Triglyceride-glucose index and health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence. METHODS: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587). RESULTS: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index. CONCLUSION: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.

The dual effects of dexmedetomidine on intestinal barrier and intestinal motility during sepsis.

BACKGROUND: Sepsis, characterized by dysregulated host responses to infection, remains a critical global health concern, with high morbidity and mortality rates. The gastrointestinal tract assumes a pivotal role in sepsis due to its dual functionality as a protective barrier against injurious agents and as a regulator of motility. Dexmedetomidine, an α2-adrenergic agonist commonly employed in critical care settings, exhibits promise in influencing the maintenance of intestinal barrier integrity during sepsis. However, its impact on intestinal motility, a crucial component of intestinal function, remains incompletely understood. METHODS: In this study, we investigated dexmedetomidine's multifaceted effects on intestinal barrier function and motility during sepsis using both in vitro and in vivo models. Sepsis was induced in Sprague-Dawley rats via cecal ligation and puncture. Rats were treated with dexmedetomidine post-cecal ligation and puncture, and various parameters were assessed to elucidate dexmedetomidine's impact. RESULTS: Our findings revealed a dichotomous influence of dexmedetomidine on intestinal physiology. In septic rats, dexmedetomidine administration resulted in improved intestinal barrier integrity, as evidenced by reduced mucosal hyper-permeability and morphological alterations. However, a contrasting effect was observed on intestinal motility, as dexmedetomidine treatment inhibited both the frequency and amplitude of contractions in isolated intestinal strips and decreased the distance of ink migration in vivo. Additionally, dexmedetomidine suppressed the secretion of pro-motility hormones while having no influence on hormones that inhibit intestinal peristalsis. CONCLUSION: The study revealed that during sepsis, dexmedetomidine exhibited protective effects on barrier integrity, although concurrently it hindered intestinal motility, partly attributed to its modulation of pro-motility hormone secretion. These findings underscore the necessity of a comprehensive understanding of dexmedetomidine's impact on multiple facets of gastrointestinal physiology in sepsis management, offering potential implications for therapeutic strategies and patient care.

Lipidomics analysis of bone marrow in a mouse model of postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMOP) is a major public health problem worldwide, afflicting many postmenopausal women. Although many studies have focused on the biological role of individual lipids in osteoporosis, no studies have systematically elucidated the lipid profile of osteoporosis. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology based on multiple reaction monitoring (MRM) method was used to compare the levels of lipid molecules in bone marrow cells of osteoporotic mice (OVX) group and sham-operation (Sham) group. Principal component analysis (PCA) was used for multivariate statistics. Differential lipids were obtained by bar graph, heatmap and volcano map. A total of 400 lipid molecules were identified. A total of 199 lipid molecules were identified to be associated with PMOP, including 6 phospholipids and 3 sphingolipids. These differential lipid molecules provide a systematic lipid profile for osteoporosis, which helps to discover new candidate osteoporosis biomarkers, and their changes at the molecular level can be used as new targets for diagnosis or prevention.

The bone marrow lipidomics of mice reveal sex-related differences.

Osteoporosis is a common skeletal disorder characterized by an imbalance between bone resorption and formation, exhibiting a higher prevalence in women compared with men. While previous studies have primarily focused on genomics and genetics in osteoporosis susceptibility, there is a lack of systematic exploration of sex-specific differences in lipid levels in mouse bone marrow. Multiple reaction monitoring-based liquid chromatography-trandem mass spectrometry (LC-MS/MS) was used to quantify lipidomic profiles in bone marrow samples from three female mice and three male mice. The LC-MS/MS technique based on the multiple reaction monitoring method identified and quantified 184 lipids from 15 lipid classes. The contents of most lipids in the bone marrow cells of female mice were higher than those in male mice, including four polyunsaturated fatty acids, three phospholipids and four sphingolipids. Among all the lipid molecules, lactosylceramide (d18:0/16:0) showed the highest fold change in female mice, while its precursor lipid, glucosylceramide, was the most up-regulated in male mice. This study, focusing on bone marrow lipidomics, elucidates significant sexual dimorphism in lipid levels within bone marrow cells. It provides novel evidence supporting the higher prevalence of osteoporosis in women and enhances our understanding of the connection between sex-specific lipid levels and the risk of osteoporosis.

Predicting pathological complete response to neoadjuvant chemotherapy in breast cancer patients: use of MRI radiomics data from three regions with multiple machine learning algorithms.

OBJECTIVE: To construct a multi-region MRI radiomics model for predicting pathological complete response (pCR) in breast cancer (BCa) patients who received neoadjuvant chemotherapy (NACT) and provide a theoretical basis for the peritumoral microenvironment affecting the efficacy of NACT. METHODS: A total of 133 BCa patients who received NACT, including 49 with confirmed pCR, were retrospectively analyzed. The radiomics features of the intratumoral region, peritumoral region, and background parenchymal enhancement (BPE) were extracted, and the most relevant features were obtained after dimensional reduction. Then, combining different areas, multivariate logistic regression analysis was used to select the optimal feature set, and six different machine learning models were used to predict pCR. The optimal model was selected, and its performance was evaluated using receiver operating characteristic (ROC) analysis. SHAP analysis was used to examine the relationship between the features of the model and pCR. RESULTS: For signatures constructed using three individual regions, BPE provided the best predictions of pCR, and the diagnostic performance of the intratumoral and peritumoral regions improved after adding the BPE signature. The radiomics signature from the combination of all the three regions with the XGBoost machine learning algorithm provided the best predictions of pCR based on AUC (training set: 0.891, validation set: 0.861), sensitivity (training set: 0.882, validation set: 0.800), and specificity (training set: 0.847, validation set: 0.84). SHAP analysis demonstrated that LZ_log.sigma.2.0.mm.3D_glcm_ClusterShade_T12 made the greatest contribution to the predictions of this model. CONCLUSION: The addition of the BPE MRI signature improved the prediction of pCR in BCa patients who received NACT. These results suggest that the features of the peritumoral microenvironment are related to the efficacy of NACT.

Cross-talk between disulfidptosis and immune check point genes defines the tumor microenvironment for the prediction of prognosis and immunotherapies in glioblastoma.

Disulfidptosis is a condition where dysregulated NAPDH levels and abnormal accumulation of cystine and other disulfides occur in cells with high SLC7A11 expression under glucose deficiency. This disrupts normal formation of disulfide bonds among cytoskeletal proteins, leading to histone skeleton collapse and triggering cellular apoptosis. However, the correlation between disulfidptosis and immune responses in relation to glioblastoma survival rates and immunotherapy sensitivity remains understudied. Therefore, we utilized The Cancer Genome Atlas and The Chinese Glioma Genome Atlas to identify disulfidptosis-related immune checkpoint genes and established an overall survival (OS) prediction model comprising six genes: CD276, TNFRSF 14, TNFSF14, TNFSF4, CD40, and TNFRSF18, which could also be used for predicting immunotherapy sensitivity. We identified a cohort of glioblastoma patients classified as high-risk, which exhibited an upregulation of angiogenesis, extracellular matrix remodeling, and epithelial-mesenchymal transition as well as an immunosuppressive tumor microenvironment (TME) enriched with tumor associated macrophages, tumor associated neutrophils, CD8 + T-cell exhaustion. Immunohistochemical staining of CD276 in 144 cases further validated its negative correlation with OS in glioma. Disulfidptosis has the potential to induce chronic inflammation and an immunosuppressive TME in glioblastoma.

M2 tumor-associated macrophages and CXCL2 induce lipid remodeling in hepatocellular carcinoma cell lines.

Primary hepatocellular carcinoma (HCC) is one of the most common malignant tumors, but its pathogenesis remains incompletely elucidated. Recently, many studies indicated that lipid remodeling plays an important role in the occurrence and development of HCC. Furthermore, lipids have been proven to be indispensable mediators in promoting communication between tumor cells and extracellular matrix in the tumor microenvironment. Thus, this study aims to comprehensively investigate the process of lipid remodeling during HCC metastasis based on the LC-electrospray ionization-MS (LC-ESI-MS) combined with multiple reaction monitoring technology. M2 tumor-associated macrophages and the recombinant human protein CXCL2 were used to simulate the tumor microenvironment. After co-incubating SMMC7721 and MHCC97-H cell lines with M2 tumor-associated macrophages or the recombinant human protein CXCL2 for 48 h, LC-ESI-MS was used to quantify the levels of two major classes of lipid molecules, namely, glycerophospholipids and sphingolipids. Our results suggest that lipid remodeling in the tumor microenvironment may promote the migration and invasion of HCC cell lines.

The arachidonic acid metabolome reveals elevation of prostaglandin E2 biosynthesis in colorectal cancer.

Arachidonic acid metabolites are a family of bioactive lipids derived from membrane phospholipids. They are involved in cancer progression, but arachidonic acid metabolite profiles and their related biosynthetic pathways remain uncertain in colorectal cancer (CRC). To compare the arachidonic acid metabolite profiles between CRC patients and healthy controls, quantification was performed using a liquid chromatography-mass spectrometry-based analysis of serum and tissue samples. Metabolomics analysis delineated the distinct oxidized lipids in CRC patients and healthy controls. Prostaglandin (PGE2)-derived metabolites were increased, suggesting that the PGE2 biosynthetic pathway was upregulated in CRC. The qRT-PCR and immunohistochemistry analyses showed that the expression level of PGE2 synthases, the key protein of PGE2 biosynthesis, was upregulated in CRC and positively correlated with the CD68+ macrophage density and CRC development. Our study indicates that the PGE2 biosynthetic pathway is associated with macrophage infiltration and progression of CRC tumors.

SH3RF2 contributes to cisplatin resistance in ovarian cancer cells by promoting RBPMS degradation.

Platinum-based chemotherapy remains one of the major choices for treatment of ovarian cancer (OC). However, primary or acquired drug resistance severely impairs their efficiency, thereby causing chemotherapy failure and poor prognosis. SH3 domain containing ring finger 2 (SH3RF2) has been linked to the development of cancer. Here we find higher levels of SH3RF2 in the tumor tissues from cisplatin-resistant OC patients when compared to those from cisplatin-sensitive patients. Similarly, cisplatin-resistant OC cells also express higher levels of SH3RF2 than normal OC cells. Through in vitro and in vivo loss-of-function experiments, SH3RF2 is identified as a driver of cisplatin resistance, as evidenced by increases in cisplatin-induced cell apoptosis and DNA damage and decreases in cell proliferation induced by SH3RF2 depletion. Mechanistically, SH3RF2 can directly bind to the RNA-binding protein mRNA processing factor (RBPMS). RBPMS has been reported as an inhibitor of cisplatin resistance in OC. As a E3 ligase, SH3RF2 promotes the K48-linked ubiquitination of RBPMS to increase its proteasomal degradation and activator protein 1 (AP-1) transactivation. Impairments in RBPMS function reverse the inhibitory effect of SH3RF2 depletion on cisplatin resistance. Collectively, the SH3RF2-RBPMS-AP-1 axis is an important regulator in cisplatin resistance and inhibition of SH3RF2 may be a potential target in preventing cisplatin resistance.

A disulfidptosis-related lncRNAs signature in hepatocellular carcinoma: prognostic prediction, tumor immune microenvironment and drug susceptibility.

Disulfidptosis, a novel type of programmed cell death, has attracted researchers' attention worldwide. However, the role of disulfidptosis-related lncRNAs (DRLs) in liver hepatocellular carcinoma (LIHC) not yet been studied. We aimed to establish and validate a prognostic signature of DRLs and analyze tumor microenvironment (TME) and drug susceptibility in LIHC patients. RNA sequencing data, mutation data, and clinical data were obtained from the Cancer Genome Atlas Database (TCGA). Lasso algorithm and cox regression analysis were performed to identify a prognostic DRLs signature. Kaplan-Meier curves, principal component analysis (PCA), nomogram and calibration curve, function enrichment, TME, immune dysfunction and exclusion (TIDE), tumor mutation burden (TMB), and drug sensitivity analyses were analyzed. External datasets were used to validate the predictive value of DRLs. qRT-PCR was also used to validate the differential expression of the target lncRNAs in tissue samples and cell lines. We established a prognostic signature for the DRLs (MKLN1-AS and TMCC1-AS1) in LIHC. The signature could divide the LIHC patients into low- and high-risk groups, with the high-risk subgroup associated with a worse prognosis. We observed discrepancies in tumor-infiltrating immune cells, immune function, function enrichment, and TIDE between two risk groups. LIHC patients in the high-risk group were more sensitive to several chemotherapeutic drugs. External datasets, clinical tissue, and cell lines confirmed the expression of MKLN1-AS and TMCC1-AS1 were upregulated in LIHC and associated with a worse prognosis. The novel signature based on the two DRLs provide new insight into LIHC prognostic prediction, TME, and potential therapeutic strategies.

The effect of FOXP3 genetic polymorphisms on correlations with hepatitis B virus-hepatocellular carcinoma: A case-control study.

Background: Previous studies have reported that transcription factor forkhead box protein 3 (FOXP3) polymorphisms are correlated with the progress of some cancers, but the relationships between the FOXP3 polymorphisms and hepatocellular carcinoma (HCC) risk remain unclear. Method: Genotypes were detected in156 hepatitis B virus (HBV)-HCC patients, 109 HBV-liver cirrhosis (LC) patients, 125 chronic hepatitis B (CHB) patients, and 188 healthy controls. The FOXP3 rs3761547 and rs3761548 polymorphisms were genotyped by polymerase chain reaction (PCR) combined with restriction fragment length polymorphism, and the rs2232365 polymorphism was genotyped using PCR with sequence-specific primers. Results: We did not obtain any significant results with the FOXP3 rs3761547, rs3761548, and rs2232365 polymorphisms in groups of patients compared to healthy controls (all p > 0.05), no matter the overall group or subgroup. Conclusions: Our findings suggest that the FOXP3 polymorphisms at rs3761547, rs3761548, and rs2232365 were not related to HBV-HCC risk in the Chinese population.

The Association between Four Common Polymorphisms in microRNA and Risk of Hepatocellular Carcinoma: An Updated Meta-Analysis.

Background: Many epidemiological studies have explored the relationship between single-nucleotide polymorphism and hepatocellular carcinoma (HCC). However, the results remain controversial. We performed a large-scale meta-analysis to draw a more precise estimation of the aforementioned association. Methods: Studies on the association between microRNA (MIR) polymorphisms and HCC risk that had been published up to Sep 30, 2021 were identified by searching the PubMed, Cochrane Library, Google Scholar, Web of Science, and Chinese Biomedical Literature electronic databases and the Excerpta Medical Database. The association between MIR polymorphisms and HCC risk was assessed using odds ratios (ORs) and their 95% confidence intervals (CIs). Results: Overall, 29 studies, with a total of 9,263 cases and 10,875 controls, were included in our meta-analysis. MicroRNA149 (MIR149) significantly decreased the risk of developing HCC on the overall population (homozygous model CC vs. TT: OR = 0.703, 95% CI = 0.549-0.899, P = 0.005), and microRNA 196 (MIR196) significantly decreased the risk of developing HCC on the overall population (recessive model TT vs. CT+CC: OR = 0.864, 95% CI = 0.751-0.993, P = 0.04) and on Caucasians (OR = 0.613, 95% CI = 0.414-0.907, P = 0.014). Conclusion: The MIR149 and MIR196 polymorphisms are the protect factors of developing HCC. The conduct of multi-center and multi-region studies with gene-gene, gene-environment should be considered.

Proteomic characterization of epithelial ovarian cancer delineates molecular signatures and therapeutic targets in distinct histological subtypes.

Clear cell carcinoma (CCC), endometrioid carcinoma (EC), and serous carcinoma (SC) are the major histological subtypes of epithelial ovarian cancer (EOC), whose differences in carcinogenesis are still unclear. Here, we undertake comprehensive proteomic profiling of 80 CCC, 79 EC, 80 SC, and 30 control samples. Our analysis reveals the prognostic or diagnostic value of dysregulated proteins and phosphorylation sites in important pathways. Moreover, protein co-expression network not only provides comprehensive view of biological features of each histological subtype, but also indicates potential prognostic biomarkers and progression landmarks. Notably, EOC have strong inter-tumor heterogeneity, with significantly different clinical characteristics, proteomic patterns and signaling pathway disorders in CCC, EC, and SC. Finally, we infer MPP7 protein as potential therapeutic target for SC, whose biological functions are confirmed in SC cells. Our proteomic cohort provides valuable resources for understanding molecular mechanisms and developing treatment strategies of distinct histological subtypes.

The application of 3D brachytherapy in cervical stump cancer: A retrospective study.

Purpose: Cervical stump cancer is a carcinoma that grows on the cervical stump after a sub-total hysterectomy. There have been no studies on the application of 3D brachytherapy in cervical stump cancer. In the present study, we aimed to compare the curative effects, toxicity, and dosimetry of 3D and 2D brachytherapy in cervical stump cancer. Material and methods: Thirty-one patients admitted between 2012 and 2021, who were concurrently treated with intensity-modulated radiation therapy and brachytherapy for cervical stump cancer were divided into three groups according to the brachytherapy techniques: 2D brachytherapy, 3D image-guided brachytherapy (3D-IGBT), and 2D + 3D. For patients undergoing 2D brachytherapy and 3D-IGBT, data on survival, complications, and dose to target area or organs at risk (OARs) were collected and compared. Furthermore, dosimetry difference was investigated by reconstructing the 2D plan into a 3D plan. Results: The median follow-up duration of all patients was 58 months. The overall 5-year progression-free survival, overall survival, and local control rates were 69.6%, 90.2%, and 78.2%, respectively. Late complications in the rectum, sigmoid colon, and bladder were milder in 3D brachytherapy than in 2D brachytherapy. Concerning the D90 value of clinical target volume (CTV) and D2cm3 value of OARs in EQD2, the 3D brachytherapy provided a lower dose to CTV (76.5 Gy vs. 95.9 Gy, on average) and OARs compared with 2D brachytherapy. Conclusions: Despite lacking statistical significance, 3D brachytherapy showed better outcomes regarding late toxicity than 2D brachytherapy, owing to the lower dose coverage in the bladder, rectum, sigmoid colon, and small intestine.

Combining network pharmacology and experimental verification to reveal the mechanism of Chaigui granules in the treatment of depression through PI3K/Akt/mTOR signaling pathways.

INTRODUCTION: Chaigui granules are a novel manufactured traditional Chinese antidepressant medicine, which is originated from the ancient classical prescription of Xiaoyaosan. It ameliorated depression-like behavior and concomitant symptoms in animal models. But its antidepressant mechanism is still unclear. Therefore, network pharmacology and molecular biology were used to explore underlying antidepressant mechanism in this study. METHODS: Firstly, network pharmacology was used to screen main active ingredients and potential targets in the treatment of depression with Chaigui granules, and to perform pathway enrichment analysis. Secondly, chronic and unpredictable mild stress-induced depression model rats were used, and behavioral tests were used to evaluate the antidepressant effect of Chaigui granules. Finally, the core targets and key pathways predicted by network pharmacology were validated by qRT-PCR and Western blot to determine the relevant gene and protein expression levels in rat hippocampus. RESULTS: The results of network pharmacology indicated that the PI3K/Akt signaling pathway may play a key role in antidepressant of Chaigui granules. The results of animal experiments showed that Chaigui granules significantly modulated behavioral indicators. Subsequently, the upregulation of relative mRNA levels of mTOR, Akt and PI3K and downregulation of GSK-3ß and FoxO3a were observed in rat hippocampus by molecular biology diagnosis. In addition, the decreased expression of Akt and mTOR in CUMS rats hippocampus was significantly reversed, and the expression levels of GSK-3ß and FoxO3a were upregulated. CONCLUSIONS: Based on the results of network pharmacology and animal experiment validation, Chaigui granules may reverse CUMS-induced depression-like behavior in rats through PI3K/Akt/mTOR signaling pathway.

Breast cancer pre-clinical screening using infrared thermography and artificial intelligence: a prospective, multicentre, diagnostic accuracy cohort study.

BACKGROUND: Given the limited access to breast cancer (BC) screening, the authors developed and validated a mobile phone-artificial intelligence-based infrared thermography (AI-IRT) system for BC screening. MATERIALS AND METHODS: This large prospective clinical trial assessed the diagnostic performance of the AI-IRT system. The authors constructed two datasets and two models, performed internal and external validation, and compared the diagnostic accuracy of the AI models and clinicians. Dataset A included 2100 patients recruited from 19 medical centres in nine regions of China. Dataset B was used for independent external validation and included 102 patients recruited from Langfang People's Hospital. RESULTS: The area under the receiver operating characteristic curve of the binary model for identifying low-risk and intermediate/high-risk patients was 0.9487 (95% CI: 0.9231-0.9744) internally and 0.9120 (95% CI: 0.8460-0.9790) externally. The accuracy of the binary model was higher than that of human readers (0.8627 vs. 0.8088, respectively). In addition, the binary model was better than the multinomial model and used different diagnostic thresholds based on BC risk to achieve specific goals. CONCLUSIONS: The accuracy of AI-IRT was high across populations with different demographic characteristics and less reliant on manual interpretations, demonstrating that this model can improve pre-clinical screening and increase screening rates.

Association of pre-diagnosis specific color groups of fruit and vegetable intake with ovarian cancer survival: results from the ovarian cancer follow-up study (OOPS).

Background: The colors of fruits and vegetables (FV) reflect the presence of pigmented bioactive compounds. The evidence of pre-diagnosis specific FV color group intake contributing to ovarian cancer (OC) survival is limited and inconsistent. Methods: A prospective cohort study was conducted between 2015 and 2020 with 700 newly diagnosed OC patients. Pre-diagnosis dietary information was assessed by a validated food frequency questionnaire. We classified FV into five groups based on the color of their edible parts (e.g., green, red/purple, orange/yellow, white, and uncategorized groups). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of specific color groups of FV before diagnosis with OC survival. Potential multiplicative and additive interactions were assessed. Results: 130 patients died during a median follow-up of 37.57 (interquartile: 24.77-50.20) months. We observed the improved survival with a higher pre-diagnosis intake of total FV (HRtertile 3 vs. tertile 1 = 0.63, 95%CI = 0.40-0.99), total vegetables (HRtertile 3 vs. tertile 1 = 0.57, 95%CI = 0.36-0.90), and red/purple FV (HRtertile 3 vs. tertile 1 = 0.52, 95%CI = 0.33-0.82). In addition, we observed significant dose-response relationships for per standard deviation increment between total vegetable intake (HR = 0.79, 95%CI = 0.65-0.96) and red/purple group intake (HR = 0.77, 95%CI = 0.60-0.99) before diagnosis with OC survival. Additionally, pre-diagnosis green FV intake was borderline associated with better OC survival (HRper standard deviation increment = 0.83; 95%CI = 0.69-1.00). In contrast, we did not observe significant associations between pre-diagnosis intake of total fruits, orange/yellow, white, and uncategorized groups and OC survival. Conclusion: Pre-diagnosis FV intake from various color groups, especially the green and red/purple ones, may improve OC survival. Further studies are needed to validate our findings.

Preclinical evaluation and pilot clinical study of [68Ga]Ga-THP-APN09, a novel PD-L1 targeted nanobody radiotracer for rapid one-step radiolabeling and PET imaging.

PURPOSE: Programmed cell death protein-1/ligand-1 (PD-1/L1) blockade has been a breakthrough in the treatment of patients with non-small cell lung cancer (NSCLC), but there is still a lack of effective methods to screen patients. Here we report a novel 68 Ga-labeled nanobody [68 Ga]Ga-THP-APN09 for PET imaging of PD-L1 status in mouse models and a first-in-human study in NSCLC patients. METHODS: [68 Ga]Ga-THP-APN09 was prepared by site-specific radiolabeling, with no further purification. Cell uptake assays were completed in the human lung adenocarcinoma cell line A549, NSCLC cell line H1975 and human PD-L1 gene-transfected A549 cells (A549PD-L1). The imaging to image PD-L1 status and biodistribution were investigated in tumor-bearing mice of these three tumor cell types. The first-in-human clinical translational trial was registered as NCT05156515. The safety, radiation dosimetry, biodistribution, and correlations of tracer uptake with immunohistochemical staining and major pathologic response (MPR) were evaluated in NSCLC patients who underwent adjuvant immunotherapy combined with chemotherapy. RESULTS: Radiosynthesis of [68 Ga]Ga-THP-APN09 was achieved at room temperature and a pH of 6.0-6.5 in 10 min with a high radiochemical yield (> 99%) and 13.9-27.8 GBq/µmol molar activity. The results of the cell uptake study reflected variable levels of surface PD-L1 expression observed by flow cytometry in the order A549PD-L1 > H1975 > A549. In small-animal PET/CT imaging, H1975 and A549PD-L1 tumors were clearly visualized in an 8.3:1 and 2.2:1 ratios over PD-L1-negative A549 tumors. Ex vivo biodistribution studies showed that tumor uptake was consistent with the PET results, with the highest A549PD-L1 being taken up the most (8.20 ± 0.87%ID/g), followed by H1975 (3.69 ± 0.50%ID/g) and A549 (0.90 ± 0.16%ID/g). Nine resectable NSCLC patients were enrolled in the clinical study. Uptake of [68 Ga]Ga-THP-APN09 was mainly observed in the kidneys and spleen, followed by low uptake in bone marrow. The radiation dose is within a reliable range. Tumor uptake was positively correlated with PD-L1 expression TPS (rs = 0.8763, P = 0.019). Tumor uptake of [68 Ga]Ga-THP-APN09 (SUVmax) in MPR patients was higher than that in non-MPR patients (median SUVmax 2.73 vs. 2.10, P = 0.036, determined with Mann-Whitney U-test). CONCLUSION: [68 Ga]Ga-THP-APN09 has the potential to be transformed into a kit-based radiotracer for rapid, simple, one-step, room temperature radiolabeling. The tracer can detect PD-L1 expression levels in tumors, and it may make it possibility to predict the response of PD-1 immunotherapy combined with chemotherapy. Confirmation in a large number of cases is needed. TRIAL REGISTRATION: Clinical Trial (NCT05156515). Registered 12 December 2021.

Transcutaneous electrical acupoint stimulation in adult patients receiving gastrectomy/colorectal resection: A randomized controlled trial.

BACKGROUND: Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery. The effects of transcutaneous electrical acupoint stimulation (TEAS) remain unclear. AIM: To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection. METHODS: Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive: (1) TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery, plus two 30-min daily sessions for 3 consecutive days after surgery (perioperative TEAS group); (2) Preoperative and intraoperative TEAS only; (3) Preoperative and postoperative TEAS only; or (4) Sham stimulation. The primary outcome was the time from the end of surgery to the first bowel sound. RESULTS: In total, 441 patients were randomized; 405 patients (58.4 ± 10.2 years of age; 247 males) received the planned surgery. The time to the first bowel sounds did not differ among the four groups (P = 0.90; log-rank test). On postoperative day 1, the rest pain scores differed significantly among the four groups (P = 0.04; Kruskal-Wallis test). Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group (1.4 ± 1.2) than in the sham stimulation group (1.7 ± 1.1; P = 0.04). Surgical complications did not differ among the four groups. CONCLUSION: TEAS provided analgesic effects in adult patients undergoing major abdominal surgery, and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients.

Abdominal Ultrasonography After Transrectal Filling With Contrast Agents in Colorectal Cancer With Severely Stenotic Lesions.

OBJECTIVE: Abdominal ultrasonography after transrectal filling with contrast agent (AU-TFCA) was retrospectively evaluated with respect to determination of T stage and lesion length in patients with colorectal cancer (CRC) who had previously failed colonoscopy because of severe intestinal stenosis. METHODS: The population comprised 83 patients with CRC with intestinal stenosis and previously failed colonoscopy who underwent AU-TFCA, and in addition contrast-enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI), 2 wk before surgery. The diagnostic performance of AU-TFCA and CECT/MRI was evaluated relative to the post-operative pathological results (PPRs) by paired sample t-test, receiver operator characteristic (ROC) curve, Pearson's χ2-test and κ and intraclass correlation coefficients. RESULTS: The T staging identified via AU-TFCA, but not CECT/MRI, was relatively consistent with that of the PPRs (linearly weighted κ coefficient: 0.558, p < 0.001, and linearly weighted κ coefficient: 0.237, p < 0.001, respectively). The overall diagnostic accuracy of T staging based on AU-TFCA (83.1%) was significantly higher than that based on CECT/MRI (50.6%). Regarding lesion length, the results of AU-TFCA and PPRs were comparable (t = 1.852, p = 0.068), but those of CECT/MRI and PPRs were significantly different (t = 8.450, p < 0.001). CONCLUSION: AU-TFCA is effective in evaluation of lesion length and T stage in patients with severely stenotic CRC lesions who previously failed colonoscopy. The diagnostic accuracy of AU-TFCA is significantly better compared with that of CECT/MRI.