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Kidney disease has become a global public health problem. Patients with end-stage kidney disease must rely on dialysis or undergo renal transplantation, placing heavy burdens on their families and society. Therefore, it is important to develop new therapeutic targets and intervention strategies during early stages of chronic kidney disease. The widespread application of liquid biopsy has led to an increasing number of studies concerning the roles of cell-free DNA (cfDNA) in kidney disease. In this review, we summarize relevant studies concerning the roles of cfDNA in kidney disease and describe various strategies for targeted removal of cfDNA, with the goal of establishing novel therapeutic approaches for kidney disease.
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The spectral quality of magnetic resonance spectroscopic imaging (MRSI) can be affected by strong magnetic field inhomogeneities, posing a challenge for 3D-MRSI's widespread clinical use with standard scanner-equipped 2nd-order shim coils. To overcome this, we designed an empirical unified shim-RF head coil (32-ch RF receive and 51-ch shim) for 3D-MRSI improvement. We compared its shimming performance and 3D-MRSI brain coverages against the standard scanner shim (2nd-order spherical harmonic (SH) shim coils) and integrated parallel reception, excitation, and shimming (iPRES) 32-ch AC/DC head coil. We also simulated a theoretical 3rd-, 4th-, and 5th-order SH shim as a benchmark to assess the UNIfied shim-RF coil (UNIC) improvements. In this preliminary study, the whole-brain coverage was simulated by using B0 field maps of twenty-four healthy human subjects (n = 24). Our results demonstrated that UNIC substantially improves brain field homogeneity, reducing whole-brain frequency standard deviations by 27% compared to the standard 2nd-order scanner shim and 17% compared to the iPRES shim. Moreover, UNIC enhances whole-brain coverage of 3D-MRSI by up to 34% compared to the standard 2nd-order scanner shim and up to 13% compared to the iPRES shim. UNIC markedly increases coverage in the prefrontal cortex by 147% and 47% and in the medial temporal lobe and temporal pole by 29% and 13%, respectively, at voxel resolutions of 1.4 cc and 0.09 cc for 3D-MRSI. Furthermore, UNIC effectively reduces variations in shim quality and brain coverage among different subjects compared to scanner shim and iPRES shim. Anticipated advancements in higher-order shimming (beyond 6th order) are expected via optimized designs using dimensionality reduction methods.
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OBJECTIVE: The lack of curative therapies for advanced prostate cancer (PCa) has prompted a search for novel treatments such as immunotherapy. In this study, we analyzed whether dendritic cells (DCs) from healthy donors transduced with a PSMA-encoding adenovirus (Ad-PSMA) and cocultured with autologous cytokine-induced killer cells (CIKs) can induce a strong specific immune response against PCa cells in vitro. MATERIALS AND METHODS: Ad-PSMA was constructed by DNA recombination. DCs and CIKs were prepared by cytokines induction from peripheral blood mononuclear cells, and flow cytometry was used to measure the phenotypes of DCs and CIKs. DCs were transduced with Ad-PSMA and then cocultured with autologous CIKs. The cytotoxicity of the cocultured cells against specific target LNCaP cells and control targets DU145 and PC3 cells was analyzed by a 4-h LDH release assay. RESULTS: DCs were transduced with Ad-PSMA with transfection efficiency of 70% and the transduction did not alter typical morphology of mature DCs. The PSMA protein was effectively expressed in DCs, which were transfected with Ad-PSMA. Ad-PSMA-transduced DCs stimulated CIKs strongly to lyse about 75% of PSMA-expressing PCa cells. Furthermore, the cocultivation of Ad-PSMA-transduced DCs with CIKs could significantly increase the production of interferon-gamma after restimulated with PSMA peptide mixtures. CONCLUSIONS: The data demonstrate that DCs, which were transduced with a PSMA-expressing adenovirus and cocultured with autologous CIKs, induce a PSMA-specific, strong immune response against PCa cells. Therefore, this approach may have a potential for an adoptive immunotherapy for patients with advanced PCa.
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Adenoviridae/genética , Antígenos de Superficie/metabolismo , Células Dendríticas/metabolismo , Glutamato Carboxipeptidasa II/metabolismo , Inmunoterapia/métodos , Técnicas de Cultivo de Célula , Membrana Celular/metabolismo , Técnicas de Cocultivo , Citocinas/metabolismo , Epítopos/química , Humanos , Sistema Inmunológico , Linfocitos/metabolismo , Masculino , Modelos Biológicos , Plásmidos/metabolismoRESUMEN
BACKGROUND & OBJECTIVE: Postoperative tissue adherence, scarring and radiotherapy often lead to extrinsic compression and stricture in the distal ureter of the patients who had history of pelvic malignancies. Our aim was to evaluate the efficacy and safety of endourologic techniques in treating this kind of ureteral obstruction. METHODS: From Jan. 1998 to Mar. 2007, 46 patients with obstruction in the distal ureter and had history of pelvic malignancies underwent endoscopic treatments at the Third Affiliated Hospital of Sun Yat-sen University for relief of the obstruction. Perioperative and follow-up data were analyzed. RESULTS: Of the 46 patients, 25 underwent laparoscopic ureterolysis and uretero-neocystostomy, 18 underwent placement of ureter stent under ureteroscope, 3 underwent percutaneous nephrostomy. No severe complication was recorded. The mean operating time was 82.5 min (range, 30-140 min). The mean blood loss was 45.5 ml (range, 5-180 ml). No blood transfusion was needed. The median follow-up time was 18.2 months (range, 3 months to 6.5 years). Three months after operation, B-ultrasonography and intravenous urography (IVU) showed that 39 (84.8%) patients had recovered normal renal function, the other 7 (15.2%) had hydronephrosis relief and renal function improvement. Nuclear renal scanning showed that the mean postoperative glomerular filtration rate (GFR) in the obstructive kidney was higher than the preoperative level (37.6 ml/min vs. 21.3 ml/min, P<0.05). No stricture in the uretero-bladder anastomotic stoma was recorded. CONCLUSION: Endoscopic operation is an effective and feasible option for managing some selected kinds of distal ureteral obstruction caused by postoperative tissue adherence and radiotherapy in the patients with history of pelvic malignancies.
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Laparoscopía/métodos , Stents , Obstrucción Ureteral/cirugía , Ureterostomía/métodos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Nefrostomía Percutánea , Neoplasias Pélvicas/radioterapia , Neoplasias Pélvicas/cirugía , Complicaciones Posoperatorias , Radioterapia/efectos adversos , Obstrucción Ureteral/etiología , Ureteroscopía/métodos , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: A percutaneous nephrostomy (PCN) done on the same side as a previous open nephrolithotomy is always technically challenging. A novel one-step PCN tube that allows the puncture and placement of a drainage tube to be done in a single step has been developed. The hydrophilic coating on the tube's surface significantly reduces friction and allows easier insertion. We evaluated the tube's efficiency and safety compared with the traditional fascial dilator system. PATIENTS AND METHODS: Sixty-five patients with a history of open nephrolithotomy were randomly allocated (with the aid of a computer-derived assignment number) into two groups to have PCN performed in one step or multiple steps. In the one-step group, a new type of PCN tube was used. In the multistep group, fascial dilators were used serially prior to tube insertion. The two groups were similar in terms of mean age, width of target calix, and baseline serum creatinine and hemoglobin concentrations. The operating times, intubation rates, and complications in the two groups were compared. RESULTS: The mean number of attempts required to access the collecting system was 1.1 +/- 0.6 in the one-step group v 2.3 +/- 1.2 in the multistep group (P = 0.002), the successful intubation rate was 96.9% v 78.8% (P = 0.012), the mean operating time was 10.2 +/- 2.4 minutes v 25.6 +/- 2.8 minutes (P = 0.029), and the rate of intraoperative and postoperative complications was 3.1% v 15.2%, respectively (P = 0.019). No major complications occurred in the one-step group. CONCLUSIONS: The one-step PCN tube is a convenient and efficacious method for accessing an anatomic region where open nephrolithotomy was done previously and is a simple method for nephrostomy tube placement.
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Hidronefrosis/cirugía , Nefrostomía Percutánea/instrumentación , Nefrostomía Percutánea/métodos , Adulto , Anciano , Humanos , Persona de Mediana Edad , Reoperación/métodosRESUMEN
AIM: To examine the impact and prognostic significance of alpha-tocopherol associated protein (TAP) expression in a series of prostate cancer patients. METHODS: Tissues from 87 patients underwent radical prostatectomy were examined for TAP expression by immunohistochemistry. The relationships of the staining results, the clinic pathological characteristics and the recurrence times were analyzed. RESULTS: Compared with the adjacent areas of normal and benign glands, immunoreactivity of TAP was reduced in areas of prostate cancer. A lower TAP-positive cell number per mm(2) of the largest cancer area (defined as TAP-PN) was associated with higher clinical stage (r = -0.248, P = 0.0322). Inverse associations were found among the TAP-PN and positive lymph nodes (r = -0.231, P = 0.0325), preoperative prostate-specific antigen (PSA) levels (r = -0.423, P = 0.0043), tumor size (r= -0.315, P= 0.0210) and elevated tumor cell proliferation, which was indicated by the staining of Ki-67 (r = -0.308, P = 0.0026). TAP-PN was a significant predictor of recurrence univariately (P = 0.0006), as well as multivariately, adjusted for known markers including preoperative PSA, clinical stage, Gleason score, surgical margin, extra-prostatic extension, seminal vesicle invasion and lymph node metastasis (P = 0.0012). CONCLUSION: Reduced expression of TAP was associated with the cell proliferation status of prostate cancer, adverse pathological parameters and the increased risk of recurrence.