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Background: Urolithiasis is a prevalent condition encountered in urology. Over the past decade, its global incidence has been on an upward trajectory; paired with a high recurrence rate, this presents considerable health and economic burdens. Although inflammatory factors are pivotal in the onset and progression of urolithiasis, their causal linkages remain elusive. Method: Mendelian randomization (MR) is predicated upon genome-wide association studies (GWASs). It integrates bioinformatics analyses to reveal causal relationships between exposures and outcomes, rendering it an effective method with minimized bias. Drawing from a publicly accessible GWAS meta-analysis comprising 8,293 samples, we identified 41 genetic variations associated with inflammatory cytokines as instrumental variables. Outcome data on upper urinary tract stones, which included renal and ureteral stones (9,713 cases and 366,693 controls), and lower urinary tract stones, including bladder and urethral stones (1,398 cases and 366,693 controls), were derived from the FinnGen Consortium R9 dataset. By leveraging the bidirectional MR methodology, we aimed to decipher the causal interplay between inflammatory markers and urolithiasis. Results: Our study comprehensively elucidated the association between genetic inflammatory markers and urolithiasis via bidirectional Mendelian randomization. Post-MR analysis of the 41 genetic inflammation markers revealed that elevated levels of circulating interleukin-2 (IL-2) (OR = 0.921, 95% CI = 0.848-0.999) suggest a reduced risk for renal stone disease, while heightened stem cell growth factor beta (SCGF-ß) (OR = 1.150, 95% CI = 1.009-1.310) and diminished macrophage inflammatory protein 1 beta (MIP-1ß) (OR = 0.863, 95% CI = 0.779-0.956) levels suggest an augmented risk for lower urinary tract stones. Furthermore, renal stone disease appeared to elevate IL-2 (ß = 0.145, 95% CI = 0.013-0.276) and cutaneous T cell-attracting chemokine (CTACK) (ß = 0.145, 95% CI = 0.013-0.276) levels in the bloodstream, whereas lower urinary tract stones were linked to a surge in interleukin-5 (IL-5) (ß = 0.142, 95% CI = 0.057-0.226), interleukin-7 (IL-7) (ß = 0.108, 95% CI = 0.024-0.192), interleukin-8 (IL-8) (ß = 0.127, 95% CI = 0.044-0.210), growth regulated oncogene alpha (GRO-α) (ß = 0.086, 95% CI = 0.004-0.169), monokine induced by interferon-gamma (MIG) (ß = 0.099, 95% CI = 0.008-0.191) and macrophage inflammatory protein 1 alpha (MIP-1α) (ß = 0.126, 95% CI = 0.044-0.208) levels. Conclusion: These discoveries intimate the instrumental role of IL-2 in the onset and progression of upper urinary tract stones. SCGF-ß and MIP-1ß influence the development of lower urinary tract stones. Urolithiasis also impacts the expression of cytokines such as IL-2, CTACK, IL-5, IL-7, IL-8, GRO-α, MIG, and MIP-1α. There is a pressing need for further investigation to ascertain whether these biomarkers can be harnessed to prevent or treat urolithiasis.
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Background: We describe a rare case of giant adrenal calcification as the main cause of sudden onset epigastric pain in a 57-year-old female patient. Case description: Computed tomography (CT) of the whole abdomen in this patient showed calcified foci measuring approximately 7.8 × 5.4 × 7.1 cm in the hepatorenal recess, and no enhancement effect was seen. Secondary causes of adrenal calcification in this patient were ruled out, and a rare diagnosis of a primary giant adrenal calcification was made. Subsequently, the right adrenal gland and calcified mass were completely resected. The calcification did not recur during 6 months of follow up. Conclusions: Although other cases of adrenal calcification of unknown origin have been reported, cases of giant idiopathic adrenal calcification are rare. In this case, huge calcification of the right adrenal gland caused abdominal pain, which disappeared after the mass was excised. The etiology, pathogenesis, clinical symptoms, and prognosis of idiopathic adrenal calcification are still unclear. Additional case reports are needed to gain a better understanding of the diagnosis and treatment of this condition.
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AIMS: Baicalin is a flavonoid derived from the root of the medicinal plant Scutellaria baicalensis Georgi (S. baicalensis) and is known for its various pharmacological properties. This study aimed to investigate the impact of baicalin (BAI) on the occurrence of kidney calcium oxalate crystal formation induced by ethylene glycol in male SD rats. MAIN METHODS: A rat model of renal stones was created and various concentrations of baicalin were used for intervention. Samples of urine, blood, and kidney tissue were taken from the rats, and they were euthanized for biochemical and histopathological examinations. KEY FINDINGS: Our results show that baicalin treatment improved the weight loss induced by ethylene glycol (EG) and ammonium chloride (AC) in rats. Baicalin also reduced the formation of calcium oxalate crystals and protected kidney function in rats with urolithiasis. Furthermore, it lowered the level of malondialdehyde (MDA) and elevated the activity of antioxidant enzymes compared to the stone control group. Additionally, baicalin notably alleviated renal inflammation in rats with urolithiasis. SIGNIFICANCE: The present study attributed clinical evidence first time that claiming the significant antiurolithic effect of baicalin and could be a cost-effective candidate for the prevention and treatment of urolithiasis.
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Etilenoglicol , Flavonoides , Inflamação , Estresse Oxidativo , Ratos Sprague-Dawley , Urolitíase , Animais , Flavonoides/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Inflamação/patologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Urolitíase/induzido quimicamente , Urolitíase/patologia , Urolitíase/tratamento farmacológico , Urolitíase/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Antioxidantes/farmacologia , Malondialdeído/metabolismo , Oxalato de Cálcio/metabolismoRESUMO
Background: Retrograde intrarenal surgery (RIRS) is the main treatments for upper urinary tract stones. The Ureteral Access Sheath (UAS) serves as a supplementary tool, facilitating direct kidney access during RIRS. High quality of evidence comparing tip bendable suction ureteral access sheath (S-UAS) with traditional UAS in RIRS for the treatment of renal and ureteral stones is lacking. The purpose of the study is to compare the efficacy and safety of S-UAS with traditional UAS in RIRS for the treatment of renal or ureteral stones ≤30 mm. Methods: An international, multicenter, and superiority randomized controlled trial included 320 intention-to-treat patients across 8 medical centers in China, the Philippines, Malaysia and Turkey from August 2023 to February 2024. The inclusion criteria were patients ≥18 years old with renal or ureteral stones ≤30 mm. RIRS was performed using either S-UAS or traditional UAS. The primary outcome was the immediately stone-free rate (SFR). Secondary outcomes included SFR 3 months after operation, operating time, hospital stay, auxiliary procedures, complications (using the Clavien-Dindo grading system), and improvement in the Quality of Life (QoL) score. Differences between proportions [risk difference (RD)]/means [mean difference (MD)] and 95% confidence intervals (CI) were presented. This study is registered at ClinicalTrials.gov: NCT05952635. Findings: The S-UAS group demonstrated a significantly higher immediately SFR (81.3% versus 49.4%; RD 31.9%; 95% CI 22.5%-41.7%; p = 0.004) compared to the traditional UAS group, as determined by the one-side superiority test. Additionally, the S-UAS group exhibited a higher SFR at 3 months post-operation (87.5% versus 70.0%; RD 17.5%; 95% CI 8.7%-26.3%; p < 0.001), lower postoperative fever rate (RD -11.9%; 95% CI -18.7% to -4.9%; p < 0.001), reduced use of stone baskets (RD -70.6%; 95% CI -77.8% to -63.5%; p < 0.001), and better QoL improvement (MD 7.25; 95% CI 2.21-12.29; p = 0.005). No statistically significant differences were observed in operation time, hospital stay, or the need for second-stage RIRS. Interpretation: In RIRS for upper urinary tract stones ≤30 mm, S-UAS exhibited superior performance compared to traditional UAS, demonstrating higher SFR, reduced postoperative fever rate, and improved QoL outcomes. S-UAS emerges as a prudent and advantageous alternative to traditional UAS for RIRS. Funding: National Natural Science Foundation of China and Guangdong Province, and Zhejiang Medicine and Health Program.
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Cancer immunotherapy, as an emerging approach to cancer treatment, has tremendous potential for application. Compared to traditional methods such as surgery, chemotherapy, and radiation therapy, it has the ability to restore the patient's immune system, leading to long-term immune memory with less damage to normal tissues. However, immunotherapy has its limitations, including limited therapeutic efficacy, restricted patient populations, and inconsistent treatment responses. Finding effective immunotherapeutic approaches has become a key focus of its clinical application. The adenosine pathway is a recently discovered tumor immune regulatory signaling pathway. It can influence the metabolism and growth of tumor cells by acting through key enzymes in the adenosine pathway, thereby affecting the development of tumors. Therefore, inhibiting the adenosine pathway is an effective cancer immunotherapy. Common adenosine pathway inhibitors include small molecules and antibody proteins, and extensive preclinical trials have demonstrated their effectiveness in inhibiting tumor growth. The short half-life, low bioavailability, and single administration route of adenosine pathway inhibitors limit their clinical application. With the advent of nanotechnology, nano-delivery of adenosine pathway inhibitors has addressed these issues. Compared to traditional drugs, nano-drugs extend the drug's circulation time and improve its distribution within the body. They also offer targeting capabilities and have low toxic side effects, making them very promising for future applications. In this review, we discuss the mechanism of the adenosine pathway in tumor immune suppression, the clinical applications of adenosine pathway inhibitors, and nano-delivery based on adenosine pathway inhibitors. In the final part of this article, we also briefly discuss the technical issues and challenges currently present in nano-delivery of adenosine pathway inhibitors, with the hope of advancing the progress of adenosine inhibitor nano-drugs in clinical treatment.
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Adenosina , Imunoterapia , Nanopartículas , Neoplasias , Humanos , Adenosina/química , Adenosina/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Imunoterapia/métodos , Nanopartículas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
BACKGROUND: This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development. METHODS: By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes. RESULTS: The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P < 0.01). Smooth muscle cells treated with PGE2 displayed increased cAMP and phosphorylated PKA. CONCLUSIONS: PGE2 binding to EP2 induces ureteral relaxation through the cAMP-PKA pathway. This will provide a new theoretical basis for the development of new therapeutic approaches for the use of PGE2 in the treatment of ureteral stones.
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Proteínas Quinases Dependentes de AMP Cíclico , AMP Cíclico , Dinoprostona , Receptores de Prostaglandina E Subtipo EP2 , Ureter , Cálculos Ureterais , Receptores de Prostaglandina E Subtipo EP2/metabolismo , AMP Cíclico/metabolismo , Dinoprostona/metabolismo , Dinoprostona/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Animais , Ureter/metabolismo , Transdução de Sinais/fisiologia , Masculino , Relaxamento Muscular/efeitos dos fármacos , Relaxamento Muscular/fisiologiaRESUMO
Malignant peripheral nerve sheath tumors (MPNSTs) are a complex group of malignant tumors originating from nerve cells or benign peripheral nerve sheath tumors and are commonly found in major plexus/nerve root sites such as the limbs, head, and neck. Malignant peripheral nerve sheath tumors originating in the ureter are extremely rare. Herein, we report the case of a 63-year-old patient with a malignant peripheral nerve sheath tumor of the right ureter who underwent laparoscopic radical resection of the right kidney and ureter. The patient also had stage 5 chronic kidney disease (CKD). Therefore, chemotherapy and radiotherapy were not considered. No tumor recurrence was observed during the follow-up period.
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Circadian rhythm is an internal timing system and harmonizes a variety of cellular, behavioral, and physiological processes to daily environment. Circadian disturbance caused by altered life style or disrupted sleep patterns inevitably contributes to various disorders. As the rapidly increased cancer occurrences and subsequent tremendous financial burdens, more researches focus on reducing the morbidity rather than treating it. Recently, many epidemiologic studies demonstrated that circadian disturbance was tightly related to the occurrence and development of cancers. For urinary system, numerous clinical researches observed the incidence and progress of prostate cancer were influenced by nightshift work, sleep duration, chronotypes, light exposure, and meal timing, this was also proved by many genetic and fundamental findings. Although the epidemiological studies regarding the relationship between circadian disturbance and kidney/bladder cancers were relative limited, some basic researches still claimed circadian disruption was closely correlated to these two cancers. The role of circadian chemotherapy on cancers of prostate, kidney, and bladder were also explored, however, it has not been regularly recommended considering the limited evidence and poor standard protocols. Finally, the researches for the impacts of circadian disturbance on cancers of adrenal gland, penis, testis were not found at present. In general, a better understanding the relationship between circadian disturbance and urological cancers might help to provide more scientific work schedules and rational lifestyles which finally saving health resource by reducing urological tumorigenesis, however, the underlying mechanisms are complex which need further exploration.
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BACKGROUND: Serum prostate-specific antigen (PSA) is a primary metric for diagnosis and prognosis of prostate cancer (PCa). Exposure to heavy metals, such as lead, cadmium, mercury, and zinc can impact PSA levels in PCa patients. However, it is unclear whether this effect also occurs in men without PCa, which may lead to the overdiagnosis of PCa. METHOD: Data on a total of 5089 American men who had never been diagnosed with PCa were obtained from the National Health and Nutrition Examination Survey performed from 2003-2010. The relationship between serum PSA levels (dependent variable) and concentrations of lead (µmol/L), cadmium (nmol/L), and mercury (µmol/L) were investigated with dietary zinc intake being used as a potential modifier or covariate in a weighted linear regression model and a generalized additive model. A series of bootstrapping analyses were performed to evaluate sensitivity and specificity using these models. RESULTS: Regression analyses suggested that, in general, lead, cadmium, or mercury did not show an association with PSA levels, which was consistent with the results of the bootstrapping analyses. However, in a subgroup of participants with a high level of dietary zinc intake (≥14.12 mg/day), a significant positive association between cadmium and serum PSA was identified (1.06, 95% CI, P = 0.0268, P for interaction=0.0249). CONCLUSIONS: With high-level zinc intake, serum PSA levels may rise in PCa-free men as the exposure to cadmium increases, leading to a potential risk of an overdiagnosis of PCa and unnecessary treatment. Therefore, environmental variables should be factored in the current diagnostic model for PCa that is solely based on PSA measurements. Different criteria for PSA screening are necessary based on geographical variables. Further investigations are needed to uncover the biological and biochemical relationship between zinc, cadmium, and serum PSA levels to more precisely diagnose PCa.
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Mercúrio , Metais Pesados , Masculino , Humanos , Estados Unidos , Antígeno Prostático Específico , Cádmio , Inquéritos Nutricionais , ZincoRESUMO
Purpose: The objective of this study was to examine the expression and role of Centromere protein W (CENPW) in bladder cancer (BLCA), as well as its potential mechanistic impact on the progression of BLCA. Methods: In this study, we conducted a comparative analysis of the mRNA expression level of CENPW in BLCA tissues and adjacent normal tissues using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we investigated the association between CENPW expression and patient prognosis. Furthermore, we performed in vitro and in vivo experiments to assess the impact of CENPW knockdown on various tumor biological phenotypes in BLCA. Finally, we conducted an analysis to elucidate the underlying mechanisms responsible for the observed phenotypic alterations in BLCA. Results: The expression of CENPW was found to be upregulated in BLCA, and its higher expression was associated with a poorer disease-specific survival (DSS). CENPW was found to have close associations with the cell cycle, mitosis, and DNA replication. In vitro and in vivo experiments demonstrated that the inhibition of CENPW led to a suppression of BLCA progression. Specifically, the knockdown of CENPW resulted in cell cycle arrest phase and induced apoptosis in BLCA by potentially inactivating the signal transducer and activator of transcription3 (STAT3) signaling pathway. Conclusion: CENPW has the potential to function as a molecular marker indicating an unfavorable prognosis in BLCA. Additionally, CENPW exhibits promise as a novel therapeutic target for BLCA.
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OBJECTIVE: To estimate the pooled prevalence, as well as the spatial and temporal distribution, of urolithiasis among subjects in China. MATERIALS AND METHODS: We conducted a comprehensive search of both Chinese and English databases to retrieve literature pertaining to the prevalence of urolithiasis in the indigenous Chinese population. A random-effects meta-analysis model was employed to calculate the pooled prevalence of urolithiasis. Subgroup analyses were conducted based on factors such as time, region, gender, and sample size. Prevalence and spatial distribution maps were created based on provinces and latitude/longitude coordinates. RESULTS: A total of 46 studies conducted in 22 provinces across China were included in this meta-analysis and the pooled prevalence of urolithiasis, kidney stones, ureteric calculi, urethral and bladder stones were 8.1% (95% confidence interval [CI] 5.6-11.1%), 7.8% (95% CI 5.8-10.0%), 3.2% (95% CI 0.6-5.7%), 0.5% (95% CI 0.1-0.9%). Most of the urolithiasis prevalence screening in China was concentrated between 100° E and 120° E, with higher rates observed in low latitude areas. Subgroup analysis of kidney stones revealed that Guangdong (12.7%) and Guangxi (10.3%) had the highest prevalence, with the eastern developed area exhibiting higher rates compared to the west. The prevalence in males was higher than in females (odds ratio 1.67, 95% CI 1.46-1.92), although the gender gap has significantly reduced since 2006. Moreover, a greater sample size is associated with a decreased prevalence of urolithiasis. CONCLUSIONS: The prevalence of urolithiasis is increasing in China, and there are noteworthy regional or provincial disparities in occurrence. It is worth noting that the current number of screening studies in some areas is insufficient. Additional investigations with appropriate sample sizes should be supplemented in time.
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Cálculos Renais , Cálculos da Bexiga Urinária , Urolitíase , Masculino , Feminino , Humanos , Prevalência , China/epidemiologia , Urolitíase/epidemiologia , Cálculos Renais/epidemiologiaRESUMO
Bladder cancer (BLCA) is a common malignant neoplasm of the urinary system. Glycolysis is an essential metabolic pathway regulated by various genes with implications for tumor progression and immune escape. Scoring the glycolysis for each sample in the TCGA-BLCA dataset was done using the ssGSEA algorithm for quantification. The results showed that the score in BLCA tissues was markedly greater than those in adjacent tissues. Additionally, the score was found to be correlated with metastasis and high pathological stage. Functional enrichment analyses of the glycolysis-related genes showed they were related to roles associated with tumor metastasis, glucose metabolism, cuproptosis, and tumor immunotherapy in BLCA. Using 3 different machine learning algorithms, we identified chondroitin polymerizing factor (CHPF) as a central glycolytic gene with high expression in BLCA. In addition, we showed CHPF is a valuable diagnostic marker of BLCA with an area under the ROC (AUC) of 0.81. Sequencing BLCA 5637 cells after siRNA-mediated CHPF silencing and bioinformatics revealed that CHPF positively correlated with the markers of epithelial-to-mesenchymal transformation (EMT), glycometabolism-related enzymes, and immune cell infiltration. In addition, CHPF silencing inhibited the infiltration of multiple immune cells in BLCA. Genes that promote cuproptosis negatively correlated with CHPF expression and were up-regulated after CHPF silencing. High CHPF expression was a risk factor for overall and progression-free survival of patients who received immunotherapy for BLCA. Finally, using immunohistochemistry, we demonstrated that the CHPF protein had high expression in BLCA, increasing in high-grade tumors and those with muscle invasion. The CHPF expression levels were also positively associated with 18F-fluorodeoxyglucose uptake in PET/CT images. We conclude that the glycolysis-related gene CHPF is an effective diagnostic and treatment target for BLCA.
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BACKGROUND: Urothelial carcinoma (UC) is a common malignancy of the urinary system that can occur anywhere from the renal pelvis to the proximal urethra. Most UCs are in the bladder and have multifocal growth. Upper urinary tract UC (UTUC), which occurs in the renal pelvis or ureter, accounts for only 5% to 10% of UCs. CASE SUMMARY: In March 2015, a 70-year-old male who initially presented to a local hospital with a complaint of painless hematuria was diagnosed with UTUC of the right renal pelvis. The doctors administered radical nephroureterectomy and bladder cuff excision. Although the doctors recommended intravesical chemotherapy and regular follow-up, he rejected this advice. In December 2016, the patient presented at our hospital with dysuria. We identified UC in the residual bladder and administered radical cystectomy and left cutaneous ureterostomy. In November 2021, he presented again with urethral bleeding. We detected urethral UC as the cause of urethral orifice bleeding and administered radical urethrectomy. Since then, he has visited regularly for 6-mo follow-ups, and was in stable condition as of December 2022. CONCLUSION: UTUC is prone to seeding and recurrence. Adjuvant instillation therapy and intense surveillance are crucial for these patients.
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BACKGROUND: Attenuated live bacterial therapy and medical BSA materials have their own advantages in anti-cancer research, and their combination is expected to overcome some of the disadvantages of conventional anti-cancer therapeutics. METHODS AND OBJECTIVE: Utilizing the high affinity between biotin and streptavidin, BSA modification on the surface of Escherichia coli (E. coli) was achieved. Then, the adhesion and targeting abilities of BSA modified E. coli was explored on different bladder cancer cells, and the underlying mechanism was also investigated. RESULTS: BSA modification on the surface of E. coli enhances its ability to adhere and target cancer cells, and we speculate that these characteristics are related to the expression of SPARC in different bladder cancer cell lines. CONCLUSION: BSA and live bacteria have their own advantages in anti-cancer research. In this study, we found that E. coli surface-modified by BSA had stronger adhesion and targeting effects on bladder cancer cells with high expression of SPARC. These findings pave the way for the future studies exploring the combination of BSA combined with live bacteria for cancer therapy.
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Soroalbumina Bovina , Neoplasias da Bexiga Urinária , Humanos , Soroalbumina Bovina/metabolismo , Escherichia coli/metabolismo , Bactérias/metabolismo , BiotinaRESUMO
Objectives: Calgranulins S100A8 and S100A9 are common in renal stones and they are up-regulated in both urinary exosomes and kidneys of stone patients. Renal sources and important regulators for S100A8 and S100A9 in nephrolithiasis were explored in this study. Materials and Methods: We identified S100A8 and S100A9 abundance in various renal cells by searching the Single Cell Type Atlas. Macrophages were polarized from human myeloid leukemia mononuclear cells. Human proximal renal tubular epithelial cells (HK-2) were stimulated with calcium oxalate monohydrate (COM). Coculture experiments involving HK-2 cells and macrophages were conducted. qPCR, Western blotting, ELISA, and immunofluorescence were used for detecting interleukin 6 (IL6), S100A8, and S100A9. Results: The Single Cell Type Atlas showed that S100A8 and S100A9 in human kidneys primarily originated from macrophages. M1 was the predominant macrophage type expressing S100A8 and S100A9. Direct culture with COM did not affect the expression of these two calgranulins in M1 macrophages but coculture with COM-treated HK-2 cells did. COM could promote HK-2 cells to secrete IL6. IL6 could up-regulate S100A8 and S100A9 expression in macrophages of M1 type. In addition, 0.5 µM SC144 (a kind of IL6 inhibitor) significantly prevented COM-treated HK-2 cells from up-regulating S100A8 and S100A9 expression in macrophages of M1 type. Conclusion: M1-polarized macrophages were the predominant cell type expressing S100A8 and S100A9 in the kidneys of nephrolithiasis patients. CaOx crystals can promote renal tubular epithelial cells to secrete IL6 to up-regulate S100A8 and S100A9 expression in macrophages of M1 type.
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Objective To screen nanobodies against prostate specific membrane antigen (PSMA). Methods Based on the naive phage display library, three rounds of screening were performed targeting the PSMA antigen, and positive clones were identified by ELISA and sequencing was performed. The positive cloned gene sequence was inserted into the pET28a prokaryotic expression vector and transformed into E.coli BL21. The expression of the recombinant protein was induced by IPTG and purified using Ni column, with the purified product verified by SDS-PAGE. Results Four PSMA nanobodies VHH1, VHH2, VHH3 and VHH4 were obtained by screening. The VHH1 failed to obtain protein expression, while the VHH2, VHH3 and VHH4 proteins were expressed. The purity of anti-PSMA nanobodies showed high and relative molecular mass (Mr) of about 17 000. Conclusion The sequence of anti-PSMA nanobody was successfully obtained by screening the naive phage nanobody library and were subjected to prokaryotic expression and purified.
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Bacteriófagos , Anticorpos de Domínio Único , Masculino , Humanos , Anticorpos de Domínio Único/genética , Bacteriófagos/genética , Próstata , Glutamato Carboxipeptidase II/genética , Glutamato Carboxipeptidase II/metabolismo , Escherichia coli/genéticaRESUMO
The differential diagnosis of renal tumors and abscesses is crucial owing to their different treatments. Although antibacterial administration and radiological examination are excellent means for distinction, misdiagnosis is common and may lead to severe consequences, such as the need for nephrectomy. Here, we report a case involving a 52-year-old Asian woman with a renal mass for which a differential diagnosis was challenging. The mass persisted after administration of intravenous antibiotic therapy for 1 month. A computed tomography scan indicated an inflammatory lesion, whereas magnetic resonance imaging suggested a diagnosis of a tumor. Despite these indications, a right renal abscess was suspected during robot-assisted laparoscopic surgery, and nephron-sparing surgery was performed, which allowed confirmation of the final pathological result by biopsy specimen. Postoperatively, the mass gradually decreased in size after antibiotic therapy for a further month. This case, in which a renal abscess mimicked a tumor and the patient almost underwent a nephrectomy, highlights the need for caution in establishing therapeutic schedules for patients with inaccurate diagnoses. The management strategies for such patients must be reviewed and improved.
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Rhabdomyosarcoma (RMS) is a soft tissue tumor, which is the most common in the head, neck, limbs, and trunk. RMS originating from the epididymis is extremely rare. Herein, we reported a 34-year-old patient with RMS on the right epididymis. For this case, right epididymal mass resection was performed and intraoperative freezing suggested a malignant tumor. Right testicular radical resection was subsequently adopted, with right epididymal alveolar RMS being pathologically diagnosed. Alternating VAC/VI chemotherapy was given after surgery, and tumor recurrence has not been found so far.
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Urachal signet ring cell carcinoma is a kind of rare but aggressive tumor, and a few cases have been reported previously. A 49-year-old male patient with primary complaints of increased frequency of urination, urodynia, and hematuria was diagnosed to have primary urachal signet ring cell carcinoma by our department. Multiple metastases were found in the sigmoid colon, terminal ileum, mesentery, and peritoneum during the operation, and palliative surgery involving partial cystectomy with en bloc resection of the urachus was then performed. A chemotherapy regimen of fluorouracil combined with cisplatin was made for this case. In addition, this patient also received anlotinib for targeted therapy. So far, this patient has done well on regular follow-up for 6 months and is in stable condition. We reported this additional urachal signet ring cell carcinoma case and conducted a literature review to strengthen our cognition of this disease.
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Background: To investigate the potential mechanisms of chemoradiotherapy resistance in patients with bladder cancer. Methods: We assessed three bladder cancer cell lines (5637, J82, and TCCSUP) for their sensitivity to chemoradiotherapy. Reverse transcription quantitative PCR (RT-qPCR) was used to detect the expression of specific genes after chemoradiotherapy or combined with olaparib. The Genome Cancer Atlas (TGCA) database was used to analyze possible radioresistance-related genes and the relationship between their expression and bladder cancer survival and prognostic indicators. Results: The 5637 cell line showed the most significant sensitivity to chemoradiotherapy. The expression levels of DNA damage repair genes in 5637 cells did not significantly change after chemoradiotherapy. In contrast, the expression levels of BRCA1 and RBBP8 genes significantly increased in J82 and TCCSUP cells after chemoradiotherapy. After combination with olaparib, which is a poly (ADP-ribose) polymerase inhibitor that initiates DNA repair, 5637 cells were significantly inhibited by chemoradiotherapy. However, chemoradiotherapy inhibition on J82 cells was weakened when combined with olaparib. A high reactive expression of BRCA1 and RBBP8 after combination with olaparib suggested that olaparib was ineffective because it did not induce synthetic lethality in which inhibiting PARP by olaparib coincided with suppression of BRCA1/2 expression result in cancer cell death. Conclusions: The expression levels of RBBP8 and BRCA1 genes were associated with sensitivity to radiotherapy and chemotherapy in bladder cancer, and an increase in reactive expression after treatment led to worse sensitivity. Therefore, the reactive expression levels of BRCA1 and RBBP8 after chemoradiotherapy may be useful in evaluating the efficacy of olaparib combination therapy.