Assessment of metabolomic variations among individuals returning to plain areas after exposure to high altitudes: a metabolomic analysis of human plasma samples with high-altitude de-acclimatization syndrome.

Background: High altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA. Methods: We established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of metabolites. Result: Although significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235 metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the metabolites between R3 and r3 and found 107 metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5). Conclusion: We observed the dynamic variation in the metabolic process of HADA. Levels of four metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.

CT-based radiomics for predicting success of shock wave lithotripsy in ureteral stones larger than 1 cm.

PURPOSE: This study aims to investigate the predictive value of CT-based radiomics in determining the success of extracorporeal shock wave lithotripsy (SWL) treatment for ureteral stones larger than 10mm in adult patients. MATERIALS AND METHODS: A total of 301 eligible patients (165/136 successful/unsuccessful) who underwent SWL were retrospectively evaluated and divided into a training cohort (n = 241) and a test cohort (n = 60) following an 8:2 ratio. Univariate analysis was performed to assess clinical characteristics for constructing a nomogram. Radiomics and conventional radiological characteristics of stones were evaluated. Following feature selection, radiomics and radiological models were constructed using logistic regression (LR), support vector machine (SVM), random forest (RF), K nearest neighbor (KNN), and XGBoost. The models' performance was compared using metrics such as the area under the receiver operating characteristic curve (AUC), precision, recall, accuracy, and F1 score. Finally, a nomogram was created incorporating the best image model signature and clinical predictors. RESULTS: The SVM-based radiomics model showed superior predictive performance in both training and test cohorts (AUC: 0.956, 0.891, respectively). The nomogram, which combined SVM-based radiomics signature with proximal ureter diameter (PUD), demonstrated further improved predictive performance in the test cohort (AUC: 0.891 vs. 0.939, P = 0.166). CONCLUSIONS: Integration of CT-derived radiomics and PUD showed excellent ability to predict SWL treatment success in patients with ureteral stones larger than 10mm, providing a promising approach for clinical decision-making.

A smartphone-adaptable fluorescent probe for visual monitoring of fish freshness and its application in fluorescent dyes.

Due to increasing food safety issues, developing intelligent, on-site, and visual methods for detecting fish freshness has attracted significant attention. Here, we have prepared a benzo[h]chromene derivative BCN that can visually detect 12 biogenic amines (BAs) with high sensitivity. The mechanism for recognizing cadaverine (Cad) is that the probe reacts with Cad to produce a Schiff base derivative, which alters the charge distribution within the molecule, resulting in significant colorimetric and fluorescence changes. The sensing label BCN/FPS was prepared by loading the probe BCN on filter paper, and a visual detection platform was constructed by combining it with a smartphone. By monitoring the correspondence between label color and TVB-N content, a working curve of (R + B)/(R + B + G) with TVB-N content was obtained, enabling visual evaluation of salmon freshness using only a mobile phone. In addition, based on the good solubility and processability of BCN, its application in fluorescent dyes including impregnating dyes, printing inks, coatings, and flexible films has been explored, which opens up new directions for the application of BCN. Therefore, BCN has the potential for real-time monitoring of meat freshness and preparation of fluorescent materials.

Development and validation of an 18F-FDG PET/CT-based radiomics nomogram for predicting the prognosis of patients with esophageal squamous cell carcinoma.

RATIONALE AND OBJECTIVES: The aim of this study was to develop and validate a nomogram, integrating clinical factors and radiomics features, capable of predicting overall survival (OS) in patients diagnosed with esophageal squamous cell carcinoma (ESCC). METHODS: In this study, we retrospectively analyzed the case data of 130 patients with ESCC who underwent 18F-FDG PET/CT before treatment. Radiomics features associated with OS were screened by univariate Cox regression (p < 0.05). Further selection was performed by applying the least absolute shrinkage and selection operator Cox regression to generate the weighted Radiomics-score (Rad-score). Independent clinical risk factors were obtained by multivariate Cox regression, and a nomogram was constructed by combining Rad-score and independent risk factors. The predictive performance of the model for OS was assessed using the time-dependent receiver operating characteristic curve, concordance index (C-index), calibration curve, and decision curve analysis. RESULTS: Five radiomics features associated with prognosis were finally screened, and a Rad-score was established. Multivariate Cox regression analysis revealed that surgery and clinical M stage were identified as independent risk factors for OS in ESCC. The combined clinical-radiomics nomogram exhibited C-index values of 0.768 (95% CI: 0.699-0.837) and 0.809 (95% CI: 0.695-0.923) in the training and validation cohorts, respectively. Ultimately, calibration curves and decision curves for the 1-, 2-, and 3-year OS demonstrated the satisfactory prognostic prediction and clinical utility of the nomogram. CONCLUSION: The developed nomogram, leveraging 18F-FDG PET/CT radiomics and clinically independent risk factors, demonstrates a reliable prognostic prediction for patients with ESCC, potentially serving as a valuable tool for guiding and optimizing clinical treatment decisions in the future.

A sensing label or gel loaded with an NIR emission fluorescence probe for ultra-fast detection of volatile amine and fish freshness.

A simple benzopyran-based fluorescence probe DCA-Apa detection of volatile amine has been synthesized. DCA-Apa can recognize volatile amines by dual channel mode (changing from blue to light yellow in sunlight, and from weak pink to orange under 365 nm) in pure water system. DCA-Apa has the advantages of ultra-fast response (∼6 s), NIR emission (655 nm), and a good fluorescence response for many amines. The sensing label or gel loaded with DCA-Apa was prepared by the dipping or mixing method using filter paper or gelatin as solid carriers, which can identify volatile amine vapor and monitor the freshness of salmon by colorimetric and fluorescent dual channels. When the color of the label changes to light yellow-green or the fluorescence of the label becomes orange fluorescence (365 nm UV lamp), it indicates that the fish has rotted. The two-channel method makes up for the deficiency of the single colorimetric method, and establishes a theoretical foundation for more precise assessment of fish freshness.

Sensitivity analysis and point mutations in BcSDHB confer cyclobutrifluram resistance in Botrytis cinerea from China.

Botrytis cinerea is one of the most destructive pathogens worldwide. It can damage over 200 crops, resulting in significant yield and quality losses. Cyclobutrifluram, a new generation of succinate dehydrogenase inhibitors, exhibits excellent inhibitory activity against B. cinerea. However, the baseline sensitivity and resistance of B. cinerea to cyclobutrifluram remains poorly understood. This study was designed to monitor the sensitivity frequency distribution, assess the resistance risk, and clarify the resistance mechanism of B. cinerea to cyclobutrifluram. The baseline sensitivity of B. cinerea isolates to cyclobutrifluram was 0.89 µg/mL. Cyclobutrifluram-resistant B. cinerea populations are present in the field. Six resistant B. cinerea isolates investigated in this study possessed enhanced compound fitness index compared to the sensitive isolates according to mycelial growth, mycelial dry weight, conidiation, conidial germination rate, and pathogenicity. Cyclobutrifluram exhibited no cross-resistance with tebuconazole, fludioxonil, cyprodinil, or iprodione. Sequence alignment revealed that BcSDHB from cyclobutrifluram-resistant B. cinerea isolates had three single substitutions (P225F, N230I, or H272R). Molecular docking verified that these mutations in BcSDHB conferred cyclobutrifluram resistance in B. cinerea. In conclusion, the resistance risk of B. cinerea to cyclobutrifluram is high, and the point mutations in BcSDHB (P225F, N230I, or H272R) confer cyclobutrifluram resistance in B. cinerea. This study provided important insights into cyclobutrifluram resistance in B. cinerea and offered valuable information for monitoring and managing cyclobutrifluram resistance in the future.

131I Induced In Vivo Proteolysis by Photoswitchable azoPROTAC Reinforces Internal Radiotherapy.

Photopharmacology, incorporating photoswitches such as azobenezes into drugs, is an emerging therapeutic method to realize spatiotemporal control of pharmacological activity by light. However, most photoswitchable molecules are triggered by UV light with limited tissue penetration, which greatly restricts the in vivo application. Here, this study proves that 131I can trigger the trans-cis photoisomerization of a reported azobenezen incorporating PROTACs (azoPROTAC). With the presence of 50 µCi mL-1 131I, the azoPROTAC can effectively down-regulate BRD4 and c-Myc levels in 4T1 cells at a similar level as it does under light irradiation (405 nm, 60 mW cm-2). What's more, the degradation of BRD4 can further benefit the 131I-based radiotherapy. The in vivo experiment proves that intratumoral co-adminstration of 131I (300 µCi) and azoPROTC (25 mg kg-1) via hydrogel not only successfully induce protein degradation in 4T1 tumor bearing-mice but also efficiently inhibit tumor growth with enhanced radiotherapeutic effect and anti-tumor immunological effect. This is the first time that a radioisotope is successfully used as a trigger in photopharmacology in a mouse model. It believes that this study will benefit photopharmacology in deep tissue.

Visualizing the crucial roles of plasma membrane and peroxynitrite during abdominal aortic aneurysm using two-photon fluorescence imaging.

Peroxynitrite (ONOO-) and cell plasma membrane (CPM) are two key factors in cell pyroptosis during the progression of abdominal aortic aneurysm (AAA). However, their combined temporal and spatial roles in initiating AAA pathogenesis remain unclear. Herein, we developed a two-photon fluorescence probe, BH-Vis, enabling real-time dynamic detection of CPM and ONOO- changes, and revealing their interplay in AAA. BH-Vis precisely targets CPM with reduced red fluorescence intensity correlating with diminished CPM tension. Concurrently, a blue shift of the fluorescence signal of BH-Vis occurs in response to ONOO- offering a reliable ratiometric detection mode with enhanced accuracy by minimizing external testing variables. More importantly, two photon confocal imaging with palmitic acid (PA) and ganglioside (GM1) manipulation, which modulating cell pyroptosis, showcases reliable fluorescence fluctuations. This groundbreaking application of BH-Vis in a mouse AAA model demonstrates its significant potential for accurately identifying cell pyroptosis levels during AAA development.

Robust Graphene-based Aerogel for Integrated 3D Asymmetric Supercapacitors with High Energy Density.

Three-dimensional asymmetric supercapacitors (3D ASC) have garnered significant attention due to their high operating window, theoretical energy density, and circularity. However, the practical application of 3D electrode materials is limited by brittleness and excessive dead volume. Therefore, we propose a controlled contraction strategy that regulates the pore structure of 3D electrode materials, eliminates dead volume in the 3D skeleton structure, and enhances mechanical strength. In this study to obtain reduced graphene oxide/manganese dioxide (rGO/MnO2) and reduced graphene oxide/carbon nanotube (rGO/CNT) composite aerogels with a stable and compact structure. MnO2 and CNT as nanogaskets, preventing the self-stacking of graphene nanosheets during the shrinkage process. Additionally, the high specific capacitor nanogaskets significantly enhance the specific energy density of the rGO aerogel electrode. The prepared rGO/MnO2//rGO/CNT 3D ASC exhibits a high mass-specific capacitance of 216.15 F g-1, a high mass energy density of 74 Wh kg-1 at 3.5 A g-1, and maintains a retention rate of capacitance at 99.89 % after undergoing 10,000 cycles of charge and discharge at 5 A g-1. The versatile and integrated assembly of 3D ASC units is achieved through the utilization of the robust mechanical structure of rGO-based aerogel electrodes, employing a mortise and tenon structural design.

A novel fluorescence probe for ultrafast detection of SO2 derivatives/biogenic amines and its multi-application: Detecting food and fish freshness, fluorescent dye and bioimaging.

In this study, we have effectively prepared a novel fluorescent probe named HDXM based on benzopyran derivatives for the ultrafast detection (within 3 s) of SO2 derivatives or biogenic amines. HDXM showed a noticeable color change after the addition of SO2 derivatives (from purple to colorless) or biogenic amines (from purple to blue), indicating that HDXM can identify two analytes with the naked eye. It is worth noting that HDXM can be used to detect SO2 derivatives in actual sugar samples, and to image HSO3-/SO32- in living cells. More importantly, sensing labels (HDXM-loaded filter paper or agarose hydrogel) enable real-time visual monitoring of salmon freshness through colorimetric and fluorescence dual channels. Compared with the Chinese national standard method, the sensing label is an effective tool for evaluating the freshness of fish. Benefiting from its excellent solubility and fluorescence performance, HDXM can be used as a versatile fluorescent material in various applications, including flexible films, glass coatings, impregnating dyes, printing, and fingerprint ink. HDXM is expected to be a promising and valuable multifunctional tool for food safety and fluorescent materials.

Exploring the impact of high-altitude de-acclimatization on renal function: The roles of oxidative and endoplasmic reticulum stress in rat models.

BACKGROUND: High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. OBJECTIVE: To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. METHODS: 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. RESULTS: Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. CONCLUSION: This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management.

Potential roles of the interactions between gut microbiota and metabolites in LPS-induced intrauterine inflammation (IUI) and associated preterm birth (PTB).

BACKGROUND: Prenatal exposure to intrauterine inflammation (IUI) is a crucial event in preterm birth (PTB) pathophysiology, increasing the incidence of neurodevelopmental disorders. Gut microbiota and metabolite profile alterations have been reported to be involved in PTB pathophysiology. METHOD AND RESULTS: In this study, IUI-exposed PTB mouse model was established and verified by PTB rate and other perinatal adverse reactions; LPS-indued IUI significantly increased the rates of PTB, apoptosis and inflammation in placenta tissue samples. LPS-induced IUI caused no significant differences in species richness and evenness but significantly altered the species abundance distribution. Non-targeted metabolomics analysis indicated that the metabolite profile of the preterm mice was altered, and differential metabolites were associated with signaling pathways including pyruvate metabolism. Furthermore, a significant positive correlation between Parasutterella excrementihominis and S4572761 (Nb-p-coumaroyltryptamine) and Mreference-1264 (pyruvic acid), respectively, was observed. Lastly, pyruvic acid treatment partially improved LPS-induced IUI phenotypes and decreased PTB rates and decreased the apoptosis and inflammation in placenta tissue samples. CONCLUSION: This study revealed an association among gut microbiota dysbiosis, metabolite profile alterations, and LPS-induced IUI and PTB in mice models. Our investigation revealed the possible involvement of gut microbiota in the pathophysiology of LPS-induced IUI and PTB, which might be mediated by metabolites such as pyruvic acid. Future studies should be conducted to verify the findings through larger sample-sized animal studies and clinical investigations.

A colorimetric and NIR fluorescent probe for ultrafast detecting bisulfite and organic amines and its applications in food, imaging, and monitoring fish freshness.

Herein, for the first time, we have successfully constructed a novel near-infrared (NIR) emission fluorescent probe Dpyt for ultrafast detecting (within 5 s) bisulfate and organic amines based on a 1,2-dihydrocyclopenta[b]chromene-barbiturate conjugation system. Upon addition of bisulfate or organic amines, Dpyt displayed a distinct color change from blue to colorless or from purple to blue, respectively, suggesting that the Dpyt can be used to detect two analytes by the naked eye. Based on quantum chemistry calculations, the fluorescence quenching of Dpyt after the addition of HSO3- is caused by the photoinduced electron transfer (PET) process of the adduct Dpyt-HSO3-. The fluorescence enhancement of Dpyt caused by most organic amines is due to the enhanced intramolecular charge transfer (ICT) process of deprotonated Dpyt. Notably, Dpyt can be applied for detecting HSO3- in actual food samples such as red wine and sugar, as well as for imaging of HSO3- and representative propylamine in living cells. And more importantly, indicator labels constructed by filter paper loaded with Dpyt can visually monitor the freshness of salmon in real-time by daylight and fluorescence dual-mode. The comparison with national standard method of China manifests that indicator labels are a valid tool to assess the freshness of seafood.

Radioactive iodine therapy for follicular thyroid cancer: a 15 years follow-up study of Chinese patients.

PURPOSE: To identify long-term predictors of distant metastases (DM) and the overall survival (OS) of follicular thyroid cancer (FTC) patients who underwent radioactive iodine (RAI) therapy. And to expand the knowledge about the clinical course and experience of RAI treatment for FTC. MATERIALS: A total of 117 FTC patients who underwent RAI therapy at our institution from 2005 to 2020 were retrospectively studied. Patient characteristics, serum stimulating thyroglobulin (sTg) and thyroglobulin antibody levels, treatment process and follow-up data were collected until 26 April 2022. RESULTS: A total of 16 patients (13.7%) were lost to follow-up. A total of 23 (19.7%) patients with DM died and all FTC without DM were still alive. DM was seen in 58.4% (59/101) of patients. The most common location for metastatic lesions was the lung. Then was bone. The mean survival time of FTC with RAI was 156 months [95% confidence interval (CI): 142-171]. Five-year and 10-year cumulative survival rates of them were 88.8% and 67.4%, respectively. As for patients with DM were 80.4% and 41.3%, respectively. Age at diagnosis [odds ratio (OR) = 1.080, P  = 0.009], RAI therapy sessions (OR = 2.959, P  = 0.001) and sTg level (OR = 1.006, P  = 0.002) were predictive of DM occurrence in FTC with RAI. In the group of FTC with DM, survival analysis showed that males were more likely to have a lower OS than females ( P  = 0.039). CONCLUSION: Age, number of RAI therapy sessions, and sTg level were predictive of the occurrence of DM in FTC patients with RAI. Sex would influence the OS of FTC patients with DM.

The RADAR technique in reconstruction of failed autologous arteriovenous fistulas due to juxta-anastomotic stenosis is equivalent to that with traditional surgery in maintenance hemodialysis patients.

OBJECTIVE: Autologous arteriovenous fistula (AVF) is recommended as superior vascular access for hemodialysis but has a high rate of failure, and juxta-anastomotic stenosis (JAS) is one of the predominant causes of fistula failure. The aim of this study was to compare the primary patency in reconstruction of failed AVFs due to JAS between the radial artery deviation and reimplantation (RADAR) technique and traditional surgery (end-vein to side-artery neo-anastomosis) in maintenance hemodialysis (MHD) patients. METHODS: A total of 1215 MHD patients with failed AVF were enrolled in this retrospective cohort study, and 614 patients with failed AVF received surgical intervention. Among these surgical interventions, 417 patients experienced AVF failure due to JAS. Finally, 25 patients who received the RADAR technique were enrolled. Controls of 50 patients received traditional surgery were randomly selected matched by age and sex. Clinical data such as age, sex, comorbidities, and blood biochemical indices were collected. Kaplan-Meier survival curves and Cox proportional hazards analyses were used to explore the difference between the RADAR group and the traditional group in reconstruction of failed AVFs. RESULTS: The RADAR group and the traditional group shared common baseline characteristics. The primary patencies of the reconstructed AVFs were 88.8%, 79.0%, 72.2%, 57.4%, and 38.3% at 12, 24, 36, 48, and 60 months among the 75 patients, respectively. Kaplan-Meier survival curve analysis demonstrated similar primary patencies in the two groups (log-rank test, p = 0.73). Compared with the traditional group, the RADAR group had no difference in predicting AVF failure after adjusting for potential confounders, with an HR of 0.92 (95% CI, 0.18-4.63). CONCLUSIONS: The primary patency of the RADAR technique and the traditional surgery in the reconstruction of failed AVFs due to JAS is almost equal in 5 years.

The influence of arm positions on mechanical dyssynchrony measured by gated myocardial perfusion imaging.

Background: In routine procedures, patient's arms are positioned above their heads to avoid potential attenuation artifacts and reduced image quality during gated myocardial perfusion imaging (G-MPI). However, it is difficult to achieve this action in the acute period following pacemaker implantation. This study aimed to explore the influence of arm positioning on myocardial perfusion imaging (MPI) in different types of heart disease. Methods: This study was conducted retrospectively. A total of 123 patients were enrolled and underwent resting G-MPI using a standard protocol with arms positioned above their heads and again with their arms at their sides. All individuals were divided into 3 groups: the normal group, the obstructive coronary artery disease (O-CAD) group, and the dilated cardiomyopathy (DCM) group. The G-MPI data were measured by QGS software and Emory Reconstruction Toolbox, including left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), end-systolic volume (ESV), extent, total perfusion deficit (TPD), summed rest score (SRS), scar burden, phase standard deviation (SD), and phase histogram bandwidth (BW). Results: In total, extent, TPD, EDV, ESV, LVEF, systolic SD, systolic BW, diastolic SD, and diastolic BW were all significantly different between the 2 arm positions (all P<0.01). On the Bland-Altman analysis, both EDV and ESV with the arm-down position were significantly underestimated (P<0.001). Meanwhile, TPD, extent, and LVEF with the arm-down position were significantly overestimated (P<0.05). Systolic SD, systolic BW, diastolic SD, and diastolic BW were systematically overestimated (P<0.001). In the DCM group (n=52), EDV, ESV, systolic SD, systolic BW, diastolic SD, and diastolic BW were identified as significantly different by the paired t-test between the 2 arm positions (P<0.05). In the O-CAD group (n=32), scar burden, ESV, LVEF, and diastolic BW were significantly different between the 2 arm positions (P<0.05). Conclusions: Systolic and diastolic dyssynchrony parameters and most left ventricular (LV) functional parameters were significantly influenced by arm position in both normal individuals and patients with heart failure (HF) with different pathophysiologies. More attention should be given to LV dyssynchrony data during clinical evaluation of cardiac resynchronization therapy (CRT) implantation procedure.

Alterations and potential roles of microbial population of pregnant mouse saliva and amniotic fluid.

PROBLEM: Prenatal exposure to intrauterine inflammation (IUI) is a crucial event in PTB pathophysiology. However, the relationship between microflora and PTB is not fully elucidated. METHOD OF STUDY: In this study, we established an intrauterine inflammation mouse model via LPS intrauterine injection. The saliva and amniotic fluid were collected for 16s RNA gene sequencing. The levels of TNF-α and IL-1ß in mouse amniotic fluid were determined by ELISA assays. RESULTS: Up to 60% of the operational taxonomic units (OTUs) in the saliva and amniotic fluid of PBS-treated mice were overlapped. LPS treatment-induced changes in the abundance of oral and amniotic fluid microorganisms. Both immune-associated probiotics, salivarius and mastitidis, were still detected in saliva (at significantly increased levels) after LPS-induced intrauterine inflammation and almost no probiotics of any type were detected in amniotic fluid, suggesting that the uterine cavity seems to be more susceptible to LPS compared to the oral cavity. Moreover, the abundance of pathogenic bacteria Escherichia coli was increased in both saliva and amniotic fluid after LPS treatment. The level of TNF-α and IL-1ß in amniotic fluid is positively related to the amniotic fluid E. coli abundance. CONCLUSIONS: The microbial composition of saliva and amniotic fluid of pregnant mice was similar. LPS-induced intrauterine inflammation decreased the consistency of microbial composition in mouse saliva and amniotic fluid, increased the abundance of E. coli in saliva and amniotic fluid, and decreased the abundance of immune-associated probiotics, especially in amniotic fluid.

Containing anti-PLA2R IgG antibody induces podocyte injury in idiopathic membranous nephropathy.

Background: Idiopathic membranous nephropathy is widely recognized as an autoimmune kidney disease that is accompanied by the discovery of several autoantibodies, and the antibody subclass in the circulation of patients with iMN is mainly IgG. However, the direct pathogenic effect of the containing anti-PLA2R IgG antibody on podocytes is not clear.Method: A protein G affinity chromatography column was used to purify serum IgG antibodies. Containing anti-PLA2R IgG antibodies from iMN patients and IgG from healthy controls were also obtained. Based on the established in vitro podocyte culture system, purified IgG antibodies from the two groups were used to stimulate podocytes, and the expression of essential podocyte proteins (podocin), the levels of inflammatory cytokines in the cell supernatant, cytoskeletal disorders, and podocyte apoptosis were analyzed.Results: Compared with that in the normal IgG group, the expression of podocin and podocin mRNA was reduced (p = 0.016 and p = 0.005, respectively), the fluorescence intensity of podocin on the surface of podocytes was reduced, the cytoskeleton of podocytes was disordered and reorganized, and the ratio of podocyte apoptosis was increased in the iMN group (p = 0.008).Conclusion: The containing anti-PLA2R IgG antibody might have a direct damaging effect on podocytes in idiopathic membranous nephropathy.

Role of lncRNAs in acute pancreatitis: pathogenesis, diagnosis, and therapy.

Acute pancreatitis (AP) is one of the most common acute abdominal diseases characterized by an injury and inflammatory disorder of the pancreas with complicated pathological mechanisms. Long non-coding RNAs (lncRNAs) have been shown to play an important role in various physiological and pathological processes in humans, and they have emerged as potential biomarkers of diagnosis and therapeutic targets in various diseases. Recently, accumulating evidence has shown significant alterations in the expression of lncRNAs, which are involved in the pathogenesis of AP, such as premature trypsinogen activation, impaired autophagy, inflammatory response, and acinar cell death. Moreover, lncRNAs can be the direct target of AP treatment and show potential as biomarkers for the diagnosis. Thus, in this review, we focus on the role of lncRNAs in the pathogenesis, diagnosis, and therapy of AP and emphasize the future directions to study lncRNAs in AP, providing new insight into understanding the cellular and molecular mechanisms of AP and seeking novel biomarkers for the diagnosis and therapeutic targets to improve clinical management in the future.

Predicting acute pancreatitis severity with enhanced computed tomography scans using convolutional neural networks.

This study aimed to evaluate acute pancreatitis (AP) severity using convolutional neural network (CNN) models with enhanced computed tomography (CT) scans. Three-dimensional DenseNet CNN models were developed and trained using the enhanced CT scans labeled with two severity assessment methods: the computed tomography severity index (CTSI) and Atlanta classification. Each labeling method was used independently for model training and validation. Model performance was evaluated using confusion matrices, areas under the receiver operating characteristic curve (AUC-ROC), accuracy, precision, recall, F1 score, and respective macro-average metrics. A total of 1,798 enhanced CT scans met the inclusion criteria were included in this study. The dataset was randomly divided into a training dataset (n = 1618) and a test dataset (n = 180) with a ratio of 9:1. The DenseNet model demonstrated promising predictions for both CTSI and Atlanta classification-labeled CT scans, with accuracy greater than 0.7 and AUC-ROC greater than 0.8. Specifically, when trained with CT scans labeled using CTSI, the DenseNet model achieved good performance, with a macro-average F1 score of 0.835 and a macro-average AUC-ROC of 0.980. The findings of this study affirm the feasibility of employing CNN models to predict the severity of AP using enhanced CT scans.