expression in vitro promoted the growth, mobility and invasion of SACC cells, and in vivo experiments showed that decreased CDH4 expression enhanced SACC tumorigenicity. Furthermore, CDH4 suppression resulted in down-regulation of E-cadherin (E-cad), which is encoded by CDH1 gene and is a well-known tumor suppressor gene by inhibition of cell proliferation and migration. These results indicate that CDH4 may play a negative role in the growth and metastasis of SACC via co-expression with E-cadherin.

It is widely accepted that body weight and adipose mass are tightly regulated by homeostatic mechanisms, in which leptin plays a critical role through hypothalamic pathways, and obesity is a result of homeostatic disorder. However, in C57BL/6J mice, we found that Rcan2 increases food intake and plays an important role in the development of age- and diet-induced obesity through a leptin-independent mechanism. RCAN2 was initially identified as a thyroid hormone (T3)-responsive gene in human fibroblasts. Expression of RCAN2 is regulated by T3 through the PI3K-Akt/PKB-mTOR-Rps6kb1 signaling pathway. Intriguingly, both Rcan2(-/-) and Rps6kb1(-/-) mutations were reported to result in lean phenotypes in mice. In this study we compared the effects of these two mutations on growth and body weight in C57BL/6J mice. We observed reduced body weight and lower fat mass in both Rcan2(-/-) and Rps6kb1(-/-) mice compared to the wild-type mice, and we reported other differences unique to either the Rcan2(-/-) or Rps6kb1(-/-) mice. Firstly, loss of Rcan2 does not directly alter body length; however, Rcan2(-/-) mice exhibit reduced food intake. In contrast, Rps6kb1(-/-) mice exhibit abnormal embryonic development, which leads to smaller body size and reduced food intake in adulthood. Secondly, when fed a normal chow diet, Rcan2(-/-) mice weigh significantly more than Rps6kb1(-/-) mice, but both Rcan2(-/-) and Rps6kb1(-/-) mice develop similar amounts of epididymal fat. On a high-fat diet, Rcan2(-/-) mice gain body weight and fat mass at slower rates than Rps6kb1(-/-) mice. Finally, using the double-knockout mice (Rcan2(-/-) Rps6kb1(-/-)), we demonstrate that concurrent loss of Rcan2 and Rps6kb1 has an additive effect on body weight reduction in C57BL/6J mice. Our data suggest that Rcan2 and Rps6kb1 mutations both affect growth and body weight of mice, though likely through different mechanisms., Competing Interests: Compliance with ethics guidelines: Jing ZHAO, Shi-wei LI, Qian-qian GONG, Ling-cui DING, Ye-cheng JIN, Jian ZHANG, Jian-gang GAO, and Xiao-yang SUN declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

Several studies have reported that FZD2 regulates tumor biology in a complex manner. The aim of the present study was to identify the role of FZD2 in the cell growth and metastasis of salivary adenoid cystic carcinomas (SACCs). The expression of FZD2 in ACC-83 and ACC-LM cells were measured with real-time PCR. Immunohistochemical staining was used to detect the expression of FZD2 in clinical SACC samples with or without metastasis. Cell proliferation and Transwell assays were performed to explore the effects of FZD2 on cell growth and migration following the silencing of FZD2 with small interference RNAs and the overexpression of FZD2 with plasmid. Our data showed that FZD2 was downregulated in ACC-LM cells, which are an adenoid cystic carcinoma cell line with high metastatic potential, compared to ACC-83 cells, which have low metastatic potential. Additionally, the expression of FZD2 was lower in SACC tissues with metastasis compared to SACC tissues without metastasis (P<0.05). Cell proliferation and migration of ACC-83 cells were increased after the knockdown of FZD2 and decreased following overexpression of FZD2. Knockdown of FZD2 downregulated the expression of PAI-1. Our results suggest that FZD2 may be a tumor suppressor gene in SACCs that inhibits cell growth and migration.

Apelin-13 inhibits neuronal apoptosis caused by hydrogen peroxide, yet apoptosis following cerebral ischemia-reperfusion injury has rarely been studied. In this study, Apelin-13 (0.1 μg/g) was injected into the lateral ventricle of middle cerebral artery occlusion model rats. TTC, TUNEL, and immunohistochemical staining showed that compared with the cerebral ischemia/reperfusion group, infarct volume and apoptotic cell number at the ischemic penumbra region were decreased in the Apelin-13 treatment group. Additionally, Apelin-13 treatment increased Bcl-2 immunoreactivity and decreased caspase-3 immunoreactivity. Our findings suggest that Apelin-13 is neuroprotective against cerebral ischemia/reperfusion injury through inhibition of neuronal apoptosis.

Previous studies have demonstrated that sirolimus has therapeutic effects for Alzheimer's disease which characterized by cognitive dysfunction. However, its underlying mechanisms have not been fully elucidated. In the present study, we aimed to investigate the mechanisms of therapeutic effects of sirolimus for cognitive dysfunction rat model which induced by chronic administration of scopolamine. Forty Wistar rats were randomly divided into 4 groups (n=10 each): saline group and scopolamine group, sirolimus plus scopolamine group and 3-methyladenine pretreatment group. Morris water maze test was applied to measure the cognitive function of rat. After behavioral test, rats were sacrificed and prefrontal cortex and hippocampus were harvested for measuring amyloid-β (Aβ), Beclin-1 and mammalian target of rapamycin (mTOR). Compared with saline group, scopolamine administered significantly decreased the cognitive performance of rats during the Morris water maze test and changed Aβ, Beclin-1 and mTOR levels in rat prefrontal cortex and hippocampus (P<0.05); In addition, rats in sirolimus plus scopolamine group significantly reversed scopolamine-induced effects (P<0.05). Most importantly, 3-methyladenine abrogated the effects of sirolimus on scopolamine-induced cognitive dysfunction (P<0.05). In conclusion, the mechanism of sirolimus exerting therapeutic effects for scopolamine-induced cognitive dysfunction is likely related to the activation of autophagy.

Background: Numerous studies have reported both the tumor-suppressive and oncogenic roles of the Notch pathway, indicating that Notch activity regulates tumor biology in a complex, context-dependent manner. The aim of the present study was to identify the role of NOTCH1 in the cell growth and metastasis of SACC., Methods: We analyzed the expression of NOTCH1 in clinical SACC samples using immunohistochemical staining. We silenced the expression of NOTCH1 and overexpressed activated NOTCH1 to elucidate the effects of NOTCH1 on proliferation, migration and invasion. NOTCH1 target genes were validated by real-time PCR., Results: Our results showed that NOTCH1 was upregulated in SACC tissues when compared with normal tissues, and this upregulation was further enhanced in SACC tissues with metastasis and recurrence when compared with SACC tissues without metastasis. Overexpression of NOTCH1 in SACC cells promoted cell growth, migration and invasion, and knockdown of NOTCH1 inhibited cell proliferation in vitro and tumorigenicity in vivo by inducing cell apoptosis., Conclusions: The results of this study suggest that NOTCH1 plays a key role in the cell growth, anti-apoptosis, and metastasis of SACC. NOTCH1 inhibitors might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis.

Previous studies have shown that lipopolysaccharide (LPS) has the potential to cause cognitive dysfunction. However, the underlying pathogenesis has yet to be fully elucidated. Increasing attention is being focused on infection in the central nervous system. Therefore, the present study aimed to investigate the behavioral performance of rats receiving intraperitoneal injections of LPS and to determine the expression levels of amyloid-β (Aβ), brain-derived neurotrophic factor (BDNF) and pro-inflammatory cytokines in the hippocampus. In total, 30 male Wistar rats were randomly divided into 3 groups (each n=10): Control and 3 and 7 day LPS administration groups. The rats were intraperitoneally injected with saline or LPS for 3 or 7 days. Following this, rats performed the Morris water maze test, in which the latency to the platform and proportion of time spent in the target quadrant were recorded. Rats were then sacrificed and the hippocampi were harvested for determination of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), Aβ and BDNF expression levels. LPS administration for 3 and 7 days significantly increased the latency to the platform and decreased the proportion of time spent in the target quadrant compared with those in the control group, (P<0.05). Administration of LPS for 3 and 7 days induced statistically significant increases in the expression levels of IL-1β, IL-6 and TNF-α in the hippocampus, compared with those in the control group (P<0.05). Additionally, the administration of LPS for 7 days induced a statistically significant increase in the expression level of Aβ in the hippocampus, compared with that in the control group (P<0.05). However, the administration of LPS did not elicit a statistically significant change in the expression level of BDNF in the hippocampus, compared with that in the control group (P>0.05). The results indicate that LPS induces cognitive dysfunction, which is associated with increased expression levels of pro-inflammatory cytokines and Aβ, but does not affect the expression of BDNF in the hippocampus.

Fluvoxamine, a common antidepressant agent, is designed to exert its pharmacological effect by inhibiting synaptic serotonin reuptake. However, increasing evidence has demonstrated that σ 1 receptors are likely to be involved in the mechanism of action of fluvoxamine. The present study aimed to observe the effects of fluvoxamine on the expression levels of mammalian target of rapamycin (mTOR), Ca 2+ /calmodulin-dependent protein kinase 2γ (Camk2γ) and glycogen synthase kinase-3β (GSK-3β) in fluvoxamine-treated N2a cells and attempted to elucidate whether σ 1 receptors mediate the pharmacological effects of fluvoxamine. The N2a cells were randomly divided into three groups (each n=6): DMEM group (D group), 0.5 μmol/l fluvoxamine group (F group) and 0.2 μmol/l BD1047 (a σ 1 receptor antagonist) + 0.5 μmol/l fluvoxamine group (BF group). Western blotting was used to determine the expression levels of mTOR, Camk2γ and GSK-3β in the cultured N2a cells after two days of incubation. The F group exhibited significant increases in the expression levels of mTOR and Camk2γ and a significant reduction in the expression levels of GSK-3β compared with those in the D group (P<0.01). By contrast, the BF group demonstrated significant reductions in the expression levels of mTOR and Camk2γ and a significant increase in the expression levels of GSK-3β, compared with those in the F group (P<0.01). These results suggest that σ 1 receptors mediate fluvoxamine-elicited changes in the expression levels of mTOR, Camk2γ and GSK-3β in N2a cells, which indicates that σ 1 receptors are likely to be involved in the pharmacological effects of fluvoxamine.

The use of ketamine is recommended in patients with sepsis undergoing surgery due to its anti-inflammatory effects. However, a paucity of data exists with regard to the anti-inflammatory effects of ketamine in the central nervous system. Therefore, the present study aimed to investigate the effect of ketamine on lipopolysaccharide (LPS)‑induced inflammatory responses in cultured Neuro2a (N2a) cells and to elucidate its potential mechanism of action. N2a cells were randomly divided into the following 3 groups (n=6): The DMEM culture solution administration alone group, the 0.5 µmol/l LPS administration alone group and the 1 µmol/l ketamine plus 0.5 µmol/l LPS administration group. The expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB and inducible nitric oxide synthase (iNOS) were determined. LPS-treated N2a cells exhibited a significant increase in the expression levels of IL-1β, IL-6, TNF-α, NF-κB and iNOS, while the administration of ketamine eliminated the LPS-induced production of IL-1β, IL-6, TNF-α, NF-κB and iNOS. Based on our data, we hypothesized that the anti-inflammatory effect exerted by ketamine on N2a cells was potentially due to the inhibition of NF-κB and iNOS.

The title mol-ecule, C(17)H(20)O(3)S, displays a U-shaped structure; the two benzene rings are nearly parallel and partially overlapped to each other, the dihedral angle and centroid-to-centroid distance being 15.0 (2)° and 3.723 (2) Å. In the crystal, weak inter-molecular C-H⋯O hydrogen bonds link the mol-ecules, forming supra-molecular chains running along the a axis.

Cadherins are found in almost all living organisms. In addition to their role in the formation and maintenance of normal tissue architecture, cadherins seem to play a crucial role in the cell-cell interactions of cancer cells in tumorigenesis, invasion and metastasis. The aim of the present study was to identify the role of CDH12 in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC). Real-time PCR results showed that CDH12 is abnormally expressed in the highly metastatic SACC cell line ACC-M, compared to ACC-2, a SACC cell line with low metastatic ability. CDH12 expression was significantly higher in clinical samples with metastasis and recurrence than in those without metastasis and recurrence (P<0.05), as demonstrated by immunohistochemical analysis. Overexpression of the CDH12 protein in ACC-M cells infected with an adenovirus vector containing CDH12 enhanced the invasive and migratory ability of ACC-M cells in vitro compared to ACC-M cells infected with empty vector. Likewise, knockdown of CDH12 by small interfering RNA efficiently inhibited the invasion and migration of ACC-M cells in vitro. These results indicate that CDH12 may play an important role in the invasion and metastasis of SACC.

The Notch signaling pathway is important for cell-cell communication; it is involved in gene regulation mechanisms that control multiple cell differentiation processes during embryonic and adult life. Notch is present in all metazoans, and vertebrates possess four different Notch receptors: Notch-1, Notch-2, Notch-3, and Notch-4. The aim of the present study was to identify the role of Notch protein in the metastasis of salivary adenoid cystic carcinoma (SACC). Real-time PCR results showed that Notch-1, Notch-2, and Notch-4 were upregulated in the highly metastatic SACC cell line ACC-M, compared to ACC-2, a SACC cell line with low metastatic ability. Knockdown of Notch-4 by small interfering RNA efficiently inhibited the invasion of ACC-M cells. Notch-4 expression was significantly higher in the clinical samples with metastasis and recurrence compared to that in control (p<0.05), shown by immunohistochemistry analysis. These results indicate that Notch-4 may play an important role in SACC metastasis.

Objective: To study the relationship between the resuscitation therapy and intensive insulin therapy on stress-induced hyperglycemia in severe sepsis and septic shock patients, and to evaluate the value on nonlinear viewpoint in the treatment of patients with sepsis., Methods: The data of 129 hospitalized patients with severe sepsis and septic shock were analyzed and they were divided into eight groups every 6 hours in ascending order for full recovery. The resuscitation therapy time of each group was compared with insulin dosage in each unit time with nonlinear least square method., Results: The relationship of the exponential function fit very well between the resuscitation therapy time of each group and the insulin dosage in each unit time. The exponential curve equation was y=e0.739 3-0.015 2x2 (a=0.739 3, b=0.015 2) and the curve fit very well (R2=0.976 943 6)., Conclusion: It conforms to the nonlinear viewpoint that the resuscitation therapy time is closely correlated with recovery of dysfunction of endocrine system during the treatment for patients with severe sepsis and septic shock. Therefore, the essence of successful treatment is to concentrate on helping the body rebuild the disorganized network and the recovery of physiological harmony rather than to support and repair the damaged organs.

Objective: To construct differential expression profiles of adenoid cystic carcinoma cell lines for screening candidate genes related to metastasis and to verify some candidate genes in adenoid cystic carcinoma., Methods: Restriction fragments differential display PCR (RFDD-PCR) was used to set up gene expression profiles of adenoid cystic carcinoma cell lines-ACC-M and ACC-2, with high and low metastasis potential respectively. Candidate genes were screened through bioinformatics analysis. Then, a gene family of these candidate genes was checked using semi-quantitative reverse transcription-PCR(RT-PCR)., Results: Two gene expression profiles including 5420 gene fragments were constructed, 12 genes of a family called matrix metalloproteinase genes (MMPs) were observed obvious differentially expressed between two cell lines. Results of semi-quantitative RT-PCR also identified this different expression of MMP2,MMP7,MMP9,MMP14,MMP15 and MMP24., Conclusion: The construction of gene expression profiles of ACC-M and ACC-2 cell lines makes the foundation for seeking the target genes of adenoid cystic carcinoma. MMP2,MMP7,MMP9 and MMP15 may be relevant with carcinogenesis, development and metastasis of adenoid cystic carcinoma, and different metastasis potential may result from different subtype of MMPs gene family.

Purpose: To study the differential expression pattern of MMPs and TIMPs in ACC-M and ACC-2 tumor model., Methods: High and low metastatic tumor models were set up by transplantion of ACC-M and ACC-2 to nude mouse respectively. Then 3 mice in each group were selected randomly to detect the mRNA level of MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 using semiquantitative RT-PCR,GAPDH was used as internal control. Meanwhile, the expression of MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 in each transplanted tumor were determined by immunohistochemical assay, and IOD value of immunohistochemical reaction was measured. All data were analyzed by SPSS11.5 software package for Student's t test., Results: The results of RT-PCR and immunohistochemistry showed an up-regulation of MMP-2, MMP-7, MMP-9 and TIMP-1 in ACC-M tumor model compared with ACC-2 model (P < 0.05), while the expression of TIMP-2 showed no significant difference between the two models (P > 0.05)., Conclusion: The differential expression pattern of MMP-2, MMP-7, MMP-9, and TIMP-1 in 2 tumor models may result in different metastasis potential; The 2 tumor models provide good study model for investigation of the metastatic mechanism of salivary adenoid cystic carcinoma.

Agrobacterium-mediated transformation was used to introduce a trypsin inhibitor gene into Taiwan cauliflower (Brassica oleracea var. botrytis L.) cultivars. The TI gene was isolated from a well-adapted Taiwan sweet potato cultivar and was expected to be especially effective in combating local pests. In vitro regeneration studies indicated that 4-day-old cauliflower seedling hypocotyl segments, pretreated with 2,4-dichlorophenoxyacetic acid for 3 days and incubated on a silver-ion-containing shoot induction medium, gave regeneration rates greater than 95%. Optimum transformation conditions were determined. G418 selection at 15 mg/l was initiated 1 week after cocultivation, and the dose was doubled 1 week later. Over 100 putative transgenic plants were produced. Transgenic status was confirmed by in vitro TI activity, and Southern and Western hybridization assays. The transgenic plants demonstrated in planta resistance to local insects to which the control plants were vulnerable.