Clinical predictors of polyps recurring in patients with chronic rhinosinusitis and nasal polyps: a systematic review and meta-analysis.

BACKGROUND: Identification of perioperative risk factors for recurrent nasal polyps (RNPs) is important for selection of further treatment and determination of appropriate follow-up period. However, the relative prognostic significance of these risk factors has not been investigated. METHODOLOGY: We compared the nasal symptoms, endoscopic polyp and Lund-Mackey computed tomography scores, and the laboratory and pathological findings of RNP and non-RNP patients. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: Patients with poor nasal symptom scores and olfactory dysfunctions and high Lund-Mackey computed tomography scores were at higher risk of postoperative RNPs, as were those with allergic conditions and elevated tissue and serum eosinophil levels. The tissue neutrophil counts/percentages were significantly lower in the RNP than the other group. The tissue eosinophil level was of higher diagnostic utility than the serum eosinophil level. The RNP diagnostic odds ratio afforded by the tissue eosinophil count or percentage was 54.1247. The area under the receiver operating characteristic curve was 0.936. The sensitivity and specificity were 0.8809 and 0.8834, respectively. CONCLUSION: The tissue eosinophil level reliably predicts RNP after endoscopic sinus surgery.

[Outcomes of implanting porcine small intestinal submucosa mesh in rabbit vesicovaginal space].

Objective: To assess surgical outcomes of implanted porcine small intestinal submucosa (SIS) mesh in the rabbit vesicovaginal space (VVS) and explore its application value in pelvic floor reconstruction surgery. Methods: Sixteen male rabbits were randomly divided into four groups, and each group had four rabbits. All groups of rabbits were implanted with SIS mesh in the vesicovaginal space. They were humanely killed after a postoperative period of 7, 30, 90 and 180 days by group. The grafted area was removed with the surrounding bladder and vaginal tissues. The specimens were embedded in paraffin and then stained with HE and Masson's trichrome stains for visual observations, cells counts, and assessment of tissues and collagen fibers. Results: (1) After HE staining, a large number of inflammatory response cells mainly eosinophils and lymphocytes infiltrated around the SIS mesh in 7 days group, and neovascularization was observed, the infiltration area of inflammatory response cells further increased in 30 days group, the infiltration area of inflammatory response cells significantly reduced in 90 days group, while the inflammatory response basically subsided in 180 days group. (2) After Masson's trichromestaining, the collagen structure of SIS mesh in 7 days group was clear and intact. While, the collagen structure of SIS mesh was partially degraded in 30 days group, the SIS meshes of 4 rabbits were completely degraded, but the collagen fragments of SIS remained in 90 days group. In 180 days group, the SIS mesh of all rabbits was degraded, and one of them had the formation of new collagen fibers. Conclusions: SIS mesh implanted into the VVS of rabbits can lead to a transient non infective inflammatory reaction, which could be completely degraded and a small amount of new collagen fibers could be produced after 180 days of implantation. Which shown that SIS mesh should be used cautiously in pelvic floor reconstruction surgery.

Inhibitory effect of the Notch pathway-inhibitor DAPT on invasion and metastasis of tongue cancer via lncRNA-KAT14 regulation.

OBJECTIVE: We aimed to identify a reliable biomarker for tongue squamous cell carcinoma (TSCC), the most common oral cancer with no established biomarkers, to predict prognosis and to select the optimal treatment. MATERIALS AND METHODS: To investigate whether DAPT exhibited antitumor functions, CAL-27 and SCC-9 cells were treated with DAPT (5 µM or 10 µM) for different times. Further, qRT-PCR was used to determine the mRNA expression levels of lncRNA-KAT14 after treatment with DAPT or si-KAT14 and both combined. Moreover, the treated cells were cultured for different times to investigate their antitumor function. The Wound-healing and Transwell assay were carried out to evaluate the migration and invasion viability of cancer cells, respectively. Finally, the Western blots were performed to determine the expression of EMT-related proteins after transfection with si-KAT14 or treatment with DAPT to investigate the effects of DAPT on EMT-related proteins. RESULTS: Proliferation was inhibited after treatment with DAPT, and the expression of lncRNA-KAT14 was upregulated. To investigate the correlation of DAPT and lncRNA-KAT14 on the metastasis and invasion in tongue cancer, the following cellular processes were assessed: proliferation, invasion, and migration ability. The Western blots were used to determine the expression of E-cadherin, N-cadherin, Vimentin, and Snail, showing that DAPT or lncRNA-KAT14 suppressed all these processes, inducing a decreased expression of N-cadherin, Vimentin, and Snail, and increased expression of E-cadherin, compared with the control group. Once transfection with si-KAT14 occurred, the evaluated cellular processes were enhanced, being this attenuated by the treatment with DAPT. CONCLUSIONS: Our results suggest that DAPT suppresses invasion and metastasis of tongue cancer by regulating lncRNA-KAT14.

[Analysis of characteristics and influence factors of diagnostic delay of endometriosis].

Objective: To access the influence factors of diagnostic delay of endometriosis. Methods: We designed a questionnaire of diagnostic delay of endometriosis. From February 2014 to February 2016, 400 patients who had dysmenorrhea and diagnosed with endometriosis by surgery in Peking University Third Hospital were surveyed retrospectively. Time and risk factors of diagnostic delay were analyzed. Results: The diagnostic delay of 400 patients was 13.0 years (0.2-43.0 years), 78.5%(314/400) patients thought pain was a normal phenomenon and didn't see the doctor. Patients who suffered dysmenorrhea at menarche experienced longer diagnostic delay than those who had dysmenorrhea after menarche (18.0 vs 4.5 years; Z=191.800, P<0.01) . Patients who suffered aggravating dysmenorrhea experienced shorter delay time than those who suffered stable or relieving dysmenorrhea (11.0 vs 12.5 vs 18.0 years; Z=8.270, P<0.05) , with the difference statistically significant, single factor analysis shows. Severe dysmenorrhea, deep infiltration endometriosis (DIE) , family history of dysmenorrhea or endometriosis, previous surgical history of endometriosis, high stage, with infertility, adenomyoma or other symptoms, could help to shorten diagnostic delay with no significant difference (P>0.05) . By multiple logistic regression analysis, the results shown that whether have dysmenorrhea at menarche and clinical diagnosis time were the independent factors affecting delayed diagnosis (P<0.01) . Conclusions: Diagnostic delay of endometriosis is common and the mean delay time is 13.0 years mainly due to the unawareness of dysmenorrhea. Dysmenorrhea at menarche, clinical diagnosis time and dysmenorrhea intensity are the factors affecting time of diagnostic delay.

[Role of oral contraceptives in preventing endometriosis-related pain progression].

Objective: To analyze the effect of oral contraceptives on dysmenorrhea in patients with endometriosis. Methods: We designed dysmenorrhea and chronic pelvic pain questionnaire.From February 2014 to February 2016 in the Gynecological Department of Peking University Third Hospital, patients suffered dysmenorrhea with or without endometriosis or adenomyosis were included.According to their own willingness, patients were divided into the research group and the control group.The research group periodically took oral contraceptives (Diane-35 or Yasmin), while the control group received no treatment.They were followed-up about dysmenorrhea every six months, and the total follow-up time was one and a half year. Results: The dysmenorrhea VAS scores of patients in research group after taking oral contraceptives for six or twelve months were significantly lower than that in baseline (VAS 4 vs 5 vs 7). The dysmenorrhea VAS scores increased after quitting medication, but remained still lower than baseline (VAS 6.5 vs 7). However, the dysmenorrhea VAS scores of patients in control group remained unchanged (VAS 6 vs 6). Patients who took pills for more than one year experienced the same severity of dysmenorrhea after six months' or one year's medication (VAS 2 vs 2), and they suffered slowly aggravating recurrent dysmenorrhea, while those who quitted after six months' medication suffered quickly recurrent dysmenorrhea.The relieving rate of dysmenorrhea in research group was significantly higher than that in control group (79.7% vs 8.2%), and the relieving rate in patients with severe pain was significantly higher than that with mild or moderate pain (87.0% vs 66.6 % vs 77.1%). The relieving rate in patients without lesions was significantly higher than patients with adenomyosis (92.6% vs 59.1%). Conclusions: Endometriosis is a progressing disease. Longterm medication of oral contraceptives can relieve the dysmenorrhea pain.The extent of pain relief was not connected with the length of medication.Dysmenorrhea recurred after quitting medication, and the longer of medication, the slower pain recurred.Patients without lesions experienced higher pain relieving rate than those with adenomyosis.

The study on specific umbilical blood Dc vaccine for Beige nude mice loaded human colorectal carcinoma to induce anti-tumor immunity.

OBJECTIVE: This study is to observe the immunosuppression of CD137L transfected umbilical blood Dcs (Dendritic cell) vaccine to tumor development of SCID/ Beige nude mice. MATERIALS AND METHODS: Samples of umbilical blood in the childbirth pregnant women were collected by density gradient centrifugation. Umbilical cord blood dendritic cells (Dcs) were transfected by specific CD137L via LipofectamineTM method and cells were harvested. Meanwhile, the peripheral blood of volunteers was collected to isolate Dcs, the Dcs were cultured for 5 days and hatched with SW-1116 cells antigen. The mature Dcs were harvested. The male SCID/Beige nude mice were subcutaneously injected with human SW-1116 cells in axillary to build colorectal carcinoma model as blank control (Blank). The naked peripheral blood Dc vaccine group (cPBMCs), the SW-1116 antigen-specific peripheral blood Dc vaccine group (pDcs) and the CD137L specific umbilical blood Dc vaccine group (tuDcs) were injected 24 h before tumor cells injection, respectively to recur the humanized immune reconstruction. The general life, living habits changes, tumor growing time and tumor size were observed. The nude mice were sacrificed 18 days after tumor formation. The tumor size, mice weight, in vitro tumor weight, liver weight and spleen weight of mice were recorded to evaluate the anti-tumor effect of the specific immune cells. RESULTS: The nude mice in pDcs group showed better general living condition, slower tumor growth, smaller tumor volume and no ulceration, necrosis, and death in nude mice. The tumor formation time in different groups was 4.71 ± 0.18 ds (blank), 7.71 ± 0.29 ds (cPBMCs), 7.86 ± 0.26 ds (pDcs) and 8.14 ± 0.69 ds (tuDcs) respectively. There were significant differences between blank and other three groups (F = 40.96, p < 0.01). Compared to mice in blank group, the tumor volume of cPBMCs group was significantly smaller (201.43 ± 69.84 mm³ vs. 436.04 ± 54.50 mm³, p < 0.01) and the tumor weight were significantly smaller (1.25 ± 0.12 g vs. 2.83 ± 0.24 g, p < 0.01). The tumor volume of tuDcs mice was significantly smaller than that of blank (92.11 ± 11.55 mm³ vs. 436.04 ± 54.50 mm³, p < 0.01) and cPBMCs mice (92.11 ± 11.55 mm³ vs. 201.43 ± 69.84 mm³, p < 0.01). Similarly, the tumor weight of tuDcs mice was significantly smaller than that of blank (0.66 ± 0.07 g vs. 2.83 ± 0.24 g, p < 0.01) and cPBMCs mice (0.66 ± 0.07 g vs. 1.25 ± 0.12 g, p < 0.01). There was no significant difference in tumor volume (92.11 ± 11.55 mm³ vs. 85.61 ± 11.59 mm³, p = 0.69) and tumor weight (0.66 ± 0.07 g vs. 0.63 ± 0.09 g, p = 0.75) between tuDcs group and pDcs group. CONCLUSIONS: The specific CD137L transfected umbilical blood Dc vaccine had significant anti-tumor effect against human colon cancer in nude mice via increasing the number of immune effector cell in tumor microenvironment.

[Quality analysis of observational studies on pelvic organ prolapse in China].

Objective: To evaluate the quality of observational studies on pelvic organ prolapse in China. Methods: The checklist of strengthening the reporting of observational studies in epidemiology (STROBE) statement was applied to evaluate the observational studies. The articles were searched in the SinoMed database using the terms: prolapse, uterine prolapse, cystocele, rectal prolapse and pelvic floor; limited to Chinese core journals in obstetrics and gynecology from January 1996 to December 2015. With two 10-year groups (1996-2005 and 2006-2015), the χ(2) test was used to evaluate inter-group differences. Results: (1) A total of 386 observational studies were selected, including 15.5%(60/386) of case-control studies, 80.6%(311/386) of cohort studies and 3.9% (15/386) of cross-sectional studies. (2) There were totally 22 items including 34 sub-items in the checklist. There were 17 sub-items (50.0%, 17/34) had a reporting ratio less than 50% in all of aticles, including: 1a (study's design) 3.9% (15/386), 6a (participants) 24.6% (95/386), 6b (matched studies) 0 (0/386), 9 (bias) 8.3% (32/386), 10 (study size) 3.9%, 11 (quantitative variables) 41.2% (159/386), 12b-12e (statistical methods in detail) 0-2.6% (10/386), 13a (numbers of individuals at each stage of study) 18.9% (73/386), 13b (reasons for non-participation at each stage) 18.9%, 13c (flow diagram) 0, 16b and 16c (results of category boundaries and relative risk) 9.6% (37/386) and 0, 19 (limitations) 31.6% (122/386), 22 (funding) 20.5% (79/386). (3) The quality of articles published in the two decades (1996-2005 and 2006-2015) were compared, and 38.2%(13/34) of sub-items had been significantly improved in the second 10-year (all P<0.05). The improved items were as follows: 1b (integrity of abstract), 2 (background/rationale), 6a (participants), 7 (variables), 8 (data sources/measurement), 9 (bias), 11 (quantitative variables), 12a (statistical methods), 17 (other analyses), 18 (key results), 19 (limitations), 21 (generalisability), 22 (funding). Conclusions: The quality of observational studies on POP in China is suboptimal in half of evaluation items. However, the quality of articles published in the second 10-year have significantly improved.

Effects of acute controlled changes in end-tidal carbon dioxide on the diameter of the optic nerve sheath: a transorbital ultrasonographic study in healthy volunteers.

Transorbital ultrasonographic measurement of the diameter of the optic nerve sheath is a non-invasive, bed-side examination for detecting raised intracranial pressure. However, the ability of the optic nerve sheath diameter to predict acute changes in intracranial pressures remains unknown. The aim of this study was to examine the dynamic changes of the optic nerve sheath diameter in response to mild fluctuations in cerebral blood volume induced by changes in end-tidal carbon dioxide. We studied 11 healthy volunteers. End-tidal carbon dioxide was controlled by a model-based prospective end-tidal targeting system (RespirAct™). The volunteers' end-tidal carbon dioxide was targeted and maintained for 10 min each at normocapnia (baseline); hypercapnia (6.5 kPa); normocapnia (baseline 1); hypocapnia (3.9 kPa) and on return to normocapnia (baseline 2). A single investigator repeatedly measured the optic nerve sheath diameter for 10 min at each level of carbon dioxide. With hypercapnia, there was a significant increase in optic nerve sheath diameter, with a mean (SD) increase from baseline 4.2 (0.7) mm to 4.8 (0.8) mm; p < 0.001. On return to normocapnia, the optic nerve sheath diameter rapidly reverted back to baseline values. This study confirms dynamic changes in the optic nerve sheath diameter with corresponding changes in carbon dioxide, and their reversibly with normocapnia.

[Safety and efficacy of Cox-maze â ¢ procedure for patients with atrial fibrillation associated with rheumatic mitral valve disease].

OBJECTIVE: To evaluate the safety and efficacy of cut-and-sew Cox-Maze (CM) Ⅲ procedure for patients with atrial fibrillation associated with rheumatic mitral valve disease. METHODS: Patients received mitral valve replacement and CM procedure between January 2007 and July 2015, were 1∶1 matched and assigned to CM Ⅳ group (undergoing surgical ablation) and CM Ⅲ group (undergoing cut-and-sew CM Ⅲ). Safety indices, mortality rate, complications and recovery rate of sinus rhythm were compared between the two groups. RESULTS: Mean extracorporeal circulation time was (154±22) min in the CM Ⅲ group and (136±21) min in the CM Ⅳ group (P<0.001), and aortic clamp time was (85±9) min in the CM Ⅲ group and (74±12) min in the CM Ⅳ group (P<0.001). One patient (1.18%) in the CM Ⅲ group died of multi-organ failure 4 day after left ventricular rupture being sucessfully repaired, and 2 patients died (2.35%) in the CM Ⅳ group ( 1 due to left ventricular rupture and 1 due to low cardiac output syndrome). There was no significant difference in mortality between the two groups. Temporary pacemaker were applied for 76 cases (89.41%) in the CM Ⅲ and 70 cases (82.35%) in the CM Ⅳ group, without a statistical difference (P=0.186). There were also no statistical difference between the two groups in intraoperative urinary volume, postoperative drainage of fluid volume, hemoglobinuria, ventilator time, ICU time, hospital stay and the incidence of the complications (all P>0.05). Sinus rhythm recovery rate was 62.35 % in the CM Ⅲ group and 57.65 % in the CM Ⅳ group, without a statistical difference (P=0.531) at the operation day, but at discharge a statistical difference was found (97.62% in the CM Ⅲ group vs 81.93% in the CM Ⅳ group, P<0.001). All patients were followed up for three months, and no deaths occurred. Sinus rhythm recovery rate was 96.43 % in the CM Ⅲ group and 86.75% in the CM Ⅳ group, with a statistical difference (P=0.024). CONCLUSION: The cut-and-sew Cox-Maze Ⅲ procedure is a safe and effective method for patients with atrial fibrillation associated with rheumatic mitral valve disease.

The TLR4-associated phospholipase D1 activation is crucial for Der f 2-induced IL-13 production.

BACKGROUND: House dust mites (HDMs) are the most important source of indoor aeroallergens that contribute to the rising incidence of allergic diseases such as allergic asthma. The major HDM, Der f 2, induces inflammatory cytokine expression. Little is known about the signaling pathway involved. OBJECTIVE: We wanted to define the Der f 2 signaling pathway from its receptor to the transcription factor responsible for IL-13 expression and production. METHODS: Human bronchial epithelial cells were stimulated with Der f 2. The release and gene expression of IL-13 were measured by means of ELISA and RT-PCR, respectively. In the airway inflammation mouse model, airway responses were assessed using ELISA, histology, BAL fluid, and methacholine responsiveness. RESULTS: Here, we show that Der f 2 binds to TLR4 and induces IL-13 expression and production. In the airway inflammation mouse model, Der f 2-induced IL-13 production significantly decreased with treatment of TAK-242, a novel TLR4 inhibitor. Activation of TLR4 by Der f 2 requires the recruitment and activation of Syk, which leads to phosphorylation of PLCγ and membrane translocation of PKCα. p38 MAPK is then activated by PKCα and stimulates PLD1 activity by phosphorylating the Thr147 residue of PLD1. PLD1 activation enhanced binding of ROCK1 to ATF-2 and leads to increased expression of IL-13. CONCLUSION: Our data extend the knowledge for a variety of possible roles of PLD1 in allergic disorders including asthma pathogenesis and suggest possible candidacy of PLD1 as a molecular target for novel therapeutic approaches.

Oridonin inhibits tumor growth in glioma by inducing cell cycle arrest and apoptosis.

Glioma is the most common malignant intracranial tumors. Despite newly developed therapies, these treatments mainly target oncogenic signals, and unfortunately, fail to provide enough survival benefit in both human patients and mouse xenograft models, especially the first-generation therapies. Oridonin is purified from the Chinese herb Rabdosia rubescens and considered to exert extensive anti-cancer effects on human tumorigenesis. In this study, we systemically investigated the role of Oridonin in tumor growth and the underlying mechanisms in human glioma. We found that Oridonin inhibited cell proliferations in a dose- and time-dependent manner in both glioma U87 and U251 cells. Moreover, these anti-cancer effects were also confirmed in a mouse model bearing glioma. Furthermore, cell cycle arrest in S phase was observed in Oridonin-mediated growth inhibition by flow cytometry. Cell cycle arrest in S phase led to eventual cell apoptosis, as revealed by Hoechst 33342 staining and annexin V/PI double-staining. The cell apoptosis might be accomplished through a mitochondrial manner. In all, we were the first to our knowledge to report that Oridonin could exert anti-cancer effects on tumor growth in human glioma by inducing cell cycle arrest and eventual cell apoptosis. The identification of Oridonin as a critical mediator of glioma growth may potentiate Oridonin as a novel therapeutic strategies in glioma treatments.

Prophylactic thyroidectomy for MEN 2-related medullary thyroid carcinoma based on predictive testing for RET proto-oncogene mutation and basal serum calcitonin in China.

INTRODUCTION: Early and normative surgery is the only curative method for multiple endocrine neoplasia type 2 (MEN 2)-related medullary thyroid carcinoma (MTC). AIMS: To study the timing of prophylactic total thyroidectomy (TT) for MEN 2-related MTC with different RET mutations in a Chinese population, and to compare the sensitivity and accuracy of fully-automated chemiluminescence immunoassay (FACLIA) and radioimmunoassay (RIA) for serum calcitonin (Ct). METHODS: We collected 24 asymptomatic individuals from 8 unrelated Chinese families with MEN 2, and analyzed RET mutation and Ct levels. Then we performed TT on 17 of the 24 individuals, including TT (2/17), TT with bilateral level VI lymph-node dissection (B-LND(VI); 12/17) and TT with B-LND(VI) + modified unilateral/bilateral/local neck dissection (3/17). RESULTS: Histopathology revealed bilateral/unilateral MTC in 15/17 (88.2%; median diameter, 1.0 cm) and bilateral C-cell hyperplasia in 2/17 (11.8%; p.V292M/R67H/R982C and p.C618Y). Lymph-node metastasis/fibro-adipose tissue invasion (p.C634R) or solely fibro-adipose tissue invasion (p.C634Y) were found in 2/17 (11.8%). Elevated pre-surgical Ct (pre-Ct) was identified by FACLIA in 17/17 (median age, 24.0), while pre-Ct by RIA was found in only 6/15 (P < 0.001). The median follow-up was 22.0 months, during which 16/17 had no abnormality (one p.C634R individual had elevated Ct), and another 7 carriers still had consistently undetectable Ct by FACLIA. CONCLUSIONS: Our study highlights the importance and feasibility of individualized prophylactic TT for MEN 2-related MTC, based on predictive integrated screening of RET and pre-Ct levels. Besides, we recommend FACLIA to measure Ct for earlier diagnosis, treatment and follow-up monitoring of MTC.

In vivo study of the initial bacterial adhesion on different implant materials.

OBJECTIVE: Biofilm formation on implant materials plays a major role in the aetiology of periimplantitis. The aim of this study was to examine in vivo the initial bacterial adhesion on six different implant materials. METHODS: The implant materials Ti-m, TiUnite®, ZiUnite®, ATZ-m, ATZ-s, TZP-A-m were tested using bovine enamel slabs as controls. All materials, fixed on splint systems, were examined after 30 min and 120 min of oral exposure. DAPI staining was used for quantitative analysis of the initially adherent microorganisms. Initial adherent microorganisms were visualised by fluorescence In situ-hybridisation (FISH) and quantified by confocal laser scanning microscopy (CLSM). The targets of the oligonucleotide probes were Eubacteria, Veillonella spp., Fusobacterium nucleatum, Actinomyces naeslundii and Streptococcus spp. RESULTS: DAPI analysis showed that increasing the time of oral exposure resulted in an increasing amount of initial adherent bacteria. The highest level of colonisation was on ZiUnite®, with the lowest occurring on the bovine enamel, followed by Ti-m. This early colonisation correlated significantly with the surface roughnesses of the materials. FISH and CLSM showed no significant differences relating to total bacterial composition. However, Streptococcus spp. was shown to be the main colonisers on each of the investigated materials. CONCLUSION: it could be shown that within an oral exposure time of 30 min and 120 min, despite the salivary acquired pellicle initial biofilm formation is mainly influenced directly or indirect by the material surface topography. Highly polished surfaces should minimise the risk of biofilm formation, plaque accumulation and possibly periimplantitis.

Effect of estradiol on the expression of renal sodium transporters in rats.

BACKGROUND: Although estradiol has been thought to perform an important role in blood pressure regulation, the effects of estradiol on the expression of renal sodium transporters are not fully understood. METHODS: Female Sprague-Dawley rats were treated with 17ß-estradiol or vehicle for 10 days after ovariectomy, and after both ovariectomy and adrenalectomy to eliminate the effect of aldosterone. RESULTS: In the ovariectomized (OVX) rats, estradiol decreased the abundance of the Na-K-2Cl cotransporter (NKCC2) (31.5% of control (OVX), p < 0.01), Na-Cl cotransporter (NCC) proteins (40.5% of control (OVX), p < 0.01) and α- and γ-subunits of the epithelial sodium channel (ENaC) (44.7% and 11.0% of control (OVX), p < 0.01). Estradiol also reduced plasma aldosterone levels (OVX + 17ß-estradiol vs. OVX, 116.3 ± 44.4 vs. 184.2 ± 33.4 pmol/l, p < 0.05) and systolic blood pressure (OVX + 17ß-estradiol vs. OVX, 115 ± 4 vs. 132 ± 2 mmHg, p < 0.05). In rats having undergone adrenalectomy and ovariectomy, estradiol did not reduce systolic blood pressure, or the expression of sodium transporters. CONCLUSION: Estradiol decreased systolic blood pressure, plasma aldosterone levels, and the expression of renal sodium transporters. After aldosterone was eliminated, estradiol did not affect blood pressure or the expression of sodium transporters, which indicates that the effect of estradiol on the renal sodium transporters is at least partly influenced by aldosterone.

The role of basolateral amygdala in the regulation of stress-induced phosphorylated extracellular signal-regulated kinase expression in the hippocampus.

Previous studies have shown that the amygdala plays a key role in the modulation of uncontrollable stress effect on hippocampal long-term potentiation and memory in rats. This study aimed to determine the effects of selective neurotoxic lesions of the basolateral amygdala (BLA) on stress-induced glucocorticoid receptor (GR) translocation and alteration of phosphorylated extracellular signal-regulated kinases (pERK) in the hippocampus. Intrinsic neurons of the BLA in rats were destroyed using N-methyl-d-aspartate and the rats were subjected to uncontrollable stress induced by restraint and electrical tail shocks. Western blot analyses showed that stress-induced GR translocation occurred in both rats with sham-operated surgery and rats with BLA lesions. As in the Western blot analyses, immunohistological analyses revealed stress-induced reduction of GR expression in CA1 and dentate gyrus (DG) of the hippocampi in control rats and rats with BLA lesions. In addition, the Western blot analyses showed that, in response to stress, the levels of hippocampal pERK were reduced in the sham-operated controls, but not in the rats with BLA lesions. Interestingly, the immunohistological analyses showed that BLA lesions prevented the stress-induced reductions in hippocampal pERK levels, only in the DG. These results suggested that the amygdala modulates stress-induced cognitive impairments by regulating the ERK signaling pathway in the hippocampus.

[The centralisation of highly complex operations]. / Centralisatie van hoogcomplexe chirurgie.

The relationship between hospital volume and outcome of care after pancreatic surgery, particularly mortality, has been described extensively in the past. Today, this relationship is frequently being used by healthcare providers and/or insurance companies to select hospitals for various surgical procedures. This concept, however, has many limitations. The conceptual model concerning the relationship between how hospital facilities are arranged and the different aspects of the process of providing healthcare is discussed in three case histories describing complicated postoperative courses after pancreatic resections. The conclusion is that, besides hospital volume, the manner in which the various facilities in hospitals are arranged as well as the process of care giving, particularly the effectiveness of multidisciplinary meetings, are of crucial importance to the quality of care. Data per illness, with adequate correction for case mix, are of crucial importance for comparing the differences in quality of care between hospitals.

Case report: a p.C618S RET proto-oncogene germline mutation in a large Chinese pedigree with familial medullary thyroid carcinoma.

We report a Chinese pedigree with familial medullary thyroid carcinoma. Direct sequencing of the entire coding sequences of Rearranged during Transfection (RET) identified a recurrent c.T1852A (p.C618S) mutation in 13 of 23 members. The polymorphisms c.A135G (p.A45A), c.A1296G (p.A432A), c.T2307G (p.L769L) and IVS19 + 15T > C were also found in 13 carriers, and c.G2073A (p.G691S) was found in 1 carrier. Of the 13 carriers, seven (mean age: 42.6 years, range: 27-64) presented MTC as the isolated clinical phenotype, with elevated basal serum calcitonin (average: 1077.9 ng/L, range: 504-2,652) and a mean diameter of thyroid nodules of 2.97 cm (range: 1.6-4.3); they underwent a total thyroidectomy with modified bilateral/unilateral neck dissection and/or level VI lymph node dissection. The other 6 carriers did not accept surgery (4 rejected, 2 awaited). These were 2 older patients (63 and 32 years) with elevated calcitonin (1359 and 41.4 ng/L) and multi-centric hypoechoic nodules (1.5 and 0.6 cm) with calcifications in both/left thyroid lobes; and Doppler ultrasound showed normal bilateral thyroids in 4 younger carriers (median age: 8.3 years, range: 4-12) but with increased calcitonin (average: 9.7 ng/L, range: 7.87-12.2) in 3 of them. The phenotype here is consistent with the clinical symptoms reported worldwide. We recommend that screening of hotspot regions of RET should be preferentially carried out, while whole-exon sequencing should be performed when clinical signs fail to reveal hotspot mutations or different phenotype discrepancies. Moreover, we strongly suggest prophylactic thyroidectomy should be performed before age 5 in carriers with p.C618S to prevent the occurrence and metastasis of MTC.

The effects of cyclophosphamide and mycophenolate on end-stage renal disease and death of lupus nephritis.

Debate continues about the optimal treatment modality of lupus nephritis (LN). We compared the efficacy and safety of intravenous cyclophosphamide (CYC) and mycophenolate mofetil (MMF) for LN treatment in Korea. After searching for systemic lupus erythematosus (SLE) patients diagnosed between 1998 and 2007 with the diagnostic code of ICD10, we selected the 71 patients who were treated with CYC or MMF without any other immunosuppressant except systemic steroid. Composite outcome was defined as progression to end-stage renal disease (ESRD) and/or all-cause mortality. The initial manifestations of the CYC group were more severe than those of the MMF group. The mean daily MMF dose was 980 ± 100 mg for 21.67 ± 18.25 months. The mean monthly dose per CYC pulse therapy was 850 ± 30 mg for 17.04 ± 13.15 months. The incidence of composite outcome was 5/20 (25%) in the MMF group and 4/51 (7.8%) in the CYC group. The relative risk (RR) for composite outcome in the CYC group was 0.249 (95% CI for RR: 0.067-0.934, p = 0.039) compared with the MMF group with Cox's hazard proportional analysis. In Kaplan-Meier analysis, the probability of composite outcome was lower in the CYC group than in the MMF group (Log rank test p-value = 0.026). The results of this retrospective study suggest that intravenous CYC therapy may be more efficacious in averting ESRD and death than MMF. These results need to be confirmed in a larger randomized controlled trial.

Increased interactions between PKA and NF-κB signaling in the hippocampus following loss of cholinergic input.

Neuropsychiatric disorders such as depression are frequently associated with Alzheimer's disease (AD) and the degeneration of cholinergic basal forebrain neurons and reductions in acetylcholine that occur in AD have been identified as potential mediators of these secondary neuropsychiatric symptomologies. Indeed, removal of cholinergic innervation to the hippocampus via selective immunolesions of septohippocampal cholinergic neurons induces dysfunction of the hypothalamic-pituitary-adrenocortical (HPA) axis and decreases glucocorticoid receptor expression (GR). A subsequent study showed that loss of cholinergic input decreases the activity of the catalytic subunit of protein kinase A (PKAc) and lessens the interaction of protein kinase A (PKA) with GR. Because cross-coupling between nuclear factor-κB (NF-κB) p65 and GR depends on PKA signaling, the present study was conducted to evaluate the status of NF-κB as well as interactions of PKA with NF-κB in the hippocampus following cholinergic denervation. Expression of cytosolic NF-κB p65 was diminished and IκB was degraded in the hippocampus of cholinergic immunolesioned rats compared to the controls. Immunolesions also increased NF-κB p65 Ser276 phosphorylation, as well as interactions between PKAc and NF-κB p65. These results indicate that loss of cholinergic input to the hippocampus results in decreased PKA activity and increased NF-κB activity. Such altered signaling may contribute to psychiatric symptoms, including depression, in patients with AD.

Mapping white matter diffusion and cerebrovascular reactivity in carotid occlusive disease.

OBJECTIVE: To characterize the relationship between cerebrovascular reactivity (CVR) and white matter (WM) diffusion in patients with internal carotid artery (ICA) occlusive disease. METHODS: In this exploratory observational study, 41 patients with severe stenosis or occlusion of the extracranial ICA and 12 healthy control subjects underwent CVR mapping using the fMRI response to hypercapnia. Conventional anatomic and diffusion-weighted MRI sequences were used to calculate maps of the apparent diffusion coefficient (ADC) and to exclude areas of previous ischemic injury. In all subjects, ADC was compared between WM with positive and negative CVR. In 27 patients with unilateral ICA involvement, ADC and CVR were compared between ipsilateral and contralateral WM while covarying for relevant clinical risk factors. RESULTS: In patients with bilateral disease and in the ipsilateral hemisphere of patients with unilateral disease, negative CVR was associated with increased WM ADC (p < 0.01 and p < 0.005, respectively). In patients with unilateral disease, the ipsilateral CVR deficit was correlated with the degree of hemispheric WM ADC elevation (p < 0.005). ADC elevation remained significant after correction for potential confounding risk factors. CONCLUSIONS: CVR impairment is associated with ADC elevation in normal-appearing WM of patients with severe stenosis or occlusion of the extracranial ICA. This finding is consistent with the presence of early, low-grade ischemic injury.