The application of large language models in medicine: A scoping review.

This study systematically reviewed the application of large language models (LLMs) in medicine, analyzing 550 selected studies from a vast literature search. LLMs like ChatGPT transformed healthcare by enhancing diagnostics, medical writing, education, and project management. They assisted in drafting medical documents, creating training simulations, and streamlining research processes. Despite their growing utility in assisted diagnosis and improving doctor-patient communication, challenges persisted, including limitations in contextual understanding and the risk of over-reliance. The surge in LLM-related research indicated a focus on medical writing, diagnostics, and patient communication, but highlighted the need for careful integration, considering validation, ethical concerns, and the balance with traditional medical practice. Future research directions suggested a focus on multimodal LLMs, deeper algorithmic understanding, and ensuring responsible, effective use in healthcare.

Production of cost-competitive bioethanol and value-added co-products from distillers' grains: Techno-economic evaluation and environmental impact analysis.

Here, Baijiu distillers' grains (BDGs) were employed in biorefinery development to generate value-added co-products and bioethanol. Through ethyl acetate extraction at a 1:6 solid-liquid ratio for 10 h, significant results were achieved, including 100 % lactic acid and 92 % phenolics recovery. The remaining BDGs also achieved 99 % glucan recovery and 81 % glucan-to-glucose conversion. Simultaneous saccharification and fermentation of remaining BDGs at 30 % loading resulted in 78.5 g bioethanol/L with a yield of 94 %. The minimum selling price of bioethanol varies from $0.149-$0.836/kg, contingent on the co-product market prices. The biorefinery processing of one ton of BDGs caused a 60 % reduction in greenhouse gas emissions compared to that of the traditional production of 88 kg corn-lactic acid, 70 kg antioxidant phenolics, 234 kg soybean protein, and 225 kg corn-bioethanol, along with emissions from BDG landfilling. The biorefinery demonstrated a synergistic model of cost-effective bioethanol production and low-carbon emission BDGs treatment.

Industrial agglomeration, FDI, and carbon emissions: new evidence from China's service industry.

In the context of economic servitization and low carbonization, the problem of carbon emissions in the service industry is worthy of attention. An essential channel for restraining carbon emissions from the service industry is industrial agglomeration. Based on provincial panel data from 2004 to 2021 in China, this study empirically analyzes the influence of the service industry's agglomeration on its CO2 emissions. The findings indicate that agglomeration significantly reduces the industry's carbon emissions. Next, producer services agglomeration has a significant carbon-reduction effect, whereas non-producer services agglomeration does not. Moreover, service industry agglomeration helps to restrain carbon emissions from the service industry in East China. However, it does not significantly affect carbon emissions in Central or West China. Regarding the moderating effect, foreign direct investment can enhance service industry agglomeration's carbon-reduction effect. Based on the results, relevant policy implications are provided.

The triglyceride-glucose index as a potential protective factor for hypertrophic obstructive cardiomyopathy without diabetes: evidence from a two-center study.

OBJECTIVE: This study aimed to investigate the relationship between the TyG (Triglyceride-glucose index) and the prognosis of patients with HOCM (hypertrophic obstructive cardiomyopathy) without diabetes. RESEARCH DESIGN AND METHODS: A total of 713 eligible patients with HOCM were enrolled in this study and divided into two groups based on treatment: an invasive treatment group (n = 461) and a non-invasive treatment group (n = 252). The patients in both two groups were then divided into three groups based on their TyG index levels. The primary endpoints of this study were Cardiogenic death during long-term follow-up. Kaplan-Meier analysis was used to study the cumulative survival of different groups. Restricted cubic spline was used to model nonlinear relationships between the TyG index and primary endpoints. Myocardial perfusion imaging/Myocardial metabolic imaging examinations were performed to assess glucose metabolism in the ventricular septum of the HOCM patients. RESULTS: The follow-up time of this study was 41.47 ± 17.63 months. The results showed that patients with higher TyG index levels had better clinical outcomes (HR, 0.215; 95% CI 0.051,0.902; P = 0.036, invasive treatment group; HR, 0.179; 95% CI 0.063,0.508; P = 0.001, non-invasive treatment group). Further analysis showed that glucose metabolism in the ventricular septum was enhanced in HOCM patients. CONCLUSIONS: The findings of this study suggest that the TyG index may serve as a potential protective factor for patients with HOCM without diabetes. The enhanced glucose metabolism in the ventricular septum of HOCM patients may provide a potential explanation for the relationship between the TyG index and HOCM prognosis.

Decoding the regulatory roles of non-coding RNAs in cellular metabolism and disease.

Non-coding RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are being studied extensively in a variety of fields. Their roles in metabolism have received increasing attention in recent years but are not yet clear. The regulation of glucose, fatty acid, and amino acid metabolism is an imperative physiological process that occurs in living organisms and takes part in cancer and cardiovascular diseases. Here, we summarize the important roles played by non-coding RNAs in glucose metabolism, fatty acid metabolism, and amino acid metabolism, as well as the mechanisms involved. We also summarize the therapeutic advances for non-coding RNAs in diseases such as obesity, cardiovascular disease, and some metabolic diseases. Overall, non-coding RNAs are indispensable factors in metabolism and have a significant role in the three major metabolisms, which may be exploited as therapeutic targets in the future.

Fate mapping RNA-sequencing reveal Malat1 regulates Sca1+ progenitor cells to vascular smooth muscle cells transition in vascular remodeling.

Regeneration of smooth muscle cells (SMCs) is vital in vascular remodeling. Sca1+ stem/progenitor cells (SPCs) can generate de novo smooth muscle cells after severe vascular injury during vessel repair and regeneration. However, the underlying mechanisms have not been conclusively determined. Here, we reported that lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was down-regulated in various vascular diseases including arteriovenous fistula, artery injury and atherosclerosis. Using genetic lineage tracing mice and veingraft mice surgery model, we found that suppression of lncRNA Malat1 promoted Sca1+ cells to differentiate into SMCs in vivo, resulting in excess SMC accumulation in neointima and vessel stenosis. Genetic ablation of Sca1+ cells attenuated venous arterialization and impaired vascular structure normalization, and thus, resulting in less Malat1 down-regulation. Single cell sequencing further revealed a fibroblast-like phenotype of Sca1+ SPCs-derived SMCs. Protein array sequencing and in vitro assays revealed that SMC regeneration from Sca1+ SPCs was regulated by Malat1 through miR125a-5p/Stat3 signaling pathway. These findings delineate the critical role of Sca1+ SPCs in vascular remodeling and reveal that lncRNA Malat1 is a key regulator and might serve as a novel biomarker or potential therapeutic target for vascular diseases.

Unraveling multifunction of low-temperature Daqu in simultaneous saccharification and fermentation of Chinese light aroma type liquor.

Chinese liquor is produced by a representative simultaneous saccharification and fermentation process. Daqu, as a starter of Chinese liquor fermentation, affects both saccharification and fermentation. However, it is still unclear how Daqu contributed to the simultaneous saccharification and fermentation process. Here, using Chinese light aroma type liquor as a case, we identified low-temperature Daqu-originated enzymes and microorganisms that contributed to the simultaneous saccharification and fermentation using metaproteomic analysis combined with amplicon sequencing analysis. α-Amylase and glucoamylase accounted for 95 % of total saccharifying enzymes and were identified as key saccharifying enzymes. Lichtheimia was the key producer of these two enzymes (> 90 %) in low-temperature Daqu. Daqu contributed 90 % α-amylase and 99 % glucoamylase to the initial liquor fermentation. These two enzymes decreased by 35 % and 49 % until day 15 in liquor fermentation. In addition, Daqu contributed key microbial genera (91 % Saccharomyces, 6.5 % Companilactobacillus) and key enzymes (37 % alcohol dehydrogenase, 40 % lactic acid dehydrogenase, 56 % aldehyde dehydrogenase) related with formations of ethanol, lactic acid and flavour compounds to the initial liquor fermentation. The average relative abundances of these fermentation-related key microorganisms and enzymes increased by 2.78 times and 1.29 times till day 15 in liquor fermentation, respectively. It indicated that Daqu provided saccharifying enzymes for starch hydrolysis, and provided both enzymes and microorganisms associated with formations of ethanol, lactic acid and flavour compounds for liquor fermentation. This work illustrated the multifunction of low-temperature Daqu in the simultaneous saccharification and fermentation of Chinese light aroma type liquor. It would facilitate improving liquor fermentation by producing high-quality Daqu.

Omics insights into spermatozoa activation induced by Fetal bovine serum in viviparous black rockfish (Sebastes schlegelii).

Black rockfish (Sebastes schlegelii) is an economically important marine species with the characteristics of viviparity. The spermatozoa were transferred into the ovary by mating and stored for several months until fertilization. Little is known about spermatozoa activation and its mechanism in black rockfish. In this study, the suitable medium for spermatozoa activation in vitro was explored, and the underlying mechanism was studied by omics analysis. Fetal bovine serum (FBS) could significantly enhance spermatozoa motility in vitro. Omics analysis showed 559 differentially expressed genes (DEGs) and 1311 differentially methylated genes (DMGs) were identified after FBS treatment. Transcriptome analysis revealed that FBS-induced spermatozoa motility activation is associated with spermatozoa capacitation regulated by the cAMP-SRC-PKA, cGMP-PKG and phospholipase D signaling pathway. Spermatozoa capacitation-related gene hsp90aa1 and chemotaxis-related gene cxcr4 were two of the important DMGs. Methylome analysis further revealed that FBS-induced epigenetic modifications are involved in spermatozoa capacitation and chemotaxis. 36 overlaps were identified between DMGs and DEGs, of which five genes were demonstrated to play a role in spermatozoa physiology, required for flagellum stability and spermatozoa motility. The results could provide new clues for understanding spermatozoa activation's molecular mechanism and help establish activation and/or immobilizing media for improving either artificial fertilization or cryopreservation in black rockfish.

Association Between Thyroid Dysfunction and Incidence of Atrial Fibrillation in Patients With Hypertrophic Obstructive Cardiomyopathy.

Objective: To explore the correlation between the incidence of atrial fibrillation (AF) and thyroid dysfunction in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Thyroid function testing in 755 consecutive patients with HOCM were examined at the National Center for Cardiovascular Diseases (China) from October 2009 to December 2013. Patients were divided into four groups according to the TSH levels: TSH<0.55 mIU/L(n=37)、0.55~2.49 mIU/L (n=490)、2.50~9.9 mIU/L (n=211) and >10.00mIU/L(n=17). Results: A total of 107 patients were diagnosed with AF (14%).(1) Compared to HOCM patients without AF,HOCM patients with AF have older age (P<0.001), higher NT-proBNP (P=0.002), higher Cr (P=0.005), larger left atrial diameter(P=0.001), lower FT3 (P=0.046), higher FT4 (P=0.004).(2) In the four groups according to the TSH levels: TSH<0.55 mIU/L, 0.55~2.49mIU/L, 2.50~9.9mIU/L and ≥10.00mIU/L, the incidence of AF was 27.02%(10/37),10.20%(50/490), 19.43%(41/211), and 35.29%(6/17), respectively. Both high and low TSH levels were associated with an increased incidence of AF. After adjusting for the common risk factor (age, NT-proBNP, and so on), stepwise multiple logistic regression analysis revealed that TSH levels were significantly related to AF incidence.Compared to patients with TSH 0.55~2.49 mlU/L, the adjusted odds ratio of AF for TSH<0.55, 2.50~9.99, ≥10.00 mIU/L were 1.481 (95% CI 0.485~4.518,P=0.490), 1.977 (95%CI 1.115~3.506, p=0.02), 4.301 (95%CI 1.059~17.476, P=0.041), respectively. Conclusion: Our results suggested that thyroid dysfunction was associated with an increased risk of AF in patients with HOCM.

Long-Term Outcomes for Chinese COPD Patients After PCI: A Propensity Score Matched, Double-Cohort Study.

Objectives: The aim of this study was to analyze long-term outcomes of Chinese coronary artery disease (CAD) patients with (and without) chronic obstructive pulmonary disease (COPD) after percutaneous coronary intervention (PCI). Background: Chronic obstructive pulmonary disease is a chronic condition which often develops in conjunction with CAD. PCI is a core therapy for CAD, although we still need to understand CAD-COPD outcomes and to identify factors that influence prognoses, across ethnicities. Methods: This double-cohort study involved 12,343 Chinese CAD patients who received PCI. Baseline characteristics were collected in two independent, specialty centers. Propensity-score matching was performed to control confounding factors, using a nearest neighbor matching method within a 0.02 caliper and on a propensity score scale of 0.1 for each center. Comorbid CAD-COPD cases were compared to non-COPD patients in terms of major adverse cardiac events (MACEs). Results: Patients with COPD were generally older than those without COPD (65.4 ± 9.2 vs. 58.2 ± 10.3, p < 0.001). There were no significant differences in the end points between COPD and non-COPD groups after PCI (All p > 0.05); however, the incidence of MACEs increased after 450 days. Further subgroup analysis suggests that COPD is approximately four times more prevalent among those aged over 75 years (HR, 3.818; 95%CI, 1.10-13.29; p = 0.027) and those aged below 55 years (HR = 4.254; 95% CI, 1.55-11.72; p = 0.003). Conclusion: Having COPD does not appear to have a significant impact on CAD outcomes 2 years after PCI, and beyond. However, an increasing number of MACEs was observed after 450 days, which suggests that there may be a double-stage effect of COPD on PCI prognosis. There is a need for focused comorbidity management, specifically for those aged below 55 years and above 75 years.

Migration of a Hem-o-Lok clip to the renal pelvis after laparoscopic partial nephrectomy: A case report.

BACKGROUND: Hem-o-Lok clip (HOLC) has been widely used in laparoscopic surgery due to its ease of application and secure clamping, though the rare complications associated with this technique should not be ignored. The rare complications of laparoscopic partial nephrectomy consist of the clip migrating into the renal pelvis and acting as a nidus for stone formation. CASE SUMMARY: The case described here involved a 63-year-old woman who was found with stones in the right kidney and upper ureter during a recent reexamination following laparoscopic partial nephrectomy. We performed percutaneous nephrolithotomy for her, but during the operation, it was found that the center of the stone within the kidney was a HOLC, which was removed with forceps. For this reason, we speculate that the HOLC, which was employed to halt tumor wound bleeding, spontaneously drifted into the renal pelvis and formed kidney stones, with the clip being initially misdiagnosed as a kidney stone. CONCLUSION: By reviewing related case reports, we conclude that in order to prevent complications related to HOLC, loose clips should be actively searched for and retrieved from the wound during urinary tract surgery, while the deployment of clips in close proximity of anastomotic stoma of collecting systems should be avoided.

Genetically Determined Lifestyle and Cardiometabolic Risk Factors Mediate the Association of Genetically Predicted Age at Menarche With Genetic Predisposition to Myocardial Infarction: A Two-Step, Two-Sample Mendelian Randomization Study.

Background: Observational studies have shown an association between early age at menarche (AAM) and myocardial infarction (MI) with recorded cases. In this Mendelian randomization (MR) study, we used large amounts of summary data from genome-wide association studies (GWASs) to further estimate the association of genetically predicted AAM with genetically predicated risk of MI and investigate to what extent this association is mediated by genetically determined lifestyles, cardiometabolic factors, and estrogen exposure. Methods: A two-step, two-sample MR study was performed by mediation analysis. Genetic variants identified by GWAS meta-analysis of reproductive genetics consortium (n = 182,416) were selected for genetically predicted AAM. Genetic variants identified by the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis plus The Coronary Artery Disease Genetics Consortium (n = 184,305) were selected for genetically predicted risk of MI. Genetic variants from other international GWAS summary data were selected for genetically determined mediators. Results: This MR study showed that increase in genetically predicted AAM was associated with lower risk of genetically predicted MI (odds ratio 0.91, 95% confidence interval 0.84-0.98). Inverse variance weighted (IVW) MR analysis also showed that decrease in genetically predicted AAM was associated with higher genetically predicted alcohol intake frequency, current smoking behavior, higher waist-to-hip ratio, and higher levels of systolic blood pressure (SBP), fasting blood glucose, hemoglobin A1c (HbA1c), and triglycerides (TGs). Furthermore, increase in genetically predicted AAM was associated with genetically predicted longer sleep duration, higher levels of high-density lipoproteins, and older age at which hormone replacement therapy was started. The most essential mediators identified were genetically predicted current smoking behavior and levels of HbA1c, SBP, and TGs, which were estimated to genetically mediate 13.9, 12.2, 10.5, and 9.2%, respectively, with a combined mediation proportion of 37.5% in the association of genetically predicted AAM with genetically predicted increased risk of MI in an MR framework. Conclusion: Our MR analysis showed that increase in genetically predicted AAM was associated with lower genetically predicted risk of MI, which was substantially mediated by genetically determined current smoking behavior and levels of HbA1c, SBP, and TGs. Intervening on the above mediators may reduce the risk of MI.

Palmitic Acid, A Critical Metabolite, Aggravates Cellular Senescence Through Reactive Oxygen Species Generation in Kawasaki Disease.

Coronary artery lesions (CALs) are severe complications of Kawasaki disease (KD), resulting in stenosis and thrombogenesis. Metabolomic profiling of patients' plasma could assist in elucidating the pathogenesis of CALs and identifying diagnostic biomarkers, which are imperative for clinical treatment. The metabolic profiles between KD patients with CALs and without CALs (non-coronary artery lesion, or NCAL, group) indicated the most significantly differentially expressed metabolite, palmitic acid (PA), showed the most massive fold change at 9.879. Furthermore, PA was proven to aggravate endothelial cellular senescence by increasing the generation of reactive oxygen species (ROS) in KD, and those two phenotypes were confirmed to be enriched among the differentially expressed genes between KD and normal samples from GEO datasets. Collectively, our findings indicate that cellular senescence may be one of the mechanisms of vascular endothelial damage in KD. PA may be a biomarker and potential therapeutic target for predicting the occurrence of CALs in KD patients. All things considered, our findings confirm that plasma metabolomics was able to identify promising biomarkers and potential pathogenesis mechanisms in KD. To conclude, Palmitic acid could be a novel target in future studies of CALs in patients with KD.

Effects of Cryopreservation on Sperm with Cryodiluent in Viviparous Black Rockfish (Sebastes schlegelii).

Black rockfish is an economically important fish in East Asia. Little mention has been paid to the sperm cryopreservation in black rockfish. In this study, the optimal cryodiluent was selected from 48 combinations by detecting various sperm parameters. Transcriptome and methylome analysis were further performed to explore the molecular mechanism of inevitable cryoinjuries. The results showed that cryopreservation had negative effects on the viability, DNA integrity, mitochondrial activity, total ATPase and LDH of sperm even with optimal cryodiluent (FBS + 15% Gly). Transcriptome and methylome analysis revealed that the expression of 179 genes and methylation of 1266 genes were affected by cryopreservation. These genes were enriched in GO terms of death, G-protein coupled receptor signaling pathway, response to external stimulus and KEGG pathways of phospholipase D signaling pathway and xenobiotic and carbohydrate metabolism pathways. The role of PIK3CA and CCNA2 were highlighted in the protein-protein interaction network, and the sperm quality-related imprinted gene mest was identified among the 7 overlapping genes between transcriptome and methylome. Overall, the cryodiluent for black rockfish sperm was optimized, providing a feasible method for cryopreservation. The transcriptome and methylome data further demonstrated the underlying molecular mechanisms of cryoinjuries, proving clues for improvement of cryopreservation method of black rockfish.

Lung cancer metastasis-related protein 1 promotes the transferring from advanced metastatic prostate cancer to castration-resistant prostate cancer by activating the glucocorticoid receptor α signal pathway.

Androgen deprivation therapy is currently the main therapeutic strategy for the treatment of advanced metastatic prostate cancer (ADPC). However, the tumor type in ADPC patients transforms into castration-resistant prostate cancer (CRPC) after 18-24 months of treatments, the underlying mechanism of which remains unclear. The present study aimed to investigate the potential pathological mechanism of the conversion from ADPC to CRPC by exploring the function of lung cancer metastasis-related protein 1 (LCMR1). We found that LCMR1 and glucocorticoid receptor α (GRα) were highly expressed in CRPC tissues, compared to ADPC tissues, and were accompanied by high concentrations of inflammatory factors. Knocking down LCMR1 or GRα in CRPC cells led to inhibition of metastasis and proliferation and induction of apoptosis. The expression of HSP90 and IL-6 was upregulated and that of androgen receptor was downregulated by knocking down LCMR1 or GRα in CRPC cells. Luciferase assay results indicated that the transcription of GRα was promoted by the LCMR1 promoter. The growth rate of CRPC cells in vivo was greatly decreased by knocking down LCMR1 or GRα. Lastly, CRPC cell sensitivity to enzalutamide treatment was found significantly enhanced by the knockdown of LCMR1. Taken together, LCMR1 might regulate the conversion of ADPC to CRPC by activating the GRα signaling pathway.

Bibliometric analysis of the 100 top-cited articles on immunotherapy of urological cancer.

PURPOSE: To highlight the scientific progress in immunotherapy of urological cancer by identifying and analyzing the 100 top-cited (T100) articles from the last 15 years. METHODS: Papers in immunotherapy of urological cancer were identified from Clarivate Web of Science Core Collection database. Data of the T100 articles and papers published in recent 2 years, including citations, topic, year of publication, country of origin, institution and authorship, were extracted and analyzed. RESULTS: Of the T100 articles, the citation number ranged from 7387 to 183 with a mean of 590.66. The USA led the field with 80 T100 articles and 53097 citations. Pro Sharma P from MD Anderson Cancer Center was at the top of list with 8 T100 articles (3 as first author and 6 as corresponding author). Memorial Sloan Kettering Cancer Center ranked first with 26 T100 articles and 22573 citations, followed by Johns Hopkins University with 21 T100 articles and 25095 citations. Forty-nine T100 articles were related to the renal cancer, followed by prostate cancer (29), bladder cancer (13) and urothelial cancer (13). According to the type of immunotherapy, most T100 articles were related to ICI (55 articles) and vaccine (19 articles). CONCLUSIONS: It is the first bibliometric analysis to identify the T100 articles on immunotherapy of urological cancer. The USA made great contribution in the field of immunotherapy related to urological cancer. Renal, bladder and prostate cancers were the major organs treated by immunotherapy especially by ICIs and vaccines. The multiple aspects of ICIs research in renal and bladder cancer and the neoantigen-based vaccine therapy will be hotspots for future research.

METTL14-mediated Lnc-LSG1 m6A modification inhibits clear cell renal cell carcinoma metastasis via regulating ESRP2 ubiquitination.

Clear cell renal cell carcinoma (ccRCC) is the most lethal urological cancer and is characterized by a high rate of metastasis and relapse. N6-Methyladenosine (m6A) is implicated in various stages of cancer development. However, a thorough understanding of m6A-modified lncRNAs in ccRCC is lacking. The results showed that METTL14 had decreased expression in ccRCC tissues. In addition, the expression of METTL14 was negatively correlated to the prognosis, stage, and ccRCC tumor grade. The silencing of METTL14 was shown to significantly increase metastasis in vitro and in vivo. High-throughput methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed that the m6A levels of Lnc-LSG1 could be regulated by METTL14. Lnc-LSG1 can directly bind to ESRP2 protein and promote ESRP2 degradation via facilitating ESRP2 ubiquitination. However, m6A modification on Lnc-LSG1 can block the interaction between Lnc-LSG1 and ESRP2 via the m6A reader, YTHDC1. Taken together, our findings unraveled the novel mechanism of METTL14 inhibiting ccRCC progression, and explored the correlation between m6A and lncRNA in ccRCC for the first time.

Metabolomic Characterization of Fatty Acids in Patients With Coronary Artery Ectasias.

Background: We used a targeted metabolomics approach to identify fatty acid (FA) metabolites that distinguished patients with coronary artery ectasia (CAE) from healthy Controls and patients with coronary artery disease (CAD). Materials and methods: Two hundred fifty-two human subjects were enrolled in our study, such as patients with CAE, patients with CAD, and Controls. All the subjects were diagnosed by coronary angiography. Plasma metabolomic profiles of FAs were determined by an ultra-high-performance liquid chromatography coupled to triple quadrupole mass spectrometric (UPLC-QqQ-MS/MS). Results: Ninety-nine plasma metabolites were profiled in the discovery sets (n = 72), such as 35 metabolites of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), 10 FAs, and 54 phospholipids. Among these metabolites, 36 metabolites of AA, EPA, and DHA showed the largest difference between CAE and Controls or CAD. 12-hydroxyeicosatetraenoic acid (12-HETE), 17(S)-hydroxydocosahexaenoic acid (17-HDoHE), EPA, AA, and 5-HETE were defined as a biomarker panel in peripheral blood to distinguish CAE from CAD and Controls in a discovery set (n = 72) and a validation set (n = 180). This biomarker panel had a better diagnostic performance than metabolite alone in differentiating CAE from Controls and CAD. The areas under the ROC curve of the biomarker panel were 0.991 and 0.836 for CAE versus Controls and 1.00 and 0.904 for CAE versus CAD in the discovery and validation sets, respectively. Conclusions: Our findings revealed that the metabolic profiles of FAs in the plasma from patients with CAE can be distinguished from those of Controls and CAD. Differences in FAs metabolites may help to interpret pathological mechanisms of CAE.

Testicular Nuclear Receptor 4 Regulates Proliferation and Apoptosis of Bladder Cancer via Bcl-2.

Testicular nuclear receptor 4 (TR4) is a member of the nuclear hormone receptor family and acts as a ligand-activated transcription factor and functions in many biological processes, such as development, cellular differentiation, and homeostasis. Recent studies have shown that TR4 plays an important role in prostate cancer, renal cell carcinoma, and hepatocellular carcinoma; however, its potential link to bladder cancer (BC) remains unknown. This study found that bladder cancer exhibited a higher expression of TR4 compared to normal tissues. Overexpressed TR4 promoted the bladder cancer cell proliferation, and knocked down TR4 with TR4-siRNA suppressed the bladder cancer cell proliferation. Mechanistic studies reveal that TR4 functions by altering the expression of Bcl-2 to regulate apoptosis in bladder cancer cells. Furthermore, knocking down Bcl-2 reversed the BC proliferation induced by TR4. In vivo, we also confirmed that TR4 knockdown mice (TR4+/-) showed slower bladder cancer growth than wild-type mice (TR4+/+) induced by the carcinogenic chemicals. Moreover, TR4+/- mice showed a lower grade of histopathology than the control group. In conclusion, these results indicate that TR4 plays a key role in bladder cancer proliferation, and targeting TR4 would probably be a potential strategy for bladder cancer treatment.

Perfect outcome of kidney recipients with ureteral stenosis after treatment with open surgery under magnetic resonance urography localization.

BACKGROUND: To evaluate the outcome of kidney recipients with ureteral stenosis after treatment with open surgery under magnetic resonance urography (MRU) localization. METHODS: We assessed 2,256 consecutive kidney transplant recipients between October 2010 and December 2018. Ureteral stenosis was detected by ultrasound, confirmed and positioned by Magnetic Resonance Urography. All patients underwent open ureteral reconstruction. The ureteral stenosis was located according to the location on the MRU during the operation. Surgical complications and recurrence rate were recorded in the stenosis group. Outcomes were compared with those of a matched control group of transplant recipients with no history of ureteric stenosis. RESULTS: The incidence of ureteral stenosis in our center was 3.1% (70/2,256). Sixty-four cases (91.4%) were confirmed to have distal stenosis and were reconstructed with ureterovesical re-implantation; six cases (8.6%) were confirmed to have mid-distal stenosis and were subjected to ureteroureterostomy with the use of native ureter. The overall success rate was 100% and the graft function was salvaged in all cases. There was no recurrence of stenosis after a mean follow-up of 38.9±26.3 months. The complication rate was 5.7%. The 110-month graft survival and patient survival were not significantly different between the stenosis and control groups.Conclusions: MRU is an effective method for non-invasive and accurate diagnosis of ureteral stenosis in kidney transplant recipients. Open ureteral reconstruction surgery under MRU localization for treatment of ureter stenosis after kidney transplantation had a high success rate, low recurrence rate and high safety.