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Objective: To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI)., Methods: Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed., Results: Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P < 0.01, P = 0.015). The DC values of the right inferior temporal area were positively correlated with the pain degree at TP1 in Group 1 (r = 0.371; P = 0.008)., Conclusion: Spontaneous brain activity and network changes in young women with non-menstrual MwoA were altered by acupuncture. The right temporal area may be an important target for acupuncture modulated brain function in young women with non-menstrual MwoA., (© 2024. The Author(s).)

When nanozymes are used in biological analysis, higher activity can improve the detection sensitivity, and better selectivity can eliminate other interference. To improve the specificity and sensitivity, we fabricated an innovative bioconjugated nanozyme with natural enzyme (BNNZ), in which natural ChOx was immobilized onto histidine-modified Fe 3 O 4 (His-Fe 3 O 4 ) with hydrophilic poly(ethylene glycol) (PEG) as a linker. ChOx could specifically catalyze the oxidation of cholesterol to generate H 2 O 2 molecule, and then the newly formed H 2 O 2 oxidized the colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue ox-TMB by peroxidase-like His-Fe 3 O 4 . According to the above cascade reaction, the BNNZ-based colorimetric strategy was proposed for the detection of cholesterol. Wherein, natural enzymes specifically catalyzed substrates, which endowed BNNZ with excellent specificity for target molecules; meanwhile, the introduction of histidine on His-Fe 3 O 4 effectively increased the peroxidase-like activity of BNNZ, which provided a guarantee for sensitivity. Furthermore, BNNZ after reaction could be rapidly separated by an external magnetic field without interfering with colorimetric quantitative detection. The proposed strategy exhibited excellent sensitivity with limit of detection of 0.446 μM and was successfully used for the detection of cholesterol in spiked human serum sample with recovery and relative standard deviation in the range of 97.9-103.5% and 2.5-4.0%, respectively. This work indicates that the bioconjugation of nanozyme and natural enzyme may be a universal strategy for synthesis of high-performance enzyme-nanozyme systems, and the new-type BNNZ will be widely used in biological detection and disease treatment., (© 2023. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Objective: To observe therapeutic effect of acupuncture on migraine without aura and the changes of brain functional connectivity (FC) using resting-state functional magnetic resonance imaging (rs-fMRI)., Methods: Thirty-four patients with migraine without aura were included into an observation group and treated with acupuncture at Baihui (GV 20), Xuanlu (GB 5), Shuaigu (GB 8), Taiyang (EX-HN 5), etc. Using G6805-Ⅱ electric acupuncture apparatus, the ipsilateral Fengchi (GB 20) and Shuaigu (GB 8) were connected and stimulated with continuous wave, 2 Hz in frequency and 0.1 mA to 1.0 mA in current intensity, depending on patient's tolerance. Acupuncture stimulation lasted 20 min each time, twice weekly (at the interval>2 days). A total of 6 weeks of treatment (12 times) was required. Matching the gender and age as those of the observation group, 16 healthy subjects were recruited into a control group and no any intervention was provided. The headache days, the score of visual analogue scale (VAS) for headache severity, the total score of headache symptoms, the score of migraine-specific quality of life questionnaire (MSQ), the score of self-rating anxiety scale (SAS), and the score of self-rating depression scale (SDS) were compared before and after acupuncture, and the clinical efficacy was assessed in the observation group. The data of the resting-state functional magnetic resonance were collected in the observation group before and after treatment as well as the control group at baseline. The periaqueductal gray (PAG) was taken as the seed to analyze the effect of acupuncture on the brain FC and the correlation between FC and VAS scores, headache days in the patients of migraine without aura., Results: After treatment, the headache days, VAS score, the total score of headache symptoms, SAS score and SDS score were all reduced ( P <0.01); and the scores of the restrictive, preventive, and emotional functional domains of the MSQ were increased ( P <0.01) in the observation group compared with those before treatment. The total effective rate was 94.1% (32/34). Compared with the control group, FC between PAG and the right cerebellum Ⅷ was decreased in the observation group before treatment ( P <0.05). FC of PAG with the bilateral cerebellum Ⅷ and the left precuneus was increased in the observation group after treatment compared with those before treatment ( P <0.05). In the observation group, the FC intensity of PAG and the right cerebellum Ⅷ was negatively correlated with VAS score ( r =-0.41, P <0.05) before treatment, while the FC intensity of PAG and the left precuneus was positively correlated with the improvement in headache days ( r =0.40, P <0.05) after treatment., Conclusion: Acupuncture is effective on migraine without aura. The brain functional connectivity is abnormal in the patients. The effect onset of acupuncture is obtained probably by regulating the abnormal brain regions and activating brain regions relevant with pain and emotions.

Breast cancer (BC) is a kind of malignant cancer in women, and it has become the most diagnosed cancer worldwide since 2020. Histone methylation is a common biological epigenetic modification mediating varieties of physiological and pathological processes. Lysine-specific demethylase 1 (LSD1), a first identified histone demethylase, mediates the removal of methyl groups from histones H3K4me1/2 and H3K9me1/2 and plays a crucial role in varieties of cancer progression. It is also specifically amplified in breast cancer and contributes to BC tumorigenesis and drug resistance via both demethylase and non-demethylase manners. This review will provide insight into the overview structure of LSD1, summarize its action mechanisms in BC, describe the therapeutic potential of LSD1 inhibitors in BC, and prospect the current opportunities and challenges of targeting LSD1 for BC therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Liu, Ding, Tao, Zhu, Shi, Wen, Niu, Li, Xu, Qin, Fei and Chen.)

Doxorubicin (DOX) is an effective chemotherapy drug, but its clinical use has adverse effects on male reproduction. However, there are few studies about the specific biological processes related to male reproduction or strategies for improving fertility protection. In this paper, we examined the effects of DOX on spermatogenesis and sperm function, and tested the possible protective role of melatonin (MLT) against DOX's reproductive toxicity. DOX-treated mice showed signs of significantly impaired spermatogenesis, including vacuolated epithelial cells, decreased testis weights, and lowered sperm counts and motility. DOX also reduced germ cell proliferation (PCNA) and meiosis-related proteins (SYCP3), but this effect could be partially improved with MLT administration. HSPA2 expression was maintained, which indicated that although MLT did not improve sperm motility, it did have a significant protective effect on elongated sperm. IVF results showed that MLT could partially promote two-cell and blastocyte development that was restricted by DOX. MLT reversed DOX-driven changes in the testes, including the antioxidant indices of SOD1, CAT and PRDX6, and the apoptotic indices of BAX and Caspase3. These results suggest that MLT effectively prevents DOX-induced early reproductive toxicity, and increase our understanding of the molecular mechanisms underlying DOX's effects on male reproduction and the protective mechanism of MLT., (© 2022. The Author(s).)

Objective: To investigate the changes in the functional connectivity (FC) in the right insula between migraine without aura (MWoA) and healthy controls by using resting-state functional magnetic resonance imaging (rs-fMRI), and to observe the instant alteration of FC in MWoA during electroacupuncture (EA) stimulation at Shuaigu (GB8)., Methods: A total of 30 patients with MWoA (PM group) and 30 healthy controls (HC group) underwent rs-fMRI scans. The PM group underwent a second rs-fMRI scan while receiving EA at GB8. The right insula subregions, including the ventral anterior insula (vAI), dorsal anterior insula (dAI) and posterior insula (PI), were selected as the seed points for FC analysis., Results: Aberrant FC, including dAI with right postcentral gyrus, PI with left precuneus, was found among PM before EA (PMa), PM during EA (PMb) and HC. Meanwhile, decreased FC between dAI and the right postcentral gyrus was found in the PMa compared to the HC and PMb. Increased FC between the PI and left precuneus was found in the PMa compared to the HC and PMb. Correlation analysis showed that the FC value of the right postcentral gyrus in PMa was negatively correlated with the scores of Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety. The FC value of the left precuneus in PMa was positively correlated with the visual analogue scale score., Conclusion: The alteration of FC between the right insula subregions and multiple brain regions may be an important index for MWoA. EA at GB8 was able to adjust the FC between the right insula subregions and parietal lobe, namely, the right dAI and right postcentral gyrus, and the right PI and left precuneus, thereby rendering an instant effect in the management of MWoA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Distinct expression of the miRNAs has rarely been explored in basal cell carcinoma (BCC) of skin, and the regulatory role of miRNAs in BCC development remains quite opaque. Here, we collected control tissues from adjacent noncancerous skin ( n = 15; control group) and tissues at tumor centers from patients with cheek BCC ( n = 15; BCC group) using punch biopsies. After six small RNA sequencing- (sRNA-seq-) based miRNA expression profiles were generated for both BCC and controls, including three biological replicates, we conducted comparative analysis on the sRNA-seq dataset, discovering 181 differentially expressed miRNAs (DEMs) out of the 1,873 miRNAs in BCCs. In order to validate the sRNA-seq data, expression of 15 randomly selected DEMs was measured using the TaqMan probe-based quantitative real-time PCR. Functional analysis of predicted target genes of DEMs in BCCs shows that these miRNAs are primarily involved in various types of cancers, immune response, epithelial growth, and morphogenesis, as well as energy production and metabolism, indicating that BCC development is caused, at least in part, by changes in miRNA regulation for biological and disease processes. In particular, the "basal cell carcinoma pathways" were found to be enriched by predicted DEM targets, and regulatory relationships between DEMs and their targeted genes in this pathway were further uncovered. These results revealed the association between BCCs and abundant miRNA molecules that regulate target genes, functional modules, and signaling pathways in carcinogenesis., Competing Interests: The authors declare no competing financial interests., (Copyright © 2021 Hai-Peng Wei et al.)

Objection: This study was a primary study to evaluate the instant and sustained effect of electroacupuncture (EA) at GV20 (Baihui) in postgraduate students with mild depression by using a special flexible head coil., Methods: A total of 20 postgraduate students with mild depression underwent EA stimulation at GV20 and 3 phases of resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Phase I: Preparation (before needle insertion); Phase II: during EA; Phase III: 15 minutes after needle removal. The Rs-fMRI data were processed using DPABI and SPSS 25., Results: 1) ReHo values showed significantly differences in the right posterior cingulate cortex, right calcarine gyrus, right angular gyrus, right precuneus, right cuneus, and bilateral postcentral gyri among Phase I, Phase II and Phase III; 2) Relative to the Phase I, increased brain activity in the Phase II was observed in the bilateral postcentral gyri, right calcarine gyrus, right cuneus. Compared with the Phase II, decreased brain activity in the Phase III was observed in the right precuneus, right posterior cingulate cortex, right angular gyrus. Relative to the Phase I, Significantly increased brain activity in the Phase III was observed in the right calcarine gyrus, right cuneus, and bilateral postcentral gyri. While decreased ReHo values were found in the right posterior cingulate cortex, right angular gyrus, right precuneus; and 3) Correlation analysis showed that the ReHo values of multiple brain regions in Phase I and Phase III were significantly correlated with the VAS and HRSD-17 scores., Conclusion: This study focuses on the instant and sustained effect in postgraduate students with depression. Our study showed that instant effect produced by EA stimulation at GV20 firstly induced changes in somatosensory and visual area, and then, sustained effect (Phase III) have a higher intensity and more extensive than instant effects. Meanwhile, we provide a visualization way to study the instant effects of head acupoints by using a flexible head coil., Competing Interests: The authors report no conflicts of interest for this work and declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (© 2021 Wei et al.)

In-tube solid-phase microextraction (IT-SPME) with capillary column as extraction device is a well-established green extraction technique with a lot of applications in the fields of biomedicine, food and environment. This article reviews the research contributions of IT-SPME for analysis of proteins. The paper first briefly describes the history of IT-SPME. Then, the development and principle of IT-SPME for analysis of proteins are introduced, in which capillary column configurations of IT-SPME and instruments for quantitative analysis of proteins are summarized. Subsequently, the synthesis strategy and recognition principle of different recognition units, including antibodies, aptamers, molecularly imprinted polymers, and boronate affinity materials, are discussed in detail. This part also introduces several rare recognition units, including lectins, restricted access materials, lysine modified with β-cyclodextrin and cell membrane. The development trend and possible future direction of IT-SPME for analysis of proteins are mentioned., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Airway stenosis is a common problem in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU). A tissue-engineered trachea is a new therapeutic method and a research hotspot. Successful vascularization is the key to the application of a tissue-engineered trachea. However, successful vascularization studies lack a complete description. In this study, it was assumed that rabbit bone marrow mesenchymal stem cells were obtained and induced by ascorbic acid to detect the tissue structure, ultrastructure, and gene expression of the extracellular matrix. A vascular endothelial cell culture medium was added in vitro to induce the vascularization of the stem cell sheet (SCS), and the immunohistochemistry and gene expression of vascular endothelial cell markers were detected. At the same time, vascular growth-related factors were added and detected during SCS construction. After the SCS and decellularized tracheal (DT) were constructed, a tetrandrine allograft was performed to observe its vascularization potential. We established the architecture and identified rabbit bone marrow mesenchymal stem cell membranes by 14 days of ascorbic acid, studied the role of a vascularized membrane in inducing bone marrow mesenchymal stem cells by in vitro ascorbic acid, and assessed the role of combining the stem cell membranes and noncellular tracheal scaffolds in vivo . Fourteen experiments confirmed that cell membranes promote angiogenesis at gene level. The results of 21-day in vitro experiments showed that the composite tissue-engineered trachea had strong angiogenesis. In vivo experiments show that a composite tissue-engineered trachea has strong potential for angiogenesis. It promotes the understanding of diseases of airway stenosis and tissue-engineered tracheal regeneration in newborns and small infants., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Zhi-Ye Yao et al.)

Caused by porcine epidemic diarrhea virus (PEDV), porcine epidemic diarrhea (PED) is an acute infectious disease which causes damage to the intestine including intestinal villus atrophy and shedding, leading to serious economic losses to the pig industry worldwide. In order to obtain detailed information about the pathogenesis and host immune response in a PEDV-infected host for first In vivo study we used high-throughput sequencing to analyze the gene expression differences of the small intestinal mucosa after infection with PEDV. Transcripts obtained were over 65,525,000 clean reads after reassembly were 22,605 genes detected, of which 22,248 were known genes and 371 new genes were predicted. Moreover, 3168 genes expression was up-regulated and 3876 genes down-regulated. (Gene Ontology) GO annotation and functional enrichment analysis indicated that all of the DEGs (differentially expressed genes) were annotated into biological process, cellular component and molecular function. Most of these unigenes are annotated in cellular processes, the cell and binding. KEGG analysis of the DEGs showed that a total of 7044 DEGs unigenes were annotated into 323 pathways classified into 6 main categories. Most of these unigenes are annotated were related to immune system response to the infectious diseases pathways. In addition, 20 DEGs were verified by quantitative real-time PCR. As the first, in vivo, RNAseq analysis of piglets and PEDV infection, our study provides knowledge about the transcriptomics of intestinal mucosa in PEDV-infected piglets, from which a complex molecular pathways and pathogenesis-related biological processes are involved in PEDV interaction with piglet intestinal mucosa., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Erectile dysfunction (ED) is considered to be incapable of obtaining or/and keeping a sufficient erection function to receive the satisfactory during the sexual intercourse. This study aims to investigate the effects of telomerase reverse transcriptase (hTERT) modified adipose tissue derived stem cells (ADSCs) autologously injected into cavernosa of the ED rats on erectile function. The ADSCs were isolated form the rat subcutaneous adipose tissue sample, and identified by examining the CD29 and CD44 molecule. The ED model was established by using 100μg/kg apomorphine (APO). The adenovirus expressing rat hTERT (Ade-hTERT vector) was established, and transfected into ADSCs and injected into ED rat model, respectively. Telomerase activity, cell growth, cell apoptosis were analyzed by using TRAP ELISA assay, CCK8 assay and flow cytometry assay, respectively. The trophic growth factors were examined by using enzyme-linked immunosorbent assay (ELISA). The mRNA and proteins were detected by using semi-quantitative PCR and western blot assay, respectively. Ade-hTERT vector was highly expressed in both ADSCs and ED rat mode. The hTERT expression enhanced the telomerase activity, inhibits cell apoptosis and enhances proliferation of ADSCs (P<0.05). hTERT expression triggers the secretory function of ADSCs and induces differentiative potential of ADSCs. hTERT expression inhibits apoptosis and increases eNOS and nNOS levels in older ED rats compared to the Ade-vector injected ED rats (P<0.05). In conclusion, the hTERT modification could enhance the ADSCs proliferation, and hTERT modified ADSCs could increase the anti-oxidative stress capacity in the ED rat model., (Copyright © 2017. Published by Elsevier Masson SAS.)

The biomarker identification of cancer is benefit for early detection and less invasion. Polyunsaturated fatty acid (PUFA) metabolite as inflammatory mediators can affect progression and treatment of cancer. In this work, the serum was collected from colorectal cancer patients and healthy volunteers, and then we tested the change of serum PUFA metabolites in both of them by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Of the 158 PUFA and their metabolites, we found that abnormal change of 2, 3-dinor-8-iso-PGF2α, 19-HETE and 12-keto-LTB4 from arachidonic acid were observed in colorectal cancer patients. Meanwhile, 9-HODE and 13-HODE from linoleic acid were significant lower in colorectal cancer patients. Our data suggested that some PUFA metabolites might be used as a potential biomarker of colorectal cancer, which might provide assistance in clinical diagnosis and treatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Pre-column dilution large volume injection (PD-LVI), a novel sample injection technique for reverse phase ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), was developed in this study. The PD-LVI UHPLC-MS/MS system was designed by slightly modifying the commercial UHPLC-MS/MS equipment with a mixer chamber. During the procedure of PD-LVI, sample solution of 200μL was directly carried by the organic mobile phase to the mixer and diluted with the aqueous mobile phase. After the mixture was introduced to the UHPLC column in a mobile phase of acetonitrile-water (15/85, v/v), the target analytes were stacked on the head of the column until following separation. Using QuEChERS extraction, no additional steps such as solvent evaporation or residue redissolution were needed before injection. The features of PD-LVI UHPLC-MS/MS system were systematically investigated, including the injection volume, the mixer volume, the precondition time and the gradient elution. The efficiency of this approach was demonstrated by direct analysis of 24 pesticides in cabbages. Under the optimized conditions, low limits of detection (0.00074-0.8 ng/kg) were obtained. The recoveries were in the range of 63.3-109% with relative standard deviations less than 8.1%. Compared with common UHPLC-MS/MS technique, PD-LVI UHPLC-MS/MS showed significant advantages such as excellent sensitivity and reliability. The mechanism of PD-LVI was demonstrated to be based on the column-head stacking effect with pre-column dilution. Based on the results, PD-LVI as a simple and effective sample injection technique of reverse phase UHPLC-MS/MS for the analysis of trace analytes in complex samples showed a great promising prospect., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Cytokinins play a critical role in controlling plant growth and development, but it is difficult to be determined in plant samples due to the extremely low concentration level of picomole/gram. So it is important for efficient sample preparation with selective enrichment and rapid separation for accurate analysis of cytokinins. Herein, a supramolecular perhydroxy-cucurbit[8]uril (PCB[8]) was fabricated into the Fe3O4 magnetic particles via chemical bonding assembly and magnetic perhydroxy-cucurbit[8]uril (MPC) materials were obtained. The MPC had good enrichment capability to cytokinins and the enrichment factors were more than 208. The interaction of MPC and cytokinins was investigated by adsorption test and density functional theory (DFT) calculation, the results showed that the main drive forces were the host-guest interaction and hydrogen-bonding interaction between the perhydroxy-cucurbit[8]uril with analytes. Combined with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), the MPC was used as a sorbent of magnetic solid-phase extraction for the analysis of cytokinins in plant samples. A sensitive and selective UPLC-MS/MS method was developed with low detection limits of 0.14-0.32 ng/L for cytokinins analysis. Five cytokinins including zeatin riboside, meta-topolin, kinetin, kinetin riboside, and zip with 6.12-87.3 ng/kg were determined in the soybean sprout and Arabidopsis thaliana. The recoveries were in the range of 76.2-110% with relative standard deviations (n = 5) of 2.3-9.7%. On the basis of these results, magnetic perhydroxy-cucurbit[8]uril materials with selective enrichment capability have good potential on the analysis of ultratrace targets from complicated sample matrixes.

Background: Platinum-based chemotherapy is the standard treatment for advanced urothelial cancer (UC) and is generally used in the first-line setting. However, the optimal salvage treatment for previously treated UC patients is unclear. We conducted a systematic review of published clinical trials of single agent versus combined chemotherapy as salvage treatment in previously treated UC patients., Methods: Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). All relevant studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), disease control rate (DCR), median progression-free and overall survival (PFS, OS), and grade 3/4 toxicities were extracted and analyzed using Comprehensive Meta Analysis software (Version 2.0)., Results: Fifty cohorts with 1,685 patients were included for analysis: 814 patients were treated with single agent chemotherapy and 871 with combined chemotherapy. Pooled OS was significantly higher at 1 year for combined chemotherapy than for single agent (relative risk [RR] 1.52; 95% CI: 1.01-2.37; P=0.03) but not for 2-year OS (RR 1.31; 95% CI: 0.92-1.85; P=0.064). Additionally, combined chemotherapy significantly improved ORR (RR 2.25; 95% CI: 1.60-3.18; P<0.001) and DCR (RR 1.12; 95% CI: 1.01-1.25, P=0.033) compared to single agent for advanced UC patients. As for grade 3 and 4 toxicities, more frequencies of leukopenia and thrombocytopenia were observed in the combined chemotherapy than in single agent group, while equivalent frequencies of anemia, nausea, vomiting, and diarrhea were found between the two groups., Conclusion: In comparison with single agent alone, combined chemotherapy as salvage treatment for advanced UC patients significantly improved ORR, DCR, and 1-year OS, but not 2-year OS. Our findings support the need to compare combined chemotherapy with single agent alone in the salvage setting in large prospective trials due to its potential survival benefit in advanced UC patients.

Objective: To investigate the effects of spinal manipulation (SM) on brain functional activity in patients with lumbar disc herniation (LDH)., Methods: Eleven patients with LDH were recruited in the study. All patients received 6 times of lumbar SM treatment and then clinical efficacy was evaluated. All patients received brain functional magnetic resonance imaging (fMRI) scans before and after SM treatment., Results: Three subjects dropped out and 8 subjects completed the study, among whom 4 cases were effective and 4 ineffective after SM treatment. The required pressure value producing the same level (VAS 50) pain was (7.43 ± 1.47) kg and (10.53 ± 0.55) kg before and after SM treatment in effective patients(P<0.05); however, there was no significant difference in ineffective patients (P>0.05). Compared to pre-treatment level, the brain functional activity in effective patients was mainly inhibited, the inhibited areas were located in the right side of prefrontal cortex and cerebellum; while the brain functional activity was generally enhanced in ineffective patients., Conclusion: SM can affect the brain functional activity of patients with LDH, the inhibited areas is mainly located in prefrontal cortex and cerebellum when SM treatment is effective.

The ZFX (zinc finger protein, X-linked) gene located on the human X chromosome controls the self-renewal of embryonic and hematopoietic stem cells as a transcriptional regulator. Recently, studies have affirmed that ZFX is associated with several human cancers, including lymphoma, laryngeal squamous cell carcinoma, prostate cancer, and liver cancer, which suggests ZFX as a potential therapeutic target in cancer. However, the functional role of ZFX in human renal cancer remains unclear. Herein, we detected the expression of ZFX in 42 patients with renal cancer and found the expression of ZFX was specifically upregulated in cancer tissues at the mRNA and protein levels. Moreover, we employed lentivirus-mediated short hairpin RNA (shRNA) to knock down ZFX expression in two human renal cell carcinoma cell lines, 786-0 and ACHN. Functional analysis indicated that ZFX silencing significantly inhibited renal cell carcinoma cell proliferation and cell cycle progression, probably because of suppression of CDK4 and cyclin D1, and induced apoptosis via activation of Bax, Caspase 3, and PUMA in a p53-dependent manner. Our findings suggest that knockdown of ZFX by shRNA may be a potential therapeutic approach for the treatment of renal cancer., (Copyright © 2014 Elsevier Inc. All rights reserved.)

An automatic versatile system which integrated solid phase extraction (SPE) with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed. Diverse commercial SPE columns can be used under an ambient pressure in this online system realized by a dual-dilution strategy. The first dilution enabled the direct injection of complex samples with minimal pretreatment, and the second dilution realized direct introduction of large volume of strong eluent into the UHPLC column without causing peak broadening or distortion. In addition, a post-column compensation mode was also designed for the matrix-effects evaluation. The features of the online system were systematically investigated, including the dilution effect, the capture of desorption solution, the column-head stacking effect and the system recovery. Compared with the offline UHPLC system, this online system showed significant advantages such as larger injection volume, higher sensitivity, shorter analysis time and better repeatability. The feasibility of the system was demonstrated by the direct analysis of three auxins from different plant tissues, including leaves of Dracaena sanderiana, buds and petals of Bauhinia. Under the optimized conditions, the whole analysis procedure took only 7min. All the correlation coefficients were greater than 0.9987, the limits of detection and the limits of quantitation were in the range of 0.560-0.800ng/g and 1.80-2.60ng/g, respectively. The recoveries of the real samples ranged from 61.0 to 117%. Finally, the post-column compensation mode was applied and no matrix-effects were observed under the analysis conditions. The automatic versatile system was rapid, sensitive and reliable. We expect this system could be extended to other target analytes in complex samples utilizing diverse SPE columns., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To investigate the clinical effectiveness of dutasteride in the treatment of benign prostatic hyperplasia by meta-analysis., Materials and Methods: Several databases were searched from inception to June 2013 for prospective clinical studies comparing dutasteride vs placebo. The continuous outcomes of therapeutic efficacy included International Prostate Symptom Score/American Urological Association Symptom Index, maximum flow rate, total prostate volume, and acute urinary retention (AUR). The dichotomous outcomes included surgery risk and the rate of sexual dysfunction. The relative risk for dichotomous outcome and the weighted mean difference for continuous outcomes were estimated using fixed effects model., Results: Four studies met the inclusion criteria and were included, in which a total of 6460 patients received dutasteride and 6475 received placebo treatment. The average symptom score was improved by 1.98 with 95% confidence interval (CI) 1.77-2.19 (P <.00001); the average maximum flow rate was increased by 1.16 mL/s with 95% CI 0.63-1.70 (P <.0001); the total prostate volume was reduced by 13.86 mL (95% CI 12.76-14.96; P <.00001); the odds ratio for AUR was 0.35 (95% CI 0.27-0.47; P <.00001). The major side effect for dutasteride was the increased rate of sexual dysfunction compared with placebo, with odds ratio of 0.41 (95% CI 0.31-0.54; P <.00001)., Conclusion: Dutasteride is highly effective in mitigating benign prostatic hyperplasia symptoms and reducing the size of enlarged prostate and the risks of AUR and surgical intervention. However, dutasteride therapy is related to an increased rate of sexual dysfunction., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Upregulation of sphingosine kinase 1 (SPHK1) protein has been reported to be associated with a poor prognosis in a variety of malignant tumors. However, the role of SPHK1 in bladder cancer (BC) has not been thoroughly elucidated. The purpose of this study was to assess SPHK1 expression and to explore its contribution to BC. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was conducted to detect SPHK1 mRNA expression in 37 pairs of fresh-frozen BC tissues and corresponding noncancerous tissues. Results showed that SPHK1 mRNA expression level in BC tissues was significantly higher than that in corresponding noncancerous tissues. To investigate the association between SPHK1 protein expression and clinicopathological characteristics of BC, immunohistochemistry (IHC) was performed in 153 archived paraffin-embedded BC samples. Interestingly, high SPHK1 expression was significantly associated with histologic grade (P = 0.045) and tumor stage (P < 0.001) of patients with BC. The Kaplan-Meier survival curve showed that patients with high SPHK1 expression had significantly reduced overall 5-year survival rates (P < 0.001). Multivariate Cox regression analysis further suggested that the increased expression of SPHK1 was an independent poor prognostic factor for this disease. In conclusion, our data offer the convincing evidence for the first time that the increased expression of SPHK1 may be involved in the pathogenesis and progression of BC. SPHK1 might be a potential marker to predict the prognosis in BC.

This study aims to investigate the efficacy and possible mechanisms of melatonin in treating interstitial cystitis (IC), as melatonin is involved in anti-inflammatory and immunomodulatory effects and plays an important role in neuroprotection. IC was induced by intraperitoneal injection of cyclophosphamide (CP) with melatonin pretreatment or vehicle pretreatment. On day 7, the voiding behaviors were observed. Bladders were harvested for histologic examination, analysis of the expressions of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) by Western blotting, and also processed for immunohistochemical staining of substance P (SP). Proinflammatory cytokines were measured by ELISA immunoassays. L6-S1 spinal cords were harvested for measurement of SP by radioimmunoassay. CP injection resulted in severe cystitis with increase in voiding behaviors, histological damage, mast cell proliferation, SP, and proinflammatory cytokine expression, which were significantly downregulated by melatonin pretreatment. Pretreatment with melatonin further enhanced the expression of HO-1 and significantly reduced iNOS expression. Melatonin significantly improved bladder symptoms and histological damages in rats with CP-induced cystitis by diminishing bladder oxidative stress, blocking iNOS, upregulation of HO-1, and downregulating the expression of SP.

Purpose: Transurethral resection of the prostate (TURP) has a high failure rate in patients with small volume benign prostate hyperplasia (BPH) with bladder outlet obstruction (BOO). We describe and report the results of an alternative surgical method, selective transurethral resection of the prostate (STURP) in combination with transurethral incision of the bladder neck (TUIBN)., Methods: Patients were randomized to receive TURP or STRUP+TUIBN in combination with TUIBN. Maximum urinary flow rate (Qmax), voided volume, and post voiding residual volume (PVR) were assessed at baseline and at 1, 3, and 6 months after surgery. Efficacy of treatment was assessed by lower urinary tract symptoms and IPSS., Results: Sixty three patients received STRUP+TUIBN and 61 received TURP. Surgical time, amount of prostate tissue resected, and blood loss was the same in both groups (all, p>0.05). The mean duration of follow-up was 9.02 and 8.53 months in patients receiving TURP and STRUP+TUIBN, respectively. At 6 months postoperatively, IPSS was 4.26±1.22 and 4.18±1.47 in patients receiving TURP and STRUP+TUIBN, respectively (p>0.05), and the Qmax in patients receiving STRUP+TUIBN was markedly higher than in those receiving TURP (28.28±6.46 mL/s vs. 21.59±7.14 mL/s; p<0.05). Bladder neck contracture and urinary tract infections were observed in 3 and 5 patients receiving TURP, respectively, and none in STURP., Conclusions: STRUP+TUIBN may offer a more effective and safer alternative to TURP for small volume BPH patients.

Global DNA hypomethylation has been associated with increased risk for cancers of the colorectum, bladder, breast, head and neck, and testicular germ cells. The aim of this study was to examine whether global hypomethylation measured at BLCA-4 repeat regions through bisulfite pyrosequencing in blood leukocyte DNA is associated with the risk of bladder cancer(BC). A total of 312 bladder cancer patients and 361 healthy control subjects were included in Chongqing, China. Global methylation in blood leukocyte DNA was estimated by analyzing BLCA-4 repeats using bisulfite-polymerase chain reaction (PCR) and pyrosequencing. The median methylation level in BC cases (percentage of 5-methylcytosine (5 mC) = 75.7 %) was significantly lower than that in controls (79.7 % 5 mC) (P = 0.002, Wilcoxon rank-sum test). The odds ratios (ORs) of BC for individuals in the third, second, and first (lowest) quartiles of BLCA-4 methylation were 1.2 (95 % confidence interval (CI) 0.8-1.9), 1.6 (95 % CI 1.1-2.3), and 2.7 (95 % CI 1.5-3.8) (P for trend <0.001), respectively, compared to individuals in the fourth (highest) quartile. A 2.1-fold (95 % CI 1.5-2.8) increased risk of BC was observed among individuals with BLCA-4 methylation below the median compared to individuals with higher (>median) BLCA-4 methylation. Our results demonstrate for the first time that individuals with global hypomethylation measured in BLCA-4 repeats in blood leukocyte DNA have an increased risk for BC. Our data provide the evidence that BLCA-4 hypomethylation may be a useful biomarker for poor prognosis of patients with BC.

The aberrant expression of microRNAs (miRNAs) has been found in various types of cancer. The present study found miR-20a to be significantly upregulated in prostate cancer compared with normal prostate tissues. The proliferation and colony formation assays revealed that the downregulation of miR-20a by miR-20a inhibitor suppresses the proliferation of MDA-PCa-2b cells in vitro and also inhibits tumor growth in vivo. Furthermore, a gap junction protein, α 1 (CX43), was identified as a direct target gene of miR-20a. The upregulation of CX43 was detected in MDA-PCa-2b cells after treatment with miR-20a inhibitor both in vitro and in vivo. In conclusion, the findings show that miR-20a significantly contributes to the progression of prostate cancer by targeting CX43.

The genome of Banana bunchy top virus (BBTV) consists of six segments of single-stranded DNA of approximately 1 kb in length. We identified and sequenced the complete genomes of two BBTV isolates, one with and one without satellite DNA, from Haikou, Hainan, China. The Haikou-2 isolate contains six genomic segments and an additional satellite DNA while the Haikou-4 isolate contains only six genomic segments. Typical of other babuviruses, each genomic segment encodes a single open reading frame and contains the highly conserved stem-loop and major common regions. Phylogenetic analysis of the two Haikou isolates together with existing sequence records in GenBank confirmed the grouping of BBTV into two large groups and further refined the geographical distribution of each group. To accommodate the changes in the BBTV geographical distribution, the two groups are proposed as the Southeast Asian group and the Pacific-Indian Oceans group. Both the Haikou-2 and Haikou-4 isolates belong to the newly proposed Southeast Asian group.

Objectives: To evaluate the association between BLCA-4 tissue expression and patients' prognosis in bladder cancer (BC)., Methods: BLCA-4 expression was analyzed using immunohistochemical staining methods on tissue samples from a consecutive series of 325 BC patients who underwent resections between 2000 and 2006. The correlation of BLCA-4 expression and patients' clinicopathological parameters was evaluated. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model., Results: BLCA-4 was highly expressed in 54.8% of the BC patients. BLCA-4 overexpression was significantly associated with tumor grade (P<0.001), and stage (P<0.001). Kaplan-Meier survival analysis showed that high expression level of BLCA-4 resulted in a significantly poor prognosis of BC patients. Multivariate analysis revealed that the BLCA-4 expression level was an independent prognostic parameter for the overall survival rate of BC patients., Conclusions: These findings provide evidence that high expression level of BLCA-4 serves as a poor prognostic biomarker for BC. BLCA-4 may be a potential target of antiangiogenic therapy for BC.

Chilli ringspot virus (ChiRSV), a novel potyvirus, was recently found in Hainan, China with high prevalence. The genomic sequence of the ChiRSV-HN/14 isolate was determined by sequencing overlapping cDNA segments generated by reverse transcription polymerase chain reaction with degenerate and/or specific primers. ChiRSV genome (GenBank Acc. no. JN008909) comprised of 9,571 nucleotides (nt) excluding the 3'-terminal poly (A) tail and contained a large open reading frame of 9,240 nt encoding a large polyprotein of 3,079 amino acids with predicted Mr of 349.1 kDa. A small, overlapping PIPO coding region was also found to span from nt 2,913 to 3,095, with a capacity to encode a peptide of 60 amino acids. ChiRSV shares sequence identities of only 48.5-65.4 and 42.9-68.7% with closely related potyviruses at the nucleotide and the amino acid levels, respectively. Phylogenetic analysis of the genomic sequences provided further evidence that ChiRSV is a distinct species of the Potyvirus genus. ChiRSV-HN/14 is most closely related to Tobacco vein banding mosaic virus and two other pepper-infecting potyviruses.

Background: The prognosis for thyroid cancer differs between metastatic and non-metastatic cases. To identify biomarkers useful for thyroid cancer diagnosis and to establish a marker panel for the early detection of metastatic thyroid carcinoma, this study compared histomorphological features and biomarker expression profiles in thyroid carcinomas according to pathological diagnoses., Patients and Methods: Thyroid carcinoma samples were obtained from 113 consecutive patients who underwent resection at multiple centers between 2001 and 2008. These cases included 63 metastatic thyroid tumors (34 papillary carcinomas, 20 follicular carcinomas, 9 undifferentiated carcinomas) and 50 non-metastatic thyroid tumors (36 papillary carcinomas, 14 follicular carcinomas). Tissue microarrays constructed using the 113 samples were analyzed by immunohistochemistry for the expression of 16 protein markers: MMP9, VEGF-C, E-cadherin, MMP2, PPARγ, PCNA, CXCR4, PTEN, C-myc, PTTG, HBME-1, p16, p53, FHIT, bFGF and hTERT. The clinicopathological variables with diagnostic significance were determined by multivariate analysis, and the predictive values of the identified biomarkers for metastasis in thyroid carcinoma were determined by receiver operating characteristic (ROC) curve analysis., Results: The expression of six proteins, VEGF-C, MMP2, CXCR4, PTTG, HBME-1 and bFGF, was up-regulated in metastatic compared to non-metastatic thyroid carcinoma. Multiple factor binary ordinal logistic regression analysis showed that MMP2, PTTG, VEGF-C, CXCR4 and bFGF were independent factors associated with the metastatic status of thyroid carcinoma. ROC curve analysis of these five proteins revealed that VEGF-C and bFGF were the most useful protein markers for the diagnosis of metastatic thyroid cancer., Conclusion: MMP2, PTTG, VEGF-C, CXCR4 and bFGF are potential cellular tumor markers for identifying thyroid cancer with greater risk for metastasis and the novel combination of VEGF-C and bFGF as biomarkers may improve the accuracy of early detection and the differential diagnosis between metastatic and non-metastatic thyroid carcinoma.

Renal angiomyolipoma is a type of benign tumor that occurs sporadically in addition to being associated with tuberous sclerosis. Preoperative embolization of large tumors is important to avoid excessive blood loss during surgery. We reported a patient with a 5505-g giant renal angiomyolipoma in a solitary kidney. The patient was treated with preoperative embolization and radical nephrectomy without complications. This type of treatment for an enormous angiomyolipoma can reduce the risk of uncontrolled hemorrhage caused by rupture of the tumor during the operation and should be considered for the treatment of similar tumors.

Aims: Purple sweet potato (PSP) pigments were proved to protect murine thymocytes from (60)Co γ-ray-induced mitochondria-mediated apoptosis in our previous study. In this study, we further investigated the effect of PSP pigments on apoptosis related ROS, p53 and Bcl-2 family., Methods: Cell viability was analyzed by MTT. Apoptosis was certified by DNA ladder detection. Reactive oxygen species (ROS) were detected using 2',7',- dichlorofluorescein diacetate (DCFH-DA) probe. P53, Bcl-2 and Bax proteins were analyzed by western blot. The activities of caspase-3 and caspase-9 were determined by fluorogenic substrates detection., Results: PSP pigments treatment prior to 4Gy (60)Co γ-ray irradiation increased the cell viability and decrease the apoptosis. In the presence of PSP pigments, ROS was scavenged and followed by a p53-depression. A shift in Bcl-2/Bax ratio towards anti-apoptosis was observed as a result of p53-depression. The activities of caspase-9 and caspase-3 were reduced by PSP pigments pretreatment., Conclusions: PSP pigments have a cytoprotective activity against γ radiation. The protective effect of PSP pigments may be involving ROS scavenging, p53 depression and Bcl-2/Bax modulation in a caspase-dependent mitochondrial way., (Copyright © 2011 S. Karger AG, Basel.)

Objectives: To determine whether caveolin-1 expression is associated with bladder pain syndrome/interstitial cystitis (BPS/IC) and to better understand the pathogenesis of BPS/IC., Methods: The study population was composed of 19 women with BPS/IC and 7 healthy women as controls. Midstream urine specimens were collected before cystoscopy and cold cup bladder biopsies were obtained from the trigone of the bladder. Caveolin-1 protein expression was determined by indirect immunofluorescence and Western blot analysis in cases and controls, using a rabbit polyclonal antibody against caveolin-1. χ(2) test and Student's t test were used in the statistical analysis., Results: A statistical difference of caveolin-1 protein expression was observed between BPS/IC and healthy controls (p < 0.05, χ(2) test). Western blot analysis showed that the mean relative integrated density value of caveolin-1 in (BPS/IC) patients was significantly higher than that in the control group (p < 0.001, Student's t test)., Conclusions: The results of our study demonstrate that there is a relationship between the raised levels of caveolin-1 expression and BPS/IC. This preliminary study may provide a basis for further investigation of the role of caveolin-1 in the pathogenesis of BPS/IC., (Copyright © 2011 S. Karger AG, Basel.)

Testicular microlithiasis (TM) in infertility is an uncommon pathologic condition of unclear etiology that is characterized by calcium deposits within the seminiferous tubules. Nanobacteria (NB), as novel microorganisms mediating tissue calcification, have been discovered in some diseases. In this study, we hypothesized that NB may participate in the pathogenesis of TM, particularly in infertility. Seventeen infertility patients with TM detected by scrotal color Doppler ultrasonography and 17 infertility patients without TM as controls were enrolled in the study. The NB were isolated and cultured from semen samples and urine samples. After 3 to 6 weeks of culture, 10 of 17 (58.8%) semen samples and 2 urine samples from infertile patients with TM showed the growth of white granular microbes that firmly attached to the bottom of the culture flask and were visible to the naked eye. In the control group, only 1 of 17 (5.9%) semen samples from infertile patients without TM showed the growth of white granular microbes. The cultured microbes were identified by indirect immunofluorescent staining (IIFS), transmission electron microscopy (TEM), and 16s rRNA gene expression. IIFS and TEM revealed NB to be coccoid and 100 to 500 nm in diameter. The BLAST result revealed that the 16s rRNA gene sequence from the cultured microbes was 97% the same as that of the known NB. Our results showed that NB may be linked to the development of TM, which may provide a potential target for the diagnosis and treatment of infertility with TM.

Early diagnosis and treatment of thyroid cancers are critical for better prognosis and better survival rates. The purpose of this study was to identify potential diagnostic markers for papillary thyroid carcinomas with distant metastasis. Fifty-eight papillary thyroid tumor specimens (27 papillary thyroid carcinomas with distant metastasis and 31 without metastasis) were examined, and protein expression of pituitary tumor-transforming gene (PTTG), E-cadherin, p27kip1, vascular endothelial growth factor (VEGF)-C, metalloproteinase (MMP) 2, MMP9, chemokine receptor CXCR4, and basic fibroblast growth factor (bFGF) in these tumors was assessed by immunohistochemistry. The clinicopathological variables with diagnostic significance were determined by multivariate analysis, and their diagnostic values were evaluated by ROC curve analysis. PTTG, VEGF-C, MMP2, MMP9, CXCR4, and bFGF were overexpressed in metastatic papillary thyroid carcinomas, whereas p27kip1 expression was elevated only in carcinomas lacking metastasis. Multiple-factor binary ordinal logistic regression analysis revealed that PTTG, VEGF-C, MMP2, and bFGF were independently related to biological metastatic behavior in thyroid tumors, suggesting their potential use as biomarkers. ROC curve analysis showed that among these four proteins, VEGF-C and bFGF were the best diagnostic biomarkers. A VEGF-C and bFGF cluster was the most useful factor for the differential diagnosis between metastatic and non-metastatic papillary thyroid cancers. Thus, the combined use of VEGF-C and bFGF as biomarkers may improve the diagnostic accuracy of papillary thyroid carcinoma and may be useful in multimodal screening programs for the clinical diagnosis of papillary thyroid carcinoma and early detection of papillary thyroid carcinoma with distant metastasis.

Introduction and Hypothesis: This study was designed to detect whether nanobacteria (NB) reside in urine and bladder tissue samples of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) and whether antibiotic therapy targeting these organisms is effective in reducing NB levels and IC/PBS symptoms., Methods: Twenty-seven IC/PBS patients underwent cystoscopy. Bladder biopsies and urine samples were obtained and cultured for NB, which were identified by indirect immunofluorescent staining and transmission electron microscopy., Results: Eleven bladder samples showed growth of microbes that were identified to be similar to NB. Homologous study of the 16S ribosomal RNA gene suggested that the NB could be the pathogen. For enrolled 11 patients, NB levels decreased dramatically after tetracycline treatment, and they reported significant reduction in the severity of IC/PBS symptoms., Conclusions: A high prevalence of NB was observed in female IC/PBS, and anti-NB treatment effectively improved the symptoms, which suggest that NB may cause some cases of IC/PBS.

Biology presents incomparable, but desirable, characteristics compared to engineered systems. Inspired by biological development, we have devised a multi-layered design architecture that attempts to capture the favourable characteristics of biological mechanisms for application to design problems. We have identified and implemented essential features of Genetic Regulatory Networks (GRNs) and cell signalling which lead to self-organization and cell differentiation. We have applied this to electronic circuit design.

When 85 cervical type spondylosis patients randomly lay on one's back and on one's right side the 8 different tresles and pillows. We survey indexes of the cervical spine anatomy, for example cervical arcs and angles of cervical spine and level line. We appraise relation of balance between different trestle or pillow and cervical spine. liquid needle-free injection, jet power, stagnation pressure

Objective: To observe the expressions of the substance P (SP) mRNA and neurokinin-1 receptor (NK-1R) in the posterior horn of the L5 - S2 spinal cord in the rat model of chronic prostatitis pain, and to investigate the changes in the activation of astrocytes and influence of SP on this activation in rat spinal cord astrocytes cultured in vitro., Methods: The rat model of chronic prostatitis pain was established by injection of complete Freund's adjuvant (CFA) and assessed by the tail flick threshold test, the control rats injected with sodium chloride and all observed at 0, 14 and 28 days. Changes in the expressions of SP mRNA, NK-1R, glial fibrillary acidic protein (GFAP), tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) in the posterior horn of the L5 - S2 spinal cord were detected by RT-PCR and Western blot. Rat spinal cord astrocytes were cultured in vitro and divided into a control group, cultured with ITS cell culture fluid, and two experiment groups, with Group 1 stimulated with SP at the concentration of 10(-9) - 10(-6) mol/L for 12 hours followed by determination of the expressions of TNF-alpha, IL-1beta, NO and NOS by ELISA and nitrate reductase and colorimetric methods, and Group 2 at 10(-7) mol/L for 0, 24, 48 and 72 hours followed by detection of the GFAP expression by Western blot., Results: The expressions of SP mRNA, NK-1 R, GFAP, TNF-alpha and iNOS in the posterior horn of the L5 - S2 spinal cord were obviously higher in the rat prostatitis pain models than in the controls, successively higher at 28 than at 14 and 0 d (P < 0.01), and so was the expression of GFAP at 28 than at 14 d in the experiment groups (P < 0.05). SP induced a gradual increase at 10(-7) mol/L in the expression of GFAP in the spinal cord astrocytes at 0 -72 h, significantly different from that of the control group (P < 0.01), and it promoted the excretion of TNF-alpha and IL-1beta and the activity of NO and NOS at 10(-9) - 10(-6) mol/L at 12 h in a concentration-dependent manner, with marked differences between the experiment and control groups (P < 0.01, P < 0.05). But a decreased excretion of IL-1 beta was observed in the 10(-6) mol/L group, though with no significant difference from the control (P > 0.05)., Conclusion: Chronic prostatitis pain could upregulate the expressions of the excitatory transmitter SP and receptor in the L5 - S2 spinal cord, and result in the activation of astrocytes and increased excretion of proinflammatory cytokines, which may be associated with the persistence and generalization of prostatitis pain.

Objective: To explore the changes of substance P in cornu dorsal medullae spinalis effected by activation of astrocytes in rats with pain from chronic prostatitis., Methods: Sixty SD rats were randomized into three groups: the control group (n=20), the chronic prostatitis pain model group (n=20) and the interference group (n=20). The model was induced by injection of complete Freund adjuvant and 3% carrageenan into the prostate. Propentofylline was given with PE-10 in the spinal cord of the rat models. The activation of astrocytes and the distribution of substance P in the spinal cord were detected with immunofluorescence and the changes of substance P observed by radioimmunoassay., Results: The activation of astrocytes was significantly increased in the models compared with controls, but significantly reduced in interfered group in comparison with the pain model group (P < 0.01), and such was the case with substance P (P <0.01)., Conclusion: The activation of astrocytes was one important reason for the changes of substance P excreted from cornu dorsal medullae spinalis in the chronic prostatitis rats.

Objective: To elucidate the details of operative technique of anastomotic posterior urethroplasty for traumatic posterior urethral strictures in attempt to offer a successful result., Methods: We reviewed the clinical data of 106 patients who had undergone anastomotic repair for posterior urethral strictures following traumatic pelvic fracture between 1979 and 2004. Patients'age ranged from 8 to 53 years (mean 27 years). Surgical repair was performed via perinea in 72 patients, modified transperineal repair in 5 and perineoabdominal repair in 29. Follow-up ranged from 1 to 23 years (mean 8 years)., Results: Among the 77 patients treated by perineal approaches, 69 (95.8%) were successfully repaired and 27 out of the 29 patients (93.1%) who were repaired by perineoabdominal protocols were successful. The successful results have sustained as long as 23 years in some cases. Urinary incontinence did not happen in any patients while impotence occurred as a result of the anastomotic surgery., Conclusions: Three important skills or principles will ensure a successful outcome, namely complete excision of scar tissues, a completely normal mucosa ready for anastomosis at both ends of the urethra, and a tension-free anastomosis. When the urethral stricture is below 2.5 cm long, restoration of urethral continuity can be accomplished by a perineal procedure. If the stricture is over 2.5 cm long, a modified perineal or transpubic perineoabdominal procedure should be used. In the presence of a competent bladder neck, anastomotic surgery does not result in urinary incontinence. Impotence is usually related to the original trauma and rarely (5.7%) to urethroplasty.

Polypeptide from Chlamys farreri (PCF) has been identified as a potent antioxidant and photoprotective agent. In this study, we investigated whether PCF could inhibit apoptosis of murine thymocytes induced by ultraviolet B (UVB) and modulate UVB induced the mitogen-activated protein kinases (MAPKs) cascade in vitro. Our results show that PCF inhibit UVB-induced apoptotic cell death in murine thymocytes. We also found that PCF potently stimulated the phosphorylation of ERKs, which is involved in the cell survival-signaling cascade. Furthermore, the specific inhibition of the ERKs pathways by PD98059 reduced the cytoprotective effect of PCF. On the other hand, the JNKs and p38 inhibitor SP600125 and SB203580 additively enhanced the cytoprotective effect of PCF. We concluded that the activation of JNKs and p38 kinase played an important role in UVB-induced apoptosis, and PCF likely exerted its cytoprotective effect in thymocytes through ERKs activation. These suggested that part of the antiapoptotic effect of PCF might be mediated by its ability to modulate the MAPKs cascade.

Studies of Rho GTPases in Drosophila and Xenopus suggest that Rho family proteins may play an important role in embryogenesis. A reverse genetic approach was employed to explore the role of Rho GTPases in murine cardiac development. Cardiac-specific inhibition of Rho family protein activities was achieved by expressing Rho GDIalpha, a specific GDP dissociation inhibitor for Rho family proteins, using the alpha-myosin heavy chain promoter, active at embryonic day (E)8.0 during morphogenesis of the linear heart tube. RhoA, Rac1 and Cdc42 activities were significantly inhibited, as shown by decreased membrane translocation of these proteins in the transgenic hearts. Transgenic F1 mice for each of two independent lines expressing the highest levels of the transgene, died around E10.5. Homozygotes of the middle copy-number lines, in which Rho GDIalpha expression was increased four-fold over normal levels, were also embryonic lethal. Cardiac morphogenesis in these embryos was disrupted, with incomplete looping, lack of chamber demarcation, hypocellularity and lack of trabeculation. Cell proliferation was inhibited in the transgenic hearts, as shown by immunostaining with anti-phosphohistone H3, a marker of mitosis. In addition, ventricular hypoplasia was associated with up-regulation of p21, an inhibitor of cyclin-dependent kinases, and with down-regulation of cyclin A, while cell survival was not affected. These results reveal new biological functions for Rho family proteins as essential determinants of cell proliferation signals at looping and chamber maturation stages in mammalian cardiac development.