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OBJECTIVES: To evaluate the efficacy and safety of tamsulosin and Hachimijiogan or Ryutanshakanto in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS: A prospective, randomized, double-blind method was used to determine the efficacy and safety of the combination or placebo at baseline and 4, 8, and 12 weeks of study. The International Prostate Symptom Score, quality of life index, complete voiding diary, and National Institutes of Health-Chronic Prostatitis Symptom Index were studied. Uroflowmetery and postvoid residual urine volume were measured and compared. Laboratory tests including prostate-specific antigen were performed. RESULTS: In all groups, International Prostate Symptom Score and quality of life showed improvement, but no significant differences were shown among the groups. Prostate volume increased after treatment, and uroflowmetric parameters showed improvements after treatment without significance among the three groups. The total score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant improvement in all groups, without significant differences among the groups. Only the pain sub-score of the National Institutes of Health-Chronic Prostatitis Symptom Index showed a significant decrease in the tamsulosin with Ryutanshakanto group compared to the control group. A total of 11 adverse reactions occurred, but they were mild and not related to the study drugs. CONCLUSION: Ryutanshakanto can provide pain relief in patients with chronic prostatitis and chronic pelvic pain syndrome. If more research is conducted, Hachimijiogan and Ryutanshakanto may be applied as add-on treatments in patients with storage symptoms with alpha-blocker monotherapy.
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Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Prostatite , Método Duplo-Cego , Quimioterapia Combinada , Medicina Herbária , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Dor , Estudos Prospectivos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Prostatite/complicações , Prostatite/tratamento farmacológico , Qualidade de Vida , Sulfonamidas/efeitos adversos , Tansulosina/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The aims of this study were to determine the predictive value of decision support analysis for the shock wave lithotripsy (SWL) success rate and to analyze the data obtained from patients who underwent SWL to assess the factors influencing the outcome by using machine learning methods. METHODS: We retrospectively reviewed the medical records of 358 patients who underwent SWL for urinary stone (kidney and upper-ureter stone) between 2015 and 2018 and evaluated the possible prognostic features, including patient population characteristics, urinary stone characteristics on a non-contrast, computed tomographic image. We performed 80% training set and 20% test set for the predictions of success and mainly used decision tree-based machine learning algorithms, such as random forest (RF), extreme gradient boosting trees (XGBoost), and light gradient boosting method (LightGBM). RESULTS: In machine learning analysis, the prediction accuracies for stone-free were 86.0, 87.5, and 87.9%, and those for one-session success were 78.0, 77.4, and 77.0% using RF, XGBoost, and LightGBM, respectively. In predictions for stone-free, LightGBM yielded the best accuracy and RF yielded the best one in those for one-session success among those methods. The sensitivity and specificity values for machine learning analytics are (0.74 to 0.78 and 0.92 to 0.93) for stone-free and (0.79 to 0.81 and 0.74 to 0.75) for one-session success, respectively. The area under curve (AUC) values for machine learning analytics are (0.84 to 0.85) for stone-free and (0.77 to 0.78) for one-session success and their 95% confidence intervals (CIs) are (0.730 to 0.933) and (0.673 to 0.866) in average of methods, respectively. CONCLUSIONS: We applied a selected machine learning analysis to predict the result after treatment of SWL for urinary stone. About 88% accurate machine learning based predictive model was evaluated. The importance of machine learning algorithm can give matched insights to domain knowledge on effective and influential factors for SWL success outcomes.
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Cálculos Renais/terapia , Litotripsia , Aprendizado de Máquina , Cálculos Ureterais/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Two new triarylmethane-based dye molecules with a dimeric structure, TAM-1 and TAM-2, were designed and synthesized as potential blue color filter materials for liquid-crystal displays. The dimeric structure of TAM-1 was designed to improve the thermal stability of a well-known blue dye, Victoria Blue BO. TAM-2 was designed to further improve the solubility of TAM-1 by introducing long alkyl ester groups. The synthesized dyes TAM-1 and TAM-2 were transmissive in the wavelength range of 410-460 nm and showed good thermal stability with 5% weight degradation temperatures (T5d) of 259 °C and 289 °C, respectively, and less than 1% of weight loss at 230 °C. Moreover, TAM-2 showed excellent solubility (20.1 wt%) as opposed to Victoria Blue BO (0.03 wt%) and TAM-1 (3.5 wt%) in PGMEA.
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A series of polystyrene (PS) copolymers containing 2,3,4,5,6-pentafluorostyrene units with different monomer ratios were prepared for antifouling applications. PS, poly(styrene-co-pentafluorostyrene) (poly(S-co-FS)), and poly(pentafluorostyrene) (PFS) were synthesized by free-radical polymerization and characterized by 1H NMR, Fourier-transform infrared spectroscopy, and gel permeation chromatography. The surface energy of the polymer films decreased with increasing content of fluorinated styrene. Protein adsorption experiments were carried out on the synthesized polymer films using fluorescein isothiocyanate-labeled bovine serum albumin as a fluorescent protein. The photo-luminescence intensity of the protein-adsorbed polymer films decreased dramatically as the content of hydrophobic fluorinated styrene increased, suggesting that poly(S-co-FS) copolymers and PFS could be used as potential antibiofouling coatings.
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Polímeros , Poliestirenos , Adsorção , Interações Hidrofóbicas e Hidrofílicas , Polimerização , Polímeros/farmacologia , Propriedades de SuperfícieRESUMO
The purpose of this study is to develop novel triazole-containing hydrogels (TGs) as drug carrier and to investigate the sustained drug release accomplished by their time-dependent swelling behavior. The synthetic pathway of TGs includes: (1) DCC-coupling on hydroxyethyl methacrylate (HEMA) to prepare HEMA-alkyne (HA), (2) click-coupling to prepare a triazole-ring-containing monomer (TM), and (3) the synthesis of a series of TGs. The aggregation between triazole rings is found to be responsible for drug release controllability. Rhodamine 6G is studied as a model anticancer drug for release experiments. The effects of pH and temperature on the properties of sustained drug release are also studied.
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Portadores de Fármacos/química , Hidrogéis/química , Triazóis/química , Alcinos/química , Antineoplásicos/química , Química Click , Concentração de Íons de Hidrogênio , Metacrilatos/química , Rodaminas/química , Temperatura , Fatores de TempoRESUMO
The modification of synaptic and neural connections in adults, including the formation and removal of synapses, depends on activity-dependent synaptic and structural plasticity. MicroRNAs (miRNAs) play crucial roles in regulating these changes by targeting specific genes and regulating their expression. The fact that somatic and dendritic activity in neurons often occurs asynchronously highlights the need for spatial and dynamic regulation of protein synthesis in specific milieu and cellular loci. MicroRNAs, which can show distinct patterns of enrichment, help to establish the localized distribution of plasticity-related proteins. The recent study using atomic force microscopy (AFM)-based nanoscale imaging reveals that the abundance of miRNA(miR)-134 is inversely correlated with the functional activity of dendritic spine structures. However, the miRNAs that are selectively upregulated in potentiated synapses, and which can thereby support prospective changes in synaptic efficacy, remain largely unknown. Using AFM force imaging, significant increases in miR-132 in the dendritic regions abutting functionally-active spines is discovered. This study provides evidence for miR-132 as a novel positive miRNA regulator residing in dendritic shafts, and also suggests that activity-dependent miRNAs localized in distinct sub-compartments of neurons play bi-directional roles in controlling synaptic transmission and synaptic plasticity.
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MicroRNAs , Microscopia de Força Atômica , Plasticidade Neuronal , Sinapses , Animais , Camundongos , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/genética , Espinhas Dendríticas/ultraestrutura , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Microscopia de Força Atômica/métodos , Plasticidade Neuronal/genética , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Sinapses/metabolismo , Sinapses/genéticaRESUMO
PURPOSE: We assessed the effectiveness and safety of using intravesical onabotulinumtoxinA (onabotA; BOTOX) injection with a low dose (75 units) for treating urinary storage symptoms in patients with detrusor overactivity with detrusor underactivity (DODU) compared to using the standard 100 units of onabotA in patients with overactive bladder (OAB). METHODS: This ambidirectional study included 121 female patients who received intravesical onabotA injections at our hospitals. A total of 87 patients with OAB and 34 patients with DODU were reviewed using a 3-day voiding diary, uroflowmetry, and questionnaires including the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score, and Patient Perception of Bladder Condition. Patients were evaluated at baseline, within 2 weeks of treatment, and beyond 3 months after treatment. RESULTS: Questionnaire scores of the DODU group demonstrated significant improvement in the short term, with a subsequent decline, but an overall improvement compared to baseline in the long term. Notably, the DODU group exhibited enhanced IPSS voiding scores after the treatment. In the OAB group, most questionnaire scores, excluding the IPSS voiding score, showed significant posttreatment improvement, which was sustained to some extent in the long term. Voiding diary parameters related to storage symptoms were enhanced in both groups. The maximum and mean flow rates decreased in the OAB group but increased in the DODU group, particularly in the short term (P=0.000). The postvoid residual volume increased in both groups after posttreatment, with a mitigated change in the long term. Safety assessments revealed manageable adverse events in both groups with comparable frequencies. CONCLUSION: Low-dose intravesical onabotA for DODU demonstrated a relatively shorter duration of efficacy than OAB. Nonetheless, the treatment improved both storage and voiding symptoms in patients with DODU without significant adverse effects.
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Our understanding of interstitial cystitis/bladder pain syndrome (IC/BPS) has evolved over time. The diagnosis of IC/BPS is primarily based on symptoms such as urgency, frequency, and bladder or pelvic pain. While the exact causes of IC/BPS remain unclear, it is thought to involve several factors, including abnormalities in the bladder's urothelium, mast cell degranulation within the bladder, inflammation of the bladder, and altered innervation of the bladder. Treatment options include patient education, dietary and lifestyle modifications, medications, intravesical therapy, and surgical interventions. This review article provides insights into IC/BPS, including aspects of treatment, prognosis prediction, and emerging therapeutic options. Additionally, it explores the application of deep learning for diagnosing major diseases associated with IC/BPS.
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PURPOSE: In this paper, we propose an optimal ureter stone detection model utilizing multiple artificial intelligence technologies. Specifically, the proposed model of urinary tract stone detection merges an artificial intelligence model and an image processing model, resulting in a multimethod approach. METHODS: We propose an optimal urinary tract stone detection algorithm based on artificial intelligence technology. This method was intended to increase the accuracy of urinary tract stone detection by combining deep learning technology (Fast R-CNN) and image processing technology (Watershed). RESULTS: As a result of deriving the confusion matrix, the sensitivity and specificity of urinary tract stone detection were calculated to be 0.90 and 0.91, and the accuracy for their position was 0.84. This value was higher than 0.8, which is the standard for accuracy. This finding confirmed that accurate guidance to the stones area was possible when the developed platform was used to support actual surgery. CONCLUSION: The performance evaluation of the method proposed herein indicated that it can effectively play an auxiliary role in diagnostic decision-making with a clinically acceptable range of safety. In particular, in the case of ambush stones or urinary stones accompanying ureter polyps, the value that could be obtained through combination therapy based on diagnostic assistance could be evaluated.
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PURPOSE: This clinical study sought to evaluate the possible clinical effectiveness and practicality of URINO, an innovative, incisionless, and disposable intravaginal device, designed for patients suffering from stress urinary incontinence. METHODS: A prospective, multicenter, single-arm clinical trial was carried out, involving women diagnosed with stress urinary incontinence who used a self-inserted, disposable intravaginal pessary device. Comparisons were made between the results of the 20-minute pad-weight gain (PWG) test at baseline and visit 3, where the device was applied. After 1 week of device usage, compliance, satisfaction, the sensation of a foreign body, and adverse events were assessed. RESULTS: Out of 45 participants, 39 completed the trial and expressed satisfaction within the modified intention-to-treat group. The average 20-minute PWG of participants was 17.2±33.6 g at baseline and significantly dropped to 5.3±16.2 g at visit 3 with device application. A total of 87.2% of participants exhibited a reduction ratio of PWG by 50% or more, surpassing the clinical trial success benchmark of 76%. The mean compliance was recorded as 76.6%±26.6%, the average visual analogue scale score for patient satisfaction was 6.4±2.6, and the sensation of a foreign body, measured on a 5-point Likert scale, was 3.1±1.2 after 1 week of device use. No serious adverse events were reported; there was 1 instance of microscopic hematuria and 2 cases of pyuria, all of which recovered. CONCLUSION: The investigated device demonstrated significant clinical effectiveness and safety for patients with stress urinary incontinence. It was easy to use, showing favorable patient compliance. We propose that these disposable intravaginal pessaries could potentially be an alternative treatment for patients with stress urinary incontinence who are seeking nonsurgical options or are unable to undergo surgery. Trial Registration: The study was registered as a clinical trial (KCT0008369).
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Commercial hydrogen (H2) sensors operate at high temperatures, which increases power consumption and poses a safety risk owing to the flammable nature of H2. Here, a polymer-noble metal-metal oxide film is fabricated using the spin-coating and printing methods to realize a highly sensitive, low-voltage operation, wide-operating-concentration, and near-monoselective H2 sensor at room temperature. The H2 sensors with an optimized thickness of Pd nanoparticles and SnO2 showed an extremely high response of 16,623 with a response time of 6 s and a recovery time of 5 s at room temperature and 2% H2. At the same time, printed flexible sensors demonstrate excellent sensitivity, with a response of 2300 at 2% H2. The excellent sensing performance at room temperature is due to the optimal SnO2 thickness, corresponding to the Debye length and the oxygen and H2 spillover caused by the optimized coverage of the Pd catalyst. Furthermore, multistructures of WO3 and SnO2 films are used to fabricate a new type of dual-signal sensor, which demonstrated simultaneous conductance and transmittance, i.e., color change. This work provides an effective strategy to develop robust, flexible, transparent, and long-lasting H2 sensors through large-area printing processes based on polymer-metal-metal oxide nanostructures.
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Colorimetria , Hidrogênio , Temperatura , Óxidos , PolímerosRESUMO
The International Neurourology Journal (Int Neurourol J, INJ) is a quarterly international journal that publishes high-quality research papers that provide the most significant and promising achievements in the fields of clinical neurourology and fundamental science. Specifically, fundamental science includes the most influential research papers from all fields of science and technology, revolutionizing what physicians and researchers practicing the art of neurourology worldwide know. Thus, we welcome valuable basic research articles to introduce cutting-edge translational research of fundamental sciences to clinical neurourology. In the editorials, urologists will present their perspectives on these articles. The original mission statement of the INJ was published on October 12, 1997. INJ provides authors a fast review of their work and makes a decision in an average of 3 to 4 weeks of receiving submissions. If accepted, articles are posted online in fully citable form. Supplementary issues will be published interim to quarterlies, as necessary, to fully allow berth to accept and publish relevant articles. Science Citation Index Expanded (SCIE, Web of Science), Scopus, PubMed, PubMed Central, KoreaMed, KoMCI, WPRIM, WorldWideScience.org, DOI/Crossref, EBSCO, Google Scholar.
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PURPOSE: This paper proposes a technological system that uses artificial intelligence to recognize and guide the operator to the exact stenosis area during endoscopic surgery in patients with urethral or ureteral strictures. The aim of this technological solution was to increase surgical efficiency. METHODS: The proposed system utilizes the ResNet-50 algorithm, an artificial intelligence technology, and analyzes images entering the endoscope during surgery to detect the stenosis location accurately and provide intraoperative clinical assistance. The ResNet-50 algorithm was chosen to facilitate accurate detection of the stenosis site. RESULTS: The high recognition accuracy of the system was confirmed by an average final sensitivity value of 0.96. Since sensitivity is a measure of the probability of a true-positive test, this finding confirms that the system provided accurate guidance to the stenosis area when used for support in actual surgery. CONCLUSION: The proposed method supports surgery for patients with urethral or ureteral strictures by applying the ResNet-50 algorithm. The system analyzes images entering the endoscope during surgery and accurately detects stenosis, thereby assisting in surgery. In future research, we intend to provide both conservative and flexible boundaries of the strictures.
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Although tibial nerve modulation has shown to induce positive changes in the overactive bladder (OAB), prolonged therapeutic effects using percutaneous stimulation have not yet been achieved. Intradetrusor onabotulinum toxin A injection can provide prolonged therapeutic effects; however, its delivery requires invasive measures. By applying local relief of tibial nerve neural entrapment with onabotulinum toxin A injection, this study investigated the feasibility and efficacy of combining the abovementioned two therapeutic strategies. An OAB animal model was developed using 12 adult Sprague-Dawley rats with cyclophosphamide intraperitoneal injection. A perineural injection site comparable to the tibial nerve perineural injection site and corresponding to that in humans was identified and developed in rats. The toxin was injected five days after establishing the OAB. The incision was made in the skin on the lateral surface of the thigh. The biceps femoris muscle was cut across, exposing the sciatic nerve and its three terminal branches: the sural, common peroneal, and tibial nerves, and 100 units of onabotulinum toxin A was injected into the surrounding tissue. Five days following injection, cystometry was performed. Inter-contraction time, contraction pressure, and interval of the disease state improved with statistical significance. The OAB animal model showed significant improvement with the tibial nerve perineural injection of botulinum toxin, thereby suggesting the possibility of a comparable treatment adaptation in humans.
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Artificial intelligence (AI) is used in various fields of medicine, with applications encompassing all areas of medical services, such as the development of medical robots, the diagnosis and personalized treatment of diseases, and personalized healthcare. Medical AI research and development have been largely focused on diagnosis, prediction, treatment, and management as an auxiliary means of patient care. AI is mainly used in the fields of personal healthcare and diagnostic imaging. In urology, substantial investments are being made in the development of urination monitoring systems in the personal healthcare field and diagnostic solutions for ureteral stricture and urolithiasis in the diagnostic imaging field. This paper describes AI applications for urinary diseases and discusses current trends and future perspectives in AI research.
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A new concept for anti-counterfeiting security films that utilize the humidity from human breath to reveal a QR code on color-tunable one-dimensional (1D) PC films is presented. The 1D PC film was fabricated on a transparent polyethylene terephthalate (PET) substrate via sequential alternate layer deposition of photo-crosslinkable poly(2-vinylnaphthalene-co-benzophenone acrylate) (P(2VN-co-BPA)) and quaternized poly(4-vinylpyridine-co-benzophenone acrylate) (P(4VP-co-BPA)) (P4QP-51%). The films exhibited remarkable color transitions with reliable reversibility and reproducibility. Films placed on a black background exhibited the full visible spectrum color in a high humidity environment. Additionally, films placed on a white background displayed three different composite colors, including yellow, magenta, and cyan. These films with vivid color transitions in a high humidity environment can be applied as anti-counterfeiting films. A hidden QR code was also laser printed on the initial PC film to enhance the film's anti-counterfeiting security capabilities. These colorimetric 1D PC films can be used as anti-counterfeiting labels and for information storage.
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The neurological regulation of the lower urinary tract can be viewed separately from the perspective of sensory neurons and motor neurons. First, in the receptors of the bladder and urethra of sensory nerves, sensations are transmitted through the periaqueductal gray matter of the midbrain to the cerebral cortex, and the cerebrum goes through the process of decision-making. Motor neurons are divided into upper motor neurons (UMNs) and lower motor neurons (LMNs). UMNs coordinate storage and micturition in the brain stem so that synergic voiding can occur. LMNs facilitate muscle contractions in the spinal cord. The muscles involved in urinary storage and micturition are innervated by the somatic branches of sympathetic, parasympathetic, and peripheral nerves. Sympathetic nerves are responsible for contractions of urethral smooth muscles, while parasympathetic nerves originate from S2-S4 and are in charge of contractions of the bladder muscle. Somatic nerves originate from the motor neurons in Onuf's nucleus, which is a specific part of somatic nerves. In this review, we will investigate the structures of the nervous systems related to the lower urinary tract and the regulatory system of innervation for the urinary storage and micturition and discuss the clinical significance and future prospects of neurourological research.
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PURPOSE: Although metformin and sildenafil can protect various organs against ischemia/reperfusion (I/R) injuries, their effects and mechanisms of action in bladder I/R injuries remain unknown. This study investigated the effects and mechanisms of action of metformin and sildenafil against bladder I/R insults in rats. METHODS: One hundred male Sprague-Dawley rats were randomly divided into 5 groups, each of which contained 20 rats: a sham-operated group, a bladder I/R group, and bladder I/R groups treated with metformin, sildenafil, or both agents. Ischemia was induced by clamping the bilateral common iliac arteries with atraumatic vascular clamps for 2 hours, followed by reperfusion for 7 days. During this period, rats were injected once daily with 4-mg/kg metformin and/or 1-mg/kg sildenafil. RESULTS: I/R injuries induced increased malondialdehyde levels and myeloperoxidase activity and decreased superoxide dismutase activity. These changes were attenuated by treatment with metformin and/or sildenafil. The I/R group had significantly higher Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK), Bax, caspase-3, and nuclear factor-kappa B (NF-κB) levels, and lower extracellular signal-regulated kinase, and Bcl-2 levels in the bladder than the sham-operated group; these changes were significantly ameliorated by metformin and/or sildenafil treatment. No differences in the levels of these markers were observed between rats coadministered metformin and sildenafil and those treated with either agent alone. CONCLUSION: Metformin and sildenafil protected the rat bladder against I/R injuries. This effect may have been due to the inhibition of reactive oxygen species production through MAPK, Bax, and Bcl-2 activation, and the restoration of inflammation through NF-κB inhibition. However, the combination of metformin and sildenafil was not more effective than either agent alone.
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We studied the long-term efficacy and safety of cystocele operation by polypropylene mesh. A total of 198 women with stage ≥2 cystocele who had anterior vaginal wall repair with transobturator four-arm polypropylene mesh during 2003 to 2015 were evaluated. Outcomes including clinical characteristics and complications were reviewed by extracting patient data from electronic medical records. In addition, telephone interviews were conducted using a validated questionnaire along with physical examination. The follow-up period was 9.3±0.3 years. The cystocele stage in patients was significantly decreased post-operation compared to that preoperation. The anatomical cure rate for cystocele was 93.4%, and that for stress urinary incontinence was 95%. Comparing the three questionnaires indicated overall average score was improved significantly, except for Female Sexual Function Index Assessment. Early complications were either resolved spontaneously or controlled medically in four cases of hematoma or abscess, three cases of vaginal infection and urinary tract infection, and four cases of difficult micturition. In late complications, four cases of pain were managed, five cases of recurrence were observed and two cases of mesh exposure were treated with ointment and local excision. Transobturator four-arms mesh is an effective and safe method for cystocele repair with low rate of recurrence and complications. We suggest that the use of transobturator four-arm mesh is a still good choice for the old patients with cystocele who are not suitable for general anesthesia and reside in areas where laparoscopy and robots are not available.
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Nickel-rich layered oxides (LiNi1-x-yCoxMnyO2; (1 - x - y) ≥ 0.6), the high-energy-density cathode materials of lithium-ion batteries (LIBs), are seriously unstable at voltages higher than 4.5 V versus Li/Li+ and temperatures higher than 50 °C. Herein, we demonstrated that the failure mechanism of a nickel-rich layered oxide (LiNi0.6Co0.2Mn0.2O2) behind the instability was successfully suppressed by employing cyanoethyl poly(vinyl alcohol) having pyrrolidone moieties (Pyrd-PVA-CN) as a metal-ion-chelating gel polymer electrolyte (GPE). The metal-ion-chelating GPE blocked the plating of transition-metal ions dissolved from the cathode by capturing the ions (anode protection). High-concentration metal-ion environments developed around the cathode surface by the GPE suppressed the irreversible phase transition of the cathode material from the layered structure to the rock-salt structure (cathode protection). Resultantly, the capacity retention was significantly improved at a high voltage and a high temperature. Capacity retention and coulombic efficiency of a full-cell configuration of a nickel-rich layered oxide with graphite were significantly improved in the presence of the GPE especially at a high cutoff voltage (4.4 V) and an elevated temperature (55 °C).