CT-guided transthoracic pulmonary artery catheterization: an experimental study in a porcine model.

OBJECTIVES: We investigated the safety and feasibility of CT-guided transthoracic pulmonary artery catheterization (TPAC) in a porcine model. METHODS: Procedures were conducted on ten mature Bama miniature pigs. After anesthesia, chest CT was performed in the left lateral decubitus position to determine the puncture route. Under the guidance of multiple CT scans, the introducer sheath was inserted from the right chest wall of the pig into the right pulmonary artery using the Seldinger technique. Then, a catheter connected with a transducer was inserted into the sheath to measure the pulmonary artery pressure. Finally, an active approximator was used to close the puncture site on the pulmonary artery. The pigs were followed up for 8 weeks to evaluate the operation-related complications and survival. RESULTS: Ten of 11 CT-guided TPAC procedures were successfully performed on ten pigs, rendering a technical success rate of 90.9%. One pig had hemoptysis while the needle was being inserted during the first operation, and a second procedure was successfully conducted 17 days later. Other complications, including pulmonary bleeding along the needle track (3 of 11; 27.3%), unclosed pulmonary artery puncture sites (3 of 10; 30%), pneumothorax (1 of 11; 9.1%), and hemopericardium (1 of 11; 9.1%), spontaneously resolved without complication-specific treatment. The mean pulmonary arterial pressure was 32 ± 17.6 mmHg. All animals survived the procedure and reached the end of the follow-up period. CONCLUSIONS: CT-guided TPAC is feasible and safe in a porcine model, serving as a potential alternative pathway for pulmonary artery intervention. KEY POINTS: • TPAC is feasible and safe in a porcine model, serving as a potential alternative pathway for pulmonary artery intervention. • This novel approach allows for faster access to the pulmonary artery, and it might be easier to operate the tip of the catheter to super-select the intent branch of the pulmonary artery. • TPAC can be an alternative pulmonary artery intervention pathway in patients with mechanical right-heart valves, great-vessel transposition, and other obstacles.

Clinical benefit and safety associated with mRNA vaccines for advanced solid tumors: A meta-analysis.

Tumor mRNA vaccines have been developed for over 20 years. Whether mRNA vaccines could promote a clinical benefit to advanced cancer patients is highly unknown. PubMed and Embase were retrieved from January 1, 2000 to January 4, 2023. Random effects models were employed. Clinical benefit (objective response rate [ORR], disease control rate [DCR], 1-year/2-year progression-free survival [PFS], and overall survival [OS]) and safety (vaccine-related grade 3-5 adverse events [AEs]) were evaluated. Overall, 984 patients (32 trials) were enrolled. The most typical cancer types were melanoma (13 trials), non-small cell lung cancer (5 trials), renal cell carcinoma (4 trials), and prostate adenocarcinoma (4 trials). The pooled ORR and DCR estimates were 10.0% (95%CI, 4.6-17.0%) and 34.6% (95%CI, 24.1-45.9%). The estimates for 1-year and 2-year PFS were 38.4% (95%CI, 24.8-53.0%) and 20.0% (95%CI, 10.4-31.7%), respectively. The estimates for 1-year and 2-year OS were 75.3% (95%CI, 62.4-86.3%) and 45.5% (95%CI, 34.0-57.2%), respectively. The estimate for vaccine-related grade 3-5 AEs was 1.0% (95%CI, 0.2-2.4%). Conclusively, mRNA vaccines seem to demonstrate modest clinical response rates, with acceptable survival rates and rare grade 3-5 AEs.

ADP-dependent glucokinase controls metabolic fitness in prostate cancer progression.

BACKGROUND: Cell metabolism plays a pivotal role in tumor progression, and targeting cancer metabolism might effectively kill cancer cells. We aimed to investigate the role of hexokinases in prostate cancer (PCa) and identify a crucial target for PCa treatment. METHODS: The Cancer Genome Atlas (TCGA) database, online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase (ADPGK) in PCa. The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo. Quantitative proteomics, metabolomics, and extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) tests were performed to evaluate the impact of ADPGK on PCa metabolism. The underlying mechanisms were explored through ADPGK overexpression and knockdown, co-immunoprecipitation (Co-IP), ECAR analysis and cell counting kit-8 (CCK-8) assays. RESULTS: ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival (OS) in prostate adenocarcinoma (PRAD). Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs. non-PCa tissues. High ADPGK expression indicates worse survival outcomes, and ADPGK serves as an independent factor of biochemical recurrence. In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration, and ADPGK inhibition suppressed malignant phenotypes. Metabolomics, proteomics, and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa. Mechanistically, ADPGK binds aldolase C (ALDOC) to promote glycolysis via AMP-activated protein kinase (AMPK) phosphorylation. ALDOC was positively correlated with ADPGK, and high ALDOC expression was associated with worse survival outcomes in PCa. CONCLUSIONS: In summary, ADPGK is a driving factor in PCa progression, and its high expression contributes to a poor prognosis in PCa patients. ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling, suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.

Developing a Nomogram-Based Scoring Tool to Estimate the Risk of Pulmonary Embolism.

Background: Pulmonary embolisms (PEs) are clinically challenging because of their high morbidity and mortality. This study aimed to develop a scoring tool for predicting PEs to improve their clinical management. Methods: Clinical, laboratory, and imaging parameters were retrospectively collected from suspected PE patients who had cough or chest pain and were hospitalized in West China Hospital of Sichuan University from May 2015 to April 2020. The final diagnosis of PE was defined based on findings from computed tomographic pulmonary angiography (CTPA). In this study, patients were randomly divided 2:1 into derivation and validation cohorts, which were used to create and validate, respectively, a nomogram. Model performance was estimated with the area under the receiver operating characteristic curve and a calibration curve. Results: Our study incorporated data on more than 100 features from 1480 patients (811 non-PE, 669 PE). The nomogram was constructed using important predictive features including D-dimer, APTT, FDP, platelet count, sodium, albumin and cholesterol and achieved AUC values of 0.692 with the derivation cohort (95% CI 0.688-0.696, P < 0.01) and 0.688 with the validation cohort (95% CI 0.653-0.723, P < 0.01). The calibration curve showed good agreement between the probability predicted by the nomogram and the actual probability. Conclusion: In this study, we successfully developed a nomogram that can predict the risk of PE, which can not only improve the clinical management of PE patients but also decrease unnecessary CTPA scans and their adverse effects.

Extending galactose-oxidation pathway of Pseudomonas putida for utilization of galactose-rich red macroalgae as sustainable feedstock.

Marine red macroalgae has attracted researchers' consideration as a non-lignocellulosic feedstock for microbial growth to produce biofuels and biochemical products. Gelidium amansii is representative galactose-rich red macroalgae biomass but studies on its galactose utilization are currently scarce. Herein, we engineered Pseudomonas putida KT2440 as a functional chassis for assimilation of galactose in addition to glucose in G. amansii hydrolysate. P. putida KT2440 was confirmed owning high ability to oxidize galactose to galactonate by glucose dehydrogenase. Thereafter galactose-oxidation pathway was extended by introducing galactonate transport and metabolism modules from Pseudomonas rhodesiae NL2019. The recombinant strains NL910 and NL911 were able to grow on galactose with high cell densities and growth rates, and simultaneously upgrade all red macroalgae streams, which is essential to develop a sustainable and cost-effective bioprocess for valorization of red macroalgae.

The role of prostate-specific antigen density and negative multiparametric magnetic resonance imaging in excluding prostate cancer for biopsy-naïve men: clinical outcomes from a high-volume center in China.

This study aimed to assess the role of prostate-specific antigen density (PSAD) and negative multiparametric magnetic resonance imaging (mpMRI) in predicting prostate cancer for biopsy-naïve men based on a large cohort of the Chinese population. From a prostate biopsy database between March 2017 and July 2021, we retrospectively identified 240 biopsy-naïve patients with negative prebiopsy mpMRI (Prostate Imaging Reporting and Data System version 2 [PI-RADS v2] score <3). Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer (csPCa). Receiver operating characteristic (ROC) curve analysis and area under the ROC curve (AUC) were performed to assess the diagnostic accuracy. The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8% (201/240) and 90.8% (218/240), respectively. ROC curve analysis indicated that PSAD was the most promising predictor, with an AUC value of 0.786 (95% confidence interval [CI]: 0.699-0.874), and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa (odds ratio [OR]: 10.99, 95% CI: 2.75-44.02, P < 0.001). Combining negative mpMRI and PSAD below 0.20 ng ml-2 obviously increased the predictive value in excluding PCa (91.0%, 101/111) or csPCa (100.0%, 111/111). If a PSAD below 0.20 ng ml-2 was set as the criterion to omit biopsy, nearly 46.3% of patients (463 per 1000) with negative mpMRI could safely avoid unnecessary biopsy, with approximately 4.2% of patients (42 per 1000) at risk of missed diagnosis of PCa and no patients with csPCa missed. A PI-RADS v2 score <3 and a PSAD <0.20 ng ml-2 could be potential criteria for the Chinese population to omit prompt biopsy safely.

Neoadjuvant chemotherapy for patients with locally advanced penile cancer: an updated evidence.

Neoadjuvant chemotherapy (NAC) has shown promising results in patients with locally advanced penile cancer. However, no consensus exists on its applications for locally advanced penile cancer. Thus, it is unclear which kind of chemotherapy regimen is the best choice. Consequently, a systematic search of PubMed, Web of Science, and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer. The Newcastle-Ottawa Scale was used to assess the risk of bias in each study. This study synthesized 14 published studies. The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response. In addition, the objective response rates (ORRs) and pathological complete response (pCR) rates were 0.57 and 0.11, respectively. The incidence of grade ≥3 toxicity was 0.36. Subgroup analysis found that the ORR and pCR of the taxane-platinum (TP) regimen group performed better than those of the nontaxane-platinum (NTP) regimen group (0.57 vs 0.54 and 0.14 vs 0.07, respectively). Moreover, the TP regimen group had more frequent toxicity than the NTP regimen group (0.41 vs 0.26). However, further studies were warranted to confirm the findings.

The comparison of survival between active surveillance or watchful waiting and focal laser ablation in patients with low-risk prostate cancer.

Prostate cancer (PCa) is the second-most common cancer among men. Both active surveillance or watchful waiting (AS/WW) and focal laser ablation (FLA) can avoid the complications caused by radical treatment. How to make the choice between these options in clinical practice needs further study. Therefore, this study aims to compare and analyze their effects based on overall survival (OS) and cancer-specific survival (CSS) to obtain better long-term benefits. We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010-2016. Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups. To eliminate bias, this study applied a series of sensitivity analyses. Moreover, Kaplan-Meier curves were plotted to obtain survival status. A total of 18 841 patients with low-risk PCa were included, with a median of 36-month follow-up. According to the multivariate Cox proportional hazard regression, the FLA group presented inferior survival benefits in OS than the AS/WW group (hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.37-3.33, P < 0.05). After adjusting for confounders, the result persisted (HR: 1.69, 95% CI: 1.02-2.81, P < 0.05). According to the results of the sensitivity analysis, the inverse probability of the treatment weighing model indicated the same result in OS. In conclusion, AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment. Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa. More relevant researches and data will be needed for further clarity.

Transcriptomic profiling of peripheral blood CD4⁺ T-cells in asthmatics with and without depression.

BACKGROUND: Cumulative studies have shown that asthma is associated with depression but the underlying mechanisms are poorly understood. This study aimed to determine whether asthma with depression is characterized by unique pathophysiological pathways by analyzing the global gene expression patterns of CD4(+) T-cells from asthmatics with or without depression. MATERIALS AND METHODS: Four groups of subjects (non-depressive asthmatics, depressive asthmatics, depression patients, and healthy controls) consisting of 6 participants in each group were studied. Peripheral CD4(+) T-cells were isolated and the global transcriptomic profiles were defined by using the Agilent SurePrint G3 Human GE 8x60K microarray. The differences in transcriptomic profiles between asthma with or without depression, depression patients and healthy controls were examined. Pathway enrichment analyses of differentially expressed genes were performed using the Ingenuity Pathway Analysis. Selected genes were verified and correlated to the clinical characteristics. RESULTS: A total of 1448 differentially expressed transcripts were identified in any of the non-depressive asthma vs. healthy control, depressive asthma vs. healthy control, or depression vs. healthy control comparisons after correction for multiple comparisons. Among these, 156 were demonstrated as differentially expressed genes only in depressive asthma vs. healthy control. Twenty significant biological pathways were identified and were involved in inflammation, metabolism, immunity, tumor and cell cycle. Increased expression of phosphoinositide-3-kinase, regulatory subunit 1 (alpha) was confirmed in depressive asthmatics and it was inversely correlated with lung function (FEV1/FVC%). CONCLUSIONS: Asthmatics with depression exhibit unique pathophysiological pathways and this result may provide clues for specific molecular mechanisms underlying asthma with depression.

Selection of suitable housekeeping genes for real-time quantitative PCR in CD4(+) lymphocytes from asthmatics with or without depression.

OBJECTIVE: No optimal housekeeping genes (HKGs) have been identified for CD4(+) T cells from non-depressive asthmatic and depressive asthmatic adults for normalizing quantitative real-time PCR (qPCR) assays. The aim of present study was to select appropriate HKGs for gene expression analysis in purified CD4(+) T cells from these asthmatics. METHODS: Three groups of subjects (Non-depressive asthmatic, NDA, n = 10, Depressive asthmatic, DA, n = 11, and Healthy control, HC, n = 10 respectively) were studied. qPCR for 9 potential HKGs, namely RNA, 28S ribosomal 1 (RN28S1), ribosomal protein, large, P0 (RPLP0), actin, beta (ACTB), cyclophilin A (PPIA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase 1 (PGK1), beta-2-microglobulin (B2M), glucuronidase, beta (GUSB) and ribosomal protein L13a (RPL13A), was performed. Then the data were analyzed with three different applications namely BestKeeper, geNorm, and NormFinder. RESULTS: The analysis of gene expression data identified B2M and RPLP0 as the most stable reference genes and showed that the level of PPIA was significantly different among subjects of three groups when the two best HKGs identified were applied. Post-hoc analysis by Student-Newman-Keuls correction shows that depressive asthmatics and non-depressive asthmatics exhibited lower expression level of PPIA than healthy controls (p<0.05). CONCLUSIONS: B2M and RPLP0 were identified as the most optimal HKGs in gene expression studies involving human blood CD4(+) T cells derived from normal, depressive asthmatics and non-depressive asthmatics. The suitability of using the PPIA gene as the HKG for such studies was questioned due to its low expression in asthmatics.