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Abstract Background Echinocandins belong to the fourth generation of antifungals, and there are no systematic studies on their risk in coagulation dysfunction; this study will predict the risk of coagulation dysfunction of echinocandins using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Method Data from January 2004 to March 2024 were obtained from FAERS. We examined the clinical characteristics of the coagulation dysfunction events and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare echinocandins with the full database. Results There were 313 reports of coagulation dysfunction related to echinocandins as the primary suspect (PS) drug. The median time to incident for coagulation dysfunction was 3 (interquartile range [IQR] 1–9) days. Compared to triazoles and polyenes, echinocandins have a stronger signal (ROR 3.18, 95%CI 2.81–3.51, p

Abstract Pipe contaminant detection holds considerable importance within various industries, such as the aviation, maritime, medicine, and other pertinent fields. This capability is beneficial for forecasting equipment potential failures, ascertaining operational situations, timely maintenance, and lifespan prediction. However, the majority of existing methods operate offline, and the detectable parameters online are relatively singular. This constraint hampers real-time on-site detection and comprehensive assessments of equipment status. To address these challenges, this paper proposes a sensing method that integrates an ultrasonic unit and an electromagnetic inductive unit for the real-time detection of diverse contaminants and flow rates within a pipeline. The ultrasonic unit comprises a flexible transducer patch fabricated through micromachining technology, which can not only make installation easier but also focus the sound field. Moreover, the sensing unit incorporates three symmetrical solenoid coils. Through a comprehensive analysis of ultrasonic and induction signals, the proposed method can be used to effectively discriminate magnetic metal particles (e.g., iron), nonmagnetic metal particles (e.g., copper), nonmetallic particles (e.g., ceramics), and bubbles. This inclusive categorization encompasses nearly all types of contaminants that may be present in a pipeline. Furthermore, the fluid velocity can be determined through the ultrasonic Doppler frequency shift. The efficacy of the proposed detection principle has been validated by mathematical models and finite element simulations. Various contaminants with diverse velocities were systematically tested within a 14 mm diameter pipe. The experimental results demonstrate that the proposed sensor can effectively detect contaminants within the 0.5−3 mm range, accurately distinguish contaminant types, and measure flow velocity.

AIM: To introduce the macular hole (MH) hydromassage technique as a potentially beneficial approach for the treatment of large or persistent MH. METHODS: This retrospective observational case series comprised 16 consecutive patients (17 eyes) diagnosed with MH. Inclusion criteria involved a hole aperture diameter larger than 600 μm or the presence of an unclosed MH larger than 600 μm following the previous vitrectomy. Standard MH repair procedures were administered in all cases, involving the manipulation and aspiration of the hole margin through the application of water flow with a soft-tip flute needle. A comprehensive assessment was conducted for each case before and after surgery, and optical coherence tomography (OCT) images were captured at every follow-up point. RESULTS: The mean preoperative aperture diameter was 747±156 μm (range 611-1180 μm), with a mean base diameter of 1390±435 μm (range 578-2220 μm). Following surgery, all cases achieved complete anatomical closure of MH, with 13 cases (76.5%) exhibiting type 1 closure and 4 cases (23.5%) demonstrating type 2 closure. No significant differences were observed in the preoperative OCT variables between the two closure types. Eyes with type 1 closure showed a significantly improved visual acuity (0.70±0.10, range 0.50-0.80) compared to those with type 2 closure (0.90±0.12, range 0.80-1.00, P=0.014). CONCLUSION: The MH hydromassage technique demonstrates promising results, achieving acceptable closure rates in cases of large or persistent MH. This technique may serve as an effective adjunctive maneuver during challenging MH surgery.

BackgroundThe infant gut microbiome’s establishment is pivotal for health and immune development. Understanding it unveils insights into growth, development, and maternal microbial interactions. Research often emphasizes gut bacteria, neglecting the phageome.MethodsTo investigate the influence of geographic or maternal factors (mode of delivery, mode of breastfeeding, gestational diabetes mellitus) on the gut microbiota and phages of newborns, we collected fecal samples from 34 pairs of mothers and their infants within 24 hours of delivery from three regions (9 pairs from Enshi, 7 pairs from Hohhot, and 18 pairs from Hulunbuir) using sterile containers. Gut microbiota analysis by Shotgun sequencing was subsequently performed.ResultsOur results showed that geographic location affects maternal gut microbiology (P < 0.05), while the effect on infant gut microbiology was not significant (P = 0.184). Among the maternal factors, mode of delivery had a significant (P < 0.05) effect on the newborn. Specific bacteria (e.g., Bacteroides, Escherichia spp., Phocaeicola vulgatus, Escherichia coli, Staphylococcus hominis, Veillonella spp.), predicted active metabolites, and bacteriophage vOTUs varied with delivery mode. Phocaeicola vulgatus significantly correlated with some metabolites and bacteriophages in the early infant gut (P < 0.05). In the GD group, a strong negative correlation of phage diversity between mother and infants was observed (R = -0.58, P=0.04).ConclusionIn conclusion, neonatal early gut microbiome (including bacteria and bacteriophages) colonization is profoundly affected by the mode of delivery, and maternal gestational diabetes mellitus. The key bacteria may interact with bacteriophages to influence the levels of specific metabolites. Our study provides new evidence for the study of the infant microbiome, fills a gap in the analysis of the infant gut microbiota regarding the virome, and emphasizes the importance of maternal health for the infant initial gut virome.

Background: Prolonged or excessive use of acid suppressants may increase the risk of Clostridioides difficile infection (CDI) by altering the intestinal microecosystem. Vonoprazan, a novel potassium-competitive acid blocker, exhibits a faster and more sustained acid-suppressive effect than proton pump inhibitors (PPIs). Therefore, vonoprazan may have a greater impact on the gut microbiota, potentially resulting in CDI. Objectives: This study aimed to explore the potential relationship between acid suppressants and CDI by the Japan Adverse Drug Event Report (JADER) and the FDA Adverse Event Reporting System (FAERS) databases. Design: A retrospective analysis of the JADER and FAERS databases was examined by disproportionality analysis. Methods: We performed signal detection analyses of CDI induced by vonoprazan and PPIs using the JADER and FAERS databases. The association between acid suppressants and CDI was calculated using the reporting odds ratio (ROR) and corresponding 95% confidence interval (95% CI). When the lower limit of the 95% CI is exceeded by 1, the association is considered statistically significant. Results: In the JADER database, the ROR (95% CI) for vonoprazan and PPIs based on suspect drug reports was 15.84 (12.23–20.50) and 2.51 (1.92–3.28), respectively. In the FAERS database, the ROR (95% CI) for vonoprazan and PPIs based on primary and secondary suspect drug reports was 11.50 (6.36–20.82) and 1.42 (1.34–1.51), respectively. Subgroup analysis showed that elderly patients aged 60 years and older were more strongly associated with CDI. The ROR (95% CI) for vonoprazan and PPIs in patients aged 60 years and older in the JADER database was 15.35 (11.59–20.33) and 1.65 (1.14–2.39), respectively. Similarly, the ROR (95% CI) for vonoprazan and PPIs in the FAERS database was 12.56 (6.26–25.20) and 1.43 (1.31–1.57), respectively. Excluding the effect of Helicobacter pylori ( H. pylori ) infection, the use of acid suppressants was still associated with CDI. Conclusion: While signal detection analysis based on the JADER and FAERS databases could not establish causality, our study demonstrated that both vonoprazan and PPIs were significantly associated with CDI. Vonoprazan showed a stronger association with CDI in both databases.

BackgroundGonadotrophin-releasing hormone analogs (GnRHas) play a significant role in addressing gynecological diseases, central precocious puberty, and cancer. However, ensuring the safety of GnRHas in real-world applications requires continuous vigilance. In light of this, we undertook a disproportionality analysis focused on adverse events (AEs) associated with GnRHas using data from both the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER). We evaluated GnRHas-associated AEs and characterized the clinical priority of unlisted AEs caused by each GnRHa from the different databases.MethodsIn the disproportionality analysis, we applied two adjusted algorithms to identify signals related to GnRHas in the FAERS and JADER databases from 2004 to 2023. Additionally, we utilized the Statistical Analysis System (SAS, 9.4) to examine potential and high-aROR (adjusted reporting odds ratio) signals associated with GnRHas. We performed clinical priority assessment for suspicious PTs and an analysis of serious/non-serious outcomes. We also gathered information on the onset times of AEs linked with GnRHas from both databases.ResultsFrom January 2004 to September 2023, FAERS and JADER recorded a total of 50,360,413 and 1,440,200 AEs, respectively. Employing two algorithms, the suspicious preferred terms (PTs) related to leuprolide (Leu) were 562 potential PTs (44 unlisted in specifications), followed by goserelin (Gos) with 189 PTs (28 unlisted), triptorelin (Tri) with 172 PTs (28 unlisted), and Leu-JADER with 85 PTs (10 unlisted). At the same PT level, the differences in GnRHas between the two databases were observed, such as cardiac failure, diabetes mellitus, liver disorder, dementia, suicidal ideation, interstitial lung disease, urinary disorders, and hypertensive crisis. In an analysis of serious vs. non-serious outcomes, a total of 43 AEs of Leu were more likely to be reported as serious AEs with p < 0.05 (such as asthenia, urinary retention, diabetes mellitus, interstitial lung disease, gait disturbance, and so on), following by Tri (6 AEs), and Gos (4 AEs). Based on the clinical priority score, 41 PTs of Leu, 26 PTs of Tri, 24 PTs of Gos, and 8 PTs of Leu-JADER were graded as weak. There were 3 PTs of Leu, 2 PTs of Tri, 4 PTs of Gos, and 2 PTs of Leu-JADER that were graded as moderate. Notably, in the assessment of the relevant evidence, 2 PTs (loss of libido and urinary tract toxicity caused by Leu), 1 PT (electrolyte imbalance caused by Tri), and 2 PTs (anorexia and suicidal ideation caused by Gos) showed a strong level of evidence with “++.” The differences in the signal strength of the same PTs from two databases were also worth noting. Moreover, the median onset time for GnRHas (Leu, Tri, and Gos) was 23 days (0, 298), 22 days (0, 181), and 217 days (29, 706), respectively, as median (Q1, Q3).ConclusionAn examination of two databases revealed suspicious AEs associated with GnRHas. Our study found potential new AE signals of GnRHas and supported continuous clinical monitoring, pharmacovigilance, regional differences, and further studies of GnRHas.

Abstract Introduction Acute leukemia often affects microcirculation perfusion. This study aimed to investigate retinal microvascular changes in patients with acute leukemia without retinopathy during clinical remission using optical coherence tomography angiography (OCTA) and to determine the correlation of these changes with systemic laboratory values. Methods Thirty-eight patients in remission from acute leukemia with no retinopathy (NLR group) and 36 age-matched healthy individuals (control group) were included in this cross-sectional study. OCTA parameters, including the central foveal thickness (CFT), foveal avascular zone (FAZ) area, FAZ perimeter, acircularity index (AI), foveal density (FD300), and the vessel densities (VDs) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris were analyzed in a 6 × 6 mm2 macular scan. Correlation and multiple linear regression analyses were conducted to identify potential systemic characteristics associated with these OCTA metrics. Results AI (P = 0.034) and FD300 (P

Abstract Objective Risk stratification plays a critical role in patients with asymptomatic carotid atherosclerotic stenosis. Heavy macrophage infiltration (HMC) is an important factor of plaque destabilization. However, in vivo imaging technologies and screening criteria for HMC remain limited. We aimed to (i) introduce algorithms for in vivo detection of macrophage infiltrations using optical coherence tomography (OCT) and (ii) to investigate the threshold of HMC and its association with plaque vulnerability. Methods Ex vivo OCT images were co‐registered with histopathology in 282 cross‐sectional pairs from 19 carotid endarterectomy specimens. Of these, 197 randomly selected pairs were employed to define the parameters, and the remaining 85 pairs were used to evaluate the accuracy of the OCT‐based algorithm in detecting macrophage infiltrations. Clinical analysis included 93 patients receiving carotid OCT evaluation. The prevalence and burden of macrophage infiltration were analyzed. Multivariable and subgroup analysis were performed to investigate the association between HMC and plaque rupture. Results The sensitivity and specificity of algorithm for detecting macrophage infiltration were 88.0% and 74.9%, respectively. Of 93 clinical patients, ruptured plaques exhibited higher prevalence of macrophage infiltration than nonruptured plaques (83.7% [36/43] vs 32.0% [16/50], p

Respiratory tract infections constitute a significant global public health concern, accounting for around 20 % of child fatalities worldwide. Modulating the gut microbiota have the potential to serve as a promising strategy for both the prevention and treatment of respiratory infections. According to our prior research, the consumption of Bifidobacterium lactis Probio-M8 can notably enhance symptoms associated with respiratory tract infections in infants and young children. The current study is a follow-up work aimed at exploring the functional role of the gut microbes in the observed beneficial effects. We analyzed the fecal metagenomes of patients in both the probiotic group (n = 50) and the placebo group (n = 49). The results showed that Probio-M8 intervention may regulate the host inflammatory response by regulating the balance of intestinal microorganisms, bioactive metabolites and related pathways. Provides new insights into the study of probiotics in alleviating diseases related to the gut-lung axis.

Introduction:Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within the VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery.Methods:Transcriptome data from the Gene Expression Omnibus Database were analyzed to assess the expression of mTOR and VDR expression in human renal tissues. Clinical samples from DKD patients and minimal change disease (MCD) controls were examined, and a DKD animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection was employed to modulate the VDR-mTOR pathway, with its components evaluated using immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA).Results:Changes in the expression of the VDR-mTOR pathway were observed in both DKD patients and the animal model. Overexpression of DDIT4 increased VDR expression and decreased levels of mTOR, p70s6k, and 4E-BP1. Furthermore, DDIT4 treatment regulated autophagy by upregulating LC3I expression and downregulating LC3II expression. Notably, DDIT4 alleviated oxidative stress by reducing the levels of lipid peroxidation product MDA, while simultaneously increasing the levels of superoxide dismutase (SOD) and glutathione (GSH), underscoring the role of DDIT4 in the pathological process of DKD and its potential as a therapeutic target.Conclusion:Unraveling DDIT4’s involvement in the VDR-mTOR pathway provides insights for innovative DKD drug discovery, emphasizing its potential as a therapeutic target for future interventions.

Abstract We calculate the next-to-leading order QCD corrections to B to scalar meson form factors from QCD light-cone sum rules with B meson light-cone distribution amplitudes. We demonstrate that the B meson-to-vacuum correlation functions can be factorized into the convolution of short-distance coefficients and light-cone distribution amplitudes at the one-loop level and find that only ϕ B + $$ {\phi}_B^{+} $$ (ω, μ) contributes to the form factors. We then employ the z-parameterization combined with constraints from strong coupling constants to reconstruct the q 2 dependence of the form factors in the whole kinematic allowed regions. Due to the large cancellations between the hard functions and the jet functions, the next-to-leading order results show a modest increase of approximately 5% compared to the leading order results. Based on the results of form factors, we predict the branching ratios of semi-leptonic B → S ℓ ν ¯ ℓ $$ S\ell {\overline{\nu}}_{\ell } $$ and B → S ν ℓ ν ¯ ℓ $$ S{\nu}_{\ell }{\overline{\nu}}_{\ell } $$ processes, as well as several angular observables, such as forward-backward asymmetries, “flat terms” and lepton polarization asymmetries. We compare these results with calculations from other methods. Experimental verification of these results is required in future experiments.

2,6-pyridine dicarboxylic acid (DPA) is an exceptional biomarker of notorious anthrax spores. Therefore, the rapid, sensitive, and selective quantitative detection of DPA is extremely significant and urgent. This paper reports a Zn(II) metal–organic framework with the formula of {[Zn6(NDA)6(DPBT)3] 2H2O·3DMF}n (MOF-1), which consists of 2,6-naphthalenedicarboxylic acid (2,6-NDA), 4,7-di(4-pyridyl)-2,1,3-benzothiadiazole (DPBT), and Zn(II) ions. Structural analysis indicated that MOF-1 is a three-dimensional (3D) network which crystallized in the monoclinic system with the C2/c space group, revealing high pH, solvent, and thermal stability. Luminescence sensing studies demonstrated that MOF-1 had the potential to be a highly selective, sensitive, and recyclable fluorescence sensor for the identification of DPA. Furthermore, fluorescent test paper was made to detect DPA promptly with color changes. The enhancement mechanism was established by the hydrogen-bonding interaction and photoinduced electron transfer transition between MOF-1 and DPA molecules.

Abstract Computational machine intelligence approaches have enabled a variety of music-centric technologies in support of creating, sharing and interacting with music content. A strong performance on specific downstream application tasks, such as music genre detection and music emotion recognition, is paramount to ensuring broad capabilities for computational music understanding and Music Information Retrieval. Traditional approaches have relied on supervised learning to train models to support these music-related tasks. However, such approaches require copious annotated data and still may only provide insight into one view of music—namely, that related to the specific task at hand. We present a new model for generating audio-musical features that support music understanding, leveraging self-supervision and cross-domain learning. After pre-training using masked reconstruction of musical input features using self-attention bidirectional transformers, output representations are fine-tuned using several downstream music understanding tasks. Results show that the features generated by our multi-faceted, multi-task, music transformer model, which we call M3BERT, tend to outperform other audio and music embeddings on several diverse music-related tasks, indicating the potential of self-supervised and semi-supervised learning approaches toward a more generalized and robust computational approach to modeling music. Our work can offer a starting point for many music-related modeling tasks, with potential applications in learning deep representations and enabling robust technology applications.

Sepsis is a heterogenous syndrome with concurrent hyperinflammation and immune suppression. A prominent feature of immunosuppression during sepsis is the dysfunction and loss of monocytes; however, the major type of cell death contributing to this depletion, as well as its underlying molecular mechanisms, are yet to be identified. In this study, we confirmed the monocyte loss in septic patients based on a pooled gene expression data of periphery leukocytes. Using the collected reference gene sets from databases and published studies, we identified ferroptosis with a greater capacity to distinguish between sepsis and control samples than other cell death types. Further investigation on the molecular drivers, by a genetic algorithm-based feature selection and a weighted gene co-expression network analysis, revealed that zrt-/irt-like protein 8 (ZIP8), encoded by SLC39A8, was closely associated with ferroptosis of monocytes during sepsis. We validated the increase of ZIP8 of monocytes with in vivo and in vitro experiments. The in vitro studies also showed that downregulation of ZIP8 alleviated the lipopolysaccharide-induced lipid peroxidation, as well as restoring the reduction of GPX4, FTH1 and xCT. These findings suggest that ferroptosis might be a key factor in the loss of monocytes during sepsis, and that the heightened expression of ZIP8 may facilitate this progression.

Background The management of nonacute symptomatic internal carotid artery occlusion remains unsatisfactory. Endovascular recanalization has been reported to be feasible but associated with a noteworthy risk of postprocedural complications in patients with symptomatic internal carotid artery occlusion. The present study aimed to investigate whether successful recanalization exerts clinical benefits over procedural risks. Methods We analyzed consecutive patients who underwent endovascular treatment of nonacute symptomatic internal carotid artery occlusion in a nationwide prospective registry. The primary outcome was the ipsilateral ischemic stroke recurrence. Other outcomes of interest included all strokes and death during follow‐up, and 30‐day symptomatic intracranial hemorrhage, and all strokes after intervention. Results The final analysis included 511 patients. Endovascular revascularization was successful in 300 patients (58.7%) but failed in 211 patients (41.3%). Patients with successful recanalization had less time from the last ischemic event to the endovascular treatment as compared with patients with failed recanalization (median [interquartile range] days, 18 [12–33] versus 22 [14–50]; P=0.003). Successful recanalization was associated with a higher rate of symptomatic intracranial hemorrhage within 30 days after intervention (odds ratio [OR], 7.99 [95% CI, 1.02–62.39]; P=0.047). Thirty‐day all strokes (OR, 1.91 [95% CI, 0.83–4.40]; P=0.128) and ischemic stroke (OR, 0.90 [95% CI, 0.33–2.46]; P=0.839) did not differ significantly. During a median follow‐up of 37 months, patients with successful recanalization demonstrated a reduced risk of ipsilateral ischemic stroke (adjusted hazard ratio, 0.28 [95% CI, 0.13–0.59]; P

Background: Vonoprazan has been reported to exert more potent and long-lasting gastric acid inhibition than proton pump inhibitors, potentially leading to a greater impact on the gut microbiota. This study aimed to clarify changes in microbial diversity and bacterial composition after VPZ treatments.Methods: We searched from PubMed, Embase, WOS, Scopus, Cochrane Library, and ClinicalTrials.gov (all years up to May 2023). The primary outcomes were alpha and beta diversity, as well as differences in gut microbiota composition between before and after VPZ treatments. We performed a meta-analysis to uncover the potential changes in human gut microbiota among VPZ users by pooled mean difference (MD) with a 95% confidence interval (CI). The risk of bias was assessed using the ROBINS-I tool.Results: A total of 12 studies were included to compare differences before and after VPZ treatments. Compared with baseline, alpha diversity was significantly reduced after VPZ treatments and gradually returned to baseline with longer follow-up. At the phylum level, there was a decrease in the relative abundance of Firmicutes and Actinobacteria, while Bacteroidetes increased compared with baseline. At the genus level, we found a significant decrease in the relative abundance of Coprococcus and Bifidobacterium and a significant increase in the relative abundance of Bacteroides compared with those before treatment. In subgroup analyses according to country and participants, we found differences in microbial changes after VPZ treatments.Conclusion: Vonoprazan can affect the changes of gut microbiota, which may be potentially associated with its strong ability of acid inhibition. However, due to the large heterogeneity, further studies are required to validate these findings.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023412265.

Reducing environmental impacts and improving N utilization are critical to ensuring food security in China. Although root-zone fertilization has been considered an effective strategy to improve nitrogen use efficiency (NUE), the effect of controlled-release urea (CRU) applied in conjunction with normal urea in this mode is unclear. Therefore, a 3-year field experiment was conducted using a no-N-added as a control and two fertilization modes (FF, furrow fertilization by manual trenching, i.e., farmer fertilizer practice; HF: root-zone hole fertilization by point broadcast manually) at 210 kg N ha–1 (controlled-release:normal fertilizer=5:5), along with a 1-year in-situ microplot experiment. Maize yield, NUE and N loss were investigated under different fertilization modes. The results showed that compared with FF, HF improved the average yield and N recovery efficiency by 8.5 and 22.3% over three years, respectively. HF had a greater potential for application than FF treatment, which led to increases in dry matter accumulation, total N uptake, SPAD value and LAI. In addition, HF remarkably enhanced the accumulation of 15N derived from fertilizer by 17.2% compared with FF, which in turn reduced the potential loss of 15N by 43.8%. HF increased the accumulation of N in the tillage layer of soils at harvest for potential use in the subsequent season relative to FF. Hence, HF could match the N requirement of summer maize, sustain yield, improve NUE and reduce environmental N loss simultaneously. Overall, root-zone hole fertilization with blended CRU and normal urea can represent an effective and promising practice to achieve environmental integrity and food security on the North China Plain, which deserves further application and investigation.

AIM: To observe the effect of soluble glycoprotein 130(sgp130)on expression of p-STAT3 and vascular endothelial growth factor(VEGF)-A in retina of mice with diabetes mellitus(DM), and explore the possibility of sgp130 in interfering with inflammatory damage of diabetic retinopathy(DR).METHODS: A total of 45 mice were randomly divided into normal group, DM group and sgp130 group. DM models were made in DM group and sgp130 group with streptozotocin. No special intervention was given to normal group and DM group, but sgp130 group was given intravitreal injection of 1.5mg/mL sgp130 2μL at the 1 and 5wk. After 10wk, all the mice were sacrificed to assess the protein expression of interleukin 6(IL-6), p-STAT3 and VEGF-A in the retina.RESULTS: The expressions of IL-6, p-STAT3 and VEGF-A in retina of DM group were higher than those of normal group at 10wk(all P

Novel potassium-competitive acid blockers (P-CABs) have emerged as effective acid-suppressive drugs in recent years, replacing proton pump inhibitors (PPIs). We aim to compare the efficacy and safety of P-CABs versus PPIs in the treatment of peptic ulcers with or without Helicobacter pylori (H. pylori) infection. We searched in PubMed, Embase, WOS, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases (all years up to January 2024). Efficacy and safety outcomes were evaluated using odds ratio (OR) and 95% confidence intervals (CI). The Surface Under the Cumulative Ranking (SUCRA) probabilities were used to rank each intervention. Among 14,056 studies screened, 56 studies involving 9792 participants were analyzed. Vonoprazan demonstrated the best efficacy in ulcer healing rate and H. pylori eradication rate (SUCRA = 86.4% and 90.7%, respectively). Keverprazan ranked second in ulcer healing rates (SUCRA = 76.0%) and was more effective in pain remission rates (SUCRA = 91.7%). The risk of adverse events was low for keverprazan (SUCRA = 11.8%) and tegoprazan (SUCRA = 12.9%), and moderate risk for vonoprazan (SUCRA = 44.3%) was demonstrated. Compared to lansoprazole, vonoprazan exhibited a higher risk of drug-related adverse events (OR: 2.15; 95% CI: 1.60–2.89) and serious adverse events (OR: 2.22; 95% CI: 1.11–4.42). Subgroup analysis on patients with H. pylori-positive peptic ulcers showed that vonoprazan was at the top of the SUCRA rankings, followed by keverprazan. Vonoprazan showed superior performance in peptic ulcers, especially for patients with H. pylori-positive peptic ulcers. However, the risk of adverse events associated with vonoprazan should be noted. Keverprazan has also shown good therapeutic outcomes and has performed better in terms of safety.

Corrosion behavior is critical to the application of lightweight aluminum/steel joints using new resistance spot welding (RSW) technology. The study investigated the corrosion mechanism and the shear strength of RSW joints comprising 1.2 mm 5182 aluminum and 1.5 mm DP780 galvanized steel. Electrochemical corrosion tests were conducted on the base materials and various positions of the welds in a 3.5% NaCl solution. This result revealed that the corrosion susceptibility of the interfacial intermetallic compound (IMC) layer was not accelerated by the aluminum nugget because of the noble corrosion potential. Subsequently, the spray acceleration test was employed to investigate the corrosion mechanism. It is noteworthy that microcracks, as well as regions enriched with silicon and oxygen at the interface front, are preferential to corrosion during salt spray exposure, instead of the IMC layer. Moreover, the shear strength of the joints decreases with the reduction in the effective joint area after the salt spray exposure of the weld joints. This research systematically explored the corrosion behavior and its relationship with the mechanical properties of Al alloy/steel RSW joints.

To protect the security of medical images and to improve the embedding ability of data in encrypted medical images, this paper proposes a permutation ordered binary (POB) number system-based hiding and authentication scheme for medical images, which includes three parts: image preprocessing, double hiding, and information extraction and lossless recovery. In the image preprocessing and double hiding phase, firstly, the region of significance (ROS) of the original medical image is segmented into a region of interest (ROI) and a region of non-interest (RONI). Then, the bit plane of the ROI and RONI are separated and cross-reorganization to obtain two new Share images. After the two new Share images are compressed, the images are encrypted to generate two encrypted shares. Finally, the embedding of secret data and attaching of authentication bits in each of these two encrypted shares was performed using the POB algorithm. In the information extraction and lossless recovery phase, the POBN algorithm is first used to extract the authentication bits to realize image tamper detection; then, the embedded secret message is extracted, and the original medical image is recovered. The method proposed in this research performs better in data embedding and lossless recovery, as demonstrated by experiments.

The new energy automobile industry is a comprehensive system that contains Exploration and Manufacture, Consumption and Promotion, Infrastructure Construction and Supporting Industries, which coordinate and supplement with each other. Accordingly, from the perspective of policy object, NEVs policies since 1991 to 2022 could be divided into four fields in China. With policy bibliometric analysis and social network analysis, in each field of policies, its policy networks can be drawn, with statistic of policies released separately, in order to comprehensively analyse the features of NEVs policy making. It is found that: (1) The structure of policy system is balanced among four fields of NEVs policies in China, though with a bias towards Consumption & Promotion, Exploration & Manufacture. (2) Policy makers in all four fields of NEVs policies preferred slightly to formulate policies jointly, rather than acting alone. While policies made by sole actors are part of policy system. (3) GOOSC, MIIT and MOT, as sole actor, played more significant roles in industry-wide, supply-side and demand-side of NEVs industry respectively. (4) Policy networks of all four fields started with the “iron four” (MIIT, NDRC, MOF, MOST), ultimately forming two different ways of development, specialization and sociability. (5) In addition to the government departments, social organizations and enterprises also influenced the policy network, at the edge of network. This paper is of positive significance for understanding the current status and characteristics of policy making in different fields of the NEV industry, beneficial to distinguish potential effective ways to impact on NEVs policy system in China.

Abstract Ultrasonic fluid bubble detection is important in industrial controls, aerospace systems and clinical medicine because it can prevent fatal mechanical failures and threats to life. However, current ultrasonic technologies for bubble detection are based on conventional bulk PZT-based transducers, which suffer from large size, high power consumption and poor integration with ICs and thus are unable to implement real-time and long-term monitoring in tight physical spaces, such as in extracorporeal membrane oxygenation (ECMO) systems and dialysis machines or hydraulic systems in aircraft. This work highlights the prospect of capacitive micromachined ultrasonic transducers (CMUTs) in the aforementioned application situations based on the mechanism of received voltage variation caused by bubble-induced acoustic energy attenuation. The corresponding theories are established and well validated using finite element simulations. The fluid bubbles inside a pipe with a diameter as small as 8 mm are successfully measured using our fabricated CMUT chips with a resonant frequency of 1.1 MHz. The received voltage variation increases significantly with increasing bubble radii in the range of 0.5–2.5 mm. Further studies show that other factors, such as bubble positions, flow velocities, fluid medium types, pipe thicknesses and diameters, have negligible effects on fluid bubble measurement, demonstrating the feasibility and robustness of the CMUT-based ultrasonic bubble detection technique.

Abstract Background The TREM2 R47H variant is one of the strongest genetic risk factors for late-onset Alzheimer’s Disease (AD). Unfortunately, many current Trem2 R47H mouse models are associated with cryptic mRNA splicing of the mutant allele that produces a confounding reduction in protein product. To overcome this issue, we developed the Trem2 R47H NSS (Normal Splice Site) mouse model in which the Trem2 allele is expressed at a similar level to the wild-type Trem2 allele without evidence of cryptic splicing products. Methods Trem2 R47H NSS mice were treated with the demyelinating agent cuprizone, or crossed with the 5xFAD mouse model of amyloidosis, to explore the impact of the TREM2 R47H variant on inflammatory responses to demyelination, plaque development, and the brain’s response to plaques. Results Trem2 R47H NSS mice display an appropriate inflammatory response to cuprizone challenge, and do not recapitulate the null allele in terms of impeded inflammatory responses to demyelination. Utilizing the 5xFAD mouse model, we report age- and disease-dependent changes in Trem2 R47H NSS mice in response to development of AD-like pathology. At an early (4-month-old) disease stage, hemizygous 5xFAD/homozygous Trem2 R47H NSS (5xFAD/Trem2 R47H NSS) mice have reduced size and number of microglia that display impaired interaction with plaques compared to microglia in age-matched 5xFAD hemizygous controls. This is associated with a suppressed inflammatory response but increased dystrophic neurites and axonal damage as measured by plasma neurofilament light chain (NfL) level. Homozygosity for Trem2 R47H NSS suppressed LTP deficits and loss of presynaptic puncta caused by the 5xFAD transgene array in 4-month-old mice. At a more advanced (12-month-old) disease stage 5xFAD/Trem2 R47H NSS mice no longer display impaired plaque-microglia interaction or suppressed inflammatory gene expression, although NfL levels remain elevated, and a unique interferon-related gene expression signature is seen. Twelve-month old Trem2 R47H NSS mice also display LTP deficits and postsynaptic loss. Conclusions The Trem2 R47H NSS mouse is a valuable model that can be used to investigate age-dependent effects of the AD-risk R47H mutation on TREM2 and microglial function including its effects on plaque development, microglial-plaque interaction, production of a unique interferon signature and associated tissue damage.

Abstract Introduction It remains controversial whether polypoidal choroidal vasculopathy (PCV) represents a subtype of neovascular age-related macular degeneration (nAMD) or is a distinct disease entity. This study aimed to compare and analyze systemic and serum risk factors for nAMD and PCV in an aging Chinese population. Methods A retrospective study was performed on 108 patients with nAMD, 131 patients with PCV, and 219 control subjects. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (APOA1), apolipoprotein B (APOB), complement 3 (C3), and complement 4 (C4) together with data on systemic risk factors, including hyperlipidemia, hypertension, diabetes mellitus (DM), coronary artery disease (CAD), and asthma, were collected. Chi-square tests, independent-samples t tests, and binary logistic regression analyses were performed to evaluate the associations of risk factors with nAMD and PCV. Results Patients with PCV and those with nAMD were likely to have hyperlipidemia (P 0.05), DM was associated with PCV development (OR = 0.535, P = 0.044). Regarding serum risk factors, HDL, LDL, TG, APOB, and C3 were significantly associated with nAMD (OR 0.05). Conclusion Our findings indicate that hyperlipidemia is significantly associated with both nAMD and PCV. Serum lipid and complement levels have an effect on the pathogenesis of nAMD and PCV, and consideration of the differences between systemic and serum risk factors should be taken into account in clinical management.

Background: A number of patients with Crohn’s disease (CD) suffer from loss of response to infliximab (IFX) therapy. Splenic volume is reported to be enlarged in patients with CD compared to normal individuals. The association between splenic volume and IFX efficacy in CD remains unclear.Methods: We performed a retrospective study of patients with CD who received regular IFX treatment at Zhongshan Hospital, Fudan University, between August 2015 and December 2021. We collected baseline characteristics and clinical features from medical records in the CD database of Zhongshan Hospital. We accurately measured the splenic volume using semi-auto spleen segmentation software, followed by the analysis of splenic volume and IFX efficacy.Results: We included 49 patients with CD receiving IFX treatment, of whom 41 responded to IFX and 8 failed to respond to IFX. Splenic volume, as well as volume adjusted for body mass index (SV/BMI) and body weight (SV/W), was significantly decreased after IFX treatment in responders but increased in non-responders compared to the volume before the treatment. Accordingly, the levels of leukocyte count, platelet count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were decreased after IFX treatment in responders. Contrarily, the levels of hemoglobin, albumin, and tumor necrosis factor (TNF)-α were elevated in responders. Moreover, both CRP and TNF-α levels were significantly positively correlated with SV/BMI in all patients.Conclusion: Splenic volume, especially SV/BMI and SV/W, was reduced after IFX treatment in CD patients responsive to IFX. SV/BMI was positively correlated with disease activity. Splenic volume is a promising indicator to evaluate IFX efficacy in CD.

Uremic toxins are chemicals, organic or inorganic, that accumulate in the body fluids of individuals with acute or chronic kidney disease and impaired renal function. More than 130 uremic solutions are included in the most comprehensive reviews to date by the European Uremic Toxins Work Group, and novel investigations are ongoing to increase this number. Although approaches to remove uremic toxins have emerged, recalcitrant toxins that injure the human body remain a difficult problem. Herein, we review the derivation and elimination of uremic toxins, outline kidney–gut axis function and relative toxin removal methods, and elucidate promising approaches to effectively remove toxins.

Protein tyrosine phosphatases (PTPs) are ubiquitous in living organisms and are promising drug targets for cancer, diabetes/obesity, and autoimmune disorders. In this study, a histone deacetylase inhibitor called suberoylanilide hydroxamic acid (SAHA) was added to a culture of marine fungi (Aspergillus sydowii DL1045) to identify potential drug candidates related to PTP inhibition. Then, the profile of the induced metabolites was characterized using an integrated metabolomics strategy. In total, 46% of the total SMs were regulated secondary metabolites (SMs), among which 20 newly biosynthesized metabolites (10% of the total SMs) were identified only in chemical epigenetic regulation (CER) broth. One was identified as a novel compound, and fourteen compounds were identified from Aspergillus sydowii first. SAHA derivatives were also biotransformed by A. sydowii DL1045, and five of these derivatives were identified. Based on the bioassay, some of the newly synthesized metabolites exhibited inhibitory effects on PTPs. The novel compound sydowimide A (A11) inhibited Src homology region 2 domain-containing phosphatase-1 (SHP1), T-cell protein tyrosine phosphatase (TCPTP) and leukocyte common antigen (CD45), with IC50 values of 1.5, 2.4 and 18.83 μM, respectively. Diorcinol (A3) displayed the strongest inhibitory effect on SHP1, with an IC50 value of 0.96 μM. The structure–activity relationship analysis and docking studies of A3 analogs indicated that the substitution of the carboxyl group reduced the activity of A3. Research has demonstrated that CER positively impacts changes in the secondary metabolic patterns of A. sydowii DL1045. The compounds produced through this approach will provide valuable insights for the creation and advancement of novel drug candidates related to PTP inhibition.

Familial exudative vitreoretinopathy (FEVR) is a complex hereditary eye disorder characterized by incomplete development of the retinal vasculature, which thereby affects retinal angiogenesis. But the genetic factors contributing to FEVR’s development or pathogenesis remain elusive. In a Chinese family with FEVR with 19 members, by using whole-exome sequencing, we identified a candidate disease-causing DNA variant in sorting nexin 31 (SNX31) (c.963delG; p. Trp321Cys), which results in a frameshift mutation. We studied the biochemical mechanism of this mutation and determined that it is deficient in β1-integrin binding and stability. The SNX31 c.963delG point mutation mouse model (SNX31m/m) was constructed with CRISPR/Cas9 technology. At 2–4 months of age, SNX31m/m mice showed fundus phenotypes similar to FEVR-like changes, including vascular leakage and retinal atrophy. Moreover, we found that VEGF and apoptotic pathways were involved in these ocular phenotypes. Hence, our study extended the FEVR mutation spectrum to include SNX31. These findings expanded our understanding of the molecular pathogenesis of FEVR and may facilitate the development of methods for the diagnosis and prevention of FEVR.

“Ulvophyceae is a remarkably morphologically and ecologically diverse clade of green algae. Here, the authors reconstruct the Ulvophyceae phylogeny, showing that these algae originated earlier than expected and may have influenced biogeochemical cycles at the Mesoproterozoic-Neoproterozoic transition.”

BackgroundAutophagy refers to the process in which cells wrap their damaged organelles or unwanted proteins into a double-membrane structure and direct them to lysosomes for degradation. Autophagy can regulate many lung diseases such as pulmonary hypertension, acute lung injury, and lung cancer. However, few bibliometric studies on autophagy are available. The aim of the present study was to clarify the role of autophagy in lung diseases by bibliometric analysis.MethodsPublications were retrieved from the 2012–2021 Science Citation Index Expanded of Web of Science Core Collection on 20 September 2022. Bibliometrix package in R software was used for data retrieval. VOSviewer and CiteSpace were used to visualize the research focus and trend regarding the effect of autophagy on lung disease.ResultsA total of 4,522 original articles and reviews on autophagy in lung diseases published between 2012 and 2021 were identified. China had the largest number of published papers and citations, whereas the United States (US) ranked first in the H-index and G-index. Moreover, cooperation network analysis showed close cooperation between the US, China, and some European countries, and the top 10 affiliates were all from these countries and regions. Bibliometric analysis showed that “autophagy” and “apoptosis” were the keywords with the highest frequency. During the past decade, most studies were concerned with basic research on pathways related to the regulatory role of autophagy in the inhibition and attenuation of lung diseases.ConclusionThe study of autophagy in lung diseases is still in the development stage. The information published in these articles has helped researchers understand further the hot spots and development trends in the field more and learn about the collaboration network information regarding authors, countries, and institutions, as well as the paper citation correlation. More studies have been performed to gain deeper insights into the pathogenesis of autophagy by focusing on the links and effects between various diseases. More recently, research in this field has paid increasing attention to the function of autophagy in COVID-19–related lung diseases.

Endogenous small molecules are metabolic regulators of cell function. Itaconate is a key molecule that accumulates in cells when the Krebs cycle is disrupted. Itaconate is derived from cis-aconitate decarboxylation by cis-aconitate decarboxylase (ACOD1) in the mitochondrial matrix and is also known as immune-responsive gene 1 (IRG1). Studies have demonstrated that itaconate plays an important role in regulating signal transduction and posttranslational modification through its immunoregulatory activities. Itaconate is also an important bridge among metabolism, inflammation, oxidative stress, and the immune response. This review summarizes the structural characteristics and classical pathways of itaconate, its derivatives, and the compounds that release itaconate. Here, the mechanisms of itaconate action, including its transcriptional regulation of ATF3/IκBζ axis and type I IFN, its protein modification regulation of KEAP1, inflammasome, JAK1/STAT6 pathway, TET2, and TFEB, and succinate dehydrogenase and glycolytic enzyme metabolic action, are presented. Moreover, the roles of itaconate in diseases related to inflammation and oxidative stress induced by autoimmune responses, viruses, sepsis and IRI are discussed in this review. We hope that the information provided in this review will help increase the understanding of cellular immune metabolism and improve the clinical treatment of diseases related to inflammation and oxidative stress.

Abstract PM2.5 has an impact on residents' physical health during travelling, especially walking completely exposed to the environment. In order to obtain the specific impact of PM2.5 on walking, 368 healthy volunteers were selected and they were grouped according to gender and age. In the experiment, the heart rate change rate (HR%) is taken as test variable. According to receiver operating characteristic (ROC) curve, the travel is divided into two states: safety and risk. Based on this, a binary logit model considering Body Mass Index (BMI) is established to determine the contribution of PM2.5 concentration and body characteristics to travel risk. The experiment was conducted on Chang'an Middle Road in Xi'an City. The analysis results show that the threshold of HR% for safety and risk ranges from 31.1 to 40.1%, and that of PM2.5 concentration ranges from 81 to 168 μg/m3. The probability of risk rises 5.8% and 11.4%, respectively, for every unit increase in PM2.5 concentration and HR%. Under same conditions, the probability of risk for male is 76.8% of that for female. The probability of risk for youth is 67.5% of that for middle-aged people, and the probability of risk for people with BMI in healthy range is 72.1% of that for non-healthy range. The research evaluates risk characteristics of walking in particular polluted weather, which can improve residents’ health level and provide suggestions for travel decision while walking.

BackgroundPyroptosis is a lytic pro-inflammatory programmed cell death mode that depends on caspase, inflammasome, and Gasdermin D (GSDMD). A growing number of studies have shown that pyroptosis is closely related to the pathophysiological mechanism of lung. The purpose of this study is to analyze the literature from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC) and visualize the current trends and hotspots in the research of pyroptosis in lung disease.MethodsOn February 20, 2022, we retrieved all articles on pyroptosis in lung disease from SCI-expanded of WoSCC. Original articles and reviews published in English from 2007 to 2021 were included in the analysis. VOSviewer 1.6.17 and CiteSpace 5.8.R2 were used to analyze the retrieved data and visualize the results.Result1798 qualified original articles and reviews on pyroptosis in lung disease were included in the bibliometric analysis. So far, the research in this field is still in a period of growth, and the number of global publications has increased yearly. Among the 66 countries that have published relevant articles, China ranked first in the number of publications, and the USA ranked first in the number of cited articles. Holian,A. was the author with the largest number of articles, including 21 published. The University of California System in the USA was the organization with the largest number of articles, totaling 55. Frontiers in Immunology was the journal with the most publications in pyroptosis. After bibliometric analysis, the frequently used keywords are: “NOD-like receptor3 (NLRP3) inflammasome”, “inflammation”, “oxidative stress”, and “acute lung injury (ALI)”.ConclusionThe research on pyroptosis in lung disease is in its growth stage. The information released in this article may help researchers better understand the hotspots and developmental trends in this field, the cooperation network information of authors, countries, and institutions, and the citation correlation between articles. With the in-depth study of the mechanism of pyroptosis, the focus has shifted to increasing research on the connections and influences of different diseases. So far, increasing attention has been paid to the research field of the relationship between ALI and pyroptosis related to COVID-19.

Abstract Background Tumor-associated macrophages (TAM) are immunosuppressive cells that contribute to impaired anti-cancer immunity. Iron plays a critical role in regulating macrophage function. However, it is still elusive whether it can drive the functional polarization of macrophages in the context of cancer and how tumor cells affect the iron-handing properties of TAM. In this study, using hepatocellular carcinoma (HCC) as a study model, we aimed to explore the effect and mechanism of reduced ferrous iron in TAM. Methods TAM from HCC patients and mouse HCC tissues were collected to analyze the level of ferrous iron. Quantitative real-time PCR was used to assess M1 or M2 signature genes of macrophages treated with iron chelators. A co-culture system was established to explore the iron competition between macrophages and HCC cells. Flow cytometry analysis was performed to determine the holo-transferrin uptake of macrophages. HCC samples from The Cancer Genome Atlas (TCGA) were enrolled to evaluate the prognostic value of transferrin receptor (TFRC) and its relevance to tumor-infiltrating M2 macrophages. Results We revealed that ferrous iron in M2-like TAM is lower than that in M1-like TAM. In vitro analysis showed that loss of iron-induced immunosuppressive M2 polarization of mouse macrophages. Further experiments showed that TFRC, the primary receptor for transferrin-mediated iron uptake, was overexpressed on HCC cells but not TAM. Mechanistically, HCC cells competed with macrophages for iron to upregulate the expression of M2-related genes via induction of HIF-1α, thus contributing to M2-like TAM polarization. We further clarified the oncogenic role of TFRC in HCC patients by TCGA. TFRC is significantly increased in varieties of malignancies, including HCC, and HCC patients with high TFRC levels have considerably shortened overall survival. Also, TFRC is shown to be positively related to tumor-infiltrating M2 macrophages. Conclusions Collectively, we identified iron starvation through TFRC-mediated iron competition drives functional immunosuppressive polarization of TAM, providing new insight into the interconnection between iron metabolism and tumor immunity.

Objective To investigate the current situation, motivation, difficulties and needs of young physicians participating in teaching activities in internal medicine department at PUMCH. Methods We surveyed young attendings and residents who worked at internal medicine wards of Peking Union Medical College Hospital from November 2018 to October 2019 about their current tasks, motivation, difficulties and needs in terms of teaching. Results Based on visual Analog Scale, the mean score of attendings'interest in teaching is 8.0±1.8, and teaching work accounted for 25.3%±14.1% of all working hours. The most important motivation for teaching is self-improvement via teaching. The biggest difficulty faced by attendings is high pressure on clinical and research work (72.4%, 42/58). The most voted need is to increase the impact of teaching on promotion (48.3%, 28/58). The mean score of residents'interest in teaching is 7.5±1.8,and teaching work accounted for 24.8%±15.2% of all working hours. The most important motivation for teaching is self-improvement via teaching. The biggest difficulties faced by residents include high pressure on clinical and research work (50.6%, 41/81) and lack of teaching skills (25.9%, 21/81), etc. The most voted need is teaching skill trainings (42%, 34/81). Conclusions Young physicians are highly motivated to teaching with self-improvement as the main driving force. Measures should be taken to support young physicians to better balance clinical, research and teaching, and to improve their teaching results.

Sorafenib resistance is often developed and impedes the benefits of clinical therapy in hepatocellular carcinoma (HCC) patients. However, the relationship between sorafenib resistance and tumor immune environment and adjuvant drugs for sorafenib-resistant HCC are not systemically identified. This study first analyzed the expression profiles of sorafenib-resistant HCC cells to explore immune cell infiltration levels and differentially expressed immune-related genes (DEIRGs). The prognostic value of DEIRGs was analyzed using Cox regression and Kaplan–Meier analysis based on The Cancer Genome Atlas. The primary immune cells infiltrated in sorafenib-resistant HCC mice were explored using flow cytometry (FCM). Finally, small-molecule drugs for sorafenib-resistant HCC treatment were screened and validated by experiments. The CIBERSORT algorithm and mice model showed that macrophages and neutrophils are highly infiltrated, while CD8+ T cells are downregulated in sorafenib-resistant HCC. Totally, 34 DEIRGs were obtained from sorafenib-resistant and control groups, which were highly enriched in immune-associated biological processes and pathways. NR6A1, CXCL5, C3, and TGFB1 were further identified as prognostic markers for HCC patients. Finally, nalidixic acid was identified as a promising antagonist for sorafenib-resistant HCC treatment. Collectively, our study reveals the tumor immune microenvironment changes and explores a promising adjuvant drug to overcome sorafenib resistance in HCC.

PurposeTo evaluate capillaries perfusion and retinal nerve fiber layer (RNFL) thickness diurnal changes of macular/optic disc regions among participants with or without obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA).MethodsIn this study, we enrolled a cohort of 35 participants including 14 patients with mild-to-moderate OSA, 12 patients with severe OSA, and 9 healthy individuals. All participants had Berlin questionnaire filled. At 20:00 and 6:30, right before and after the polysomnography examination, a comprehensive ocular examination was conducted. The systemic and ocular clinical characteristics were collected, and OCTA scans were performed repeatedly. Blood flow and RNFL thickness parameters were then exported using built-in software and analyzed accordingly.ResultsAfter sleep, the overall vessel density (VD) variables, especially macular and choriocapillaris VDs, were relatively comparative and stable. One exception was the RPC vessel density at the inside-disc region with a decreasing trend in the mild-to-moderate group (p=0.023). RNFL changes before and after sleep in the nasal-inferior and peripapillary region were statistically significant (p=0.003; p=0.043) among three groups. And multiple testing correction verified the significant difference in diurnal changes between the mild-to-moderate group and the control group in pairwise comparisons (p=0.006; p=0.02).ConclusionsThe changes of imperceptible blood flow and RNFL thickness overnight around optic disc areas could be observed in OSA patients. Despite physiological fluctuations, aberrant diurnal changes might be useful for identifying a decrease in micro-environmental stability associated with the development of various ocular diseases such as glaucoma. Other VD variables, especially macular and choriocapillaris VDs, are relatively stable in eyes of patients having OSA with different severity.

Background and purposeThis study aimed to explore the association between triglyceride–glucose (TyG) index and stroke recurrence in elderly patients with ischemic stroke in China.MethodsWe enrolled ischemic stroke patients aged ≥ 65 years from the Nanjing Stroke Registry Program. The primary endpoint was defined as recurrent stroke within one year after the index stroke. We used multivariable Cox proportional hazards regression models to investigate the association between TyG index and stroke recurrence. We assessed the discriminative ability of TyG index with the receiver operative characteristic and the area under the curve.ResultsA total of 955 patients (median age, 70.0 [67.0, 75.0]; male sex, 67.2%) from the Nanjing Stroke Registry Program were enrolled. During one year follow-up, 97 (10.2%) elderly patients experienced stroke recurrence. In multivariable analyses, the association between TyG index and stroke recurrence remained significant after adjusting for confounders (quartile 4 versus quartile 1; hazard ratio, 2.073, 95% confidence interval, 1.158-3.711; P = 0.014). The restricted cubic spline showed an increasing trend for TyG index and stroke recurrence (P for non-linearity = 0.072). The area under the curve to predict stroke recurrence with TyG index was 0.719 (95% confidence interval, 0.666-0.772). Besides, TyG index slightly improved the prediction for stroke recurrence.ConclusionElevated TyG index was associated with stroke recurrence in elderly patients with ischemic stroke. Further studies are warranted to assess the role of TyG index in the development of stroke recurrence in the elderly.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Fatty acid metabolism takes part in malignancy progression. However, the roles fatty acid metabolism plays in LUAD are still unclear.Methods: The transcriptomic and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were extracted. ssGSEA, WGCNA, univariable Cox regression, and LASSO Cox regression analyses were performed to identify the fatty acid metabolism-related genes which influenced the overall survival (OS) and build a fatty acid-related risk score (FARS) model. A nomogram was established based on the FARS and other clinicopathological features, and ROC and calibration plots were used to validate the prediction accuracy. The tumor microenvironment (TME) of patients with high and low FARS was compared.Results: A total of 38 genes were identified to be independently related to the survival outcome and put into a FARS model. High FARS patients exhibited significantly worse OS. The nomogram included the FARS and pathological stage, and the AUC of the nomogram predicting 1-, 2-, 3-, 4-, and 5-year OS was 0.789, 0.807, 0.798, 0.809, and 0.753, respectively. Calibration plots also indicated good accuracy. Moreover, the samples of the high FARS had higher expression of PDL1.Conclusion: We constructed a FARS model which could accurately predict the survival outcome of the LUAD patients. The genes of the FARS are related to the tumor microenvironment and patients with high FARS can potentially benefit more from anti-PD1/PDL1 immunotherapy. In addition, the mechanisms of the genes in the FARS affecting prognosis are worthy of further research to develop new gene-targeted drugs.

Background and aimsCyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) are key components of the innate immune system. This study aims to evaluate the research of cGAS-STING pathway and predict the hotspots and developing trends in this field using bibliometric analysis.MethodsWe retrieved publications from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC) in 1975-2021 on 16 March 2022. We examined the retrieved data by bibliometrix package in R software, VOSviewer and CiteSpace were used for visualizing the trends and hotspots of research on the cGAS-STING pathway.ResultsWe identified 1047 original articles and reviews on the cGAS-STING pathway published between 1975 and 2021. Before 2016, the publication trend was increasing steadily, but there was a significant increase after 2016. The United States of America (USA) produced the highest number of papers (Np) and took the highest number of citations (Nc), followed by China and Germany. The University of Texas System and Frontiers in Immunology were the most prolific affiliation and journal respectively. In addition, collaboration network analysis showed that there were tight collaborations among the USA, China and some European countries, so the top 10 affiliations were all from these countries and regions. The paper published by Sun LJ in 2013 reached the highest local citation score (LCS). Keywords co-occurrence and co-citation cluster analysis revealed that inflammation, senescence, and tumor were popular terms related to the cGAS-STING pathway recently. Keywords burst detection suggested that STING-dependent innate immunity and NF-κB-dependent broad antiviral response were newly-emerged hotspots in this area.ConclusionsThis bibliometric analysis shows that publications related to the cGAS-STING pathway tend to increase continuously. The research focus has shifted from the mechanism how cGAS senses dsDNA and cGAMP binds to STING to the roles of the cGAS-STING pathway in different pathological state.

Purpose: To reveal molecular mechanisms of diabetic retinopathy (DR) in Asians and facilitate the identification of new therapeutic targets through untargeted metabolomics. To determine the differences in serum metabolites and metabolic pathways between different stages of diabetic retinopathy in patients with type 2 diabetic mellitus (T2DM) and proliferative DR (PDR) and non-proliferative DR (NPDR) and identify differential metabolites between T2DM and DR (NPDR and PDR) patients.Methods: This prospective observational registration study described the differential metabolites between 45 T2DM patients and 15 control cases with no significant differences in clinical characteristics. Their biospecimens and clinical information were collected and recorded in their medical reports. DR phenotypes of the subjects were verified by retina specialists. Serum metabolites were analyzed using high-resolution mass spectrometry with liquid chromatography. Untargeted metabolomics was performed on serum samples from 15 T2DM patients, 15 non-proliferative diabetic retinopathy patients, 15 proliferative diabetic retinopathy patients, and 15 diabetic controls. Discriminatory metabolic features were identified through partial least squares discriminant analysis (PLS-DA), hierarchical clustering analysis (HCA), and generalized linear regression models.Result: Through untargeted metabolomics, 931 features (523 in positive and 408 in negative modes) with 102 common metabolites highly relevant to the presence of DR were detected. In the adjusted analysis, 67 metabolic features differed significantly between T2DM and NPDR patients. Pathway analysis revealed alterations in metabolisms of amino acids and fatty acids. Glutamate, phosphatidylcholine, and 13-hydroperoxyoctadeca-9,11-dienoic acid (13-PHODE) were key contributors to these pathway differences. A total of 171 features distinguished PDR patients from T2DM patients, and pathway analysis revealed alterations in amino acid metabolism, fatty acid metabolism, nitrogen metabolism, and tricarboxylic acid cycle. Aspartate, glutamate, glutamine, ornithine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, citrate, succinate, N-(L-arginino)succinate, 2-oxoglutarate, 13-hydroperoxyoctadeca-9,11-dienoic acid, methionine, lysine, threonine, phenylalanine, N(pi)-methyl-l-histidine, phosphatidylcholine, and linoleate were major contributors to the pathway differences. Between NPDR patients and PDR patients, there were 79 significant differential metabolites. Enrichment pathway analysis showed changes in amino acid metabolism, fatty acid metabolism, pantothenate, and CoA biosynthesis. Aspartate, glutamine, N-acetyl-l-glutamate, N-acetyl-l-aspartate, pantothenate, dihomo-gamma-linolenate, docosahexaenoic acid, and icosapentaenoic acid were key factors for the differences of these pathways.Conclusion: This study demonstrated that the pathways of arginine biosynthesis metabolism, linoleic acid metabolism, alanine, aspartate, and glutamate metabolism, as well as d-glutamine and d-glutamate metabolism, were dysregulated in DR patients of the Asian population. Increased levels of glutamate, aspartate, glutamine, N-acetyl-l-glutamate, and N-acetyl-l-aspartate and decreased levels of dihomo-gamma-linolenate, docosahexaenoic, and icosapentaenoic were considered as the metabolic profile that could distinguish PDR from NPDR in Asians. Phosphatidylcholine and 13-PHODE were identified as two major novel metabolite markers in advanced stages of DR in our study.

BackgroundThis study discusses the developmental trends and research hotspots in bronchoscopy anesthesia in the past six decades.MethodsThe original and review articles published from 1975 to June 2021 related to bronchoscopy anesthesia were retrieved from the Web of Science Core Collection (WoSCC). Three different scientometric tools (CiteSpace, VOSviewer, and Bibliometrix) were used for this comprehensive analysis.ResultsThere was a substantial increase in the research on bronchoscopy anesthesia in recent years. A total of 1,270 publications were retrieved up to June 25, 2021. Original research articles were 1,152, and reviews were 118, including 182 randomized controlled trials (RCTs). These publications were cited a total of 25,504 times, with a mean of 20.08 citations per publication. The US had the largest number of publications (27.6%) and the highest H-index of 44. The sum of publications from China ranked second (11.5%), with an H-index of 17. Keyword co-occurrence and references co-citation visual analysis showed that the use of sedatives such as dexmedetomidine in the process of bronchoscopy diagnosis and treatment was gradually increasing, indicating that bronchoscopy anesthesia was further progressing toward safety and comfort.ConclusionBased on a bibliometric analysis of the publications over the past decades, a comprehensive analysis indicated that the research of bronchoscopy anesthesia is in a period of rapid development and demonstrated the improvement of medical instruments and surgical options that have significantly contributed to the field of bronchoscopy anesthesia. The data would provide future directions for clinicians and researchers in relation to bronchoscopy anesthesia.

With the imminent threat of the energy crises, innovation in energy technologies is happening world-wide. The aim is to reduce our reliance on fossil fuels. Electric vehicles with fuel-cells that use hydrogen as an energy carrier are touted to be one of the most important potential replacements of the gasoline vehicle in both future transportation scenarios and emerging smart energy grids. However, hydrogen storage is a major technical barrier that lies between where we are now and the mass application of hydrogen energy. Further exploration of onboard hydrogen storage systems (OHSS) is urgently needed and, in this regard, a comprehensive technology opportunity analysis will help. Hence, with this research, we drew on scientific papers and patents related to OHSS and developed a novel methodology for investigating the past, present, and future development trends in OHSS. Specifically, we constructed a heterogeneous knowledge network using a unique multi-component structure with three core components: hydrogen carriers, hydrogen storage materials, and fuel cells. From this network, we extracted both the developed and underdeveloped technological solutions in the field and applied a well-designed evaluation system and prediction model to score the future development potential of these technological solutions. What emerged was the most promising directions of research in the short, medium, and long term. The results show that our methodology can effectively identify technology opportunities in OHSS, along with providing valuable decision support to researchers and enterprise managers associated with the development and application of OHSS.

Radiation-induced lung injuries (RILI) is one of the serious complications of radiotherapy posed by the damage of alveolar cells and inflammation over-reaction. We aimed to investigate the potential protective effects of doxepin on RILI (20 Gy total dose at 3 Gy/min of X-ray irradiation), as well as its underlying mechanism. For animal experiments, such parameters as Immunohistochemistry and hematoxylin and eosin (H&E) staining, WBC (white blood cell), CRP (C-reactive protein), Western blot, and q-PCR were detected. The results indicated that both survival status and weight increase of irradiated rats treated by doxepin (3 mg/kg/day, rat) were higher than those of treated with irradiation alone (Dosing started the day before irradiation). Further, histological examinations showed doxepin could tenuate the radiation injury, as indicated as alveolar inflammatory exudation and there was only mild interstitial inflammation infiltration. Western blotting and q-PCR showed that expression of NF-κβ in X group were higher than that in XMD group. For the first time, we reported doxepin functioned as a radioprotectant candidate, which provide a promising application of doxepin for protecting radiotherapy injuries.

Background: Urolithiasis or kidney stones is a common and frequently occurring renal disease; calcium oxalate (CaOx) crystals are responsible for 80% of urolithiasis cases. Phyllanthus niruri L. (PN) has been used to treat urolithiasis. This study aimed to determine the potential protective effects and molecular mechanism of PN on calcium oxalate-induced renal injury.Methods: Microarray data sets were generated from the calcium oxalate-induced renal injury model of HK-2 cells and potential disease-related targets were identified. Network pharmacology was employed to identify drug-related targets of PN and construct the active ingredient-target network. Finally, the putative therapeutic targets and active ingredients of PN were verified in vitro and in vivo.Results: A total of 20 active ingredients in PN, 2,428 drug-related targets, and 127 disease-related targets were identified. According to network pharmacology analysis, HMGCS1, SQLE, and SCD were identified as predicted therapeutic target and ellagic acid (EA) was identified as the active ingredient by molecular docking analysis. The increased expression of SQLE, SCD, and HMGCS1 due to calcium oxalate-induced renal injury in HK-2 cells was found to be significantly inhibited by EA. Immunohistochemical in mice also showed that the levels of SQLE, SCD, and HMGCS1 were remarkably restored after EA treatment.Conclusion: EA is the active ingredient in PN responsible for its protective effects against CaOx-induced renal injury. SQLE, SCD, and HMGCS1 are putative therapeutic targets of EA.

Purpose: To report a case of unilateral isolated optic nerve infiltration combined with central retinal artery occlusion in a patient with acute myeloid leukemia. Observations: A 28-year-old acute myeloid leukemia patient with systemic remission after hematopoietic stem cell transplantation presented with optic nerve infiltration combined with central retinal artery occlusion. Fundus examination showed diffuse papillary swelling with blurred margins and whitening macular with cherry-red spot. CBFβ-MYH11 fusion transcript analysis revealed central nervous system relapse of acute myeloid leukemia and optic nerve infiltration. Conclusions and importance: Isolated optic nerve infiltration combined with central retinal artery occlusion is an extremely rare presentation in acute myeloid leukemia. Even in the absence of cytological and radiographic evidence from cerebrospinal fluid, optic nerve infiltration should not be ignored.