Discovery of a Long Half-Life AURKA Inhibitor to Treat MYC-Amplified Solid Tumors as a Monotherapy and in Combination with Everolimus.

Aurora kinase inhibitors, such as alisertib, can destabilize MYC-family oncoproteins and have demonstrated compelling antitumor efficacy. In this study, we report 6K465, a novel pyrimidine-based Aurora A inhibitor, that reduces levels of c-MYC and N-MYC oncoproteins more potently than alisertib. In an analysis of the antiproliferative effect of 6K465, the sensitivities of small cell lung cancer (SCLC) and breast cancer cell lines to 6K465 were strongly associated with the protein levels of c-MYC and/or N-MYC. We also report DBPR728, an acyl-based prodrug of 6K465 bearing fewer hydrogen-bond donors, that exhibited 10-fold improved oral bioavailability. DBPR728 induced durable tumor regression of c-MYC- and/or N-MYC-overexpressing xenografts including SCLC, triple-negative breast cancer, hepatocellular carcinoma, and medulloblastoma using a 5-on-2-off or once-a-week dosing regimen on a 21-day cycle. A single oral dose of DBPR728 at 300 mg/kg induced c-MYC reduction and cell apoptosis in the tumor xenografts for more than 7 days. The inhibitory effect of DBPR728 at a reduced dosing frequency was attributed to its uniquely high tumor/plasma ratio (3.6-fold within 7 days) and the long tumor half-life of active moiety 6K465. Furthermore, DBPR728 was found to synergize with the mTOR inhibitor everolimus to suppress c-MYC- or N-MYC-driven SCLC. Collectively, these results suggest DBPR728 has the potential to treat cancers overexpressing c-MYC and/or N-MYC.

Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES: We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS: The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS: The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS: Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.

Aurantimonas marianensis sp. nov., isolated from deep-sea sediment of the Mariana Trench.

A novel strain, designated as LRZ36T, was isolated from deep-sea sediment (from a depth of 5400 m) from the Mariana Trench. Cells of this strain are rod-shaped, Gram-stain-negative, strictly aerobic and non-motile. Phylogenetic analysis of LRZ36T based on 16S rRNA gene sequences revealed a lineage in the family Aurantimonadaceae but distinct from the most closely related species Aurantimonas marina CGMCC 1.17725T, 'Aurantimonas litoralis' KCTC 12094 and Aurantimonas coralicida DSM 14790T with sequence identities of 99.4 %, 98.0 and 97.9 %, respectively. The genome of LRZ36T was 3.8 Mbp in size with a DNA G+C content of 64.8 %, containing 3623 predicted coding genes. LRZ36T showed average nucleotide identity values of 89.8 %, 78.7 and 78.5 % and digital DNA-DNA hybridization values of 38.9 %, 21.7 and 21.6 % with A. marina CGMCC 1.17725T, 'A. litoralis' KCTC 12094 and A. coralicida DSM 14790T, respectively. The major respiratory quinone was ubiquinone-10 (Q-10), and the predominant fatty acids were C18 : 1ω7c (74.4 %) and C16 : 0 (12.1 %). The polar lipids in LRZ36T are diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, phosphatidylinositol mannoside, an unidentified aminophospholipid, three unidentified lipids, three unidentified phospholipids and two unidentified aminolipids. On the basis of genotypic and phenotypic evidence, LRZ36T represents a novel species of the genus Aurantimonas, for which the name Aurantimonas marianensis sp. nov. is proposed. The type strain is LRZ36T (= KCTC 92065T = GDMCC 1.2985T=MCCC 1K07227T).

Recent Advances in Discovery, Bioengineering, and Bioactivity-Evaluation of Ribosomally Synthesized and Post-translationally Modified Peptides.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are of increasing interest in natural products as well as drug discovery. This empowers not only the unique chemical structures and topologies in natural products but also the excellent bioactivities such as antibacteria, antifungi, antiviruses, and so on. Advances in genomics, bioinformatics, and chemical analytics have promoted the exponential increase of RiPPs as well as the evaluation of biological activities thereof. Furthermore, benefiting from their relatively simple and conserved biosynthetic logic, RiPPs are prone to be engineered to obtain diverse analogues that exhibit distinct physiological activities and are difficult to synthesize. This Review aims to systematically address the variety of biological activities and/or the mode of mechanisms of novel RiPPs discovered in the past decade, albeit the characteristics of selective structures and biosynthetic mechanisms are briefly covered as well. Almost one-half of the cases are involved in anti-Gram-positive bacteria. Meanwhile, an increasing number of RiPPs related to anti-Gram-negative bacteria, antitumor, antivirus, etc., are also discussed in detail. Last but not least, we sum up some disciplines of the RiPPs' biological activities to guide genome mining as well as drug discovery and optimization in the future.

Engineered Biosynthesis of Complex Disorazol Polyketides in a Streamlined Burkholderia thailandensis.

Engineering the biosynthetic pathways of complex natural products is a significant approach to obtain derivatives with improved properties. Here, we constructed a streamlined engineered biosynthesis system of myxobacterium-derived complex polyketide disorazol in a heterologous host, Burkholderia thailandensis E264. Inactivation of dehydratase domains in the disorazol biosynthetic pathway led to the production of two hydroxylated derivatives. Module deletion allowed the generation of an unnatural derivative with a truncated macrolactone ring, and the ACP-KS linker was the optimal fusion region for module deletion in this trans-AT polyketide synthase. These disorazol derivatives showed different activities against human cancer cell lines ranging from the nanomolar to micromolar level, suggesting the primary structure-activity relationship. The PKS engineering enables structural derivatization of disorazol, facilitating the in-depth engineered biosynthesis of polyketides.

Argenteolides A and B, Glycosylated Polyketide-Peptide Hybrid Macrolides from an Actinomycete Streptomyces argenteolus.

Two novel glycosylated polyketide-peptide hybrid macrolides, argenteolides A (1) and B (2), were isolated from an actinomycete Streptomyces argenteolus. Argenteolide A (1) contains a unique 5/5/5 tricyclic system in a 20-membered macrocycle. Their structures were elucidated by extensive spectroscopic analysis, and their stereochemical configurations were established through the application of chemical derivatization, J-based configuration analysis, DP4+ calculation, and electronic circular dichroism calculation. The analysis of the genome sequence revealed a plausible biosynthesis mechanism, and isotope-labeled feeding studies suggested their biogenetic origins. Argenteolides A and B exhibited moderate cytotoxicities against A549, p388, and Hela human carcinoma cell lines as well as antibacterial activities against Staphylococcus aureus and Escherichia coli ATCC25922.

[New advances in the diagnosis and treatment of biliary atresia]. / 胆道闭锁的诊断及治疗新进展.

The diagnosis of biliary atresia (BA) is mainly based on clinical manifestations, screening, and related biochemistry tests. In recent years, the development of blood biomarkers and the improvement in ultrasound examination have made it possible for BA to be diagnosed at a younger age. In particular, matrix metalloproteinase-7 shows high sensitivity and specificity and has a higher diagnostic efficiency than existing biochemical parameters, thereby holding a promise for clinical application. Sound touch elastography can increase the diagnostic efficiency for BA in terms of diagnosis and prognostic evaluation. Surgery is still the only method for the treatment of BA at present, with the preferred surgical treatment regimen of Kasai portoenterostomy combined with pharmacotherapies for alleviating infection and inflammation, and the patients who fail Kasai portoenterostomy or have liver dysfunction may require liver transplantation to save their lives. Therefore, the current research on BA should focus on the biomarkers for early diagnosis, specifically targeted drugs, and drugs for preventing progressive liver fibrosis. This article reviews the current diagnosis and treatment methods for BA and discusses the potential research directions.

Multi-disciplinary treatment of maxillofacial skeletal deformities by orthognathic surgery combined with periodontal phenotype modification: A case report.

BACKGROUND: Maxillofacial deformities are skeletal discrepancies that cause occlusal, functional, and esthetic problems, and are managed by multi-disciplinary treatment, including careful orthodontic, surgical, and periodontal evaluations. However, thin periodontal phenotype is often overlooked although it affects the therapeutic outcome. Gingival augmentation and periodontal accelerated osteogenic orthodontics (PAOO) can effectively modify the periodontal phenotype and improve treatment outcome. We describe the multi-disciplinary approaches used to manage a case of skeletal Class III malocclusion and facial asymmetry, with thin periodontal phenotype limiting the correction of deformity. CASE SUMMARY: A patient with facial asymmetry and weakness in chewing had been treated with orthodontic camouflage, but the treatment outcome was not satisfactory. After examination, gingiva augmentation and PAOO were performed to increase the volume of both the gingiva and the alveolar bone to allow further tooth movement. After orthodontic decompensation, double-jaw surgery was performed to reposition the maxilla-mandibular complex. Finally, implant placement and chin molding were performed to restore the dentition and to improve the skeletal profile. The appearance and function were significantly improved, and the periodontal tissue remained healthy and stable. CONCLUSION: In patients with dentofacial deformities and a thin periodontal phenotype, multi-disciplinary treatment that includes PAOO could be effective, and could improve both the quality and safety of orthodontic-orthognathic therapy.

Antioxidant Capacities and Enzymatic Inhibitory Effects of Different Solvent Fractions and Major Flavones from Celery Seeds Produced in Different Geographic Areas in China.

To extend the application of celery (Apium graveolens L.) seeds, the antioxidant and enzymatic inhibitory activities of different fractions and their main flavones were investigated. The n-butanol fractions possessed the highest total phenolic content (TPC) and total flavonoid content (TFC) values. The n-butanol fractions from Northeast China samples exhibited the strongest free radical scavenging (DPPH IC50 = 20.27 µg/mL, ABTS IC50 = 15.11 µg/mL) and ferric reducing antioxidant power (FRAP 547.93 mg trolox (TE)/g) capacity, while those collected from Hubei China showed the optimal cupric reducing antioxidant capacity (CUPRAC) values (465.78 mg TE/g). In addition, the dichloromethane fractions from Jiangsu samples displayed a maximum Fe2+ chelating capacity (20.81 mg ethylene diamine tetraacetic acid (EDTA)/g). Enzyme level experiments indicated polyphenolic compounds might be the main hypoglycemic active components. Subsequently, the enzyme inhibitory activity of nine main flavones was evaluated. Chrysoeriol-7-O-glucoside showed better α-glucosidase inhibitory activity than others. However, apigenin showed the best inhibitory effect on α-amylases, while the presence of glycosides would reduce its inhibitory effect. This study is the first scientific report on the enzymatic inhibitory activity, molecular docking, and antioxidant capacity of celery seed constituents, providing a basis for treating or preventing oxidative stress-related diseases and hyperglycemia.

Dexmedetomidine Improves Non-rapid Eye Movement Stage 2 Sleep in Children in the Intensive Care Unit on the First Night After Laparoscopic Surgery.

Background: Previous studies have reported that children who were admitted to the ICU experienced a significant decrease in sleep quality compared to home. We investigated the effects of dexmedetomidine as an adjunct to sufentanil on the sleep in children admitted to the ICU on the first night after major surgery. Methods: This is a prospective study From January to February 2022. Clinical trial number: ChiCTR2200055768, http://www.chictr.org.cn. Fifty-four children aged 1-10 years old children undergoing major laparoscopic surgery were recruited and randomly assigned to either the DEX group, in which intravenous dexmedetomidine (0.3 ug/kg/h) and sufentanil (0.04 ug/kg/h) were continuously infused intravenously for post-operative analgesia; or the SUF group, in which only sufentanil (0.04 ug/kg/h) was continuously infused. Patients were monitored with polysomnography (PSG) on the first night after surgery for 12 h. PSG, sleep architecture, physiologic variables and any types of side effects related to anesthesia and analgesia were recorded. The differences between the two groups were assessed using the chi-square and Wilcoxon rank-sum tests. Results: Fifty-four children completed data collection, of which thirty-four were 1-6 years old and twenty were aged >6 years. Compared to the SUF group, subjects in the DEX group aged 1-6 years displayed increased stage 2 sleep duration (P = 0.02) and light sleep duration (P = 0.02). Subjects aged >6 years in the DEX group also displayed increased stage 2 sleep duration (P = 0.035) and light sleep duration (P = 0.018), but decreased REM sleep percentage (P = 0). Additionally, the heart rate and blood pressure results differed between age groups, with the heart rates of subjects aged >6 years in DEX group decreasing at most time points compared to SUF group (P < 0.05). Conclusion: Dexmedetomidine prolonged N2 sleep and light sleep duration in the pediatric ICU after surgery but had different effects on the heart rate and blood pressure of subjects in different age groups.

Plasma metabolomics in the perioperative period of defect repair in patients with pulmonary arterial hypertension associated with congenital heart disease.

The quality of life and survival rates of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) have been greatly improved by defect-repair surgery and personalized treatments. However, those who survive surgery may remain at risk of persistent PAH, the prognosis may be considerably worse than those unoperated. Dynamic monitoring of clinical measures during the perioperative period of shunt correction is therefore indispensable and of great value. In this study, we explored the plasma-metabolite profiling in 13 patients with CHD-PAH during the perioperative period of defect repair. Plasma was harvested at four time points: prior to cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. Untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. A total of 193 distinguishing metabolites were determined at different time points, enriched in pathways such as oxidation of branched-chain fatty acids. We found that 17 metabolite alterations were significantly correlated with the reduction in mean pulmonary arterial pressure (MPAP) at T48 versus Pre. Gradients in diastolic pulmonary arterial pressure (DPAP), bicarbonate in radial artery (aHCO3), bicarbonate in superior vena cava (svcHCO3), and the partial pressure of dissolved CO2 gas in radial artery (aPCO2) were positively correlated with MPAP gradient. Notably, these clinical-measure gradients were correlated with alterations in shunt-correction-associated metabolites. In total, 12 out of 17 identified metabolites in response to defect repair were increased at both T24 and T48 (all P < 0.05, except propionylcarnitine with P < 0.05 at T24). In contrast, galactinol dihydrate, guanosine monophosphate, and hydroxyphenylacetylglycine tended to decline at T24 and T48 (only galactinol dihydrate with P < 0.05 at T48). In conclusion, 17 metabolites that respond to shunt correction could be used as suitable noninvasive markers, and clinical measures, including DPAP, aHCO3, svcHCO3, and aPCO2, would be of great value in disease monitoring and evaluating future therapeutic interventions.

Utility of cooling patches to prevent hand-foot syndrome caused by pegylated liposomal doxorubicin in breast cancer patients.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands, producing toxic free radicals and oxidative damage, resulting in hand-foot syndrome (HFS). Regional cooling can induce vasoconstriction to reduce the release of drugs in the limbs and reduce the accumulation of drugs in sweat glands; thus, decreasing the incidence and severity of HFS. AIM: To study the efficacy of cooling patches to prevent HFS caused by PLD in the short-term. METHODS: This is a retrospective cohort study. Female breast cancer patients (n = 101) who were treated with PLD in two breast wards at our department from February 2020 to February 2021 were enrolled in the study and were randomly divided into the cooling group (51 patients) and the control group (50 patients). Patients in the control group only received routine care, while the patients in the cooling group applied cooling patches, based on routine care, to the palm and back of the hands 15 min before chemotherapy infusion for 10 h. All patients took a corresponding dose of dexamethasone orally one day before chemotherapy, on the day of chemotherapy, and one day after chemotherapy. SPSS23.0 version was used to analyze the data in this study. The occurrence and severity of HFS was analyzed by the Mann-Whitney U test, and scores were analyzed by the Student's t test or Wilcoxon rank-sum test. A P value < 0.05 was regarded as statistically significant. RESULTS: In this study, neither group of patients developed Grade 3 HFS. In the control group, the incidence of Grade 1 HFS and Grade 2 HFS was 38% and 2%, respectively. However, in the cooling group, only one person developed Grade 1 HFS (2%), and none of the patients developed Grade 2 HFS. These findings showed that cooling patches can effectively reduce the frequency and severity of HFS (P < 0.0001) in the short-term. Before the fourth chemotherapy cycle, although general self-efficacy scale scores in the cooling group were low, they were still significantly higher than those in the control group (17.22 ± 5.16 vs 19.63 ± 6.42, P = 0.041). Compared with the control group, the mean Hand-Foot Skin Reaction and Quality of Life Questionnaire score in the cooling group was significantly lower (18.08 ± 7.01 vs 14.20 ± 7.39, P = 0.008). CONCLUSION: Cooling patches can effectively reduce the frequency and severity of HFS caused by PLD in the short-term. In addition, it may help delay the decline in patients' self-efficacy.

Venom of the Annulated Sea Snake Hydrophis cyanocinctus: A Biochemically Simple but Genetically Complex Weapon.

Given that the venom system in sea snakes has a role in enhancing their secondary adaption to the marine environment, it follows that elucidating the diversity and function of venom toxins will help to understand the adaptive radiation of sea snakes. We performed proteomic and de novo NGS analyses to explore the diversity of venom toxins in the annulated sea snake (Hydrophis cyanocinctus) and estimated the adaptive molecular evolution of the toxin-coding unigenes and the toxicity of the major components. We found three-finger toxins (3-FTxs), phospholipase A2 (PLA2) and cysteine-rich secretory protein (CRISP) in the venom proteome and 59 toxin-coding unigenes belonging to 24 protein families in the venom-gland transcriptome; 3-FTx and PLA2 were the most abundant families. Nearly half of the toxin-coding unigenes had undergone positive selection. The short- (i.p. 0.09 µg/g) and long-chain neurotoxin (i.p. 0.14 µg/g) presented fairly high toxicity, whereas both basic and acidic PLA2s expressed low toxicity. The toxicity of H. cyanocinctus venom was largely determined by the 3-FTxs. Our data show the venom is used by H. cyanocinctus as a biochemically simple but genetically complex weapon and venom evolution in H. cyanocinctus is presumably driven by natural selection to deal with fast-moving prey and enemies in the marine environment.

Influential factors and prediction model of mammographic density among Chinese women.

ABSTRACT: To evaluate the characteristics and influential factors of breast density and establish a new model for predicting breast density in Chinese women, so as to provide a basis for breast cancer screening techniques and duration.A total of 9412 women who were selected from screening and intervention techniques for Breast and Cervical Cancer Project between April 2018 and June 2019 were enrolled in this study. Selected women were randomly assigned to training and validation sets in a ratio of 1:1. Univariable and multivariable analyzes were performed by Logistic regression model. Nomogram was generated according to the results of multivariate analysis. Calibration, area under curve (AUC) and akaike information criterion (AIC) were used for measuring accuracy of prediction model.There were 377 (4.0%) women in breast imaging reporting and data system (BI-RADS) A category, 2164 (23.0%) in B category, 5749 (61.1%) in C category and 1122 (11.9%) in D category. Age duration, educational attainment, history of benign diseases, breastfeeding history, menopausal status, and body mass index (BMI) were imputed as independent influential factors for breast density in multivariable analysis. The AUC and AIC of training and validation set were 0.7158, 0.7139, and 4915.378, 4998.665, respectively.This study indicated that age, educational attainment, history of benign breast disease, breastfeeding history, menopausal status and BMI were independent influential factors of breast density. Nomogram generated on the basis of these factors could relatively predict breast density, which in turn could be used for recommendations of breast cancer screening techniques.

Setd4 controlled quiescent c-Kit+ cells contribute to cardiac neovascularization of capillaries beyond activation.

Blood vessels in the adult mammal exist in a highly organized and stable state. In the ischemic heart, limited expansion capacity of the myocardial vascular bed cannot satisfy demands for oxygen supply and the myocardium eventually undergoes irreversible damage. The predominant contribution of endogenous c-Kit+ cells is understood to be in the development and homeostasis of cardiac endothelial cells, which suggests potential for their targeting in treatments for cardiac ischemic injury. Quiescent cells in other tissues are known to contribute to the long-term maintenance of a cell pool, preserve proliferation capacity and, upon activation, facilitate tissue homeostasis and regeneration in response to tissue injury. Here, we present evidence of a Setd4-expressing quiescent c-Kit+ cell population in the adult mouse heart originating from embryonic stages. Conditional knock-out of Setd4 in c-Kit-CreERT2;Setd4f/f;Rosa26TdTomato mice induced an increase in vascular endothelial cells of capillaries in both neonatal and adult mice. We show that Setd4 regulates quiescence of c-Kit+ cells by the PI3K-Akt-mTOR signaling pathway via H4K20me3 catalysis. In myocardial infarction injured mice, Setd4 knock-out resulted in attenuated cardiomyocyte apoptosis, decreased infarction size and improved cardiac function. Lineage tracing in Setd4-Cre;Rosa26mT/mG mice showed that Setd4+ cells contribute to each cardiac lineage. Overall, Setd4 epigenetically controls c-Kit+ cell quiescence in the adult heart by facilitating heterochromatin formation via H4K20me3. Beyond activation, endogenous quiescent c-Kit+ cells were able to improve cardiac function in myocardial infarction injured mice via the neovascularization of capillaries.

Discovery and Synthesis of a Pyrimidine-Based Aurora Kinase Inhibitor to Reduce Levels of MYC Oncoproteins.

The A-type Aurora kinase is upregulated in many human cancers, and it stabilizes MYC-family oncoproteins, which have long been considered an undruggable target. Here, we describe the design and synthesis of a series of pyrimidine-based derivatives able to inhibit Aurora A kinase activity and reduce levels of cMYC and MYCN. Through structure-based drug design of a small molecule that induces the DFG-out conformation of Aurora A kinase, lead compound 13 was identified, which potently (IC50 < 200 nM) inhibited the proliferation of high-MYC expressing small-cell lung cancer (SCLC) cell lines. Pharmacokinetic optimization of 13 by prodrug strategies resulted in orally bioavailable 25, which demonstrated an 8-fold higher oral AUC (F = 62.3%). Pharmacodynamic studies of 25 showed it to effectively reduce cMYC protein levels, leading to >80% tumor regression of NCI-H446 SCLC xenograft tumors in mice. These results support the potential of 25 for the treatment of MYC-amplified cancers including SCLC.

The characteristic computed tomography findings of pulmonary B-cell non-Hodgkin's lymphoma and their role in predicting patient survival.

BACKGROUND: To assess the value of characteristic computed tomography (CT) findings in predicting the survival of patients with pulmonary B-cell non-Hodgkin's lymphoma (NHL). METHODS: Eighty-four patients who were histopathologically confirmed with pulmonary B-cell NHL between 2004 and 2018 were retrospectively enrolled. All patients underwent chest CT scan at the time of initial diagnosis in our hospital. Characteristic CT findings and clinicopathological features of the patients were analyzed, and Cox regression models were used to determine the relationship of CT findings with overall survival (OS) and progression-free survival (PFS). RESULTS: Air bronchogram occurred more frequently in patients with early-stage disease, primary pulmonary lymphoma (PPL) and the indolent histological type of lymphoma than in patients with advanced-stage disease, secondary pulmonary lymphoma (SPL), and the aggressive histological type (all P<0.05). The halo sign was observed most in the SPL group (19/48, 40%; P=0.004), while the presence of cross-lobe sign was higher in patients with PPL (13/36, 36%; P=0.010). Pleural involvement and hilar/mediastinal lymphadenopathy were observed more in patients with SPL and the aggressive histological type (33/48 and 27/48; 31/46 and 26/46, respectively; all P<0.05). Survival analyses showed that the number of lung lesions, cross-lobe sign, and pleural involvement were independent prognostic factors for PFS, while the halo sign and pleural involvement were significantly correlated with OS (all P<0.05). More aggressive, advanced-stage cases and male patients showed worse outcomes. CONCLUSIONS: The halo sign and pleural involvement are independent prognostic factors for OS, while the number of lung lesions, cross-lobe sign, and pleural involvement are correlated with PFS.

Pancreatic Neuroendocrine Neoplasms: CT Spectral Imaging in Grading.

RATIONALE AND OBJECTIVES: The purpose of this study was to define the CT spectral imaging characteristics of pancreatic neuroendocrine neoplasms (PNENs) and evaluate their potential for differential diagnosis of nonlow grade (non-LG) PNENs from low grade (LG) PNENs. MATERIALS AND METHODS: CT spectral imaging data of 54 pathologically proven PNENs were retrospectively reviewed. Patients were divided into two groups: 40 cases with grade 1 in LG PNENs group and 14 cases with grade 2 and grade 3 in non-LG PNENs group. RESULTS: Gender, calcification, inhomogeneity, invasiveness, PD dilatation, lymph node enlargement, size, normalized iodine (water) concentration in arterial phase (AP) (Iodine (ap)), normalized effective-Z (Zap), slope of normalized CT spectral curves in both AP, and portal venous phase were found to be significant variables for differentiating non-LG PNENs from LG PNENs (p < 0.05). Non-LG PNENs had larger size and lower Zap and Iodine (ap) than LG PNENs. The tumor size, Zap and Iodine (ap) had fair to good diagnostic performance with the area under receiver-operating-characteristic curve (AUC) 0.843, 0.733, and 0.728, respectively. Multivariate analysis with logistic regression had higher AUC (p<0.05) than all the single parameters except for size. CONCLUSION: There were significant differences in CT spectral imaging parameters between non-LG and LG PNENs. Tumor size was the most promising independent parameter and the combination of quantitative parameters with qualitative parameters is the best predictor in differentiating of non-LG PNENs from LG PNENs. CT spectral imaging can help determine the malignancy of PNENs, which can better assist in surgical planning.

The Effect of Intraoperative Cerebral Oximetry Monitoring on Postoperative Cognitive Dysfunction and ICU Stay in Adult Patients Undergoing Cardiac Surgery: An Updated Systematic Review and Meta-Analysis.

AIM: Determining whether intraoperative cerebral oximetry monitoring-guided intervention reduces the risk of postoperative cognitive dysfunction remains controversial. The objective of this study was to conduct an up-to-date meta-analysis to comprehensively assess the effects of regional cerebral oxygen saturation (rSO2) monitoring-guided intervention on cognitive outcomes after cardiac surgery. METHODS: PubMed, EMBASE, Ovid, and Cochrane Library databases were systematically searched using the related keywords for cardiac surgical randomized-controlled trials (RCTs) published from their inception to July 31, 2021. The primary outcome was postoperative delirium (POD). The secondary outcomes were postoperative cognitive decline (POCD) and other major postoperative outcomes. The odds ratio (OR) or weighted mean differences (WMDs) with 95% confidence interval (CI) were used to pool the data. The random-effect model was used for the potential clinical inconsistency. We performed meta-regression and subgroup analyses to assess the possible influence of rSO2 monitoring-guided intervention on clinical outcomes. RESULTS: In total, 12 RCTs with 1,868 cardiac surgical patients were included. Compared with controls, the incidences of POD (n = 6 trials; OR, 0.28; 95% CI, 0.09-0.84; p = 0.02; I 2 = 81%) and POCD (n = 5 trials; OR, 0.38; 95% CI, 0.16-0.93; p = 0.03; I 2 = 78%) were significantly lower in the intervention group. Cerebral oximetry desaturation also showed a positive association with the incidence of POD (n = 5 trials; OR, 2.02; 95% CI, 1.25-3.24; p = 0.004; I 2 = 81%). The duration of intensive care unit (ICU) stay was markedly shorter in the intervention group than in the control group (n = 10 trials; WMD, -0.22 days; 95% CI, -0.44 to -0.00; p = 0.05; I 2 = 74%). Univariate meta-regression analyses showed that the major sources of heterogeneity were age (p = 0.03), body mass index (BMI, p = 0.05), and the proportion of congenital heart disease (CHD, p = 0.02) for POD, age (p = 0.04) for POCD, diabetes mellitus (DM, p = 0.07), cerebrovascular accident (CVA, p = 0.02), and chronic obstructive pulmonary disease (COPD, p = 0.09) for ICU stay. Subsequent subgroup analyses also confirmed these results. CONCLUSION: Available evidence from the present study suggests that an intraoperative cerebral oximetry desaturation is associated with an increased POD risk, and the rSO2 monitoring-guided intervention is correlated with a lower risk of POD and POCD, and a shorter ICU stay in adults undergoing cardiac surgery. These clinical benefits may be limited in patients with older age, diabetes status, high BMI, non-CHD, non-COPD, or a previous cardiovascular accident.Systematic Review Registration: [PROSPREO], identifier: [CRD42021252654].

Unhealthy Lifestyle Is an Important Risk Factor of Idiopathic BPPV.

Background: Benign paroxysmal positional vertigo (BPPV) is a self-limiting and recurrent disease but the cost is considerable. The number of patients with BPPV increased significantly under the quarantine policy in Hangzhou. The unhealthy lifestyle risk factors of BPPV have not yet been investigated. Thus, the objective is to analyze whether an unhealthy lifestyle is a risk factor of BPPV. Methods: One hundred and sixty three patients with idiopathic BPPV aged 22-87 years (BPPV group), and 89 aged 23-92 years sex-matched control subjects (non-BPPV group) were enrolled in this study. All BPPV patients received a definitive diagnosis which excluded secondary BPPV. Non-BPPV cases excluded BPPV, sudden deafness, Meniere's disease, ear or craniofacial surgery, vestibular neuritis, and head trauma history. We obtained a blood lipids profile, serum uric acid, total bilirubin, and related diagnostic information through the electronic medical record system. To get the time of physical activities and recumbent positions, we asked the patient or their family from February 2020 to June 2020, and the rest of the patient's information was acquired by phone or WeChat. Data Analyses: The t-test or chi-squared test, univariate, and multiple logistic regression analyses were performed for the two groups. For each factor, odds ratios were calculated with 95% confidence intervals (CIs). Moreover, test equality of two or more receiver operating characteristic (ROC) analyses were applied to the physical activities, and recumbent position time; area under curve (AUC) measures were calculated with 95% CIs and compared with each other. Results: The BPPV group had unhealthy lifestyles such as poor physical activities, prolonged recumbent position time, and low rate of calcium or VD supplementation in univariate logistic regression analyses (P < 0.05). Poor physical activities and prolonged recumbent position time were independently associated with BPPV in multiple logistic regression models (OR = 18.92, 95% CI: 6.34-56.43, p = 0.00 and OR = 1.15, 95% CI: 1.01-1.33, p < 0.04). In the comparison of ROC curves of recumbent position time and physical activities in identifying BPPV, AUCs were 0.68 (0.61-0.74), and 0.68 (0.63-0.73), respectively. Conclusion: We conclude that poor physical activities and prolonged recumbent position time may be independent risk factors for BPPV patients, but hypertension, hyperuricemia, hyperlipidemia, hemoglobin, diabetes, serum bilirubin, CHD, and CI, may not be.