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.

Retroperitoneal laparoscopic adrenalectomy versus transperitoneal laparoscopic adrenalectomy for pheochromocytoma: a systematic review and meta-analysis.

Introduction: To compare the efficacy and safety of retroperitoneal laparoscopic adrenalectomy (RLA) vs. transperitoneal laparoscopic adrenalectomy (TLA) for pheochromocytoma (PHEO). Aim: To perform a systematic review and meta-analysis to evaluate the efficacy and safety of RLA versus TLA for PHEO. Material and methods: A systematic research of PubMed, Ovid, Scopus (up to June 2022), and citation lists was performed for all comparative eligible studies of RLA versus TLA for PHEO. Statistical analysis was performed using RevMan 5.4. Results: Overall, six studies including 597 patients (RLA 243; TLA 354) were included. RLA was associated with lower BMI compared to TLA (WMD = -0.81 kg/m2, 95% CI: -1.53 to -0.10; p = 0.03). RLA was associated with smaller tumor size (WMD = -0.90 cm, 95% CI: -1.59 to -0.20; p = 0.01). RLA was associated with shorter operative time (WMD = -34.58 min, 95% CI: -40.80 to -28.36; p < 0.001), lower EBL (WMD = -107.91 ml, 95% CI: -145.09, -70.74; p < 0.001), and a slightly higher HI rate (OR = 1.54, 95% CI: 1.03 to 2.29; p = 0.03). There were no statistically significant differences for complications (p = 0.71) and Clavien-Dindo score ≥ 3 complications (p = 0.19) for RLA compared to TLA. RLA was associated with shorter length of hospital stay (WMD = -1.94 days, 95% CI: -2.60 to -1.29; p < 0.001). Conclusions: For selected PHEO patients, RLA has advantages in terms of operative time, EBL, and length of hospital stay, but the HI rate is higher. Since the lower BMI and smaller tumor size of RLA reduced the difficulty of surgery, these results need to be confirmed by further studies.