MMP-9 gene polymorphisms on cancer risk: an updated systematic review and meta-analysis.

To provide a comprehensive account of the association of MMP-9 gene polymorphisms (rs3918242) with susceptibility to cancer. A literature search for eligible candidate gene studies published before May 27, 2022 was conducted in PubMed, Medline, Google Scholar and Web of Science. Potential sources of heterogeneity were sought out across subgroups and sensitivity analysis. Publication bias were also estimated. Overall, a total of 37 articles with 7616 cases and 8165 controls for rs3918242 gene polymorphisms were enrolled. Our meta-analysis suggests that MMP-9 rs3918242 might be associated with breast cancer and gastric cancer susceptibility, and perhaps reduce the risk of lung cancer.

CDK13 promotes lipid deposition and prostate cancer progression by stimulating NSUN5-mediated m5C modification of ACC1 mRNA.

Cyclin-dependent kinases (CDKs) regulate cell cycle progression and the transcription of a number of genes, including lipid metabolism-related genes, and aberrant lipid metabolism is involved in prostate carcinogenesis. Previous studies have shown that CDK13 expression is upregulated and fatty acid synthesis is increased in prostate cancer (PCa). However, the molecular mechanisms linking CDK13 upregulation and aberrant lipid metabolism in PCa cells remain largely unknown. Here, we showed that upregulation of CDK13 in PCa cells increases the fatty acyl chains and lipid classes, leading to lipid deposition in the cells, which is positively correlated with the expression of acetyl-CoA carboxylase (ACC1), the first rate-limiting enzyme in fatty acid synthesis. Gain- and loss-of-function studies showed that ACC1 mediates CDK13-induced lipid accumulation and PCa progression by enhancing lipid synthesis. Mechanistically, CDK13 interacts with RNA-methyltransferase NSUN5 to promote its phosphorylation at Ser327. In turn, phosphorylated NSUN5 catalyzes the m5C modification of ACC1 mRNA, and then the m5C-modified ACC1 mRNA binds to ALYREF to enhance its stability and nuclear export, thereby contributing to an increase in ACC1 expression and lipid deposition in PCa cells. Overall, our results disclose a novel function of CDK13 in regulating the ACC1 expression and identify a previously unrecognized CDK13/NSUN5/ACC1 pathway that mediates fatty acid synthesis and lipid accumulation in PCa cells, and targeting this newly identified pathway may be a novel therapeutic option for the treatment of PCa.

Oblique supine position versus prone position for percutaneous nephrolithotomy: a systematic review and meta-analysis.

Introduction: To compare the efficacy and safety of percutaneous nephrolithotomy (PCNL) in the oblique supine position (OSP) and the prone position (PP). Aim: To perform a systematic review and meta-analysis to evaluate the efficacy and safety of OSP versus PP for PCNL. Material and methods: A systematic literature search of PubMed, Ovid, SCOPUS, and citation lists was conducted to identify eligible comparative studies up to November 2022. All studies comparing OSP versus PP for PCNL were included. Statistical analysis was performed with the Collaboration's Review Manager (RevMan) 5.4 software. Results: Overall, eight studies were included involving 1185 patients (OSP = 634; PP = 551). There were no statistically significant differences between OSP and PP in age (WMD = -0.95 years; 95% CI: -2.12 to 0.21; p = 0.83) or proportion of male patients (OR = 0.02; 95% CI: -0.03 to 0.08; p = 0.43). We found that OSP was performed more frequently for smaller stone size and patients with higher BMI (WMD = -0.1 cm, 95% CI: -0.18 to -0.02; p = 0.01) and patients with higher BMI (WMD = 0.66 kg/m2; 95% CI: 0.29 to 1.03; p = 0.0005). The operation time was shorter in OSP than PP (WMD = -14 min; 95% CI: -27.00 to -1.00; p = 0.03). The reduction of hemoglobin was lower in OSP than PP (WMD = -0.39 g/dl; 95% CI: -0.60 to -0.13; p = 0.03). There was no significant difference in stone-free rate and hospitalization between the two groups (OR = 1.32; 95% CI: 0.98 to 1.78; p = 0.07; WMD = -5.99 h; 95% CI: -17.15 to 5.16; p = 0.29). The overall complications were fewer in OSP than in PP (OR = 0.59; 95% CI: 0.43 to 0.81; p = 0.001), but no difference was observed between the positions with regard to the major complications (Clavien-Dindo score ≥ 3) (OR = 0.76; 95% CI: 0.43 to 1.34; p = 0.35). Conclusions: OSP showed non-inferior stone-free rate, blood loss, and hospitalization compared with PP. OSP may be superior in terms of operative time and complications than PP.

The LMR-SSIGN-MAPS model predicts disease-free survival in patients with localized clear cell renal cell carcinoma.

Introduction: Prediction models are increasingly being used to predict outcomes after surgery, and such a model would be a precious tool for patients with clear cell renal cell carcinoma (ccRCC) after surgery. Aim: To develop a comprehensive model for predicting disease-free survival (DFS) in patients with localized ccRCC. Material and methods: In a retrospective analysis of 612 patients, least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to identify significant predictors, and then risk factors were used to construct a prognostic model. Harrell's concordance index (C-index) was used to assess the accuracy of the model. Results: The lymphocyte-to-monocyte ratio (LMR), Mayo Clinic stage, size, grade, necrosis score (SSIGN), and Mayo adhesive probability score (MAPS) were the significant risk factors screened by LASSO Cox regression and reconfirmed by multivariate Cox regression analysis in 44 variables. Then a model was constructed by combining the LMR, SSIGN, and MAPS. The C-index of the LMR-SSIGN-MAPS model was greater than the SSIGN score alone. Kaplan-Meier survival analysis demonstrated a significant association between higher LMR-SSIGN-MAPS score and poorer DFS. Conclusions: The LMR-SSIGN-MAPS model, which consists of preoperative inflammation biomarkers, a perinephric adipose tissue image-based scoring system, and pathological features, showed the strengths of easy-to-use and high predictability and might also be used as a promising prognosis model in predicting DFS for patients with localized ccRCC.

Cuproptosis related gene PDHB is identified as a biomarker inversely associated with the progression of clear cell renal cell carcinoma.

BACKGROUND: Cuproptosis is a newly discovered programmed cell death dependent on mitochondrial respiratory disorder induced by copper overload. Pyruvate dehydrogenase E1 subunit beta (PDHB) is one of the cuproptosis genesand is a nuclear-encoded pyruvate dehydrogenase, which catalyzes the conversion of pyruvate to acetyl coenzyme A. However, the mechanism of PDHB in clear cell renal cell carcinoma (ccRCC) remains unclear. METHODS: We used data from TCGA and GEO to assess the expression of PDHB in normal and tumor tissues. We further analyzed the relationship between PDHB and somatic mutations and immune infiltration. Finally, we preliminarily explored the impact of PDHB on ccRCC. RESULTS: The expression level of PDHB was lower in tumor tissue compared with normal tissue. Meanwhile, the expression level of PDHB was also lower in high-grade tumors than low-grade tumors. PDHB is positively correlated with prognosis in ccRCC. Furthermore, PDHB may be associated with decreased risk of VHL, PBRM1 and KDM5C mutations. In 786-O cells, copper chloride could promote the expression of cuproptosis genes (DLAT, PDHB and FDX1) and inhibit cell growth. Last but not least, we found that PDHB could inhibit the proliferation and migration of ccRCC cells. CONCLUSION: Our results demonstrated that PDHB could inhibit the proliferation, migration and invasion in ccRCC cells, which might be a prognostic predictor of ccRCC. Targeting this molecular might provide a new therapeutic strategy for patients with advanced ccRCC.

eNOS polymorphisms on male infertility: An updated systematic review and meta-analysis.

BACKGROUND: This meta-analysis was performed to examine the association of 3 endothelial nitric oxide synthase (eNOS) gene polymorphisms with male infertility. METHODS: The literature on the relation between the mutant of eNOS and male infertility before July 1, 2022, was conducted in Pubmed, Medline, and Web of Science. The search strategy is as follows: (eNOS OR ECNOS OR nitric oxide synthase 3 OR NOS3) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (male infertility). Statistical analysis was performed with the web of MetaGenyo, Stata 12, trial sequential analysis 0.9Beta, and the web of GTEx. RESULTS: Overall, 13 studies (26 case-controls) were included involving 6518 cases and 5461 controls for 3 polymorphisms (rs2070744, rs1799983, rs61722009) of eNOS. We found that eNOS rs2070744 was correlated with an increased risk of male infertility (C vs. T: odds ratio [OR], 1.48; 95% confidence interval [CI], [1.19-1.85]; CC vs. TT: OR, 2.59; 95% CI, [1.40-4.80]; CT vs. TT: OR, 1.17; 95% CI, [1.00-1.38]; CC vs. CT + TT: OR, 2.50; 95% CI, [1.35-4.62]; CC + CT vs. TT: OR, 1.41; 95% CI, [1.21-1.64]). And eNOS rs1799983 was correlated with an increased risk of male infertility (allele contrast T vs. G: OR, 1.41; 95% CI, [1.01-1.96]; P = .043; recessive model TT vs. TG + GG: OR, 2.00; 95% CI, [1.03-3.90]; P = .042). In the stratified analysis of rs61722009, we found Asians might be correlated with an increased risk of male infertility (4a vs. 4b: OR, 1.50; 95% CI, [0.94-2.38]; 4a4a vs. 4b4b: OR, 2.56; 95% CI, [0.70-9.38]; 4a4b vs. 4b4b: OR, 1.36; 95% CI, [0.87-2.13]; 4a4a vs. 4a4b + 4b4b: OR, 2.57; 95% CI, [0.91-7.30]; 4a4a + 4a4b vs. 4b4b: OR, 1.44; 95% CI, [0.87-2.40]). CONCLUSION: The eNOS rs2070744 polymorphism and rs1799983 are associated with the risk of male infertility, and rs61722009 might be a risk factor for Asians.

ESR2 polymorphisms on prostate cancer risk: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis was performed to address the association of 2 ESR2 gene polymorphisms (rs1256049 and rs4986938) with susceptibility to cancer. METHODS: An extensive literature search for eligible candidate gene studies published before May 10, 2022, was conducted in PubMed, Medline, and Web of Science. The search strategy was as follows: (ESR2 OR ERß OR ER beta OR estrogen receptor beta) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (PCa OR PC OR prostate cancer). Potential sources of heterogeneity were sought out via trial sequential analysis, subgroup, and sensitivity analysis. RESULTS: Overall, a total of 10 articles involving 18,064 cases and 19,556 controls for 2 polymorphisms of the ESR2 gene were enrolled. In the stratified analysis of rs1256049, we found that Caucasians might be correlated with an increased risk of prostate cancer (PCa), while less susceptibility was found in Asians. We observed that rs4986938 was not associated with PCa risk. CONCLUSION: ESR2 rs1256049 polymorphism is associated with a higher risk of PCa in the Caucasian population and a lower risk of PCa in the Asian population.

MNS16A polymorphism of the TERT gene on cancer risk: a systematic review and meta-analysis.

Some studies have suggested that MNS16A polymorphism in telomerase reverse transcriptase (TERT) gene is associated with cancer risk in various populations and types of cancer. However, the results of previous studies exploring this link have been inconclusive. To be able to accurately assess the association between TERT MNS16A polymorphism and cancer risk, we performed a meta-analysis based on 17 studies described in 12 articles, including 13,764 controls and 7,132 cases. Combined odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to assess the strength of the association in either a fixed-effects model or, if applicable, a random-effects model. Heterogeneity between articles and their publication bias were also tested. Overall, pooled results showed that no significant association between this polymorphism and cancer was found in the five gene models tested.Considering that there may be too many negative studies in the included studies, diluting the results of the total sample size, we stratified these studies according to ethnicity, source of controls and cancer type. In the stratified analysis, a statistically significant association was observed between Asians and population-based studies. We also analyzed by cancer type and found a significantly increased risk of brain cancer in five genetic models. Our results suggest that TERT MNS16A polymorphism is likely to contribute to increased cancer risk.

Laparoscopic ureterolithotomy versus percutaneous nephrolithotomy for large proximal ureteral stones: a systematic review and meta-analysis.

Introduction: Both percutaneous nephrolithotomy (PCNL) and laparoscopic ureterolithotomy (LU) are effective treatment options for large proximal ureteral stones. Aim: To perform a meta-analysis on this topic to assess the efficacy, safety, and potential complications of the two procedures. Material and methods: A systematic literature search was performed using PubMed, Ovid and Scopus to identify eligible suitable studies until May 2022. All studies comparing LU vs PCNL in large proximal ureteral stones were included. The Cochrane Collaboration's Review Manager (RevMan) 5.4 software was used to analyze statistical significance. Results: A total of nine publications involving 933 patients (LU 465; PCNL 468) were included, of which 4 were randomized control trails (RCTs) and 5 were non-RCTs. The meta-analysis of available data showed that compared with PCNL, LU had a higher initial stone-free rate (OR = 3.26; p = 0.004), but longer operative time (WMD = 35.08 min; p = 0.0003). However, the final stone-free rate (OR = 2.08; p = 0.07) and length of hospital stay (WMD = 0.32 d; p = 0.48) were comparable between the two groups. Meanwhile, LU had a lower transfusion rate (OR = 0.13; p = 0.007) than PCNL. There was no significant difference in terms of complications (OR = 0.97; p = 0.84), Clavien-Dindo score ≥ 3 complications (OR = 1.03; p = 0.93), auxiliary procedures (OR = 0.44; p = 0.08), or ureteral stenosis (OR = 0.24; p = 0.13) between LU and PCNL. Conclusions: Our meta-analysis revealed that LU is a safe and feasible option for large proximal ureteral stones with a higher initial stone-free rate and lower transfusion rate compared with PCNL.

DDX58 expression promotes inflammation and growth arrest in Sertoli cells by stabilizing p65 mRNA in patients with Sertoli cell-only syndrome.

Sertoli cell -only syndrome (SCOS) is a type of testicular pathological failure that causes male infertility and no effective treatment strategy, is available for this condition. Moreover, the molecular mechanism underlying its development remains unknown. We identified DExD/H-Box helicase 58 (DDX58) as a key gene in SCOS based on four datasets of testicular tissue samples obtained from the Gene Expression Synthesis database. DDX58 was significantly upregulated in SCOS testicular Sertoli cells. Moreover, high expression of DDX58 was positively correlated with the expression of several testicular inflammatory factors, such as IL -1ß, IL-18, and IL-6. Interestingly, DDX58 could be induced in the D-galactose (D-gal)-stimulated TM4 cell injury model. Whereas silencing of DDX58 inhibited D-gal -mediated p65 expression, inflammatory cytokine release, and growth arrest. Mechanistically, we found that DDX58 acts as an RNA-binding protein, which enhances p65 expression by promoting mRNA stability. Furthermore, p65 gene silencing decreased the expression of inflammatory cytokines and inhibition of cell growth in D-gal-induced cells. In conclusion, our findings demonstrate that DDX58 promotes inflammatory responses and growth arrest in SCOS Sertoli cells by stabilizing p65 mRNA. Accordingly, the DDX58/p65 regulatory axis might be a therapeutic target for SCOS.

An amplification-free CRISPR/Cas12a-based fluorescence assay for ultrasensitive detection of nuclease activity.

Nuclease, such as RNase H and DNase I, plays key roles in plenty of cellular processes and could be potential therapeutic target for drug development. It is necessary to establish rapid and simple-to-use methods to detect nuclease activity. Herein, we develop a Cas12a-based fluorescence assay without any nucleic acid amplification steps for ultrasensitive detection of RNase H or DNase I activity. By our design, the pre-assembled crRNA/ssDNA duplex triggered the cleavage of fluorescent probes in the presence of Cas12a enzymes. However, the crRNA/ssDNA duplex was selectively digested with the addition of RNase H or DNase I, which leaded to fluorescence intensity changes. Under optimized conditions, the method exhibited good analytical performance, achieving a limit of detection (LOD) as low as 0.0082 U/mL for RNase H and 0.13 U/mL for DNase I, respectively. The method was feasible for analysis of RNase H in human serum and cell lysates, as well as for screening of enzyme inhibitors. Moreover, it can be adopted to image RNase H activity in living cells. Together, this study provides a facile platform for nuclease detection and could be expanded for other biomedical research and clinical diagnostics.

SF3B4 promotes Twist1 expression and clear cell renal cell carcinoma progression by facilitating the export of KLF 16 mRNA from the nucleus to the cytoplasm.

Splicing factor 3B subunit 4 (SF3B4) plays important functional roles not only in pre-mRNA splicing, but also in the regulation of transcription, translation, and cell signaling, and its dysregulation contributes to various diseases including Nager syndrome and tumorigenesis. However, the role of SF3B4 and underlying mechanisms in clear cell renal cell carcinoma (ccRCC) remain obscure. In the present study, we found that the expression of SF3B4 was significantly elevated in ccRCC tissues and negatively correlated with the overall survival of ccRCC patients. Upregulation of SF3B4 promotes migration and invasion of ccRCC cells in vitro and in vivo. The promoting effect of SF3B4 on cell migration and invasion is mediated by Twist1, a key transcription factor to mediate EMT. Interestingly, SF3B4, a component of the pre-mRNA spliceosome, is able to promote KLF16 expression by facilitating the transport of KLF16 mRNA into the cytoplasm. Mechanistically, SF3B4 promotes the export of KLF16 mRNA from the nucleus to the cytoplasm and thus enhances KLF16 expression, and in turn elevated KLF16 directly binds to the Twist1 promoter to activate its transcription, leading to EMT and ccRCC progression. Our findings provide evidence that the SF3B4-KLF16-Twist1 axis plays important functional roles in the development and progression of ccRCC, and manipulating this pathway may be a novel therapeutic target for the treatment of ccRCC.

Downregulated RBM5 Enhances CARM1 Expression and Activates the PRKACA/GSK3ß Signaling Pathway through Alternative Splicing-Coupled Nonsense-Mediated Decay.

Downregulated RNA-binding motif protein 5 (RBM5) promotes the development and progression of various tumors, including bladder cancer (BC). Alternative splicing (AS) plays a crucial role in the progression of cancer by producing protein isomers with different functions or by promoting nonsense-mediated mRNA decay (NMD). However, whether RBM5 modulates the progression of BC through AS-NMD remains unexplored. In this study, we revealed that the downregulation of RBM5 expression promoted the expression of coactivator-associated arginine methyltransferase 1 (CARM1) in BC cells and tissues. Increased expression of CARM1 facilitated the activation of the Wnt/ß-catenin axis and cell proliferation, which then contributed to the poor prognosis of patients with BC. Interestingly, RBM5 bound directly to CARM1 mRNA and participated in AS-NMD, downregulating the expression of CARM1. In addition, we revealed that protein kinase catalytic subunit alpha (PRKACA) functioned as a phosphorylated kinase of GSK3ß, was regulated by CARM1 at the transcription level, and promoted the growth and progression of BC cells. Furthermore, in this study, we demonstrated a regulatory mechanism of Wnt/ß-catenin activation through the RBM5/CARM1/PRKACA axis and identified a novel potential target for treating BC.

Solar X-ray and EUV imager on board the FY-3E satellite.

The solar X-ray and Extreme Ultraviolet Imager (X-EUVI), developed by the Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences (CIOMP), is the first space-based solar X-ray and Extreme ultraviolet (EUV) imager of China loaded on the Fengyun-3E (FY-3E) satellite supported by the China Meteorological Administration (CMA) for solar observation. Since started work on July 11, 2021, X-EUVI has obtained many solar images. The instrument employs an innovative dual-band design to monitor a much larger temperature range on the Sun, which covers 0.6-8.0 nm in the X-ray region with six channels and 19.5 nm in the EUV region. X-EUVI has a field of view of 42', an angular resolution of 2.5″ per pixel in the EUV band and an angular resolution of 4.1″ per pixel in the X-ray band. The instrument also includes an X-ray and EUV irradiance sensor (X-EUVS) with the same bands as its imaging optics, which measures the solar irradiance and regularly calibrates the solar images. The radiometric calibration of X-EUVS on the ground has been completed, with a calibration accuracy of 12%. X-EUVI is loaded on the FY-3E satellite and rotates relative to the Sun at a uniform rate. Flat-field calibration is conducted by utilizing successive rotation solar images. The agreement between preliminarily processed X-EUVI images and SDO/AIA and Hinode/XRT images indicates that X-EUVI and the data processing algorithm operate properly and that the data from X-EUVI can be applied to the space weather forecast system of CMA and scientific investigations on solar activity.

Integrative Analysis Identifies TCIRG1 as a Potential Prognostic and Immunotherapy-Relevant Biomarker Associated with Malignant Cell Migration in Clear Cell Renal Cell Carcinoma.

Background: TCIRG1, also known as V-ATPase-a3, is critical for cellular life activities through its dependent acidification. Prior to the present research, its relationship with prognostic and tumor immunity in clear cell renal cell carcinoma (ccRCC) had not yet been investigated. Methods: We assessed TCIRG1 expression in normal and tumor tissues using data from TCGA, GEO, GTEX, and IHC. We also analyzed the relationship between TCIRG1 and somatic mutations, TMB, DNA methylation, cancer stemness, and immune infiltration. We evaluated the relevance of TCIRG1 to immunotherapy and potential drugs. Finally, we explored the effect of TCIRG1 knockdown on tumor cells. Results: TCIRG1 was overexpressed in tumor tissue and predicted a significantly unfavorable clinical outcome. High TCIRG1 expression may be associated with fewer PBRM1 and more BAP1 mutations and may reduce DNA methylation, thus leading to a poor prognosis. TCIRG1 was strongly associated with CD8+ T-cell, Treg, and CD4+ T-cell infiltration. Moreover, TCIRG1 was positively correlated with TIDE scores and many drug sensitivities. Finally, experiments showed that the knockdown of TCIRG1 inhibited the migration of ccRCC cells. Conclusions: TCIRG1 may have great potential in identifying prognostic and immunomodulatory mechanisms in tumor patients and may provide a new therapeutic strategy for ccRCC.

ACPY2 gene polymorphisms on cancer risk: a systematic review and meta-analysis.

To provide a comprehensive account of the association of ACYP2 gene polymorphisms with susceptibility to cancer. A literature search for eligible candidate gene studies published before April 20, 2022 was conducted in the PubMed, Medline and Web of Science. The following combinations of main keywords were used: (ACYP2 OR acylphosphatase 2) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (cancer OR tumor OR neoplasm OR malignancy OR carcinoma OR adenocarcinoma). Potential sources of heterogeneity were sought out via subgroup and sensitivity analysis. Publication bias were also estimated. Overall, a total of 10 articles with 5,230 cases and 5,086 controls for thirteen polymorphisms of ACYP2 gene were enrolled. We found that ACYP2 rs11125529, rs11896604, rs12615793, rs17045754, rs6713088, rs843645, rs843706, rs843711 and rs843752 were correlated with an increased risk of cancer. However, we found that ACYP2 rs12621038 might have less susceptibility to cancer. While for other polymorphisms, the results showed no significant association with cancer risk. ACYP2 rs11125529, rs11896604, rs12615793, rs17045754, rs6713088, rs843645, rs843706, rs843711 and rs843752 are associated with cancer risk. ACYP2 rs12621038 polymorphism is inversely associated with cancer risk.

Right laparoscopic adrenalectomy vs. left laparoscopic adrenalectomy: a systematic review and meta-analysis.

INTRODUCTION: Due to more complex anatomical features, right laparoscopic adrenalectomy (RLA) could be more challenging than left laparoscopic adrenalectomy (LLA). However, this opinion remains elusive. AIM: To evaluate the perioperative and postoperative outcomes of RLA versus LLA. MATERIAL AND METHODS: A systematic literature research of the PubMed, Ovid, Scopus databases (up to March 2021) and citation lists were performed to identify eligible studies. All studies comparing RLA versus LLA were included. Data were analysed using RevMan 5.4 software. RESULTS: Overall, 5 studies including 780 patients (RLA 361; LLA 419) were included. The operative time was similar in both groups (WMD -9.38 min, 95% CI: -21.04 to 2.28; p = 0.11). Compared with LLA, RLA showed greater volume of estimated blood loss (EBL) (WMD 13.82 ml, 95% CI: 3.77, 23.88; p = 0.007) and higher conversion rate (OR = 3.45, 95% CI: 1.12 to 10.57; p = 0.03). RLA had comparable complications (OR = 0.88, 95% CI: 0.44 to 1.76; p = 0.71), Clavien Dindo score ≥ 3 complications (OR = 0.38, 95% CI: 0.09 to 1.65; p = 0.20), and length of hospital stay (WMD -0.07 days, 95% CI: -0.35 to 0.21; p = 0.61). The transperitoneal approach analysis showed consistent results. CONCLUSIONS: RLA is associated with a higher risk of bleeding and higher conversion rate.

Efficacy and safety of laparoendoscopic single-site adrenalectomy versus conventional laparoscopic adrenalectomy: an updated systematic review and meta-analysis.

INTRODUCTION: Laparoendoscopic single-site adrenalectomy (LESSA) has the advantages of early recovery and better cosmetic appearance. However, there are still debates on the efficacy and safety of LESSA and conventional laparoscopic adrenalectomy (CLA). AIM: To reevaluate the efficacy and safety of LESSA vs CLA for adrenal lesions. MATERIAL AND METHODS: A systematic literature research of PubMed, Ovid, Scopus (up to February 2021), and citation lists was performed to identify eligible studies. All studies comparing LESSA versus CLA were included. Data were analyzed using the RevMan 5.4 software. RESULTS: Overall, eighteen studies including 1307 patients (LESSA 520; CLA 787) were included. LESSA was associated with smaller mean tumor size (weighted mean difference (WMD) = 0.53 cm, 95% CI: -0.81 to -0.24; p < 0.001). The operative time for LESSA was longer than CLA (WMD = 13.86 min, 95% CI: 4.43 to 23.30; p = 0.004). LESSA had a better visual analog scale (VAS) score (WMD = -0.56, 95% CI: -1.01 to -0.11; p = 0.02), shorter return to diet time (WMD = -0.27 days, 95% CI: -0.52 to -0.03; p = 0.03), shorter length of hospital stay (WMD = -0.56 days, 95% CI: -1.01 to -0.11; p = 0.01), and comparable postoperative complications (OR = 0.98, 95% CI: 0.56 to 1.70; p = 0.93). The wound size of LESSA was definitely smaller (WMD = -2.72 cm, 95% CI: -3.50 to -1.94; p < 0.001). The subgroup analysis of studies via the transperitoneal approach showed reasonable results. CONCLUSIONS: LESSA is significantly better in terms of postoperative pain, time to diet, length of hospital stay and wound size, but the operative time is significantly longer.

Estrogen receptor beta increases clear cell renal cell carcinoma stem cell phenotype via altering the circPHACTR4/miR-34b-5p/c-Myc signaling.

Early clinical studies indicated that estrogen receptor beta (ERß) might play key roles to impact the progression of clear cell renal cell carcinoma (ccRCC). The detailed molecular mechanisms, however, remain unclear. Here, we found ERß could increase the cancer stem cell (CSC) population via altering the circPHACTR4/miR-34b-5p/c-Myc signaling. Mechanism dissection revealed that ERß could suppress circular RNA PHACTR4 (circPHACTR4) expression via direct binding to the estrogen response elements (EREs) on the 5' promoter region of its host gene, phosphatase and actin regulator 4 (PHACTR4) to decrease miR-34b-5p expression. The decreased miRNA-34b-5p could then increase c-Myc mRNA translation via targeting its 3' untranslated region (3' UTR). The in vivo mouse model with subcutaneous xenografts of ccRCC cells also validated the in vitro data. Importantly, analysis results from ccRCC TCGA database and our clinical data further confirmed the above in vitro/in vivo data. Together, these results suggest that ERß may increase CSC population in ccRCC via altering ERß/circPHACTR4/miR-34b-5p/c-Myc signaling and that targeting this newly identified signal pathway may help physicians to better suppress ccRCC progression.

Neutrophil extracellular traps-associated modification patterns depict the tumor microenvironment, precision immunotherapy, and prognosis of clear cell renal cell carcinoma.

Background: Neutrophil extracellular traps (NETs) are web-like structures formed by neutrophils, and their main function is antimicrobial defense. Moreover, NETs have numerous roles in the pathogenesis and progression of cancers. However, the potential roles of NET-related genes in renal cell carcinoma remain unclear. In this study, we comprehensively investigated the NETs patterns and their relationships with tumor environment (TME), clinicopathological features, prognosis, and prediction of therapeutic benefits in the clear cell renal cell carcinoma (ccRCC) cohort. Methods: We obtained the gene expression profiles, clinical characteristics, and somatic mutations of patients with ccRCC from The Cancer Genome Atlas database (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress datasets, respectively. ConsensusCluster was performed to identify the NET clusters. The tumor environment scores were evaluated by the "ESTIMATE," "CIBERSORT," and ssGSEA methods. The differential analysis was performed by the "limma" R package. The NET-scores were constructed based on the differentially expressed genes (DEGs) among the three cluster patterns using the ssGSEA method. The roles of NET scores in the prediction of immunotherapy were investigated by Immunophenoscores (TCIA database) and validated in two independent cohorts (GSE135222 and IMvigor210). The prediction of targeted drug benefits was implemented using the "pRRophetic" and Gene Set Cancer Analysis (GSCA) datasets. Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to identify the reliability of the core genes' expression in kidney cancer cells. Results: Three NET-related clusters were identified in the ccRCC cohort. The patients in Cluster A had more metabolism-associated pathways and better overall survival outcomes, whereas the patients in Cluster C had more immune-related pathways, a higher immune score, and a poorer prognosis than those in Cluster B. Based on the DEGs among different subtypes, patients with ccRCC were divided into two gene clusters. These gene clusters demonstrated significantly different immune statuses and clinical features. The NET scores were calculated based on the ten core genes by the Gene Set Variation Analysis (GSVA) package and then divided ccRCC patients into two risk groups. We observed that high NET scores were associated with favorable survival outcomes, which were validated in the E-MTAB-1980 dataset. Moreover, the NET scores were significantly associated with immune cell infiltration, targeted drug response, and immunotherapy benefits. Subsequently, we explored the expression profiles, methylation, mutation, and survival prediction of the 10 core genes in TCGA-KIRC. Though all of them were associated with survival information, only four out of the 10 core genes were differentially expressed genes in tumor samples compared to normal tissues. Finally, RT-PCR showed that MAP7, SLC16A12, and SLC27A2 decreased, while SLC3A1 increased, in cancer cells. Conclusion: NETs play significant roles in the tumor immune microenvironment of ccRCC. Identifying NET clusters and scores could enhance our understanding of the heterogeneity of ccRCC, thus providing novel insights for precise individual treatment.