Respiratory physiological mechanism of two types of equal-intensity inspiratory muscle training in stable patients with chronic obstructive pulmonary disease.

PURPOSE: This study aimed to investigate the respiratory physiological changes resulting from short-term inspiratory resistance training (R-IMT) and inspiratory threshold training (T-IMT) in patients with chronic obstructive pulmonary disease (COPD) and to compare the mechanisms of the two training methods. PATIENTS AND METHODS: A total of 75 stable patients with COPD combined with inspiratory muscle weakness were randomly allocated to three groups: R-IMT (n = 26), T-IMT (n = 24), and control (n = 25). Before and after 8 weeks of inspiratory muscle training(IMT), cardiopulmonary exercise tests were conducted to assess respiratory patterns, respiratory central drive, exercise tolerance, and ventilation efficiency. RESULTS: After 8 weeks of IMT, Inspiratory muscle strength, represented by MIP (maximum inspiratory mouth pressure) and exercise capacity increased during exercise in both IMT groups (P < 0.05). In the R-IMT group, inspiratory time (Ti) prolonged (P < 0.05), tidal volume (Vt) increased (P < 0.05), ventilation efficiency (represented by ventilation-center coupling) increased (P < 0.05) during exercise. Conversely, the T-IMT group did not exhibit any of these changes after IMT (P > 0.05). CONCLUSION: In summary, the improvement in exercise tolerance was associated with an increase in inspiratory muscle reserve in both R-IMT and T-IMT. However, only R-IMT was associated with deeper and slower breathing, as well as improved ventilation efficiency.

Tumor micro-environment induced TRAIL secretion from engineered macrophages for anti-tumor therapy.

The high plasticity and long-term persistency make macrophages excellent vehicles for delivering anti-tumor cytokines. Macrophage delivery of chemokines and cytokines shows potential in tumor therapy. TRAIL, a promising anti-tumor cytokine, induces apoptosis in tumor cells with low toxicity to normal cells. However, its off-target toxicity and limited stability have limited its clinical progress. Here, we engineered macrophages with Mono-TRAIL and Tri-TRAIL and found that Tri-TRAIL had higher cytotoxic activity against tumor cells than Mono-TRAIL in vitro. To target the tumor microenvironment (TME), we generated macrophages secreting trimeric TRAIL (Tri-TRAIL-iM) induced by the TME-specific promoter Arg1. The Tri-TRAIL-iM cells displayed high specific activatable activity in cell-based co-culture assay and tumor-baring mice models. In addition, we demonstrated that compared to macrophages over-expressing TRAIL under a non-inducible promoter, Tri-TRAIL-iM could more effectively induce apoptosis in cancer cells, inhibit tumor growth, and reduce systemic side effects. This strategy of inducing TRAIL delivery holds great potential for cancer therapy. It is promising to be combined with other engineering methods to maximize the therapeutic effects of solid tumors.

Prokaryotic Expression and Functional Verification of Antimicrobial Peptide LRGG.

The antimicrobial peptide LRGG (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LRGG and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LRGG, and the resulting corresponding fusion protein GFP-LRGG was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LRGG was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LRGG displays a broad-spectrum antibacterial effect on Gram-negative bacteria, and its minimum inhibitory activity (MIC) against Escherichia coli can reach 2 µg/mL. Compared to the chemically synthesized LRGG, the prokaryotic-expressed LRGG exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LRGG showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a Galleria mellonella infection model. The mechanism by which LRGG causes bacterial death was found to be the disruption of the Gram-negative cell membrane.

GPC3-targeted CAR-M cells exhibit potent antitumor activity against hepatocellular carcinoma.

Chimeric antigen receptor (CAR)-modified macrophages are a promising treatment for solid tumor. So far the potential effects of CAR-M cell therapy have rarely been investigated in hepatocellular carcinoma (HCC). Glypican-3 (GPC3) is a biomarker for a variety of malignancies, including liver cancer, which is not expressed in most adult tissues. Thus, it is an ideal target for the treatment of HCC. In this study, we engineered mouse macrophage cells with CAR targeting GPC3 and explored its therapeutic potential in HCC. First, we generated a chimeric adenoviral vector (Ad5f35) delivering an anti-GPC3 CAR, Ad5f35-anti-GPC3-CAR, which using the CAR construct containing the scFv targeting GPC3 and CD3ζ intracellular domain. Phagocytosis and killing effect indicated that macrophages transduced with Ad5f35-anti-GPC3-CAR (GPC3 CAR-Ms) exhibited antigen-specific phagocytosis and tumor cell clearance in vitro, and GPC3 CAR-Ms showed significant tumor-killing effects and promoted expression of pro-inflammatory (M1) cytokines and chemokines. In 3D NACs-origami spheroid model of HCC, CAR-Ms were further demonstrated to have a significant tumor killing effect. Together, our study provides a new strategy for the treatment of HCC through CAR-M cells targeting GPC3, which provides a basis for the research and treatment of hepatocellular carcinoma.

Ultrasonic-assisted extraction of a low molecular weight polysaccharide from Nostoc commune Vaucher and its structural characterization and immunomodulatory activity.

In the current study, a novel crude polysaccharide (cNCEP) was extracted from N. commune Vaucher utilizing ultrasonic-assisted extraction (UAE) with 60 % ethanol, employing response surface methodology. The optimal yield of cNCEP was determined to be 8.07 ± 0.08 mg/g, achieved through ultrasonic-assisted extraction under the conditions of a material-to-liquid ratio of 1:22, temperature of 56 °C, power of 570 W, and duration of 147 min. Subsequent purification of NCEP via Sephadex G75 resulted in a novel polysaccharide with a molecular weight of 20.466 kDa. NCEP exhibited significant scavenging activites against DPPH and hydroxyl radicals, as well as notable in vitro immunomodulatory properties. Furthermore, the mechanisms underlying the immunomodulatory effects of NCEP, involving enhancement of immunity, were investigated, revealing potential regulation of MAPK and TLR4-IRF7-NF-κB signaling pathways through RNA-Seq and Western blot analyses. These findings highlight the promising potential of NCEP as an organic immunomodulatory agent and functional food ingredient.

Putative Risk Biomarkers of Bipolar Disorder in At-risk Youth.

Bipolar disorder is a highly heritable and functionally impairing disease. The recognition and intervention of BD especially that characterized by early onset remains challenging. Risk biomarkers for predicting BD transition among at-risk youth may improve disease prognosis. We reviewed the more recent clinical studies to find possible pre-diagnostic biomarkers in youth at familial or (and) clinical risk of BD. Here we found that putative biomarkers for predicting conversion to BD include findings from multiple sample sources based on different hypotheses. Putative risk biomarkers shown by perspective studies are higher bipolar polygenetic risk scores, epigenetic alterations, elevated immune parameters, front-limbic system deficits, and brain circuit dysfunction associated with emotion and reward processing. Future studies need to enhance machine learning integration, make clinical detection methods more objective, and improve the quality of cohort studies.

The distinct effects of fearful and disgusting scenes on self-relevant face recognition.

Self-face recognition denotes the process by which a person can recognize their own face by distinguishing it from another's face. Although many research studies have explored the inhibition effect of negative information on self-relevant face processing, few researchers have examined whether negative scenes influence self-relevant face processing. Fearful and disgusting scenes are typical negative scenes, but little research to data has examined their discriminative effects on self-relevant face recognition. To investigate these issues, the current study explored the effect of negative scenes on self-relevant face recognition. In Study 1, 44 participants (20 men, 24 women) were asked to judge the orientation of a target face (self-face or friend-face) pictured in a negative or neutral scene, whereas 40 participants (19 men, 21 women) were asked to complete the same task in a fearful, disgusting, or neutral scene in Study 2. The results showed that negative scenes inhibited the speed of recognizing self-faces. Furthermore, the above effect of negative scenes on self-relevant face recognition occurred with fearful rather than disgusting scenes. Our findings suggest the distinct effects of fearful scenes and disgusting scenes on self-relevant face processing, which may be associated with the automatic attentional capture to negative scenes (especially fearful scenes) and the tendency to escape self-awareness.

Genipin improves obesity through promoting bile secretion and changing bile acids composition in diet-induced obese rats.

OBJECTIVES: Bile acids (BAs), as signaling molecules to regulate metabolism, have received considerable attention. Genipin is an iridoid compound extracted from Fructus Gradeniae, which has been shown to relieve adiposity and metabolic syndrome. Here, we investigated the mechanism of genipin counteracting obesity and its relationship with BAs signals in diet-induced obese (DIO) rats. METHODS: The DIO rats were received intraperitoneal injections of genipin for 10 days. The body weight, visceral fat, lipid metabolism in the liver, thermogenic genes expressions in brown fat, BAs metabolism and signals, and key enzymes for BAs synthesis were determined. KEY FINDINGS: Genipin inhibited fat synthesis and promoted lipolysis in the liver, and upregulated thermogenic gene expressions in brown adipose tissue of DIO rats. Genipin increased bile flow rate and upregulated the expressions of aquaporin 8 and the transporters of BAs in liver. Furthermore, genipin changed BAs composition by promoting alternative pathways and inhibiting classical pathways for BAs synthesis and upregulated the expressions of bile acid receptors synchronously. CONCLUSIONS: These results suggest that genipin ameliorate obesity through BAs-mediated signaling pathways.

Weissella cibaria Relieves Gut Inflammation Caused by Escherichia coli through Inflammation Modulation and Gut Microbiota Regulation.

The emergence of multi-drug-resistant (MDR) pathogens has considerably challenged the development of new drugs. Probiotics that inhibit MDR pathogens offer advantages over chemical antibiotics and drugs due to their increased safety and fewer side effects. This study reported that Weissella cibaria P-8 isolated from pickles showed excellent antibacterial activity against intestinal pathogens, particularly the antibacterial activity against MDR Escherichia coli B2 was the highest. This study showed that the survival rates of W. cibaria P-8 at pH 2.0 and 0.3% bile salt concentration were 72% and 71.56%, respectively, and it still had antibacterial activity under pepsin, trypsin, protease K, and catalase hydrolysis. Moreover, W. cibaria P-8 inhibits the expression of inflammatory factors interleukin-1ß, tumor necrosis factor-α, and interleukin-6, upregulates the interleukin-10 level, and increases total antioxidant capacity and superoxide dismutase enzyme activity in serum. W. cibaria P-8 also efficiently repairs intestinal damage caused by E. coli infection. The gut microbiota analysis demonstrated that W. cibaria P-8 colonizes the intestine and increases the abundance of some beneficial intestinal microorganisms, particularly Prevotella. In conclusion, W. cibaria P-8 alleviated MDR E. coli-induced intestinal inflammation by regulating inflammatory cytokine and enzyme activity and rebalancing the gut microbiota, which could provide the foundation for subsequent clinical analyses and probiotic product development.

Prognostic analysis of high-flow nasal cannula therapy and non-invasive ventilation in mild to moderate hypoxemia patients and construction of a machine learning model for 48-h intubation prediction-a retrospective analysis of the MIMIC database.

Background: This study aims to investigate the clinical outcome between high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) therapy in mild to moderate hypoxemic patients on the first ICU day and to develop a predictive model of 48-h intubation. Methods: The study included adult patients from the MIMIC III and IV databases who first initiated HFNC or NIV therapy due to mild to moderate hypoxemia (100 < PaO2/FiO2 ≤ 300). The 48-h and 30-day intubation rates were compared using cross-sectional and survival analysis. Nine machine learning and six ensemble algorithms were deployed to construct the 48-h intubation predictive models, of which the optimal model was determined by its prediction accuracy. The top 10 risk and protective factors were identified using the Shapley interpretation algorithm. Result: A total of 123,042 patients were screened, of which, 673 were from the MIMIC IV database for ventilation therapy comparison (HFNC n = 363, NIV n = 310) and 48-h intubation predictive model construction (training dataset n = 471, internal validation set n = 202) and 408 were from the MIMIC III database for external validation. The NIV group had a lower intubation rate (23.1% vs. 16.1%, p = 0.001), ICU 28-day mortality (18.5% vs. 11.6%, p = 0.014), and in-hospital mortality (19.6% vs. 11.9%, p = 0.007) compared to the HFNC group. Survival analysis showed that the total and 48-h intubation rates were not significantly different. The ensemble AdaBoost decision tree model (internal and external validation set AUROC 0.878, 0.726) had the best predictive accuracy performance. The model Shapley algorithm showed Sequential Organ Failure Assessment (SOFA), acute physiology scores (APSIII), the minimum and maximum lactate value as risk factors for early failure and age, the maximum PaCO2 and PH value, Glasgow Coma Scale (GCS), the minimum PaO2/FiO2 ratio, and PaO2 value as protective factors. Conclusion: NIV was associated with lower intubation rate and ICU 28-day and in-hospital mortality. Further survival analysis reinforced that the effect of NIV on the intubation rate might partly be attributed to the other impact factors. The ensemble AdaBoost decision tree model may assist clinicians in making clinical decisions, and early organ function support to improve patients' SOFA, APSIII, GCS, PaCO2, PaO2, PH, PaO2/FiO2 ratio, and lactate values can reduce the early failure rate and improve patient prognosis.

Primary hyperparathyroidism: predictors of sporadic multi-gland disease.

In this review, we discuss the definition, prevalence, and etiology of sporadic multiglandular disease (MGD), with an emphasis on its preoperative and intraoperative predictors. Primary hyperparathyroidism (PHPT) is the third-most common endocrine disorder, and multiglandular parathyroid disease (MGD) is a cause of PHPT. Hereditary MGD can be definitively diagnosed with detailed family history and genetic testing, whereas sporadic MGD presents a greater challenge in clinical practice, and parathyroidectomy for MGD is associated with a higher risk of surgical failure than single gland disease (SGD). Therefore, it is crucial to be able to predict the presence of sporadic MGD in a timely manner, either preoperatively or intraoperatively. Various predictive methods cannot accurately identify all cases of sporadic MGD, but they can greatly optimize the management of MGD diagnosis and treatment and optimize the cure rate. Future research will urge us to investigate more integrative predictive models as well as increase our understanding of MGD pathogenesis.

'Let's Talk About Children' family focused practice for children of parents with schizophrenia and bipolar disorder: protocol for a randomized controlled trial.

INTRODUCTION: 'Let's Talk About Children' is a brief family focused intervention developed to improve mental health outcomes of children of parents with mental illness (COPMI). This study aims to assess the efficacy of LTC in improving mental health of children of parents with schizophrenia or bipolar disorder in China. METHODS: The planned study is a multicentre parallel group randomized wait-list controlled trial. A total of 400 eligible families with children aged 8 to 18 years will be recruited, 200 each for families with parental schizophrenia or bipolar disorder. The intervention group will receive Let's Talk About Children delivered by a trained therapist, while the control group will receive treatment as usual. The primary outcomes are child mental health measured by the strengths and difficulties questionnaire and parent-child communication measured using the parent-adolescent communication scale. Parental mental health and family functioning are secondary outcomes. This study also plans to explore mediating factors for the effect of Let's Talk About Children on child mental health, as well as conduct a cost-effectiveness analysis on using Let's Talk About Children in China. CONCLUSION: The present study will provide evidence for the efficacy of Let's Talk About Children in families with parental schizophrenia and bipolar disorder in China. In addition, it will evaluate potential mechanisms of action and cost-effectiveness of Let's Talk About Children, providing a basis for future implementation. TRIAL REGISTRATION: ChiCTR2300073904.

Predicting epithelial ovarian cancer prognosis: correlation of posttreatment 18F-fluorodeoxyglucose positron emission tomography-computed tomography metabolic parameters, serum carbohydrate antigen, and human epididymis protein levels with overall survival.

Background: Identifying reliable prognostic indicators can aid in improving patient care. The aim of this study was to establish the association of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) whole-body metabolic parameters, serum carbohydrate antigen 125 (CA125), and human epididymis protein 4 (HE4) with overall survival (OS) in patients with epithelial ovarian cancer (EOC) after surgery combined with platinum-based chemotherapy. Methods: From May 2014 to May 2019, a total of 79 patients with EOC who underwent posttreatment 18F-FDG PET/CT in the First Affiliated Hospital of Chongqing Medical University were included. Clinical data and laboratory indicators were obtained. The whole-body maximum standardized uptake value (WBSUVmax), whole-body metabolic tumor volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) were measured and calculated on 18F-FDG PET/CT. The follow-up was conducted until February 2023, and the endpoint was death from any cause. Pearson correlation analysis, Kaplan-Meier, and Cox proportional regression were used in this study. Results: The PET-positive (PET-P) patients had significantly decreased OS based on either Kaplan-Meier survival analysis (P<0.001) or univariate Cox regression analysis [hazard ratio (HR) =40.177, 95% confidence interval (CI): 2.690-600.134; P=0.007]. "Ln" is a logarithmic transformation with a base of "e" (natural logarithm). LnWBMTV, lnWBTLG, and therapy after PET were independent predictors of OS in a cohort of 63 PET-P patients. The difference in OS between groups sorted by the median WBMTV (4.16; P<0.001) and WBTLG (14.71; P<0.001) was statistically significant. There were statistically significant differences in CA125 and HE4 levels between patients in the PET-P and PET-negative (PET-N) groups (P<0.001). In the PET-P patient cohort, serum HE4 levels were substantially correlated with WBMTV and WBTLG. Kaplan-Meier survival analysis suggested a reduction in OS after treatment in patients with EOC positive for CA125, HE4, and PET (P<0.001). Conclusions: Post-PET/CT treatment strategy, WBMTV, and WBTLG demonstrated significant prognostic utility in predicting posttreatment OS in patients with EOC. Patients who tested positive for both tumor markers CA125 and HE4 and had a positive PET scan demonstrated a significantly poorer prognosis in terms of posttreatment OS.

Altered HCAR3 expression may underlying the blunted niacin responses of the psychiatric disorders and the risk of schizophrenia.

AIM: Blunted niacin response (BNR) was an endophenotype of schizophrenia, but the underlying mechanism remains unclarified. The objective of this study was to verify whether genes associated with BNR pathway constitute the genetic basis and the pathological mechanism of BNR phenotypic psychiatric patients. METHODS: Two independent sample sets consisting of 971 subjects were enrolled in this study. A total of 62 variants were genotyped in the discovery set, then the related variants were verified in the verification set. The published PGC GWAS data were used to validate the associations between the variants and psychiatry disorders. RT-PCR analysis, eQTL data, and Dual-Luciferase Reporter experiment were used to investigate the potential molecular mechanisms of the variants underlying BNR. RESULTS: The results showed that two SNPs, rs56959712 in HCAR2 and rs2454721 in HCAR3 were significantly associated with niacin response. The risk allele T of rs2454721 could affect the niacin responses of psychiatric patients through elevated HCAR3 gene expression. These two genes, especially HCAR3, were significantly associated with the risk of schizophrenia, as identified in this study and verified using the published GWAS data. CONCLUSION: HCAR3 is a novel schizophrenia susceptibility gene which is significantly associated with blunted niacin response in schizophrenia. In-depth investigation of HCAR3 is of great significance for uncovering the pathogenesis and propose new therapeutic targets for psychiatric disorders, especially for the BNR subgroup patients.

Serum levels of folate, vitamin B6, and vitamin B12 are associated with cognitive impairments in depression patients.

INTRODUCTION: Depression is a common mental disorder that endangers physical and mental health. In our study, we aimed to explore whether B vitamins are associated with depression and cognitive dysfunction. METHODS: We enrolled a total of 220 patients with depression and selected 100 controls at the same time. We determined depression and cognitive impairment by assessments. We recorded the basic parameters of the participants and collected blood samples. In addition, we measured serum levels of B vitamins and brain-derived neurotrophic factor (BDNF). RESULTS: We found significant differences in the duration of depression, education, and Hamilton Depression Rating Scale scores between the D-NCI and D-CI groups. We also identified the independent risk factors for patients with depression and cognitive dysfunction. Compared with the healthy controls, serum folate, vitamin B6, and vitamin B12 positively correlated with cognitive dysfunction. The patients with depression and cognitive dysfunction had the lowest levels of B vitamins compared with the other two groups. Our results also showed that the levels of serum folate, vitamin B6, and vitamin B12 in the patients with depression had a positive correlation with each other. CONCLUSION: Our results indicate that vitamin B is associated with depression and cognitive dysfunction and is positively associated with cognitive dysfunction.

Identification of circulating miRNA as early diagnostic molecular markers in malignant glioblastoma base on decision tree joint scoring algorithm.

PURPOSE: The lack of clinical markers prevents early diagnosis of glioblastoma (GBM). Many studies have found that circulating microRNAs (miRNAs) can be used as early diagnostic markers of malignant tumours. Therefore, the identification of novel circulating miRNA biomolecular markers could be beneficial to clinicians in the early diagnosis of GBM. METHODS: We developed a decision tree joint scoring algorithm (DTSA), systematically integrating significance analysis of microarray (SAM), Pearson hierarchical clustering, T test, Decision tree and Entropy weight score algorithm, to screen out circulating miRNA molecular markers with high sensitivity and accuracy for early diagnosis of GBM. RESULTS: DTSA was developed and applied for GBM datasets and three circulating miRNA molecular markers were identified, namely, hsa-miR-2278, hsa-miR-555 and hsa-miR-892b. We have found that hsa-miR-2278 and hsa-miR-892b regulate the GBM pathway through target genes, promoting the development of GBM and affecting the survival of patients. DTSA has better classification effect in all data sets than other classification algorithms, and identified miRNAs are better than existing markers of GBM. CONCLUSION: These results suggest that DTSA can effectively identify circulating miRNA, thus contributing to the early diagnosis and personalised treatment of GBM.

The protective effect of Nostoc commune Vauch. polysaccharide on alcohol-induced acute alcoholic liver disease and gut microbiota disturbance in mice.

BACKGROUND: In recent years, the incidence of alcoholic liver disease (ALD) has gradually increased, the development of ALD is attached great attentions. Nostoc commune Vauch. polysaccharide (NCVP) is beneficial to maintain the gut health, but the protective effect of NCVP on the liver has not been reported yet. PURPOSE: To study the protective effect and the underlying mechanisms of NCVP on ALD, a mouse model of acute ALD was established. STUDY DESIGN AND METHODS: We built an acute ALD mouse model and explored the protective effect of NCVP through the detection of cytokines, histological examination, determination of short chain fatty acids, and 16S rRNA analysis of gut microbiota. RESULTS: NCVP had hepatoprotective effects on acute alcohol-induced mice by improving antioxidant capacity, reducing oxidative stress and the serum cytokine levels (IL-1ß, IL-6, and TNF-α). Simultaneously, histopathological changes in liver indicated that NCVP could inhibit local hepatocyte necrosis, cytoplasmic vacuolation and inflammatory cell infiltration induced by alcohol. NCVP also increased the level of total short-chain fatty acids of acute ALD mice. In addition, NCVP could significantly decrease the Firmicutes/Bacteroidetes ratio and the abundance of Patescibacteria, Helicobacter, and Actinomycetes and increase the abundance of Lachospiraceae, Prevotellaceae-UCG-003, Lactobacillaceae, and Desulfovibrio. CONCLUSION: Our study proved that NCVP had in vivo hepatoprotective effect on acute ALD mice and provided scientific evidences that NCVP might be a promising drug candidate for the prevention and treatment of ALD.

Prophylactic antibiotics for preventing ventilator-associated pneumonia: a pairwise and Bayesian network meta-analysis.

BACKGROUND: The role of prophylactic antibiotics in preventing ventilator-associated pneumonia (VAP) in patients undergoing invasive mechanical ventilation (IMV) remains unclear. This network meta-analysis compared the efficacy and safety of antibiotic prophylaxis in preventing VAP in an IMV population in intensive-care units (ICUs). METHODS: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases from inception to December 2021, to identify relevant studies assessing the impact of prophylactic antibiotics on the incidence of VAP, the mortality, and the duration of ICU stays and hospitalization to perform a meta-analysis. RESULTS: Thirteen studies (2144 patients) were included, 12 of which were selected for the primary analysis, which revealed that treatment with prophylactic antibiotics resulted in a lower VAP rate compared with control groups [risk ratio (RR) = 0.62]. Bayesian network meta-analysis indicated that aerosolized tobramycin and intravenous ampicillin-sulbactam presented the greatest likelihood being the most efficient regimen for reducing VAP. CONCLUSIONS: Antibiotic prophylaxis may reduce the incidence of VAP, but not the mortality, for adult patients undergoing IMV in ICUs. Tobramycin via nebulization and ampicillin-sulbactam via intravenous administration presented the greatest likelihood of being the most efficient regimen for preventing VAP. However, well-designed randomized studies are warranted before definite recommendations can be made.

The value of Gallium-68 prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) PET/CT and 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET/CT in the detection of thyroid cancer lesions: a prospective head-to-head comparison.

OBJECTIVE: Thyroid cancer is increasing in incidence. Prostate-specific membrane antigen (PSMA) targeted radionuclide imaging and treatment demonstrated remarkable value in prostate cancer patients. Studies have shown that PSMA is also expressed in thyroid cancer. Our purpose is to evaluate the clinical usefulness of [68Ga]Ga-PSMA-11 PET/CT for the diagnosis of thyroid cancer. METHODS: We enrolled 23 DTC and 17 RAIR-DTC patients prospectively. All patients underwent [68Ga]Ga-PSMA-11 PET/CT and 2-[18F]FDG PET/CT. PSMA expression was determined by immunohistochemistry on histological samples of lymphatic metastasis of 12 patients. We compared the detection rates and semi-quantitative parameters between [68Ga]Ga-PSMA-11PET/CT and 2-[18F]FDG PET/CT. RESULTS: A total of 72 lesions were detected. Detection rates of DTC and RAIR-DTC by [68Ga]Ga-PSMA-11 PET/CT were lower than those by 2-[18F]FDG PET/CT (60.00% vs 90.00%, p = 0.004; 59.38% vs 96.88%). Compared with DTC, RAIR-DTC had higher semi-quantitative parameters of 2-[18F]FDG PET/CT. There was no significant difference in semi-quantitative parameters of [68Ga]Ga-PSMA-11 PET/CT between DTC and RAIR-DTC. Immunohistochemistry showed a significantly higher PSMA expression for RAIR-DTC than for DTC. However, there was no significant correlation between PSMA expression and SUVmax on 68Ga-PSMA [68Ga]Ga-PSMA-11 PET/CT. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT can detect thyroid cancer metastases but its detection rate was lower than that of 2-[18F]FDG PET/CT. There was a difference in PSMA expression levels between DTC and RAIR-DTC, but the difference was not reflected on [68Ga]Ga-PSMA-11 PET/CT. ADVANCES IN KNOWLEDGE: [68Ga]Ga-PSMA-11 PET/CT has potential value in the diagnosis of thyroid cancer. [68Ga]Ga-PSMA-11 PET/CT could screen out patients who may benefit from PSMA targeted radionuclide therapy.