ABSTRACT
Schistosomiasis is a parasitic disease characterized by liver fibrosis, a process driven by the activation of hepatic stellate cells (HSCs) and subsequent collagen production. Previous studies from our laboratory have demonstrated the ability of Schistosoma japonicum protein P40 (SjP40) to inhibit HSCs activation and exert an antifibrotic effect. In this study, we aimed to elucidate the molecular mechanism underlying the inhibitory effect of recombinant SjP40 (rSjP40) on HSCs activation. Using a cell model in which rSjP40 inhibited LX-2 cell activation, we performed RNA-seq analyses and identified ATF3 as the most significantly altered gene. Further investigation revealed that rSjP40 inhibited HSCs activation partly by suppressing ATF3 activation. Knockdown of ATF3 in mouse liver significantly alleviated S. japonicum-induced liver fibrosis. Moreover, our results indicate that ATF3 is a direct target of microRNA-494-3p, a microRNA associated with anti-liver fibrosis effects. rSjP40 was found to downregulate ATF3 expression by upregulating microRNA-494-3p in LX-2 cells. This downregulation led to the inhibition of the expression of liver fibrosis proteins α-SMA and COL1A1, ultimately alleviating liver fibrosis caused by S. japonicum.
Subject(s)
Activating Transcription Factor 3 , Helminth Proteins , Hepatic Stellate Cells , Liver Cirrhosis , MicroRNAs , Schistosoma japonicum , Schistosomiasis japonica , Animals , Activating Transcription Factor 3/metabolism , Activating Transcription Factor 3/genetics , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/parasitology , Schistosomiasis japonica/parasitology , Schistosomiasis japonica/metabolism , Schistosomiasis japonica/genetics , Liver Cirrhosis/parasitology , Liver Cirrhosis/genetics , Liver Cirrhosis/pathology , Liver Cirrhosis/metabolism , Mice , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Helminth Proteins/genetics , Helminth Proteins/metabolism , Actins/metabolism , Actins/genetics , Cell Line , Gene Expression Regulation , Liver/metabolism , Liver/parasitology , Liver/pathology , Disease Models, Animal , Antigens, HelminthABSTRACT
Ubiquitin Conjugating Enzyme 2C (UBE2C) is an emerging target gene for tumor progression. However, the tumorigenic effect and mechanism of UBE2C in adrenocortical carcinoma (ACC) remains unclear. Systematic investigation of the tumorigenic effect of UBE2C may help in understanding its prognostic value in adrenocortical carcinoma. First, we exploited the intersection on DFS-related genes, OS-related genes, highly expressed genes in adrenocortical carcinoma as well as differentially expressed genes (DEGs) between tumor and normal, and then obtained 20 candidate genes. UBE2C was identified to be the most significant DEG between tumor and normal. It is confirmed that high expression of UBE2C was strongly associated with poor prognosis in patients with ACC by analyzing RNA-seq data of ACC obtained from the Cancer Genome Atlas (TCGA) database implemented by ACLBI Web-based Tools. UBE2C expression could also promote m6A modification and stemness in ACC. We found that UBE2C expression is positively associated with the expression of CDC20, CDK1, and CCNA2 using ACLBI Web-based Tools, indicated the hyperactive cell cycle progression present in ACC with high UBE2C expression. In addition, UBE2C knockdown could significantly inhibit the proliferation, migration, invasion, EMT of adrenocortical carcinoma cells as well as the cell cycle progression in vitro. Notably, pan-cancer analysis also identified UBE2C as an oncogene in various tumors. Taken together, UBE2C was strongly associated with poor prognosis of patients with ACC by promoting cell cycle progression and EMT. This study provides a new theoretical basis for the development of UBE2C as a molecular target for the treatment of ACC.
Subject(s)
Adrenal Cortex Neoplasms , Adrenocortical Carcinoma , Humans , Adrenocortical Carcinoma/genetics , Ubiquitin-Conjugating Enzymes/genetics , Ubiquitin-Conjugating Enzymes/metabolism , Prognosis , Adrenal Cortex Neoplasms/genetics , Oncogenes/genetics , Gene Expression Regulation, NeoplasticABSTRACT
BACKGROUND: Neonatal resuscitation training is a requirement for all obstetric anesthesia fellows. However, while the majority of anesthesiologists who work on labor and delivery report having been involved in the resuscitation of a newborn, most do not have NRP training. OBJECTIVE: By studying a national cohort of anesthesiologists, our objective was to identify factors associated with knowledge and comfort with neonatal resuscitation and to inform decisions about neonatal resuscitation in obstetric anesthesia fellowship training. MATERIALS AND METHODS: After receiving exempt status, a survey assessing knowledge and comfort with neonatal resuscitation was sent to US academic institutions. Univariable and multiple variable regression analyses were performed to assess factors associated with knowledge and comfort. All statistical analyses were performed using R software (R version 3.4.3 [2017-11-30]; R Foundation for Statistical Computing, Vienna, Austria). RESULTS: Responses were received from 32 (84%) of 38 academic institutions that participated. A total of 245 surveys were collected from 20 December 2018 to 27 September 2019. The mean (standard deviation (SD)) percentage of correct knowledge answers in the cohort was 43.3% (22.6%). Knowledge scores were associated with obstetric anesthesia fellowship training, regularly working with infants, and current neonatal resuscitation program (NRP) training. The mean (SD) sum of comfort ratings from the individual questions was 49.9 (17.9). Comfort ratings were associated with pediatric anesthesia fellowship training, regularly working with infants, current NRP training, and having at least one year of general pediatrics residency training. CONCLUSIONS: Obstetric anesthesiologists have the knowledge but appear to lack the comfort to perform neonatal resuscitation. As obstetric anesthesiologists are sometimes involved in neonatal resuscitation, maintenance of certification is important in maintaining comfort with neonatal resuscitation if not regularly working with infants.
Subject(s)
Anesthesia , Resuscitation , Child , Fellowships and Scholarships , Health Knowledge, Attitudes, Practice , Humans , Infant, Newborn , Resuscitation/education , Surveys and QuestionnairesABSTRACT
OBJECTIVE: The activation of hepatic stellate cells (HSCs) is a key event in schistosome-induced liver fibrosis. Previous studies have shown that soluble egg antigens and the recombinant P40 protein from Schistosoma japonicum eggs inhibit HSC activation. In the present study, we observed the direct effect of the S. japonicum recombinant (r)SjE16 protein on HSCs. METHODS: The sequence of SjE16 was analyzed by bioinformatics. Then western blotting, quantitative PCR, and MTT assays were performed to observe the effects of rSjE16 on HSCs. RESULTS: The SjE16 protein has no signal peptide or transmembrane region. rSjE16 significantly inhibited expression levels of α-smooth muscle actin and collagen I protein in LX-2 cells. rSjE16 also significantly increased the expression levels of interleukin (IL)-6 and IL-8, and enhanced the expression of matrix metalloproteinase (MMP)-2, MMP-9, and peroxisome proliferator-activated receptor-γ in LX-2 cells. LX-2 cell viability was not inhibited by rSjE16. CONCLUSION: rSjE16 may be involved in the progression of HSC activation via a complex molecular mechanism, which requires further study to fully understand.
Subject(s)
Schistosoma japonicum , Schistosomiasis japonica , Animals , Hepatic Stellate Cells/pathology , Liver Cirrhosis/pathology , Recombinant Proteins/genetics , Schistosomiasis japonica/geneticsABSTRACT
BACKGROUND: ß-Glucosidase (ß-Glu) can activate amygdalin to kill prostate cancer cells, but the poor specificity of this killing effect may cause severe general toxicity in vivo, limiting the practical clinical application of this approach. MATERIALS AND METHODS: In this study, starch-coated magnetic nanoparticles (MNPs) were successively conjugated with ß-Glu and polyethylene glycol (PEG) by chemical coupling methods. Cell experiments were used to confirm the effects of immobilized ß-Glu on amygdalin-mediated prostate cancer cell death in vitro. Subcutaneous xenograft models were used to carry out the targeting experiment and magnetically directed enzyme/prodrug therapy (MDEPT) experiment in vivo. RESULTS: Immobilized ß-Glu activated amygdalin-mediated prostate cancer cell death. Tumor-targeting studies showed that PEG modification increased the accumulation of ß-Glu-loaded nanoparticles in targeted tumor tissue subjected to an external magnetic field and decreased the accumulation of the nanoparticles in the liver and spleen. Based on an enzyme activity of up to 134.89 ± 14.18mU/g tissue in the targeted tumor tissue, PEG-ß-Glu-MNP/amygdalin combination therapy achieved targeted activation of amygdalin and tumor growth inhibition in C57BL/6 mice bearing RM1 xenografts. Safety evaluations showed that this strategy had some impact on liver and heart function but did not cause obvious organ damage. CONCLUSION: All findings indicate that this magnetically directed enzyme/prodrug therapy strategy has the potential to become a promising new approach for targeted therapy of prostate cancer.
Subject(s)
Amygdalin/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Nanoparticles/chemistry , Prostatic Neoplasms/drug therapy , beta-Glucosidase/metabolism , Animals , Cell Line, Tumor , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , Humans , Magnetic Fields , Magnetic Phenomena , Male , Mice, Inbred C57BL , Nanoparticles/therapeutic use , Polyethylene Glycols/chemistry , Prodrugs/pharmacology , Prostatic Neoplasms/pathology , Starch/chemistry , beta-Glucosidase/chemistryABSTRACT
Since the emergence of the concept of chemical topology, interlocked molecular assemblies have graduated from academic curiosities and poorly defined species to become synthetic realities. Coordination-directed synthesis provides powerful, diverse, and increasingly sophisticated protocols for accessing interlocked molecules. Originally, metal ions were employed solely as templates to gather and position building blocks in entwined or threaded arrangements. Recently, metal centers have increasingly featured within the backbones of the integral structural elements, which in turn use noncovalent interactions to self-assemble into intricate topologies. By outlining ingenious recent examples as well as seminal classic cases, this Review focuses on the role of metal-ligand paradigms in assembling molecular links. In addition, the ever-evolving approaches to efficient assembly, the structural features of the resulting architectures, and their prospects for the future are also presented.
ABSTRACT
BACKGROUND: Emerging asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were detected and multiple cases were found to be SARS-CoV-2 positive again, which raised an alarm for the patients hospitalized after the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: We investigated the risk and prevention of hospital transmission of SARS-CoV-2 to hospitalized urological patients. DESIGN SETTING AND PARTICIPANTS: This is a retrospective study of 319 hospitalized urological patients enrolled between April 20, 2020 and May 11, 2020 from two tertiary hospitals in Wuhan, China. INTERVENTION: Chest computed tomography (CT) images, nucleic acid tests (NATs), and serum antibody were examined at the outpatient department and 1 wk after admission for all patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The chest CT images, NATs, serum antibody results, and clinical data were collected and analyzed. RESULTS AND LIMITATIONS: None of the 319 patients was found to be SARS-CoV-2 NAT positive. Ten and four patients were detected to be immunoglobulin (Ig)G and IgM positive, respectively. The chest CT features of 116 patients showed abnormal lung findings. During the 1-wk isolation, one patient initially being IgG positive only was found to be IgM positive, and another initially IgM-positive patient had a rising IgG level. Through risk assessment, we identified seven patients with very high and high risk for hospital transmission, and delayed the surgery while maintaining close follow-up. Five intermediate-risk patients were operated on successfully under paravertebral block or epidural anesthesia to avoid opening the airway with endotracheal intubation. The remaining 104 low-risk and 203 normal patients underwent normal surgery. CONCLUSIONS: Of the 319 patients, seven were identified as very high and high risk, which reinforced the importance of epidemic surveillance of discharged COVID-19 patients and asymptomatic infections. Five intermediate-risk patients were operated on successfully under regional anesthesia. PATIENT SUMMARY: Our experience of risk assessment and management practice may provide a strategy to prevent severe acute respiratory syndrome coronavirus 2 transmission to hospitalized urological patients after the coronavirus disease 2019 (COVID-19) pandemic.
ABSTRACT
A template-free Cp*Ir-based molecular Solomon link and an unusual trefoil knot induced by stacking interactions were realized via selection of the nonrigid dipyridyl ligand 4,4'-bis(pyridin-4-ylmethyl)-1,1'-biphenyl (BpmBp). In addition, a novel heterobimetallic tetranuclear (IrIII2 + AgI2) complex featuring argentophilic interaction was synthesized in high yield. Remarkably, the reversible topological transformation between the Solomon link and an unusual trefoil knot can be achieved by utilizing the chemical reactivity of silver(I) ions under mild conditions, as demonstrated by a detailed X-ray crystallographic study.
ABSTRACT
A novel template-free Cp*Rh-based molecular Solomon link has been established through selection of the flexible ligand L as a linker and the half-sandwich rhodium(III) dinuclear fragment B1 as a rigid capping unit. Furthermore, we demonstrate that the self-assembly of the Solomon link based on the flexible ligand is both solvent- and concentration-dependent: the Solomon link is formed in concentrated methanolic solutions, whereas formation of a dinuclear trapezoidal rectangle is favored at low concentrations or in acetonitrile or DMF solutions. Remarkably, alteration of the solvent or concentration can promote a unique and dynamic interconversion between the two molecular species, accompanying conformational change of the ligand. The synthetic outcomes are supported by single-crystal X-ray diffraction analysis.
ABSTRACT
BACKGROUND: Acute uncomplicated lower urinary tract infection (UTI) is one of the most common bacterial infections. Patients usually present with dysuria, urinary urgency, urinary frequency, and suprapubic pain or tenderness. Approximately 150 million people are diagnosed with UTI each year worldwide. The high recurrence rate of lower UTI is a common problem of clinical treatment. The misuse of antibiotics has led to the emergence of a number of resistant bacterial strains. Thus, traditional Chinese medicine is considered as an alternative option for treating acute uncomplicated lower UTI. Thus, this study aims to evaluate the efficacy and safety of Sanjin tablets (SJT) for the treatment of acute uncomplicated lower UTI, explore whether SJT can reduce or substitute the use of antibiotics, and reduce the recurrence rate in the treatment of acute uncomplicated lower UTI. METHODS/DESIGN: In this study, a randomized, double-blind, double-dummy, parallel control of positive drug, multicenter clinical study will be established. A total of 252 patients with acute uncomplicated lower UTI (syndrome of dampness-heat in the lower jiao) will be randomly allocated in the ratio of 1:1:1 to three groups: experimental group; control group 1; and control group 2. The experimental group receives Sanjin tablets plus levofloxacin tablets (LT) placebo; the control group 1 receives LT plus SJT placebo; and the control group 2 receives SJT plus LT on the first five days, SJT plus LT placebo on the last two days. Each group will be treated for seven days and followed-up 1-2 times. The primary outcome measures of effective rate and recurrence rate are symptoms. Secondary outcome measures of effective rate and recurrence rate are the urine leukocytes, bacteriology examination, and safety assessment. Outcomes will be assessed at baseline and after treatment. DISCUSSION: This study protocol will provide the research data of efficacy and safety of SJT for the treatment of acute uncomplicated lower UTI. The first aim is to determine whether Sanjin tablets can reduce the use of antibiotics; the second aim is to determine whether Sanjin tablets can substitute the use of antibiotics. The recurrence rate will be assessed after cured to determine whether SJT can reduce the recurrence rate. The results of this study will improve the rational use of drugs, especially the rational application of antibiotics. It will also enable safety evaluation from laboratory indices and adverse events, which will provide reliable evidence for clinical treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03658291 . Registered on 4 September 2018.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Drugs, Chinese Herbal/administration & dosage , Levofloxacin/administration & dosage , Lower Urinary Tract Symptoms/drug therapy , Urinary Tract Infections/drug therapy , Administration, Oral , Adult , Anti-Bacterial Agents/adverse effects , China , Double-Blind Method , Drugs, Chinese Herbal/adverse effects , Female , Humans , Levofloxacin/adverse effects , Lower Urinary Tract Symptoms/diagnosis , Lower Urinary Tract Symptoms/microbiology , Male , Middle Aged , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Tablets , Time Factors , Treatment Outcome , Urinary Tract Infections/diagnosis , Urinary Tract Infections/microbiology , Young AdultABSTRACT
Herein, we present a new synthetic approach to achieve selective supramolecular transformations and construct different interlocked metallacycles featuring a π-electron-deficient thiazolo[5,4-d]thiazole-derived ligand. We demonstrate that the formation of mono-rings, interlocked rings ([2]catenanes) and Borromean rings can be controlled by adjusting the length of the binuclear half-sandwich RhIII and IrIII building blocks. Furthermore, a concentration effect or D-A stacking interaction between the pyrene guest and the thiazolo[5,4-d]thiazole-based ligand promotes a unique and reversible conversion between catenane structures and metalla-rectangles. The synthetic results are supported by single-crystal X-ray diffraction analysis.
ABSTRACT
A series of supramolecular transformation cascades are presented here, employing ligand exchange reactions, concentration-dependent Borromean ring (BR) linking and unlinking, and inverse electron-demand Diels-Alder (IEDDA) reactions. The new family of template-free, tetrazine-edged BRs are constructed by using ligand exchange reactions, and their concentration-dependent linking and unlinking reactions have been observed. Moreover, Borromean precursors have been demonstrated to further undergo supramolecular structural transformations induced by rapid and efficient IEDDA reactions to afford corresponding post-assembly modified architectures. Remarkably, subtle steric increases of the pyridazine fragments obtained by IEDDA reactions is regarded to induce controlled topological transformations in the cascade, unlinking the Borromean structures by using electron-rich dienophiles as triggering signals.
ABSTRACT
A series of metallosupramolecular architectures have been prepared, including rectangles, prisms and cages, that feature half-sandwich rhodium(III) fragments at the vertices. Remarkably, a stable cage-like heteropolymetallic complex possessing eight rhodium(III) and two silver(I) metal ions (3) has been obtained following a multistep procedure. The RhIII /AgI mixed macrocage enables the separation of dihalogenated benzene derivatives with high selectivity. Furthermore, a detailed X-ray crystallographic study confirmed that the discriminative encapsulation of para-dihalobenzene (dichlorobenzene, dibromobenzene and diiodobenzene) is favored by Ag-π interactions and steric effects.
ABSTRACT
A series of bimetallic and trimetallic complexes has been prepared by N-alkylation of mononuclear half-sandwich rhodium and iridium di-NHC complexes featuring bidentate chelate ligands composed of a classical NHC and a C-azolato donor. The shape and the separation between metal centers in the obtained complexes are highly dependent on the alkylating agent used. While the polynuclear complexes were formed as diastereomeric mixtures according to NMR spectroscopy, X-ray diffraction analysis revealed their remarkable preference to crystallize as meso compounds. The reactivity of the bimetallic, olefin-bridged complexes in electrophilic addition reactions has been investigated.
ABSTRACT
Three aromatic ligands containing carboxyl- or nitrogen-substituted groups were employed in the construction of half-sandwich complexes via C-H activation-directed assembly, leading to the construction of eleven multinuclear organometallic iridium or rhodium complexes, including those of bi-, tetra-, hexa- and octanuclear, under mild conditions, with the help of N-donor linkers. These complexes were characterized by proton NMR, IR spectroscopy, elemental analysis, electrospray ionization (ESI) mass spectrometry and single-crystal X-ray diffraction analysis. In these complexes, two complexes were observed to exist as isomers, and several racemic enantiomers can be found. X-ray crystal structure determinations show that a series of supramolecular tunnel architectures are formed by stacking through hydrogen-bond interactions, and solvent or trifluoromethylsulfonate anion guests were found to be located in certain parts of the channels. This work represents the first successful construction of octanuclear half-sandwich complexes based on the cleavage of C-H bonds.
ABSTRACT
In the present study, the aim was to investigate the role of microRNA-1180 (miR-1180) in the growth and apoptosis of prostate cancer, as well as to identify its direct targets. Initially, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to examine the expression of miR-1180 in the prostate cancer tissues and adjacent normal prostate tissues of 30 patients, as well as in DU145 and RWPE-1 cells. Next, DU145 cells were transfected with miR-1180 mimics, and the expression levels of associated proteins were determined by western blot assay. In addition, the role of miR-1180 in the proliferation, apoptosis, invasion and migration of DU145 cells was investigated by MTT, flow cytometry, cell invasion and wound healing assays, respectively. A dual-luciferase reporter assay was also performed to examine whether TNF receptor associated factor 1 (TRAF1) and B-cell lymphoma-2-associated athanogene 2 (BAG2) are direct targets of miR-1180. It was observed that miR-1180 expression was significantly decreased in the prostate cancer tissues compared with the normal prostate tissues, and was also inhibited in DU145 cells compared with RWPE-1 cells. Furthermore, transient overexpression of miR-1180 inhibited the proliferation, migration and invasion, and promoted the apoptosis of DU145 cells, as well as alleviated expression of associated proteins. The dual-luciferase reporter assay confirmed that TRAF1 and BAG2 are direct targets of miR-1180. These results suggested that miR-1180 contributed to prostate cancer by targeting TRAF1/BAG2 and by nuclear factor-κB signaling pathway activation.
ABSTRACT
Although reversible photo-dimerization or oxygenation of anthracene and its derivatives is a common reaction, light-initiated reversible conversion of endoperoxide organometallic frameworks has only rarely been addressed. Herein, a series of tetranuclear organometallic macrocycles, [Cp*2Rh2(µ-C2O4-κO)]2(BP4VA)2(OTf)4 (4), [Cp*2Rh2(BiBzIm)]2(BP4VA)2(OTf)4 (5), and [Cp*2Rh2(DHBQ)]2(BP4VA)2(OTf)4 (6), were obtained in good yields from the reactions of the binuclear half-sandwich rhodium precursors [Cp*2Rh2(µ-C2O4-κO)Cl2] (1), [Cp*2Rh2(BiBzIm)Cl2] (2), and [Cp*2Rh2(DHBQ)Cl2] (3) with the 9,10-bis((E)-2-(pyrid-4-yl)vinyl)anthracene (BP4VA) ligand. The photochemical reaction of these metallarectangles was investigated by NMR and UV/vis spectroscopy. We have demonstrated that complexes 4, 5, and 6 can be reversibly and nearly quantitatively converted to the macrocyclic endoperoxides 4-O2, 5-O2, and 6-O2. Meanwhile, the structure of the endoperoxide photoproducts was unambiguously confirmed by 1H/13C NMR spectroscopy, IR spectroscopy, elemental analyses, and X-ray crystallography.
ABSTRACT
Template-free molecular Borromean rings (BRs) and open-ended molecular capsules were realized by strategic selection of the polypyridyl ligand tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j] phenazine (TPPHZ) with a large surface area and specific geometry. The topology of these intricate architectures was constructed via precisely controlled stacking interactions, as evidenced from single-crystal X-ray analysis.
ABSTRACT
OBJECTIVE: To asset the efficacy and safety of EPVL plus ESWL compared with ESWL alone for the treatment of simple upper urinary stones (< 15 mm). MATERIALS AND METHODS: All patients with upper urinary stones (< 15 mm) were prospectively randomized into two groups. In treatment group, patients were assigned to immediate EPVL after ESWL, while in control group, ESWL alone was offered. All patients were reexamined at 1, 2, and 4 weeks after ESWL. Stone size, stone location, stone-free rate (SFR), and complication rate were compared. RESULTS: 56 males and 20 females in treatment group were compared to 52 male and 25 females in control group (p = 0.404). Median ages were 42.9 ± 1.5 years in treatment group and 42.7 ± 1.3 years in control group (p = 0.943). Median stone size was 10.0 ± 0.4 mm (3-15 mm) in treatment group and 10.4 ± 0.4 mm (4-15 mm) in control group (p = 0.622). The stone clearance rate in treatment and control group at 1 week after ESWL was 51.3% (39/76) and 45.4% (35/77) (p > 0.05), at 2 weeks was 81.6% (62/76) and 64.9% (50/77) (p < 0.05), and at 4 weeks was 90.8% (69/76) and 75.3% (58/77) (p < 0.05), respectively. CONCLUSIONS: EPVL is a noninvasive, effective, and safe adjunctive treatment which increases and accelerates upper urinary stones discharge after ESWL treatment.
Subject(s)
Kidney Calculi/therapy , Lithotripsy/methods , Ureteral Calculi/therapy , Vibration/therapeutic use , Adult , Female , Humans , Hydronephrosis/etiology , Kidney Calculi/complications , Kidney Pelvis , Male , Prospective Studies , Severity of Illness Index , Treatment Outcome , Ureteral Calculi/complicationsABSTRACT
BACKGROUND: Recent large high-quality trials have questioned the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones. OBJECTIVE: To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo. DESIGN, SETTING, AND PARTICIPANTS: We conducted a double-blind, placebo-controlled study of 3296 patients with distal ureteral stones, across 30 centers, to evaluate the efficacy and safety of tamsulosin. INTERVENTION: Participants were randomly assigned (1:1) into tamsulosin (0.4mg) or placebo groups for 4 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point of analysis was the overall stone expulsion rate, defined as stone expulsion, confirmed by negative findings on computed tomography, over a 28-d surveillance period. Secondary end points included time to stone expulsion, use of analgesics, and incidence of adverse events. RESULTS AND LIMITATIONS: Among 3450 patients randomized between September 1, 2011, and August 31, 2013, 3296 (96%) were included in the primary analysis. Tamsulosin benefits from a higher stone expulsion rate than the placebo (86% vs 79%; p<0.001) for distal ureteral stones. Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones (>5mm). Considering the secondary end points, tamsulosin-treated patients reported a shorter time to expulsion (p<0.001), required lower use of analgesics compared with placebo (p<0.001), and significantly relieved renal colic (p<0.001). No differences in the incidence of adverse events were identified between the two groups. CONCLUSIONS: Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic. Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones >5mm, but no effect for stones ≤5mm. PATIENT SUMMARY: In this report, we looked at the efficacy and safety of tamsulosin for the treatment of distal ureteral stones. We find that tamsulosin significantly facilitates the passage of distal ureteral stones and relieves renal colic.