Single-cell analysis revealing the metabolic landscape of prostate cancer.

ABSTRACT: Tumor metabolic reprogramming is a hallmark of cancer development, and targeting metabolic vulnerabilities has been proven to be an effective approach for castration-resistant prostate cancer (CRPC) treatment. Nevertheless, treatment failure inevitably occurs, largely due to cellular heterogeneity, which cannot be deciphered by traditional bulk sequencing techniques. By employing computational pipelines for single-cell RNA sequencing, we demonstrated that epithelial cells within the prostate are more metabolically active and plastic than stromal cells. Moreover, we identified that neuroendocrine (NE) cells tend to have high metabolic rates, which might explain the high demand for nutrients and energy exhibited by neuroendocrine prostate cancer (NEPC), one of the most lethal variants of prostate cancer (PCa). Additionally, we demonstrated through computational and experimental approaches that variation in mitochondrial activity is the greatest contributor to metabolic heterogeneity among both tumor cells and nontumor cells. These results establish a detailed metabolic landscape of PCa, highlight a potential mechanism of disease progression, and emphasize the importance of future studies on tumor heterogeneity and the tumor microenvironment from a metabolic perspective.

A comparison of visual discomfort experienced by surgeons in wireless versus conventional endoscopy in laparoscopic surgery.

Background: This study was performed to introduce a new wireless endoscopic system. Research and development were based on fifth-generation transmission technology. Eye symptoms and visual discomfort induced by the novel endoscopic system were compared with those induced by the conventional endoscopic system before and during laparoscopic pelvic surgery. Materials and methods: Twenty surgeons successfully conducted laparoscopic pelvic surgeries using a conventional endoscopic system and a wireless endoscopic system. Subjective and objective data were measured to evaluate visual discomfort before and 2 hours after surgery. Results: In the conventional endoscopic and wireless endoscopic system groups, no significant differences were found in the presurgical or postsurgical questionnaires. In both groups, tear film breakup times significantly decreased after surgery. However, after comparing the 2 groups, no statistically significant difference was found. Conclusions: Compared with the conventional endoscopic system, the novel wireless endoscopic system does not cause additional visual discomfort for experienced surgeons.

Fabrication and application of a wireless high-definition endoscopic system in urological surgeries.

OBJECTIVE: To introduce a wireless high-definition endoscopic system (WHES) and compare it with a Storz high-definition (HD) system for image resolution, colour resolution, weight, and costs. MATERIALS AND METHODS: The WHES incorporated a portable light-emitting diode light source and a wireless camera module, which can be compatible with different types of endoscopes. Images were wirelessly transmitted to a monitor or mobile platform such as smartphone through a receiver. The International Standards Organization 12233 resolution chart image was used for the comparison of image resolution and Munsell Colour Checker Chart for colour resolution. In all, 38 endourologists used a Likert questionnaire to blindly evaluate cystoscopic images from a patient with haematuria. The surgical team was asked about the overall performance of the WHES in 20 laparoscopic adrenalectomies using a unvalidated subjective survey. RESULTS: There was no difference in image resolution between the two systems (5.82 vs 5.89 line pairs/mm). Without lens and respective light sources, there were better purple (ΔE = 21.48 vs 28.73), blue (ΔE = 34.88 vs 38.6) and red colour resolution (ΔE = 29.01 vs 35.45) for the WHES camera (P < 0.05), but orange (ΔE = 43.45 vs 36.52) and yellow (ΔE = 52.7 vs 35.93) resolutions were better for the Storz HD camera (P < 0.05). Comparing the WHES to a Storz laparoscopic system, the Storz system still had better resolution of orange and yellow, while the resolution of purple, blue, and red was similar for the two systems. The expert comments on resolution, brightness, and colour for cystoscopy were not statistically different, but the ergonomics score for the WHES was higher (3.7 vs 3.33, P = 0.038). The overall cost of the WHES was $23 000-25 000 compared with $45 000-50 000 for a Storz system. There were 100% general satisfaction for the WHES in the survey. CONCLUSION: We developed a new WHES that provides the same resolution images as a Storz laparoscopic system and acceptable colour resolution with the advantages of wireless connection, small volume, low cost, portability, and high-speed wireless transmission.

hOGG1 rs1052133 Polymorphism and Prostate Cancer Risk: A Chinese Case-Control Study and Meta-Analysis.

BACKGROUND We performed a case-control study and an updated meta-analysis to assess the relationship between the hOGG1 rs1052133 polymorphism and prostate cancer (PCa) risk. MATERIAL AND METHODS We recruited 160 PCa cases and 243 healthy controls. For the meta-analysis, relevant studies were recruited from diverse databases up to April 2022. Genetic risk was evaluated by using an odds ratio (OR) with a corresponding 95% confidence interval (95% CI). The genotypes of this polymorphism were genotyped via the SNaPshot genotyping method. RESULTS In the case-control study, we failed to identify any association between the hOGG1 rs1052133 polymorphism and PCa risk. Negative results were also obtained when stratified analyses were performed based on the patient's prostatic-specific antigen (PSA) level and Gleason score, as well as tumor, node, and metastasis (TNM) stage. To enlarge the sample size, we performed a restricted updated meta-analysis by recruiting 10 case-control studies (including the current one), and the results suggested that genotypes of rs1052133 polymorphism were significantly associated with an elevated risk of PCa in 2 genetic models - the heterozygote and dominant models. In the stratification analysis by population ethnicity, a significant association of this polymorphism with susceptibility to PCa was found both in the Asian populations and White populations. CONCLUSIONS Our case-control and updated meta-analysis study suggest that the hOGG1 rs1052133 polymorphism is a susceptibility factor for PCa, but still needs to be further verified in the Chinese population.

Identification of a Novel Stem Cell Subtype for Clear Cell Renal Cell Carcinoma Based on Stem Cell Gene Profiling.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer and is characterized by high rates of metastasis. Cancer stem cell is a vital cause of renal cancer metastasis and recurrence. However, little is known regarding the change and the roles of stem cells during the development of renal cancer. To clarify this problem, we developed a novel stem cell clustering strategy. Based on The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) genomic datasets, we used 19 stem cell gene sets to classify each dataset. A machine learning method was used to perform the classification. We classified ccRCC into three subtypes-stem cell activated (SC-A), stem cell dormant (SC-D), and stem cell excluded (SC-E)-based on the expressions of stem cell-related genes. Compared with the other subtypes, C2(SC-A) had the highest degree of cancer stem cell concentration, the highest level of immune cell infiltration, a distinct mutation landscape, and the worst prognosis. Moreover, drug sensitivity analysis revealed that subgroup C2(SC-A) had the highest sensitivity to immunotherapy CTLA-4 blockade and the vascular endothelial growth factor receptor (VEGFR) inhibitor sunitinib. The identification of ccRCC subtypes based on cancer stem cell gene sets demonstrated the heterogeneity of ccRCC and provided a new strategy for its treatment.

Lack of Association between Common Polymorphisms in Selenoprotein P Gene and Susceptibility to Colorectal Cancer, Breast Cancer, and Prostate Cancer: A Meta-Analysis.

METHOD: We search the PubMed, Embase, Google Scholar, and Wanfang (China) databases (up to December 1, 2020) to identify all eligible publications. The pooled odds ratio (OR) correspondence with 95% confidence interval (CI) was calculated to evaluate the associations. RESULTS: Finally, nine eligible studies with 7,157 cases and 6,440 controls and five studies with 2,278 cases and 2,821 controls were enrolled in rs3877899 and rs7579 polymorphisms, individually. However, a null significant association was detected between the two polymorphisms in SEPP1 and susceptibility to colorectal, breast, and prostate cancer in all comparison models. Subsequently, subgroup analysis based on tumor type, no significant association was identified for prostate, breast, and colorectal cancer. In addition, when the stratification analyses were conducted by the source of control, HWE status, and ethnicity, yet no significant association was found. CONCLUSIONS: The current meta-analysis shows that SEPP1 rs3877899 and rs7579 polymorphisms may not be associated with susceptibility to colon cancer, breast cancer, and prostate cancer, and further well-designed studies with a larger sample size are warranted to validate our findings.

Application of Contrast-Enhanced Ultrasonography (CEUS) in the Assessment of Kidney Wound Recovery After Nephron-Sparing Surgery.

PURPOSE: To investigate feasibility, repeatability and usefulness of contrast-enhanced ultrasonography (CEUS) in the assessment of kidney wound recovery after laparoscopic nephron-sparing surgery (LNSS) or robot-assisted nephron-sparing surgery (RANSS) and preliminarily research the clinical factors associated with the length of extravasation (LOE). PATIENTS AND METHODS: From April 2019 to January 2020, 130 patients that underwent LNSS or RANSS in our hospital were included, and 90 patients (90/130) received CEUS examinations each one day from the postoperative day 1. The discovery of the cessation of contrast medium extravasation from the renal wound was the primary endpoint named "ultrasonic healing", and LOE ranged from the day of surgery to "ultrasonic healing". Patient, tumor, perioperative factors and LOE were collected. Univariate analysis and multivariate linear regression analysis were applied for the determination of factors associated with LOE. RESULTS: The average postoperative LOE was 1.76 days (standard deviation, 1.115; 95% confidence interval: 1.52-1.99). Ultrasonic healing within three days was observed in 95.6% patients (86/90). Univariable and multivariable analyses showed that R and A components in R.E.N.A.L. nephrometry score were associated with LOE. Anterior location and R component score of 2 (tumor size>4cm) were related to longer LOE than posterior location and R score of 1 (tumor size<4cm). The incidence of complications in patients with LOE over one day was higher than those with LOE of one day. CONCLUSION: CEUS was feasible, repeatable and useful in the assessment of kidney wound recovery. Tumor size and location were related to LOE after minimally invasive nephron-sparing surgery (MINSS). Length of stay after MINSS within three days might be relatively safe.

Long noncoding RNA LINC00339 promotes renal tubular epithelial pyroptosis by regulating the miR-22-3p/NLRP3 axis in calcium oxalate-induced kidney stone.

This study aims to investigate the role of long noncoding RNA (lncRNA) long intergenic nonprotein coding RNA 339 (LINC00339) in regulating renal tubular epithelial pyroptosis in kidney stones and to explore the underlying mechanism. The human renal proximal tubular epithelial (HK-2) cells were treated with calcium oxalate monohydrate (COM) for 72 hours to establish the cell model of renal tubular injury. Relative expression of LINC00339 and miR-22-3p was measured by real-time quantitative reverse transcription polymerase chain reaction. Expression of pyroptosis-related molecules was measured by Western blot analysis (NLRP3, ASC, and cleaved caspase-1 p10) and enzyme-linked immunosorbent assay (interleukin-1ß [IL-1ß] and IL-18). Pyroptosis was also determined by lactate dehydrogenase release and active caspase-1-propidium iodide double staining. Luciferase reporter assays were performed to verify whether miR-22-3p could bind to LINC00339 or NLRP3. We observed increased LINC00339, decreased miR-22-3p, NLRP3 inflammasome activation, and enhanced cell pyroptosis in COM-treated HK-2 cells. Furthermore, overexpression of both LINC00339 and NLRP3 activated NLRP3 inflammasome and promoted pyroptosis in COM-treated HK-2 cells, whereas miR-22-3p mimic and NLRP3 knockdown exerted the opposite effects. Mechanically, LINC00339 functioned as a competitive endogenous RNA by sponging miR-22-3p to facilitate NLRP3 expression. In conclusion, lncRNA LINC00339 promotes cell pyroptosis by sponging miR-22-3p to regulate NLRP3 expression in COM-treated HK-2 cells.

Modification of biochar by Fe2O3 for the removal of pyridine and quinoline.

The biochar produced by pyrolysis at 600°C from powdered mango bark impregnated with iron, namely Fe2O3/biochar, was recognized as a multifunctional material for environmental applications. This work aims at using the above material for the removal of pyridine and quinoline from aqueous solutions. The physico-chemical properties of synthesized biochars were studied systematically with several commonly used material characterization methods including scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Fourier transform infrared spectrometer (FTIR). Structural and morphological analyses of the biochars showed that Fe2O3 particles were nanosized and distributed evenly on the surface of biochar, and thus exhibited great adsorption capacity for the removal of pyridine and quinoline. In addition, the results suggested that the main magnetic phase is maghemite (Fe2O3). The modified biochar showed high removal capacity (99%) for quinoline, but the removal capacity of pyridine was only 73%. The pH experiment in this passage indicated that both pyridine and quinoline reached a maximum adsorption amount at pH near 9.0. Adsorption kinetics suggested that the pseudo-second-order was well fitting the experiment data. The equilibrium study showed that the Langmuir model can adequately describe the adsorption process for pyridine and quinoline. The main mechanism of pyridine and quinoline removal was possibly electrostatic interactions and π-π interactions between the modified biochar and the adsorbate.

Renal Primitive Neuroectodermal Tumor: A Case Report.

Primitive neuroectodermal tumor (PNET) is a malignant small round cell tumor and typically arises from bone or soft tissue in adolescents and young adults. Renal PNET is extraordinarily rare and exhibits highly aggressive biological behavior with poor prognosis.We present here a new case of renal PNET in a 31-year-old female. The patients were referred to our hospital because of left flank pain with nausea and vomiting for 1 week. A computed tomography scan revealed a 14.7 × 12.7 cm well-defined, unevenly mass lesion with both solid and cystic components and the tumor was not enhanced uniformly.A preoperative diagnosis of cystic renal cell carcinoma and urinary tract infection was made. The patient undergone anti-inflammatory therapy followed by a left radical nephrectomy. Taken with morphological pattern and immunohistochemical markers, a diagnosis of renal PNET was made. Two cycles of combined chemotherapy were executed. At the 14-month follow-up, no evidence of metastasis or recurrence was indicated.This case reminds clinicians that for adolescents and young adults with a suspicious renal mass, a diagnosis of renal PNET should be always considered. An initial surgery followed by radiotherapy and chemotherapy is suggested for the therapeutic management.

A Comparative Study of Distinct Ocular Symptoms After Performing Laparoscopic Surgical Tasks Using a Three-Dimensional Surgical Imaging System and a Conventional Two-Dimensional Surgical Imaging System.

BACKGROUND AND PURPOSE: Stereoscopic imaging systems have improved the surgical accuracy and patient safety but have induced unwanted visual disturbance, nausea, and ocular symptoms simultaneously. We measured and compared visual discomfort and visual fatigue induced by three-dimensional (3D) surgical imaging system and two-dimentional (2D) surgical imaging system, respectively. METHODS: This study compared ocular symptoms and visual functions immediately after four laparoscopic tasks including pick beans, paper cut, pass the curved needle, and knot tying. Ten participants started with 3D laparoscopy, 9 participants with 2D laparoscopy on the first day, and reversed the laparoscopy for the participants on the second day. Before performing the tasks and immediately after performing the tasks for 1 hour, the participants underwent an interview with questions on ocular symptoms, and then received the systematic measurements of the visual functions objectively. The ocular symptoms were compared between the two groups, and the visual functions were compared in each group and between the two groups. RESULTS: When comparing the 3D laparoscopy group with the 2D laparoscopy group, symptom scores showed statistically significant differences in blurred vision during the task (z=-3.64, P=0.00), irritated or burning eyes (z=-2.17, P=0.03), dry eyes (z=-2.72, P=0.01), eyestrain (z=-3.11, P=0.00), headache (z=-3.20, P=0.00), discomfort in eyes (z=-3.74, P=0.00). The objective visual functional parameters such as distance exophoria (P=0.83), near exophoria (P=0.88), distance esophoria (P=0.93), near esophoria (P=0.80), the fusion range (P=0.09), the accommodative convergence/accommodation (P=0.56), and the tear film breakup time (P=0.48) had no significant difference between the two groups. CONCLUSIONS: When the passively polarized 3D surgical imaging system was compared with the 2D surgical imaging system, although subjective feelings were uncomfortable, there was no objective evidence to indicate that the 3D surgical imaging system resulted in an increment of visual fatigue. The visual fatigue and discomforts were moderate and could be tolerated by the surgeons.