Deciphering the role of zinc homeostasis in the tumor microenvironment and prognosis of prostate cancer.

BACKGROUND: Dysregulation of zinc homeostasis is widely recognized as a hallmark feature of prostate cancer (PCa) based on the compelling clinical and experimental evidence. Nevertheless, the implications of zinc dyshomeostasis in PCa remains largely unexplored. METHODS: In this research, the zinc homeostasis pattern subtype (ZHPS) was constructed according to the profile of zinc homeostasis genes. The identified subtypes were assessed for their immune functions, mutational landscapes, biological peculiarities and drug susceptibility. Subsequently, we developed the optimal signature, known as the zinc homeostasis-related risk score (ZHRRS), using the approach won out in multifariously machine learning algorithms. Eventually, clinical specimens, Bayesian network inference and single-cell sequencing were used to excavate the underlying mechanisms of MT1A in PCa. RESULTS: The zinc dyshomeostasis subgroup, ZHPS2, possessed a markedly worse prognosis than ZHPS1. Moreover, ZHPS2 demonstrated a more conspicuous genomic instability and better therapeutic responses to docetaxel and olaparib than ZHPS1. Compared with traditional clinicopathological characteristics and 35 published signatures, ZHRRS displayed a significantly improved accuracy in prognosis prediction. The diagnostic value of MT1A in PCa was substantiated through analysis of clinical samples. Additionally, we inferred and established the regulatory network of MT1A to elucidate its biological mechanisms. CONCLUSIONS: The ZHPS classifier and ZHRRS model hold great potential as clinical applications for improving outcomes of PCa patients.

Identifying molecular subgroups of patients with preeclampsia through bioinformatics.

Preeclampsia (PE) is a pregnancy-related disorder associated with serious complications. Its molecular mechanisms remain undefined; hence, we aimed to identify molecular subgroups of patients with PE using bioinformatics to aid treatment strategies. R software was used to analyze gene expression data of 130 patients with PE and 138 healthy individuals from the Gene Expression Omnibus database. Patients with PE were divided into two molecular subgroups using the unsupervised clustering learning method. Clinical feature analysis of subgroups using weighted gene co-expression network analysis showed that the patients in subgroup I were primarily characterized by early onset of PE, severe symptoms at disease onset, and induced labor as the main delivery method. Patients in subgroup II primarily exhibited late PE onset, relatively mild symptoms, and natural delivery as the main delivery method. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the significant enrichment of calcium ion channels in subgroup II indicated the potential efficacy of calcium antagonists and magnesium sulfate therapy. In conclusion, the establishment of PE molecular subgroups can aid in diagnosing and treating PE.

Pelvic drain placement after robot-assisted radical prostatectomy: meta-analysis.

BACKGROUND: It is not clear whether the routine placement of a pelvic drain after robot-assisted radical prostatectomy is a necessity. The aim of this study was to investigate this through a meta-analysis of RCTs and non-randomized studies. METHODS: A search was performed in PubMed/MEDLINE, Embase, the Cochrane Library, and the Web of Science, up to 9 March 2023, for clinical trials comparing no drain with pelvic drain placement for patients with prostate cancer after robot-assisted radical prostatectomy. Two researchers independently conducted literature screening, data extraction, and quality assessment. A random-effect model was assumed for all analyses. The Cochrane Collaboration's risk-of-bias tool was used to evaluate the methodological quality of RCTs and, for non-randomized studies, the ROBINS-I tool was used (where ROBINS-I stands for Risk Of Bias In Non-randomized Studies - of Interventions). This meta-analysis was prospectively registered in PROSPERO, the international prospective register of systematic reviews (CRD42023406429). RESULTS: A total of six studies with 1480 patients were included in the meta-analysis. Both the meta-analysis of RCTs and the meta-analysis of non-randomized studies showed that patients without drains had a similar estimated blood loss (mean difference 40.49 ml, 95% c.i. -59.75 to 140.74 ml, P = 0.430, and mean difference -14.20 ml, 95% c.i. -32.26 to 3.87 ml, P = 0.120 respectively), overall complication rate (OR 0.60, 95% c.i. 0.35 to 1.04, P = 0.070, and OR 0.90, 95% c.i. 0.59 to 1.39, P = 0.640 respectively), Clavien-Dindo grade I-II complication rate (OR 0.62, 95% c.i. 0.34 to 1.13, P = 0.120, and OR 0.83, 95% c.i. 0.28 to 2.51, P = 0.750 respectively), Clavien-Dindo grade III-V complication rate (OR 0.60, 95% c.i. 0.10 to 3.69, P = 0.590, and OR 0.92, 95% c.i. 0.25 to 3.39, P = 0.900 respectively), and duration of hospital stay (mean difference -0.08 days, 95% c.i. -0.45 to 0.29 days, P = 0.670, and mean difference -0.64 days, 95% c.i. -2.67 to 1.39 days, P = 0.540 respectively) compared with routinely drained patients. Meta-analysis of non-randomized studies revealed that the duration of operation for patients without drains was shorter than that for patients with drains (mean difference -34.88 min, 95% c.i. -43.58 to -26.18 min, P < 0.001), but the meta-analysis of RCTs indicated that there was no significant difference between the two groups (mean difference -7.64 min, 95% c.i. -15.61 to 0.32 min, P = 0.060). CONCLUSION: The intraoperative and postoperative outcomes of patients without drains were not inferior to those of patients with drains. In selected patients, pelvic drains can be omitted after robot-assisted radical prostatectomy.

Head-to-head comparison of prostate-specific membrane antigen PET and multiparametric MRI in the diagnosis of pretreatment patients with prostate cancer: a meta-analysis.

OBJECTIVES: To compare prostate-specific membrane antigen (PSMA) PET with multiparametric MRI (mpMRI) in the diagnosis of pretreatment prostate cancer (PCa). METHODS: Pubmed, Embase, Medline, Web of Science, and Cochrane Library were searched for eligible studies published before June 22, 2022. We assessed risk of bias and applicability by using QUADAS-2 tool. Data synthesis was performed with Stata 17.0 software, using the "midas" and "meqrlogit" packages. RESULTS: We included 29 articles focusing on primary cancer detection, 18 articles about primary staging, and two articles containing them both. For PSMA PET versus mpMRI in primary PCa detection, sensitivities and specificities in the per-patient analysis were 0.90 and 0.84 (p<0.0001), and 0.66 and 0.60 (p <0.0001), and in the per-lesion analysis they were 0.79 and 0.78 (p <0.0001), and 0.84 and 0.82 (p <0.0001). For the per-patient analysis of PSMA PET versus mpMRI in primary staging, sensitivities and specificities in extracapsular extension detection were 0.59 and 0.66 (p =0.005), and 0.79 and 0.76 (p =0.0074), and in seminal vesicle infiltration (SVI) detection they were 0.51 and 0.60 (p =0.0008), and 0.93 and 0.96 (p =0.0092). For PSMA PET versus mpMRI in lymph node metastasis (LNM) detection, sensitivities and specificities in the per-patient analysis were 0.68 and 0.46 (p <0.0001), and 0.91 and 0.90 (p =0.81), and in the per-lesion analysis they were 0.67 and 0.36 (p <0.0001), and 0.99 and 0.99 (p =0.18). CONCLUSION: PSMA PET has higher diagnostic value than mpMRI in the detection of primary PCa. Regarding the primary staging, mpMRI has potential advantages in SVI detection, while PSMA PET has relative advantages in LNM detection. CLINICAL RELEVANCE STATEMENT: The integration of prostate-specific membrane antigen (PSMA) PET into the diagnostic pathway may be helpful for improving the accuracy of prostate cancer detection. However, further studies are needed to address the cost implications and evaluate its utility in specific patient populations or clinical scenarios. Moreover, we recommend the combination of PSMA PET and mpMRI for cancer staging. KEY POINTS: • Prostate-specific membrane antigen PET has higher sensitivity and specificity for primary tumor detection in prostate cancer compared to multiparametric MRI. • Prostate-specific membrane antigen PET also has significantly better sensitivity and specificity for lymph node metastases of prostate cancer compared to multiparametric MRI. • Multiparametric MRI has better accuracy for extracapsular extension and seminal vesicle infiltration compared to ate-specific membrane antigen PET.

[Genetic analysis of a Chinese pedigree with chronic kidney disease due to variant of PAX2 gene].

OBJECTIVE: To explore the genetic basis of a Chinese pedigree affected with chronic kidney disease (CKD). METHODS: A Chinese pedigree comprised of 10 individuals from four generation who had visited the First Affiliated Hospital of Dali University from August 15, 2018 to July 5, 2021 was selected as the study subject. Clinical data of the proband were collected, and a pedigree survey was conducted. The proband was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The proband, a 41-year-old female, has been diagnosed with chronic nephritis for more than 4 years. Routine urinary examination showed proteinuria and blood creatinine of 1 130 µmol/L. Renal biopsy has revealed hyperplastic glomerulonephritis, moderate tubulointerstitial disease and renal arteriosclerosis. Her elder sister, younger brother, younger sister and mother were all diagnosed with CKD stage 5. Except for her elder sister, all of them had deceased, whilst no abnormality was found in the remainders. Genetic testing revealed that the proband and four family members had harbored a c.467G>A missense variant of the PAX2 gene. The variant has been associated with focal segmental glomerulosclerosis and classified as likely pathogenic (PS1+PP3+PP4) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION: The c.167G＞A variant of the PAX2 gene probably underlay the CKD in this Chinese pedigree.

Construction of gene subgroups of Crohn disease based on transcriptome data.

BACKGROUND: The global prevalence of Crohn disease (CD), a chronic inflammatory disease of the intestine, has been increasing; however, the etiology and pathogenesis of this disease have not been fully elucidated. Therefore, in the present study, we aimed to better understand the molecular mechanisms underlying CD to aid the development of novel therapeutic strategies for this condition. METHODS: Based on the transcriptome data from patients with CD, this study used an unsupervised learning method to construct gene co-expression molecular subgroups and the R and SPSS software to identify the biological, clinical, and genetic characteristics and signatures of each subgroup. RESULTS: Two subgroups were analyzed. Compared to subgroup II, subgroup I consisted of older patients with a more limited range of disease presentation and had a higher number of smokers. The specific genes associated with this subgroup, including CDKN2B, solute carrier family 22 member 5, and phytanoyl-CoA 2-hydroxylase, can be targeted for managing intestinal dysbacteriosis. The number of patients showing infiltrating lesions was higher, the number of smokers was lower, and CD severity was worse in patients in subgroup II than those in subgroup I. The specific genes relevant to subgroup II included cluster of differentiation 44, tryptophanyl-tRNA synthetase, and interleukin 10 receptor, alpha subunit, which may be related to viral infection. CONCLUSION: The present study segregated patients with CD into 2 subgroups; the findings reported herein provide a new theoretical basis for the diagnosis and treatment of CD and could aid a thorough identification of potential therapeutic targets for this disease.

Utilizing Ubiquitination Patterns to Predict Prostate Cancer Prognosis and Devise a Therapeutic Response.

BACKGROUND: Ubiquitination, a post-translational modification, is crucial for cancer regulation. However, the predictive significance of ubiquitination-related genes (URGs) for prostate adenocarcinoma (PRAD) remains unclear. OBJECTIVES: The objectives of the study were to investigate the role of URGs in PRAD and their potential impact on patient prognosis. METHODS: This study acquired data for more than 800 patients with PRAD from public databases. The unique ubiquitination-related patterns of PRAD were detected by unsupervised clustering approach. URGs relevant to the prognosis of patients with PRAD and a ubiquitination-related prognostic index (URPI) were identified and generated using the log-rank test, univariate and multivariate Cox proportional hazards regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and bootstrap strategy. RESULTS: Four ubiquitination-related subpopulations were then defined, and 39 ubiquitination-related differentially expressed genes in prostate cancer and paracancerous samples were screened, with LASSO analysis distinguishing six of them. The URPI was built and verified using the identified URGs that played critical roles in survival stratification. Several potential URPI-targeting drugs were also analyzed. Subsequently, the URPI was combined with clinical characteristics, which provided a more accurate estimate of PRAD survival and was a superior choice for PRAD prognostic forecasts. CONCLUSIONS: This investigation has thus established and verified a URPI, which may provide unique insights to improve survival estimations for patients with PRAD.

Utilizing Ubiquitination Patterns to Predict Prostate Cancer Prognosis and Devise a Therapeutic Response

Background: Ubiquitination, a post-translational modification, is crucial for cancer regulation. However, the predictive significance of ubiquitination-related genes (URGs) for prostate adenocarcinoma (PRAD) remains unclear. Objectives: The objectives of the study were to investigate the role of URGs in PRAD and their potential impact on patient prognosis. Methods: This study acquired data for more than 800 patients with PRAD from public databases. The unique ubiquitination-related patterns of PRAD were detected by unsupervised clustering approach. URGs relevant to the prognosis of patients with PRAD and a ubiquitination-related prognostic index (URPI) were identified and generated using the log-rank test, univariate and multivariate Cox proportional hazards regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and bootstrap strategy. Results: Four ubiquitination-related subpopulations were then defined, and 39 ubiquitination-related differentially expressed genes in prostate cancer and paracancerous samples were screened, with LASSO analysis distinguishing six of them. The URPI was built and verified using the identified URGs that played critical roles in survival stratification. Several potential URPI-targeting drugs were also analyzed. Subsequently, the URPI was combined with clinical characteristics, which provided a more accurate estimate of PRAD survival and was a superior choice for PRAD prognostic forecasts. Conclusions: This investigation has thus established and verified a URPI, which may provide unique insights to improve survival estimations for patients with PRAD (AU)

Robotic-assisted versus laparoscopic radical prostatectomy for prostate cancer: the first separate systematic review and meta-analysis of randomised controlled trials and non-randomised studies.

BACKGROUND: Due to the lack of sufficient evidence, it is not clear whether robotic-assisted radical prostatectomy (RARP) or laparoscopic radical prostatectomy (LRP) is better for prostate cancer. The authors conducted this study by separately pooling and analysing randomised controlled trials (RCTs) and non-randomised studies to compare the perioperative, functional, and oncologic outcomes between RARP and LRP. METHODS: A systematic literature search was performed in March 2022 using Cochrane Library, Pubmed, Embase, Medline, Web of Science, and China National Knowledge Infrastructure. Two independent reviewers performed literature screening, data extraction and quality assessment according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Subgroup analysis and sensitivity analysis were performed. RESULTS: A total of 46 articles were included, including 4 from 3 RCTs and 42 from non-randomised studies. For RCTs, meta-analysis showed that RARP and LRP were similar in blood loss, catheter indwelling time, overall complication rate, overall positive surgical margin and biochemical recurrence rates, but quantitative synthesis of non-randomised studies showed that RARP was associated with less blood loss [weighted mean difference (WMD)=-71.99, 95% CI -99.37 to -44.61, P <0.001], shorter catheterization duration (WMD=-1.03, 95% CI -1.84 to -0.22, P =0.010), shorter hospital stay (WMD=-0.41, 95% CI -0.68 to -0.13, P =0.004), lower transfusion rate (OR=0.44, 95% CI 0.35-0.56, P <0.001), lower overall complication rate (OR=0.72, 95% CI 0.54-0.96, P =0.020), and lower biochemical recurrence rate (OR=0.78, 95% CI 0.66-0.92, P =0.004), compared with LRP. Both meta-analysis of RCTs and quantitative synthesis of non-randomised studies showed that RARP was associated with improved functional outcomes. From the results of the meta-analysis of RCTs, RARP was higher than LRP in terms of overall continence recovery [odds ratio (OR)=1.60, 95% CI 1.16-2.20, P =0.004), overall erectile function recovery (OR=4.07, 95% CI 2.51-6.60, P <0.001), continence recovery at 1 month (OR=2.14, 95% CI 1.25-3.66, P =0.005), 3 (OR=1.51, 95% CI 1.12-2.02, P =0.006), 6 (OR=2.66, 95% CI 1.31-5.40, P =0.007), and 12 months (OR=3.52, 95% CI 1.36-9.13, P =0.010) postoperatively, and potency recovery at 3 (OR=4.25, 95% CI 1.67-10.82, P =0.002), 6 (OR=3.52, 95% CI 1.31-9.44, P =0.010), and 12 months (OR=3.59, 95% CI 1.78-7.27, P <0.001) postoperatively, which were consistent with the quantitative synthesis of non-randomised studies. When sensitivity analysis was performed, the results remained largely unchanged, but the heterogeneity among studies was greatly reduced. CONCLUSION: This study suggests that RARP can improve functional outcomes compared with LRP. Meanwhile, RARP has potential advantages in perioperative and oncologic outcomes.

Construction of molecular subgroups in childhood systemic lupus erythematosus using bioinformatics.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder. In patients with childhood SLE (cSLE), the onset of the disease occurs before 18 years of age and accounts for a high proportion of childhood autoimmune diseases. Adult SLE and cSLE differ in terms of clinical manifestations, gene expression profiles, and treatment. Because current diagnostic methods do not meet clinical requirements, researchers currently use transcriptome analysis to investigate the characteristics of the cSLE genome. In the present study, we used bioinformatics methods to genotype cSLE and identify potential therapeutic targets. METHODS: The transcriptomes of 952 patients with cSLE and 94 normal controls were obtained from the Gene Expression Omnibus using unsupervised class learning to determine the genotypes in the microarray dataset, and the clinical characteristics, differentially expressed genes, and biological characteristics of the subtypes were analyzed. RESULTS: Patients with cSLE were accordingly classified into three subgroups. Subgroup I was associated with lupus nephritis, female patients, and a high SLE disease activity index, and the disease in this subgroup was more severe than that in other subgroups. The SLE disease activity index in subgroup II was low; this subgroup may be related to lupus vasculitis. Subgroup III mostly included male patients and was associated with neuropsychiatric manifestations of lupus. CONCLUSION: We divided patients with cSLE into three subgroups with different characteristics based on transcriptome data. Our findings provide molecular evidence for future diagnosis and individualized treatment of cSLE.

Robot-assisted thoracic surgery versus video-assisted thoracic surgery for lung lobectomy or segmentectomy in patients with non-small cell lung cancer: a meta-analysis.

BACKGROUND: It remains no clear conclusion about which is better between robot-assisted thoracic surgery (RATS) and video-assisted thoracic surgery (VATS) for the treatment of patients with non-small cell lung cancer (NSCLC). Therefore, this meta-analysis aimed to compare the short-term and long-term efficacy between RATS and VATS for NSCLC. METHODS: Pubmed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Medline, and Web of Science databases were comprehensively searched for studies published before December 2020. The quality of the articles was evaluated using the Newcastle-Ottawa Scale (NOS) and the data analyzed using the Review Manager 5.3 software. Fixed or random effect models were applied according to heterogeneity. Subgroup analysis and sensitivity analysis were conducted. RESULTS: A total of 18 studies including 11,247 patients were included in the meta-analyses, of which 5114 patients were in the RATS group and 6133 in the VATS group. Compared with VATS, RATS was associated with less blood loss (WMD = - 50.40, 95% CI -90.32 ~ - 10.48, P = 0.010), lower conversion rate (OR = 0.50, 95% CI 0.43 ~ 0.60, P < 0.001), more harvested lymph nodes (WMD = 1.72, 95% CI 0.63 ~ 2.81, P = 0.002) and stations (WMD = 0.51, 95% CI 0.15 ~ 0.86, P = 0.005), shorter duration of postoperative chest tube drainage (WMD = - 0.61, 95% CI -0.78 ~ - 0.44, P < 0.001) and hospital stay (WMD = - 1.12, 95% CI -1.58 ~ - 0.66, P < 0.001), lower overall complication rate (OR = 0.90, 95% CI 0.83 ~ 0.99, P = 0.020), lower recurrence rate (OR = 0.51, 95% CI 0.36 ~ 0.72, P < 0.001), and higher cost (WMD = 3909.87 USD, 95% CI 3706.90 ~ 4112.84, P < 0.001). There was no significant difference between RATS and VATS in operative time, mortality, overall survival (OS), and disease-free survival (DFS). Sensitivity analysis showed that no significant differences were found between the two techniques in conversion rate, number of harvested lymph nodes and stations, and overall complication. CONCLUSIONS: The results revealed that RATS is a feasible and safe technique compared with VATS in terms of short-term and long-term outcomes. Moreover, more randomized controlled trials comparing the two techniques with rigorous study designs are still essential to evaluate the value of robotic surgery for NSCLC.

Robotic versus laparoscopic gastrectomy for gastric cancer: a systematic review and meta-analysis.

BACKGROUND: To date, robotic surgery has been widely used worldwide. We conducted a systematic review and meta-analysis to evaluate short-term and long-term outcomes of robotic gastrectomy (RG) in gastric cancer patients to determine whether RG can replace laparoscopic gastrectomy (LG). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was applied to perform the study. Pubmed, Cochrane Library, WanFang, China National Knowledge Infrastructure (CNKI), and VIP databases were comprehensively searched for studies published before May 2020 that compared RG with LG. Next, two independent reviewers conducted literature screening and data extraction. The quality of the literature was assessed using the Newcastle-Ottawa Scale (NOS), and the data analyzed using the Review Manager 5.3 software. Random effects or fixed effects models were applied according to heterogeneity. RESULTS: A total of 19 studies including 7275 patients were included in the meta-analyses, of which 4598 patients were in the LG group and 2677 in the RG group. Compared with LG, RG was associated with longer operative time (WMD = -32.96, 95% CI -42.08 ~ -23.84, P < 0.001), less blood loss (WMD = 28.66, 95% CI 18.59 ~ 38.73, P < 0.001), and shorter time to first flatus (WMD = 0.16 95% CI 0.06 ~ 0.27, P = 0.003). There was no significant difference between RG and LG in terms of the hospital stay (WMD = 0.23, 95% CI -0.53 ~ 0.98, P = 0.560), overall postoperative complication (OR = 1.07, 95% CI 0.91 ~ 1.25, P = 0.430), mortality (OR = 0.67, 95% CI 0.24 ~ 1.90, P = 0.450), the number of harvested lymph nodes (WMD = -0.96, 95% CI -2.12 ~ 0.20, P = 0.100), proximal resection margin (WMD = -0.10, 95% CI -0.29 ~ 0.09, P = 0.300), and distal resection margin (WMD = 0.15, 95% CI -0.21 ~ 0.52, P = 0.410). No significant differences were found between the two treatments in overall survival (OS) (HR = 0.95, 95% CI 0.76 ~ 1.18, P = 0.640), recurrence-free survival (RFS) (HR = 0.91, 95% CI 0.69 ~ 1.21, P = 0.530), and recurrence rate (OR = 0.90, 95% CI 0.67 ~ 1.21, P = 0.500). CONCLUSIONS: The results of this study suggested that RG is as acceptable as LG in terms of short-term and long-term outcomes. RG can be performed as effectively and safely as LG. Moreover, more randomized controlled trials comparing the two techniques with rigorous study designs are still essential to evaluate the value of the robotic surgery for gastric cancer.