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Abstract Background Accurate preoperative localization is a challenge in thoracoscopic surgery for multiple pulmonary nodules. In this study, we aimed to assess the accuracy and feasibility of electromagnetic navigation (EN)-guided percutaneous localization. Methods We enrolled 50 patients with multiple pulmonary nodules for EN-guided (EN group) or CT-guided (CT group) localization. The primary outcome was the localization accuracy, and the primary analysis was to assess the noninferiority (noninferiority margin of 5 mm) of EN-induced localization deviation compared with that of CT-induced deviation. The secondary outcomes included the procedural duration, anxiety score, and incidence of complications. Results Among the 50 patients randomized to the EN- and CT-guided groups, 24 patients (53 nodules) underwent EN-guided preoperative marking, and 25 patients (54 nodules) underwent CT-guided preoperative marking. The demographic, clinical, and radiological characteristics did not differ significantly between the groups (P > 0.05). Among these patients, the EN group was noninferior in terms of localization deviation compared with the CT group (9.0 [6.5] vs. 7.5 [6.0] mm; P = 0.33; absolute difference 0.9 [95% CI] 0.03–1.77]). Furthermore, the procedural duration was 16.3 (4.2) minutes for the EN group and 22.3 (8.2) minutes for the CT group (P = 0.002). Additionally, the EN group exhibited significant improvements compared with the CT group on the basis of the Amsterdam Preoperative Anxiety and Information Scale, particularly in relation to the S and C subscales’ cumulative scores. Conclusions EN was found to be noninferior to CT in terms of localization accuracy, as it significantly decreased the procedural duration and relieved psychological stress for patients who underwent simultaneous surgery for multiple pulmonary nodules. Clinical Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2200056734.

BackgroundThe pervasive integration of digital devices into daily life has raised concerns about their potential health impacts. This study aimed to explore the causal relationships between digital device use and the risk of migraine using Mendelian randomization (MR).MethodsGenetic data on digital device use and migraines were sourced from large-scale genome-wide association studies conducted by the UK Biobank, the FinnGen study, and the International Headache Genetics Consortium. Univariable MR (UVMR), meta-analysis, and multivariable MR (MVMR) approaches were conducted to explore and verify the causal effects of digital device use (including mobile phone use, computer use, playing computer games, and watching television) on migraine risk. Sensitivity analyses were conducted using Cochran’s Q, MR-Egger intercept test, MR pleiotropy residual sum and outlier, MR Radial, MR Steiger, and leave-one-out methods.ResultsUVMR analyses revealed that genetically predicted mobile phone use was significantly associated with an increased risk of overall migraine (odds ratio [OR] = 2.39, p = 9.78e-5) and migraine without aura (MO) (OR = 2.25, p = 0.024). Additionally, there were significant positive associations between genetically predicted television watching and the risk of overall migraine (OR = 1.63, p = 2.12e-5) and MO (OR = 2.10, p = 4.98e-5). These results were further supported by the meta-analysis and MVMR analysis. Sensitivity analysis indicated no heterogeneity or pleiotropy.ConclusionThis comprehensive MR study provides preliminary evidence for the causal impact of mobile phone use and television watching on the risk of migraines. Further studies are needed to explore these associations across different populations.

Abstract Background This study aimed to compare the analgesic efficacy of transthoracic intercostal nerve block (TINB) and percutaneous intercostal nerve block (PINB) for video-assisted thoracic surgery (VATS) using a retrospective analysis. Methods A total of 336 patients who underwent VATS between January 2021 and June 2022 were reviewed retrospectively. Of the participants, 194 received TINB and were assigned to the T group, while 142 patients received PINB and were assigned to the P group. Both groups received 25 ml of ropivacaine via TINB or PINB at the end of the surgery. The study measured opioid consumption, pain scores, analgesic satisfaction, and safety. Propensity score matching (PSM) analysis was performed to minimize selection bias due to nonrandom assignment. Results After propensity score matching, 86 patients from each group were selected for analysis. The P group had significantly lower cumulative opioid consumption than the T group (p 0.05). The analgesic satisfaction in the P group was higher than in the T group (p 0.05). Conclusion The study suggests that PINB provides superior analgesia for patients undergoing thoracic surgery compared to TINB without any extra adverse effects.

IntroductionAdenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are considered pre-invasive forms of lung adenocarcinoma (LUAD) with a 5-year recurrence-free survival of 100%. We investigated genomic profiles in early tumorigenesis and distinguished mutational features of preinvasive to invasive adenocarcinoma (IAC) for early diagnosis.MethodsMolecular information was obtained from a 689-gene panel in the 90 early-stage LUAD Chinese patients using next-generation sequencing. Gene signatures were identified between pathology subtypes, including AIS/MIA (n=31) and IAC (n=59) in this cohort. Mutational and clinicopathological information was also obtained from the Cancer Genome Atlas (TCGA) as a comparison cohort.ResultsA higher mutation frequency of TP53, RBM10, MUC1, CSMD, MED1, LRP1B, GLI1, MAP3K, and RYR2 was observed in the IAC than in the AIS/MIA group. The AIS/MIA group showed higher mutation frequencies of ERBB2, BRAF, GRIN2A, and RB1. Comparable mutation rates for mutually exclusive genes (EGFR and KRAS) across cohorts highlight the critical transition to invasive LUAD. Compared with the TCGA cohort, EGFR, KRAS, TP53, and RBM10 were frequently mutated in both cohorts. Despite limited gene mutation overlap between cohorts, we observed variant mutation types in invasive LUAD. Additionally, the tumor mutation burden (TMB) values were significantly lower in the AIS/MIA group than in the IAC group in both the Chinese cohort (P=0.0053) and TCGA cohort (P

Objectives: The efficacy of dexamethasone palmitate in extending durations of local anesthetic blocks is uncertain. In a randomized, double-blind study of patients undergoing video-assisted thoracoscopic surgery, we tested whether intravenous or perineural dexamethasone palmitate caused prolonged analgesia after intercostal nerve block. Methods: A total of 90 patients subjected to video-assisted thoracoscopic surgery between May and December 2022 were randomly assigned to one of three intercostal nerve blocks study arms (n = 30 each), requiring the addition of 0.5% ropivacaine (23 ml) as follows: controls (C group), 2 ml saline; IV-DXP group, 2 ml saline + 2 ml (8 mg) intravenous dexamethasone palmitate; and PN-DXP group, 2 ml (8 mg) perineural dexamethasone palmitate. Time to first postoperative remedial analgesia served as primary outcome measure. Secondary endpoints included postoperative opioid consumption, pain scores by Visual Analog Scale, analgesia satisfaction, and related adverse effects. Results: Compared with controls or the IV-DXP group, time to first postoperative remedial analgesia was longer and postoperative opioid consumption for rescue analgesia was lower in the PN-DXP group (p 0.05). Conclusions: Perineural dexamethasone palmitate is a promising adjunct to ropivacaine intercostal nerve block by prolonging analgesia with almost no related adverse effects.

Abstract Several mutations that cause Parkinson’s disease (PD) have been identified over the past decade. These account for 15–25% of PD cases; the rest of the cases are considered sporadic. Currently, it is accepted that PD is not a single monolithic disease but rather a constellation of diseases with some common phenotypes. While rodent models exist for some of the PD-causing mutations, research on the sporadic forms of PD is lagging due to a lack of cellular models. In our study, we differentiated PD patient-derived dopaminergic (DA) neurons from the induced pluripotent stem cells (iPSCs) of several PD-causing mutations as well as from sporadic PD patients. Strikingly, we observed a common neurophysiological phenotype: neurons derived from PD patients had a severe reduction in the rate of synaptic currents compared to those derived from healthy controls. While the relationship between mutations in genes such as the SNCA and LRRK2 and a reduction in synaptic transmission has been investigated before, here we show evidence that the pathogenesis of the synapses in neurons is a general phenotype in PD. Analysis of RNA sequencing results displayed changes in gene expression in different synaptic mechanisms as well as other affected pathways such as extracellular matrix-related pathways. Some of these dysregulated pathways are common to all PD patients (monogenic or idiopathic). Our data, therefore, show changes that are central and convergent to PD and suggest a strong involvement of the tetra-partite synapse in PD pathophysiology.

ABSTRACT During yeast stationary phase, a single spherical vacuole (lysosome) is created by the fusion of several small ones. Moreover, the vacuolar membrane is reconstructed into two distinct microdomains. Little is known, however, about how cells maintain vacuolar shape or regulate their microdomains. Here, we show that Fat1p, a fatty acyl coenzyme A (acyl-CoA) synthetase and fatty acid transporter, and not the synthetases Faa1p and Faa4p, is essential for vacuolar shape preservation, the development of vacuolar microdomains, and cell survival in stationary phase of the yeast Saccharomyces cerevisiae. Furthermore, Fat1p negatively regulates general autophagy in both log- and stationary-phase cells. In contrast, Fat1p promotes lipophagy, as the absence of FAT1 limits the entry of lipid droplets into the vacuole and reduces the degradation of liquid droplet (LD) surface proteins. Notably, supplementing with unsaturated fatty acids or overexpressing the desaturase Ole1p can reverse all aberrant phenotypes caused by FAT1 deficiency. We propose that Fat1p regulates stationary phase vacuolar morphology, microdomain differentiation, general autophagy, and lipophagy by controlling the degree of fatty acid saturation in membrane lipids. IMPORTANCE The ability to sense environmental changes and adjust the levels of cellular metabolism is critical for cell viability. Autophagy is a recycling process that makes the most of already-existing energy resources, and the vacuole/lysosome is the ultimate autophagic processing site in cells. Lipophagy is an autophagic process to select degrading lipid droplets. In yeast cells in stationary phase, vacuoles fuse and remodel their membranes to create a single spherical vacuole with two distinct membrane microdomains, which are required for yeast lipophagy. In this study, we discovered that Fat1p was capable of rapidly responding to changes in nutritional status and preserving cell survival by regulating membrane lipid saturation to maintain proper vacuolar morphology and the level of lipophagy in the yeast S. cerevisiae. Our findings shed light on how cells maintain vacuolar structure and promote the differentiation of vacuole surface microdomains for stationary-phase lipophagy.

Abstract Background Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) are beneficial in patients with lung cancer. We explored the clinical value of [99mTc]Tc-Galacto-RGD2 single-photon emission computed tomography (SPECT/CT) in patients with lung cancer, integrin αvβ3 expression, and neovascularization in lung cancer subtypes was also addressed. Methods A total of 185 patients with lung cancer and 25 patients with benign lung diseases were enrolled in this prospective study from January 2013 to December 2016. All patients underwent [99mTc]Tc-Galacto-RGD2 imaging. The region of interest was drawn around each primary lesion, and tumour uptake of [99mTc]Tc-Galacto-RGD2 was expressed as the tumour/normal tissue ratio(T/N). The diagnostic efficacy was evaluated by receiver operating characteristic curve analysis. Tumour specimens were obtained from 66 patients with malignant diseases and 7 with benign disease. Tumour expression levels of αvβ3, CD31, Ki-67, and CXCR4 were further analysed for the evaluation of biological behaviours. Results The lung cancer patients included 22 cases of small cell lung cancer (SCLC), 48 squamous cell carcinoma (LSC), 97 adenocarcinoma (LAC), and 18 other types of lung cancer. The sensitivity, specificity, and accuracy of [99mTc]Tc-Galacto-RGD2 SPECT/CT using a cut-off value of T/N ratio at 2.5 were 91.89%, 48.0%, and 86.67%, respectively. Integrin αvβ3 expression was higher in non-SCLC compared with SCLC, while LSC showed denser neovascularization and higher integrin αvβ3 expression. Integrin αvβ3 expression levels were significantly higher in advanced (III, IV) than early stages (I, II). However, there was no significant correlation between tumour uptake and αvβ3 expression. Conclusions [99mTc]Tc-Galacto-RGD2 SPECT/CT has high sensitivity but limited specificity for detecting primary lung cancer, integrin expression in the tumour vessel and tumour cell membrane contributes to the tumour uptake.

Abstract Background Mulberry (Morus multicaulis) branch bark powder have showed effective hypoglycemic activity in our previous research. This study aims to explore the mechanism of protect effect on diabetes mice of mulberry branch bark as food supplement based on non-targeted GC-MS metabolomics’ platform. Methods Animal model of double diabetes was established with high fat diet and Streptozotocin injection. Mice were fed with mulberry branch bark powder (MBBP) for five weeks to study its therapeutic effect. The metabolite feature of diabetes model and treatment group mice were characterized using a gas chromatography-mass spectrometry-based metabolomics, complemented with the biochemical evaluation, histological inspection, immunohistochemistry observations and enzyme protein detection. Results A panel of endogenous metabolites were revealed that are relevant to disturbed metabolic processes among groups. The serum metabolic profiles were significantly different between the model group and treatment group. The manner of MBBP treatment showed to be significantly dose dependent and 20% MBBP treatment gain a relatively greater benefit than others. The metabolic disorders in model group include enhanced activation of the sorbitol pathway and galactose metabolite, increased activities of gluconeogenesis, fatty acid oxidation, proteins catabolism and attenuated activities of pentose phosphate pathway, glycolysis and aerobic oxidation pathways, internal synthesis of cholesterol, inositol production. MBBP treatment ameliorate these abnormal metabolize as revealed by differential metabolites comparing with that of model mice, such as decreasing the accumulation of ketone body, enhancing NADPH biosynthesis, partially reversing oxidative stress and energy metabolism disturbance. Conclusions Mulberry branch bark had a re-balancing effect on the disturbed metabolic pathways in the diabetic mice. Based on the metabolic pathways network, oral administration of MBBP could ameliorate the hyperglycemia and hyperlipidemia symptoms in a global scale and restore the abnormal metabolic state to a near normal level in a dose dependent pattern.

Abstract Background Long terminal repeat (LTR) retrotransposons are highly abundant in plant genomes and require transcriptional activity for their proliferative mode of replication. These sequences exist in plant genomes as diverse sublineages within the main element superfamilies (i.e., gypsy and copia). While transcriptional activity of these elements is increasingly recognized as a regular attribute of plant transcriptomes, it is currently unknown the extent to which different sublineages of these elements are transcriptionally active both within and across species. In the current report, we utilize next generation sequencing methods to examine genomic copy number abundance of diverse LTR retrotransposon sublineages and their corresponding levels of transcriptional activity in three diploid wild sunflower species, Helianthus agrestis, H. carnosus and H. porteri. Results The diploid sunflower species under investigation differ in genome size 2.75-fold, with 2C values of 22.93 for H. agrestis, 12.31 for H. carnosus and 8.33 for H. porteri. The same diverse gypsy and copia sublineages of LTR retrotransposons were identified across species, but with gypsy sequences consistently more abundant than copia and with global gypsy sequence abundance positively correlated with nuclear genome size. Transcriptional activity was detected for multiple copia and gypsy sequences, with significantly higher activity levels detected for copia versus gypsy. Interestingly, of 11 elements identified as transcriptionally active, 5 exhibited detectable expression in all three species and 3 exhibited detectable expression in two species. Conclusions Combined analyses of LTR retrotransposon genomic abundance and transcriptional activity across three sunflower species provides novel insights into genome size evolution and transposable element dynamics in this group. Despite considerable variation in nuclear genome size among species, relatively conserved patterns of LTR retrotransposon transcriptional activity were observed, with a highly overlapping set of copia and gypsy sequences observed to be transcriptionally active across species. A higher proportion of copia versus gypsy elements were found to be transcriptionally active and these sequences also were expressed at higher levels.

Background We occasionally noticed that native collateral blood flow showed a recessive trend in the early stages of acute myocardial infarction in rats, which greatly interferes with the accurate assessment of native collateral circulation levels. Here, we sought to recognize the coronary collateral circulation system in depth, especially the microcirculation part, on this basis. Methods and Results In this study, we detected native collateral flow with positron emission tomography perfusion imaging in rats and found that the native flow is relatively abundant when it is initially recruited. However, this flow is extremely unstable in the early stage of acute myocardial infarction and quickly fails. We used tracers to mark the collateral in an ischemic area and a massive preformed collateral network was labeled. The ultrastructures of these collateral microvessels are flawed, which contributes to extensive leakage and consequent interstitial edema in the ischemic region. Conclusions An unrecognized short‐lived native coronary collateral microcirculation reserve is widely distributed in rat hearts. Recession of collateral blood flow transported by coronary collateral microcirculation reserve contributes to instability of native collateral blood flow in the early stage of acute myocardial infarction. The immature structure determines that these microvessels are short‐lived and provide conditions for the development of early interstitial edema in acute myocardial infarction.

Based on blockiness and the matter-element extension theory,this article introduces BET method(classification method based on blockiness and the extension theory) especially suitable for roof stability analysis. The integrity of roof rock was reflected by blockiness in three-dimensional space,and an evaluation system was constructed with blockiness,uniaxial compressive strength,joint condition and groundwater condition as evaluating indicators. The classical domain,the segment and the object element of the model were established,the incompatible problems between these indexes were analyzed,and the index weights were calculated by the extension method. After the correlation degree was comprehensively calculated,the stability classification method and standard were determined. Selecting four test areas of fractured rock mass in Guangxi Tongkeng Mine,an engineering application study of BET classification method was carried out. The results of traditional classification methods,such as RMR method,RSR method and Q method,were respectively compared to that of BET method. It is shown that compared with these traditional classification methods,the index system selected by BET method is more comprehensive and its evaluation method is more objective and scientific.

Our goal was to validate the feasibility of 99m Tc-duramycin as a potential apoptosis probe for monitoring tumor response to paclitaxel in breast cancer xenografts. The binding of 99m Tc-duramycin to phosphatidylethanolamine was validated in vitro using paclitaxel-treated human breast carcinoma MDA-MB-231 cells. Female BALB/c mice (n = 5) bearing breast cancer xenografts were randomized into 2 groups and intraperitoneally injected with 40 mg/kg paclitaxel or phosphate-buffered saline. 99m Tc-duramycin (37-55.5 MBq) was injected at 72 hours posttreatment, and single-photon emission computed tomography/computed tomography was performed at 2 hours postinjection. Apoptotic cells and activated caspase 3 in explanted tumor tissue were measured by flow cytometry. Cellular ultrastructural changes were assessed by light and transmission electron microscopy. 99m Tc-duramycin with radiochemical purity of >90% exhibited rapid blood clearance and predominantly renal clearance. The tumor-to-muscle ratio in the paclitaxel-treated group (5.29 ± 0.62) was significantly higher than that in the control. Tumor volume was decreased dramatically, whereas tumor uptake of 99m Tc-duramycin (ex vivo) significantly increased following paclitaxel treatment, which was consistent with apoptotic index, histological findings, and ultrastructural changes. Our data demonstrated the feasibility of 99m Tc-duramycin for early detection of apoptosis after paclitaxel chemotherapy in breast carcinoma xenografts.

Abstract Background The target-controlled infusion-III (SLOG/TCI-III) system was derived from a model set up by the local pediatric population for target control infusion of propofol. Methods The current study aimed at evaluating the difference between target concentrations of propofol and performance, which was measured using the SLOG/TCI-III system in children. Thirty children fulfilling the I-II criteria according to American Society of Anesthesiology were enrolled in the study. The target plasma concentration of propofol was fed into the SLOG/TCI-III system and compared with the measured concentrations of propofol. Blood samples were collected and analyzed by high performance liquid chromatography with fluorescence detector. The performance error (PE) was determined for each measured blood propofol concentration. The performances of the TCI-III system were determined by the median performance error (MDPE), the median absolute performance error (MDAPE), and Wobble (the median absolute deviation of each PE from the MDPE), respectively. Results Concentration against target concentration showed good linear correlation: concentration = 1.3428 target concentration - 0.2633 (r = 0.8667). The MDPE and MDAPE of the pediatric system were 10 and 22%, respectively, and the median value for Wobble was 24%. MDPE and MDAPE were less than 15 and 30%, respectively. Conclusions The performance of TCI-III system seems to be in the accepted limits for clinical practice in children.

Vibrio parahaemolyticus (V. parahaemolyticus) is a major food-borne pathogen which causes human gastroenteritis. Since the characteristics of V. parahaemolyticus remain unknown, 220 isolates selected from clinical and environmental samples in Dapeng of Shenzhen were tested for the presence of two hemolysin-expressing genes tdh and trh. Among 27 clinical isolates, 26 carrired the tdh gene, and the other one carried both tdh and trh genes, however neither genes were detected in environmental isolates. Meanwhile, antimicrobial susceptibility profiles revealed the isolates with high frequency of resistance to ampicillin (77.73%) and colistin (71.82%) and medium to streptomycin (57.27%). Genetically, by whole genome sequencing (WGS), comparative genomics studies was performed on isolates from various districts and GenBank. Data analysis showed that antimicrobial resistance genes (ARGs) blaCARB , tet(34) and tet(35) were harbored in all genomes and other ARGs was absent in the genomes of 27 clinical isolates. Besides, little regional difference was observed. As for virulence factors, MAM7, T3SS1, T3SS1 secret effector, T3SS2, T3SS2 secret effector, and VpadF were carried by most isolates. Two isolates from other districts were tdh gene positive which clustered with clinical isolates from Dapeng in the same clade, indicating close genetic distance. This study revealed the widely distribution of V. parahaemolyticus in Shenzhen and the diverse ARGs and virulence genes it carried. Furthermore, pathways that pathogen disseminated through were discussed. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of positive anti-thyroid peroxidase (TPO) antibodies on fertility, embryo quality, and pregnancy outcomes in women with normal thyroid function. A cross-sectional study of 1223 infertile women who received assisted reproductive technology (ART) treatment for the first time was conducted at our hospital from January 2019 to March 2022. Overall, 263 infertile women were included, comprising 263 cycles and 1813 embryos, and were divided into a positive group and a control group based on TPO antibody levels. The positive group was further divided into two subgroups according to the median antibody titer, and the therapeutic indices and pregnancy outcomes for each group were compared. The results showed that the AMH level in the positive group was significantly lower than that in the control group (2.37 (1.26-3.63) ng/ml vs. 3.54 (1.74-5.41) ng/ml, p < 0.001). The high-quality embryo rate (40.04% vs. 45.49%, p = 0.034) and live birth rate (23.26% vs. 36.16, p = 0.035) of the positive group were lower than those of the control group; the miscarriage rate was higher than that of the control group (37.50% vs. 17.95%, p = 0.035). The live birth rate in the low-titer group was significantly higher than that in the high-titer group (32.56% vs. 13.95%, p = 0.041). Studies have shown that positive anti-thyroid peroxidase antibodies are associated with a decreased ovarian reserve and decreased embryo quality. High titers of anti-thyroid peroxidase antibodies can reduce the live birth rate. [ABSTRACT FROM AUTHOR]