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INTRODUCTION: Paclitaxel (PTX) cannot effectively treat glioma because it cannot cross the bloodbrain barrier (BBB). A specific mode electroacupuncture stimulation (SMES) can temporarily open the BBB, thereby improving drug delivery to the brain. This study aimed to observe SMES-mediated accumulation of PTX in the brain and its anti-glioma effect and explore the role of the Hedgehog pathway. METHODS: The acupoint selectivity of SMES in opening the BBB was examined in normal rats. The penetration and anti-glioma activity were determined in a C6-Luc glioma rat model. SMES was performed using 2/100â¯Hz, 3â¯mA, 6-6â¯s, and 40â¯min The survival curve was analysed by the KaplanMeier method, brain tumour pathology and size was observed by HE staining, and in vivo imaging system respectively. RESULTS: SMES-induced BBB opening had acupoint selectivity. SMES could improve PTX accumulation in brain and SMES-mediated PTX delivery showed enhanced anti-glioma activity due to better brain penetration. Hedgehog pathway was involved in SMES-mediated PTX delivery by regulating Occludin expression. CONCLUSION: SMES at the head acupoints to deliver PTX is a feasible and effective method for treating glioma. The Hedgehog pathway may play a key role in SMES-mediated PTX delivery across the BBB.
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Antineoplásicos Fitogênicos , Barreira Hematoencefálica , Neoplasias Encefálicas , Eletroacupuntura , Glioma , Proteínas Hedgehog , Paclitaxel , Animais , Eletroacupuntura/métodos , Paclitaxel/farmacologia , Proteínas Hedgehog/metabolismo , Glioma/terapia , Glioma/metabolismo , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Masculino , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Ratos Sprague-Dawley , Linhagem Celular Tumoral , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacosRESUMO
To explore a new method that patients with brain diseases such as stroke sequelae are hindered by blood-brain barrier (BBB) in clinical treatment. Research preliminarily found that acupuncture with specific mode electro-stimulation (EA) to open BBB-assisted drug delivery may be is an effective means to improve the clinical efficacy of brain disease patients. So here we further explore the features and mechanism. Middle cerebral artery occlusion/R recovery rats were employed as the animal model. Laser Doppler monitoring cerebral blood flow decreased to 45â ±â 10% of the baseline value as modeling criteria and TTC staining observed infarcted areas of brain tissue. The permeability of FITC-Dextran and EB in the frontal lobe of rats was observed by microscope. After that, Western blot and Immunofluorescence staining for the detection of the shh and Gli1 signal molecule, Claudin-5 Occludin ZO-1 tight junction (TJ) proteins. EA can open the BBB stably and effectively, and has the characteristics of starting to close soon after the end of EA; EA inhibits the Shh-Gli1 signaling pathway, and downregulates Occludin ZO-1 TJ proteins. These results suggest that EA is safe and reversible in opening the BBB, and its mechanism is related to the inhibition of Shh signaling pathway to down-regulate the expression of TJ proteins.
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Terapia por Acupuntura , Barreira Hematoencefálica , Humanos , Ratos , Animais , Ocludina/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteínas de Junções Íntimas/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: To examine the relationships between polyunsaturated fatty acids (PUFAs) dietary intake and asthma in children. METHODS: In this cross-sectional study, a total of 14,727 participants from the United States National Health and Nutrition Examination Survey (NHANES) database in 1999-2018 were included, and the baseline characteristics of all participants were gathered. The description analysis was used to explore the possible covariates. Weighted multivariate logistic regression models were adopted to assessed the association between PUFAs dietary intake and asthma in children. In addition, we also performed subgroup analysis based on gender, age, and maternal smoking during pregnancy to investigate this relationship. RESULTS: The prevalence of asthma approximately was 15.38% in the present study. The result of weighted multivariate logistic regression indicated that, docosahexaenoic [weighted odds ratio (OR) = 0.37, 95% confidence interval (CI) 0.19-0.74], total n - 3 PUFAs (weighted OR = 0.63, 95%CI 0.43-0.91), and eicosapentaenoic (weighted OR = 0.35, 95%CI 0.13-0.95) dietary intake were negatively associated with asthma in children. The subgroup analysis described that when children were male (weighted OR = 0.28, 95%CI 0.10-0.84), or were 5-7 years (weighted OR = 0.04, 95%CI 0.01-0.37), were 7-12 years (weighted OR = 0.46, 95%CI 0.24-0.90), or their maternal smoking during pregnancy (weighted OR = 0.16, 95%CI 0.03-0.90), docosahexaenoic dietary intake was negatively related to childhood asthma. CONCLUSION: Docosahexaenoic dietary intake was negatively associated with the asthma in children, especially if children were male, or were 5-12 years, or their maternal smoking during pregnancy.
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Asma , Criança , Feminino , Gravidez , Humanos , Masculino , Estudos Transversais , Inquéritos Nutricionais , Asma/epidemiologia , Asma/etiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Ácidos Graxos InsaturadosRESUMO
BACKGROUND AND AIMS: The etiology of polycystic ovary syndrome (PCOS) is unclear. This study aimed to evaluate the role of classic and 11-oxygenated (11oxyC19) androgens in two typical signs of PCOS, polycystic ovary morphology (PCOM) and menstrual cycle prolongation. MATERIALS AND METHODS: A total of 462 infertile women with diagnosed PCOS and/or commonly accompanied metabolic disorders were recruited. Classic and 11oxyC19 androgens were determined with a sensitive high-performance liquid chromatography-differential mobility spectrometry tandem mass spectrometry apparatus. Least absolute shrinkage and selection operator logistic regression with fivefold cross-validation was applied to construct prediction models. RESULTS: For PCOM, the most significant contributing androgen was testosterone (T), with the weight of 51.6%. The AUC of the prediction model was 0.824 in validation set. For menstrual cycle prolongation, androstenedione (A4) was the most significant contributing androgen with weights of 77.5%. The AUC the prediction model was less than 0.75. When including other variables, the most significant variable turned to be AMH both in PCOM and in menstrual cycle prolongation. CONCLUSION: Androgens had more contribution in PCOM than in menstrual cycle prolongation. The classic androgen T or A4 contributed more than 11oxyC19 androgens. However, their contributions were diminished when other factors were considered, especially AMH.
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Infertilidade Feminina , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/metabolismo , Androgênios , Hormônio Antimülleriano/metabolismo , Ciclo MenstrualRESUMO
Background: The anti-Müllerian hormone (AMH) is gaining attention as a key factor in determining ovarian reserve and polycystic ovarian syndrome, and its clinical applications are becoming more widespread worldwide. Objective: To identify the most accurate formula for converting AMH assay results between different platforms, so that the developed AMH converter can be used to reduce the need for multiple AMH tests at different hospitals. Methods: Assuming that the Beckman Access, Kangrun, and Roche Elecsys® AMH assays fit a linear relationship from the lowest to the highest concentration (a global relationship), we used Passing-Bablok regression to determine the conversion equation between each two assays. When the relationship between two AMH assays was a local one, spline regression was used. Bland-Altman plots were drawn to check systemic bias and heterogeneity of variance across different ranges of values. The fitting effects of the models were evaluated using the squared coefficient of determination (r2), adjusted r2, root mean square error (RMSE), Akaike information criterion (AIC), and corrected AIC. Results: The coefficient of variance for multiple controls in the Kangrun, Roche, and Beckman assays was lower than 5%, and the bias of multiple controls was lower than 7%. A global linear relationship was observed between the Kangrun and Roche assays, with the intercept being zero, for which Passing-Bablok regression was employed for data conversion between the two platforms. For the other two pairs of platforms, i.e., Roche and Kangrun or Beckman and Kangrun, spline regression was applied, with the intercepts not including zero. The six corresponding formulas were developed into an online AMH converter (http://121.43.113.123:8006/). Conclusion: This is the first time Passing-Bablok plus spline regression has been used to convert AMH concentrations from one assay to another. The formulas have been developed into an online tool, which makes them convenient to use in practical applications.
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Reserva Ovariana , Hormônios Peptídicos , Aranhas , Animais , Hormônio Antimülleriano , Bioensaio , Hospitais , Nonoxinol , Fator de Crescimento Transformador betaRESUMO
Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers. However, the vast dynamic range renders the profiling of proteomes extremely challenging. Here, we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY. Specifically, zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY (NaY-PPC), followed by conventional protein identification using liquid chromatography-tandem mass spectrometry. NaY was able to significantly enhance the detection of low-abundance plasma proteins, minimizing the "masking" effect caused by high-abundance proteins. The relative abundance of middle- and low-abundance proteins increased substantially from 2.54% to 54.41%, and the top 20 high-abundance proteins decreased from 83.63% to 25.77%. Notably, our method can quantify approximately 4000 plasma proteins with sensitivity up to pg/mL, compared to only about 600 proteins identified from untreated plasma samples. A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states. In summary, this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.
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RATIONALE: It is very likely that we will miss Bing-Neel syndrome (BNS) when its initial sign is anemia.Patient concerns: A 59-year-old woman presented with episodic loss of consciousness, anemia, and extremity muscle strength scores (5-) and extremity tendon reflexes (++). DIAGNOSES: Magnetic Resonance Imaging (MRI) showed abnormal signal in the left hippocampus, left insula, and right occipital lobe. Quantitative serum immunoglobulins showed elevated immunoglobulinm (IgM) (60.6g/L). Bone marrow biopsy showed lymphoplasmacytic lymphoma (LPL) and tested positive for the MYD88 L265P mutation suggesting Waldenström macroglobulinemia (WM). INTERVENTIONS: The patient underwent 3 plasma exchange treatments in the department of hematology followed by chemotherapy (cyclophosphamide for injection, bortezomib for injection). OUTCOMES: The patient's condition improved after treatment. LESSONS: Clinicians must remain vigilant, as BNS may be the only sign of WM progression in a patient well-controlled on treatment.
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Anemia , Encefalopatias , Doenças Neurodegenerativas , Macroglobulinemia de Waldenstrom , Feminino , Humanos , Pessoa de Meia-Idade , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológicoRESUMO
Purpose: Abnormal methylation of Grainyhead-like 2 (GRHL2) is associated with a substantial role in the malignant phenotype of tumor patients. Our present research is aimed at studying the abnormal expression of GRHL2 and the association of methylation in patients with acute leukemia and its relationship with prognosis. Materials and Methods: We used quantitative real-time polymerase chain reaction (qRT-PCR) for detecting the aberrant expression level of GRHL2 in 60 patients with acute leukemia and 60 normal controls. We analyzed the significant correlation between the expression level of GRHL2 with clinicopathological features and patients' prognosis in acute leukemia using the corresponding statistical methods. Secondly, we employed qRT-PCR and Western blotting to detect the mRNA and protein levels of GRHL2 in leukemia cell lines. Next, we used methylation-specific polymerase chain reaction (MSP) technology for detecting the methylation of GRHL2 in clinical samples with acute leukemia and cell lines. Then we investigated the demethylating effect of arsenic trioxide and 5-azacitidine on the mRNA and protein expression levels of GRHL2 in cell lines of acute leukemia. Finally, we studied the effects of arsenide trioxide and 5-azacitidine on the proliferation of leukemia cells and the TGF-ß signaling pathway. Results: We found a lower level of GRHL2 expression not only in acute leukemia patients but also in cell lines when compared with normal controls. At the same time, the expression level of GRHL2 in patients with acute leukemia was significantly correlated with leukocyte count, platelet count, and cytogenetic risk grouping. In addition, the lower GRHL2 expression group showed a significantly lower overall survival rate in acute leukemia patients than that of patients with a higher GRHL2 expression group. Univariate and multivariate analyses revealed that the expression of GRHL2 is an independent risk factor in acute leukemia patients. The methylation level of the GRHL2 promoter region in acute leukemia patients and cell lines was significantly higher than the normal control group, and we found the elevated mRNA and protein levels of GRHL2 in acute leukemia cell lines after the use of the demethylation drug arsenic trioxide and 5-azacitidine. At the same time, arsenide trioxide and 5-azacitidine are associated with the inhibition of cellular proliferation of acute leukemia cells and also promote the elevated expression of TGF-ß signaling pathway-linked proteins, including TGF-ß, Smad2, Smad3, and Smad4. Conclusion: Increased expression and methylation level of GRHL2 are closely associated with the prognosis and malignant phenotype of acute leukemia patients and play an irreplaceable role in the occurrence and development of patients with acute leukemia.
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Phosphorus in the form of phosphate (Pi) is an essential element for metabolic processes, including lipid metabolism. In yeast, the inositol polyphosphate kinase vip1 mediated synthesis of inositol heptakisphosphate (IP7) regulates the phosphate-responsive (PHO) signaling pathway, which plays an important role in response to Pi stress. The role of vip1 in Pi stress and lipid metabolism of Candida albicans has not yet been studied. We found that when vip1Δ/Δ was grown in glucose medium, if Pi was supplemented in the medium or mitochondrial Pi transporter was overexpressed in the strain, the lipid droplet (LD) content was reduced and membrane damage was alleviated. However, further studies showed that neither the addition of Pi nor the overexpression of the Pi transporter affected the energy balance of vip1Δ/Δ. In addition, the LD content of vip1Δ/Δ grown in Pi limitation medium PNMC was lower than that grown in SC, and the metabolic activity of vip1Δ/Δ grown in PNMC was also lower than that grown in SC medium. This suggests that the increase in Pi demand by a high energy metabolic rate is the cause of LD accumulation in vip1Δ/Δ. In addition, in the vip1Δ/Δ strains, the core transcription factor PHO4 in the PHO pathway was transported to the vacuole and degraded, which reduced the pathway activity. However, this does not mean that knocking out vip1 completely blocks the activation of the PHO pathway, because the LD content of vip1Δ/Δ grown in the medium with ß-glycerol phosphate as the Pi source was significantly reduced. In summary, the increased Pi demand and the decreased PHO pathway activity in vip1Δ/Δ ultimately lead to LD accumulation and cell membrane damage.
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Metabolismo Energético/fisiologia , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Candida albicans/metabolismo , Membrana Celular/metabolismo , Expressão Gênica/genética , Regulação Fúngica da Expressão Gênica/genética , Fosfatos de Inositol , Gotículas Lipídicas/metabolismo , Fosfatos/metabolismo , Fosforilação , Fosfotransferases (Aceptor do Grupo Fosfato)/fisiologia , Transdução de Sinais , Fatores de Transcrição/metabolismo , Vacúolos/metabolismoRESUMO
Cytidine ribonucleosides were furnished at O5' with fixed-charge 6-trimethylammoniumhexan-1-aminecarbonyl tags and studied by UV-vis photodissociation action spectroscopy in the gas phase to probe isolated nucleobase chromophores in their neutral, protonated, and hydrogen-adduct radical forms. The action spectrum of the doubly charged cytidine conjugate showed bands at 310 and 270 nm that were assigned to the N3- and O2-protonated cytosine tautomers formed by electrospray, respectively. In contrast, cytidine conjugates coordinated to dibenzo-18-crown-6-ether (DBCE) in a noncovalent complex were found to strongly favor protonation at N3, forming a single-ion tautomer. This allowed us to form cytidine N3-H radicals by electron transfer dissociation of the complex and study their action spectra. Cytidine radicals showed only very weak absorption in the visible region of the spectrum for dipole-disallowed transitions to the low (A and B) excited states. The main bands were observed at 360, 300, and 250 nm that were assigned with the help of theoretical vibronic spectra obtained by time-dependent density functional theory calculations of multiple (>300) radical vibrational configurations. Collision-induced dissociations of cytidine radicals proceeded by major cleavage of the N1-C1' glycosidic bond leading to loss of cytosine and competitive loss of N3-hydrogen atom. These dissociations were characterized by calculations of transition-state structures and energies using combined Born-Oppenheimer molecular dynamics and DFT calculations. Overall, cytidine radicals were found to be kinetically and thermodynamically more stable than previously reported analogous adenosine and guanosine radicals.
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Transvaginal meshes repair for treating pelvic organ prolapse (POP) was halted by the U. S. Food and Drug Administration (FDA) because they can lead to severe complications. Therefore, investigations of new therapeutic strategies are urgently needed. Cell-based regenerative therapy holds great promise for the repair and restoration of damaged tissue. Here, we generated a bioengineered graft by seeding human umbilical cord mesenchymal stem cells (HUMSCs) on bioscaffolds to reconstruct the damaged vagina. In the in vitro study, HUMSCs proliferated well and the density was appropriate after 5 days of culture. Besides, we demonstrated that the differentiation potential of HUMSCs was maintained with external growth factor stimulation. The complete transcriptomic profile of HUMSCs revealed that HUMSCs cultured on grafts produced significantly higher levels of proangiogenic cytokines than cells cultured in tissue culture plates (TCPs). Three months after implantation of the bioengineered grafts into ovariectomized (OVX) rhesus monkeys via sacrocolpopexy, extracellular matrix reorganization, large muscle bundle formation, angiogenesis and, mechanical properties of the vagina were enhanced. To our knowledge, this is the first demonstration of the utility of stem cell-based bioengineered grafts for repairing damaged vaginal tissue in rhesus monkeys. These results elucidate a new approach for vagina repair and provide new ideas for treating POP.
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Células-Tronco Mesenquimais , Prolapso de Órgão Pélvico , Animais , Matriz Extracelular , Feminino , Macaca mulatta , Cordão UmbilicalRESUMO
We report the generation of gas-phase riboguanosine radicals that were tagged at ribose with a fixed-charge 6-(trimethylammonium)hexane-1-aminocarbonyl group. The radical generation relied on electron transfer from fluoranthene anion to noncovalent dibenzocrown-ether dication complexes which formed nucleoside cation radicals upon one-electron reduction and crown-ether ligand loss. The cation radicals were characterized by collision-induced dissociation (CID), photodissociation (UVPD), and UV-vis action spectroscopy. Identification of charge-tagged guanosine radicals was challenging because of spontaneous dissociations by loss of a hydrogen atom and guanine that occurred upon storing the ions in the ion trap without further excitation. The loss of H proceeded from an exchangeable position on N-7 in guanine that was established by deuterium labeling and was the lowest energy dissociation of the guanosine radicals according to transition-state energy calculations. Rate constant measurements revealed an inverse isotope effect on the loss of either hydrogen or deuterium with rate constants kH = 0.25-0.26 s-1 and kD = 0.39-0.54 s-1. We used time-dependent density functional theory calculations, including thermal vibronic effects, to predict the absorption spectra of several protomeric radical isomers. The calculated spectra of low-energy N-7-H guanine-radical tautomers closely matched the action spectra. Transition-state-theory calculations of the rate constants for the loss of H-7 and guanine agreed with the experimental rate constants for a narrow range of ion effective temperatures. Our calculations suggest that the observed inverse isotope effect does not arise from the isotope-dependent differences in the transition-state energies. Instead, it may be caused by the dynamics of post-transition-state complexes preceding the product separation.
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OBJECTIVE: The aim was to evaluate the voiding function and voiding dysfunction 3 months after laparoscopic uterosacral ligament suspension (LUSLS). We identified risk factors for postoperative voiding dysfunction. STUDY DESIGN: This retrospective study included 57 women with apical prolapse who underwent LUSLS with stage II or greater apical prolapse and without advanced anterior vaginal prolapse (stage III or IV). Data were collected from electronic medical records. Voiding function was assessed by uroflowmetry, PVR examination, and self-report questionnaires (the Pelvic Floor Distress Inventory-20 and the Urinary Impact Questionnaire) at baseline and 3 months after surgery. Voiding dysfunction was defined as an average flow rate (Qave)ï¼10 ml/s, a maximum flow rate (Qmax)ï¼15 ml/s, or a postvoid residual volume (PVR)ï¼50 ml. Statistical analyses were performed using paired-sample t tests, χ2 tests, and multivariate logistic regression. RESULTS: Thirty-five percent of women suffered from voiding dysfunction preoperatively. Uroflowmetry parameters and PVR, objective symptoms including voiding difficulties, incomplete empty, frequency and urinary incontinence didn't show significant improvement postoperatively (all pï¼0.05). Low Qave was identified as an independent risk factor of post voiding dysfunction (odds ratio, 0.558; 95 % CI, 0.324-0.963). CONCLUSIONS: Approximately one-third of women suffering from apical prolapse without advanced anterior vaginal wall had evidence of voiding dysfunction preoperatively. LUSLS has no obvious effect on uroflowmetry parameters and clinical symptoms.
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Laparoscopia , Prolapso de Órgão Pélvico , Prolapso Uterino , Feminino , Humanos , Ligamentos/cirurgia , Prolapso de Órgão Pélvico/cirurgia , Estudos Retrospectivos , Prolapso Uterino/cirurgiaRESUMO
OBJECTIVE: To evaluate the necessity of postoperative repetitive uroflowmetry and postvoid residual volume (PVR) in women with advanced anterior vaginal prolapse. METHOD: Women with anterior vaginal prolapse stages III and IV who underwent surgery were included in this prospective cohort study. The surgical procedures included laparoscopic sacrocolpopexy (LSC), transvaginal mesh repair (TVM) and native tissue repair (NTR). Uroflowmetry, a PVR examination, the Urinary Distress Inventory-6 (UDI-6) and the Urinary Impact Questionnaire-7 (UIQ-7) were administered pre- and postoperatively. Moreover, pre- and postoperative uroflowmetry parameters were compared in women with/without an improvement in voiding difficulties according to the answer of questionnaires at one year after surgery. Paired sample t-tests, Wilcoxon signed-rank test, χ2 tests were used for analyses. RESULTS: A total of 85 women were included in the study, and data were available for 47 of them at 1-year follow-up. Approximately half of women with advanced anterior vaginal prolapse had symptoms of voiding dysfunction, the rate of which decreased to approximately 10% postoperatively. The UDI-6 and UIQ-7 indicated a significant improvement postoperatively from baseline (both p<0.05). The PVR decreased significantly after surgery (p = 0.000). Uroflowmetry parameters remained stable within 1 year after surgery (all pï¼0.05) both in the improved and unimproved groups (both pï¼0.05). CONCLUSION: Symptoms of voiding dysfunction are improved significantly after surgery. Postoperative uroflowmetry appears to be unnecessary one year after pelvic floor reconstructive surgery.
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Prolapso de Órgão Pélvico , Procedimentos de Cirurgia Plástica , Prolapso Uterino , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Prolapso de Órgão Pélvico/cirurgia , Período Pós-Operatório , Estudos Prospectivos , Telas Cirúrgicas , Inquéritos e Questionários , Resultado do Tratamento , Vagina/cirurgiaRESUMO
STUDY OBJECTIVE: To study the long-term outcomes of laparoscopically assisted uterovaginal canalization and vaginoplasty in patients with congenital cervical and vaginal atresia and to introduce the surgery step by step. DESIGN: A prospective observational study from January 2016 to September 2019. SETTING: A tertiary teaching hospital. PATIENTS: Ten women diagnosed with congenital cervical and vaginal atresia. INTERVENTIONS: All women underwent laparoscopically assisted uterovaginal canalization and vaginoplasty. MEASUREMENTS AND MAIN RESULTS: All procedures went smoothly, with no case requiring conversion to laparotomy, and no intraoperative complications occurred. Postoperative febrile morbidity occurred in 1 patient (1/10, 10%). The median (interquartile range) follow-up time was 26.0 (21.3, 48.3) months. All patients resumed menstruation, including 9 patients (9/10, 90%) with regular monthly menstruation. Eight patients (8/10, 80%) experienced mild to moderate dysmenorrhea; the remaining 2 patients (2/10, 20%) had no dysmenorrhea. Cervical restenosis occurred in 1 patient (1/10, 10%) 12 months postoperatively, and cervical dilation was performed. So far, 8 months after the second surgery, no restenosis has been found. The mean postoperative vaginal length was 7.9 ± 1.3-cm at the time of the last follow-up. Only 1 patient attempted to conceive for 2 years, but she had not conceived yet. CONCLUSION: Laparoscopically assisted uterovaginal canalization and vaginoplasty is an easy, safe, and promising management option for correcting congenital cervical and vaginal atresia.
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Colo do Útero , Vagina , Colo do Útero/cirurgia , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Menstruação , Resultado do Tratamento , Vagina/cirurgiaRESUMO
Aim: Inositol polyphosphate kinases are involved in regulation of many cellular processes in eukaryotic cells. In this study, we investigated the functions of the inositol polyphosphate kinase Vip1 in autophagy and pathogenicity of Candida albicans. Results: Loss of Vip1 caused significantly increased sensitivity to nitrogen source starvation, abnormal localization and degradation of autophagy protein, higher vacuolar pH and higher (rather than lower) intracellular ATP levels compared with control strains. Besides, the mutant showed attenuated hyphal development and virulence during systemic infection to mice. Conclusion: The results reveal that Vip1 is important to autophagy of C. albicans. The maintenance of vacuolar acidic pH contributed to the role of Vip1 in autophagy. Vip1 is also required for pathogenicity of C. albicans.
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Autofagia , Candida albicans/patogenicidade , Proteínas Fúngicas/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Autofagossomos/metabolismo , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Candidíase/microbiologia , Citoplasma/metabolismo , Proteínas Fúngicas/genética , Concentração de Íons de Hidrogênio , Hifas/crescimento & desenvolvimento , Fosfatos de Inositol/metabolismo , Rim/microbiologia , Camundongos , Mutação , Nitrogênio/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/genética , Vacúolos/química , Vacúolos/metabolismo , VirulênciaRESUMO
OBJECTIVE: This study evaluated changes in voiding function at 3 months and 1 year after transvaginal mesh (TVM) repair in women with advanced anterior vaginal prolapse (AVP) and identified predictive risk factors of postoperative voiding dysfunction (PVD). STUDY DESIGN: Women with stage≥3 AVP who underwent TVM repair surgery were included in this retrospective cohort study. Voiding dysfunction was defined as an average flow rate (Qave)ï¼10 ml/s, a maximum flow rate (Qmax)ï¼15 ml/s, or a postvoid residual volume (PVR)ï¼50 ml. Pre- and postoperative voiding function was assessed by uroflowmetry, PVR examination, and the Urinary Distress Inventory-6 (UDI-6) and the Urinary Impact Questionnaire-7 (UIQ-7). Statistical analyses were performed using paired-sample t tests, χ2 tests, and multivariate logistic regression. RESULTS: Sixty-two women were included in this study, uroflowmetry data were available for 35 of them at 1-year follow-up. Forty-three percent of women showed evidence of voiding dysfunction preoperatively. The PVR decreased significantly from baseline to 1 year postoperatively (17.97 ± 38.48 vs. 0.00 ± 0.00, p < 0.001). Voiding difficulties decreased significantly postoperatively (55 % vs. 5%, pï¼0.001); frequency, urgency and urinary incontinence symptoms did not exhibit significant improvement (pï¼0.05). The UDI-6 and UIQ-7 indicated significant improvement postoperatively (both pï¼0.001). Multivariate analysis identified low Qave as an independent predictor of PVD (odds ratio, 0.40; 95 % CI, 0.16-0.98). CONCLUSION: Nearly half of the patients had advanced AVP accompanied by preoperative voiding dysfunction. Improvement in voiding function was observed at 3 months and could last for one year postoperatively.
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Prolapso de Órgão Pélvico , Incontinência Urinária , Prolapso Uterino , Feminino , Humanos , Prolapso de Órgão Pélvico/cirurgia , Estudos Retrospectivos , Telas Cirúrgicas/efeitos adversos , Prolapso Uterino/cirurgiaRESUMO
OBJECTIVE: The aim of the study was to evaluate sexual function in women before and after tension-free vaginal tape (TVT) surgery for the treatment of stress urinary incontinence (SUI). METHODS: Between August 2014 and August 2018, 105 sexually active patients with SUI who underwent TVT surgery were enrolled in this prospective cohort study. The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire Short Form (PISQ-12) was administered pre- and postoperatively. Statistical analyses were performed using paired-sample t tests. RESULTS: The sexual function of 105 patients 1 year after the TVT procedure improved in 81 (77.1%) patients, remained unchanged in 18 (17.1%) patients, and deteriorated in 6 (5.7%) patients. The mean PISQ-12 score increased from 29.65 at baseline to 33.04 at the 1-year follow-up (Pâ<â0.001). Improvement was prominent in the physical domain of the PISQ-12 (Pâ<â0.001), but the emotional (Pâ=â0.948) and partner-related (Pâ=â0.915) domains showed no significant changes. The increase in the physical domain score caused the increase of the total PISQ-12 score. Compared with preoperative values, there was no significant change in the score of pain during sexual intercourse (Pâ=â0.425) at 1 year after the TVT procedure. Women experienced less coital incontinence (Pâ<â0.001), less fear of incontinence during intercourse (Pâ<â0.001), and less negative emotional reactions (Pâ<â0.001) during intercourse after the TVT operation than before the TVT operation. CONCLUSIONS: Sexual function was improved in patients with SUI after TVT surgery.
Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse , Feminino , Humanos , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Incontinência Urinária por Estresse/cirurgiaRESUMO
AIM: To identify factors associated with unsuccessful pessary fitting in a large cohort of patients with symptomatic pelvic organ prolapse (POP). METHODS: This prospective observational study included 611 consecutive women with symptomatic POP in a tertiary-care hospital. Patients were initially fitted with a ring pessary with support. Those who failed were fitted with a Gellhorn pessary. A successful pessary fitting was defined as a patient who was fitted or refitted with a pessary and continued to use it 2 weeks later. Parametric and nonparametric tests were used for the data analysis. RESULTS: A total of 524 patients had successful pessary fittings (85.8% success rate). The success rate of the ring pessary with support was 57.9%, of the Gellhorn pessary was 69.1%. Stage IV prolapse (odds ratio [OR], 2.12), posterior compartment prolapse (OR, 1.92), genital hiatus (OR, 1.41), and vaginal introitus (OR, 1.40) were independent predictors of unsuccessful ring with support pessary fitting. Vaginal length (OR, 0.74/0.60 for ring with support/Gellhorn) and history of POP reconstructive surgery (OR, 2.50/2.58 for ring with support/Gellhorn) were independent predictors of both ring with support and Gellhorn pessary fitting. CONCLUSIONS: Stage IV prolapse, posterior compartment prolapse, large genital hiatus, and wide vaginal introitus were risk factors for unsuccessful fitting of ring pessary with support. Short vaginal length and a history of POP reconstructive surgery were risk factors for unsuccessful fitting of both pessaries.
Assuntos
Prolapso de Órgão Pélvico/terapia , Pessários , Vagina , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate the success rate of pessary fitting and continuation rate for symptomatic pelvic organ prolapse (POP) patients with a hysterectomy and to explore potential predictors. METHODS: In this prospective observational study, 119 symptomatic POP patients with a prior hysterectomy received pessary treatment between April 2015 and February 2019. A successful pessary fitting was defined as a patient who was fitted with a pessary and continued to use it 2 weeks later. Patients with successful pessary fitting were followed until February 2020. Data analysis was performed with t tests, nonparametric tests, chi-square tests, and logistic regression. RESULTS: The success rate of pessary fitting was 63.2%. A history of POP reconstructive surgery (ORâ=â2.6, 95% CI 1.0-6.7, Pâ=â0.043) and a short total vaginal length <7.3âcm, (ORâ=â0.5, 95% CI 0.3-0.9, Pâ=â0.014) were potential risk factors for unsuccessful pessary fitting. A total of 78.1% of the patients continued pessary use for a median duration of 26 months. Among patients who discontinued, 75% ceased within 1 year. Older age (ORâ=â1.1, 95% CI 1.0-1.2, Pâ=â0.038) and prolapse score improvement at 3 months less than 50% (ORâ=â2.8, 95% CI 1.1-7.2, Pâ=â0.035) were potential risk factors for discontinuation. CONCLUSIONS: Pessaries remain a useful approach to treat prolapse in women who had a hysterectomy. Patients with POP reconstructive surgery and total vaginal length<7.3âcm should be informed that they might have lower success rate of pessary fitting. Age and prolapse score improvement at 3 months were potential predictors for continuation.