Research progress on the mechanism and signalling pathway of ferroptosis and its potential role in dermatosis research.

Ferroptosis is a novel type of cell death that is dependent on lipid peroxidation and iron accumulation, which distinguishes it from other types of programmed cell death. Current research indicates a significant association between ferroptosis and various pathological conditions, including cancer, neurological disorders, and cardiovascular diseases, albeit with a relatively unexplored role in dermatological afflictions. This paper elaborates on the mechanisms and signalling pathways of ferroptosis, summarizing the recent studies on ferroptosis and its related factors in dermatosis. Our objective is to shed light on novel perspectives and therapeutic strategies for dermatosis, enhancing the understanding of this under-researched area through this comprehensive review.

Characterization of volatile compounds and identification of key aroma compounds in different aroma types of Rougui Wuyi rock tea.

In this study, we characterized the aroma profiles of different Rougui Wuyi rock tea (RGWRT) aroma types and identified the key aroma-active compounds producing these differences. The roasting process was found to have a considerable effect on the aroma profiles. Eleven aroma compounds, including linalool, ß-ionone, geraniol, indole, and (E)-nerolidol, strongly affected the aroma profiles. An RGWRT aroma wheel was constructed. The rich RGWRT aroma was found to be dominated by floral, cinnamon-like, and roasty aromas. Human olfaction was correlated with volatile compounds to determine the aromatic characteristics of these compounds. Most key aroma-active compounds were found to have floral, sweet, and herbal aromas (as well as some other aroma descriptors). The differences in key compounds of different aroma types were found to result from the methylerythritol phosphate, mevalonic acid and shikimate metabolic pathways and the Maillard reaction. Linalool, geraniol, and (E,E)-2,4-heptadienal were found to spontaneously bind to olfactory receptors.

Anti-idiotype isolation of a broad and potent influenza A virus-neutralizing human antibody.

The VH6-1 class of antibodies includes some of the broadest and most potent antibodies that neutralize influenza A virus. Here, we elicit and isolate anti-idiotype antibodies against germline versions of VH6-1 antibodies, use these to sort human leukocytes, and isolate a new VH6-1-class member, antibody L5A7, which potently neutralized diverse group 1 and group 2 influenza A strains. While its heavy chain derived from the canonical IGHV6-1 heavy chain gene used by the class, L5A7 utilized a light chain gene, IGKV1-9, which had not been previously observed in other VH6-1-class antibodies. The cryo-EM structure of L5A7 in complex with Indonesia 2005 hemagglutinin revealed a nearly identical binding mode to other VH6-1-class members. The structure of L5A7 bound to the isolating anti-idiotype antibody, 28H6E11, revealed a shared surface for binding anti-idiotype and hemagglutinin that included two critical L5A7 regions: an FG motif in the third heavy chain-complementary determining region (CDR H3) and the CDR L1 loop. Surprisingly, the chemistries of L5A7 interactions with hemagglutinin and with anti-idiotype were substantially different. Overall, we demonstrate anti-idiotype-based isolation of a broad and potent influenza A virus-neutralizing antibody, revealing that anti-idiotypic selection of antibodies can involve features other than chemical mimicry of the target antigen.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

The Prevalence of Mild Cognitive Impairment in China: Evidence from a meta-analysis and systematic review of 393525 Adults.

OBJECTIVE: This study aims to precisely determine the prevalence of Mild Cognitive Impairment (MCI) in China, acknowledging its significance as a preclinical stage of dementia and a potential "intervention window". The acceleration of the aging process in China underscores the urgency of this research. METHODS: A comprehensive search was conducted across PubMed, Embase, Web of Science, CNKI, WFD, VIP, and CBM databases from their inception until March 1, 2023. The Agency for Healthcare Research and Quality (AHRQ) methodology checklist guided our quality assessment. A random-effects model meta-analysis was employed to synthesize the pooled prevalence data of MCI in China. RESULTS: Our analysis encompassed 139 studies, incorporating data from 393,525 individuals aged 40 years and above. The studies were predominantly rated as moderate-to-high quality. The overall prevalence of MCI was determined to be 19.6% (95% CI: 17.7%-21.6%). Subgroup analyses indicated variations in prevalence: 20.8% (95% CI: 18.9%-22.7%) for P-MCI compared to 16.2% (95% CI: 11.7%-20.7%) for DSM criteria. Geographically, prevalence in Southern China (21.0%, 95% CI: 18.1%-23.9%) exceeded that in Northern China (17.6%, 95% CI: 15.9%-19.4%). Notably, prevalence in hospitals (61.7%, 95% CI: 27.8%-95.7%) was significantly higher than in nursing homes (16.1%, 95% CI: 14.3%-17.9%) and communities (25.3%, 95% CI: 17.4%-33.2%), especially after the COVID-19 outbreak. CONCLUSION: The study confirms a 19.6% prevalence rate of MCI in China, influenced by factors such as sample sources, beginning year of survey, and regional differences. It highlights the need for targeted screening and resource allocation to subpopulations at risk, aiming to prevent the progression to dementia.

Transcriptome and metabolome revealed the effects of ABA promotion and inhibition on flavonoid and amino acid metabolism in tea plant.

Flavonoids (especially anthocyanins and catechins) and amino acids represent the high abundance of health-promoting metabolites. Although we observed ABA accumulation in purple leaves and low levels in albino tea leaves, the specific mechanism behind its impact on flavor compounds remains unclear. In this study, we treated tea leaves with exogenous ABA and ABA biosynthesis inhibitors (Flu), measured physiological indicators, and conducted comprehensive transcriptomic and metabolomic analyses to elucidate the potential mechanisms underlying color change. Our results demonstrate that ABA treatment induces purple coloration, while Flu treatment causes discoloration in tea leaves. Metabolomic analysis revealed higher levels of four anthocyanins and six catechins in the group treated with ABA in comparison to the control group. Additionally, there was a notable increase in 15 amino acids in the Flu-treated group. Notably, the levels of flavonoids and amino acids showed an inverse relationship between the two treatments. Transcriptomic comparison between the treatments and the control group revealed upregulation of differentially expressed genes (DEGs) encoding DFR and UFGT in the ABA-treated group, leading to the accumulation of identified anthocyanins and catechins. In contrast, DEGs encoding NR and NRT exhibited elevated expression in the group treated with Flu, consequently facilitating the accumulation of amino acids, specifically L-theanine and L-glutamine. Furthermore, our co-expression network analysis suggests that MYB and bHLH transcription factors (TFs) may play crucial roles in regulating the expression of DEGs involved in the biosynthesis of flavonoids and amino acids. This study provides insights for targeted genetic engineering to enhance the nutritional and market value of tea, together with the potential application of purple and albino tea leaves as functional beverages. It also offers guidance for future breeding programs and production.

Analysis of the Genetic Relationship and Inbreeding Coefficient of the Hetian Qing Donkey through a Simplified Genome Sequencing Technology.

The Hetian Qing donkey is an excellent local donkey breed in Xinjiang. It is of great significance to accelerate breeding and the speed of breeding and rejuvenation, as well as to understand the genetic basis of the strategies and population. This study collected a total of 4 male donkeys and 28 female donkeys. It then obtained genotype data through Simplified Genomic Sequencing (GBS) technology for data analysis. The results detected a total of 55,399 SNP loci, and the genotype detection rate of individuals was ≥90%. A total of 45,557 SNP loci were identified through quality control, of which 95.5% were polymorphic. The average minimum allele frequency was 0.250. The average observed heterozygosity was 0.347. The average expected heterozygosity was 0.340. The average IBS (state homologous) genetic distance was 0.268. ROH: 49 (homozygous fragments), with 73.47% of the length between 1 and 5 Mb. The average per-strip ROH length was 1.75 Mb. The mean inbreeding coefficient was 0.003. The 32 Hetian green donkeys could be divided into six families. The number of individuals in each family is significant. To sum up, the Hetian Qing donkey population has low heterozygosity, few families, and large differences in the number of individuals in each family, which can easily cause a loss of genetic diversity. In the subsequent process of seed protection, seed selection should be conducted according to the divided pedigree to ensure the long-term protection of the genetic resources of Hetian green donkeys.

Identification of root canal morphology in fused-rooted mandibular second molars from X-ray images based on deep learning.

Understanding the intricate anatomical morphology of fused-rooted mandibular second molars (MSMs) is essential for root canal treatment. The present study utilized a deep learning approach to identify the three-dimensional root canal morphology of MSMs from two-dimensional X-ray images. METHODS: A total of 271 fused-rooted MSMs were included in the study. Micro-computed tomography (micro-CT) reconstruction images and two-dimensional X-ray projection images were obtained. The ground truth of three-dimensional root canal morphology was determined through micro-CT images, which were classified into merging, symmetrical, and asymmetrical types. To amplify the X-ray image dataset, traditional augmentation techniques from the python package Augmentor and a multi-angle projection method were employed. Identification of root canal morphology was conducted using the pre-trained VGG19, ResNet18, ResNet50, and EfficientNet-b5 on X-ray images. The classification results from convolutional neural networks (CNNs) were then compared with those performed by endodontic residents. RESULTS: The multi-angle projection augmentation method outperformed the traditional approach in all CNNs except for EfficientNet-b5. ResNet18 combined with the multi-angle projection method outperformed all other combinations, with an overall accuracy of 79.25%. In specific classifications, accuracies of 81.13%, 86.79%, and 90.57% were achieved for merging, symmetrical, and asymmetrical types, respectively. Notably, CNNs surpassed endodontic residents in classification performance; the average accuracy for endodontic residents were only 60.38% (P< 0.05). CONCLUSIONS: CNNs were more effective than endodontic residents in identifying the three-dimensional root canal morphology of MSMs. The result indicates that CNNs possess the capacity to employ two-dimensional images effectively in aiding three-dimensional diagnoses.

Research on the impact of pilot free trade zones on urban green development: A case study based on the Yangtze River Economic Belt in China.

Green development is an important component of China's new development concept. Pilot Free Trade Zones (PFTZs), as "experimental fields" for promoting reform, deepening opening-up, and raising the level of an open economy, are important open areas for China to promote green development. However, existing related research is not extensive. This article takes PFTZs as quasi-natural experiments, with the Yangtze River Economic Belt (YREB) as the research area. Based on urban panel data from 2006 to 2020, using multi-period differences-in-differences and spatial differences-in-differences models, it explores the impact effects of PFTZs on urban green development and their potential mechanisms. The research findings indicate: (1) Overall, PFTZs significantly promote urban green development, with variations in impact effects due to different batches and locations of establishment. (2) Mechanism tests show that PFTZs mainly promote urban green development by stimulating technological innovation, industrial upgrading, and reducing government intervention. (3) From the perspective of spatial spillover effects, the establishment of PFTZs not only promotes the green development process in the host cities but also has a promoting effect on the green development of surrounding cities.

Multimodality quantitative ultrasound envelope statistics imaging based support vector machines for characterizing tissue scatterer distribution patterns: Methods and application in detecting microwave-induced thermal lesions.

Ultrasound envelope statistics imaging, including ultrasound Nakagami imaging, homodyned-K imaging, and information entropy imaging, is an important group of quantitative ultrasound techniques for characterizing tissue scatterer distribution patterns, such as scatterer concentrations and arrangements. In this study, we proposed a machine learning approach to integrate the strength of multimodality quantitative ultrasound envelope statistics imaging techniques and applied it to detecting microwave ablation induced thermal lesions in porcine liver ex vivo. The quantitative ultrasound parameters included were homodyned-K α which is a scatterer clustering parameter related to the effective scatterer number per resolution cell, Nakagami m which is a shape parameter of the envelope probability density function, and Shannon entropy which is a measure of signal uncertainty or complexity. Specifically, the homodyned-K log10(α), Nakagami-m, and horizontally normalized Shannon entropy parameters were combined as input features to train a support vector machine (SVM) model to classify thermal lesions with higher scatterer concentrations from normal tissues with lower scatterer concentrations. Through heterogeneous phantom simulations based on Field II, the proposed SVM model showed a classification accuracy above 0.90; the area accuracy and Dice score of higher-scatterer-concentration zone identification exceeded 83% and 0.86, respectively, with the Hausdorff distance <26. Microwave ablation experiments of porcine liver ex vivo at 60-80 W, 1-3 min showed that the SVM model achieved a classification accuracy of 0.85; compared with single log10(α),m, or hNSE parametric imaging, the SVM model achieved the highest area accuracy (89.1%) and Dice score (0.77) as well as the smallest Hausdorff distance (46.38) of coagulation zone identification. We concluded that the proposed multimodality quantitative ultrasound envelope statistics imaging based SVM approach can enhance the capability to characterize tissue scatterer distribution patterns and has the potential to detect the thermal lesions induced by microwave ablation.

The interactive effect of the career horizon and power of CEO on invention patents.

Invention patents are of great importance to firms, and thus understanding how invention patents are achieved is becoming increasingly important in the literature. Although previous research has shown that both CEO career horizon and CEO power are important for invention patents, little attention has been paid to their potential interactive effect. Investigating their interactive effect would be both theoretically meaningful and practically valuable. Using a sample of firms listed on the A-share market of the Shanghai and Shenzhen stock exchanges from 2010 to 2022, it is found that there is an interactive effect between CEO career horizon and CEO power, and that their interaction has a negative impact on invention patents. Furthermore, the interactive effect varies across different kinds of firms. This paper contributes to the literature on upper echelons theory by highlighting the interactive effects of multiple CEO characteristics on firm innovation.

Roles of Sleep Quality, Self-Efficacy, and Coping Style in the Frailty of Community-Dwelling Older Adults: A Cross-Sectional Study.

OBJECTIVES: Although the association between sleep disorders and frailty has been well established, little is known about the cognitive appraisal mechanisms underlying this association. Building on the transactional theory of stress and coping, this study explores the role of self-efficacy and coping style in the association between sleep quality and frailty among community-dwelling older adults. METHODS: In this cross-sectional study, 585 community-dwelling older adults were investigated using the Pittsburgh Sleep Quality Index, Tilburg Frailty Indicator, General Self-Efficacy Scale, and Simplified Coping Style Questionnaire. Descriptive statistics and hierarchical regression were performed. A moderated mediation model was established using the PROCESS macro. RESULTS: Poor sleep quality affects frailty directly (B = 0.193, p < .01) and indirectly via self-efficacy (B = 0.063, p < .01). The negative impact of poor sleep on frailty through self-efficacy was moderated by both positive and negative coping style (index = -0.007). The moderating effect was stronger when participants' negative coping tendencies increased. CONCLUSIONS: Poor sleep quality indirectly influences frailty by modifying self-efficacy. Effective coping strategies can help attenuate this association. CLINICAL IMPLICATIONS: Timely sleep assessment and tailored strategies such as psychoeducational programs and targeted coping skills training may be beneficial for preventing frailty in older adults.

Classification of Caries Based on CBCT: A Deep Learning Network Interpretability Study.

This study aimed to create a caries classification scheme based on cone-beam computed tomography (CBCT) and develop two deep learning models to improve caries classification accuracy. A total of 2713 axial slices were obtained from CBCT images of 204 carious teeth. Both classification models were trained and tested using the same pretrained classification networks on the dataset, including ResNet50_vd, MobileNetV3_large_ssld, and ResNet50_vd_ssld. The first model was used directly to classify the original images (direct classification model). The second model incorporated a presegmentation step for interpretation (interpretable classification model). Performance evaluation metrics including accuracy, precision, recall, and F1 score were calculated. The Local Interpretable Model-agnostic Explanations (LIME) method was employed to elucidate the decision-making process of the two models. In addition, a minimum distance between caries and pulp was introduced for determining the treatment strategies for type II carious teeth. The direct model that utilized the ResNet50_vd_ssld network achieved top accuracy, precision, recall, and F1 score of 0.700, 0.786, 0.606, and 0.616, respectively. Conversely, the interpretable model consistently yielded metrics surpassing 0.917, irrespective of the network employed. The LIME algorithm confirmed the interpretability of the classification models by identifying key image features for caries classification. Evaluation of treatment strategies for type II carious teeth revealed a significant negative correlation (p < 0.01) with the minimum distance. These results demonstrated that the CBCT-based caries classification scheme and the two classification models appeared to be acceptable tools for the diagnosis and categorization of dental caries.

Precisely Controlling Polymer Acceptors with Weak Intramolecular Charge Transfer Effect and Superior Coplanarity for Efficient Indoor All-Polymer Solar Cells with over 27% Efficiency.

Indoor photovoltaics (IPVs) are garnering increasing attention from both the academic and industrial communities due to the pressing demand of the ecosystem of Internet-of-Things. All-polymer solar cells (all-PSCs), emerging as a sub-type of organic photovoltaics, with the merits of great film-forming properties, remarkable morphological and light stability, hold great promise to simultaneously achieve high efficiency and long-term operation in IPV's application. However, the dearth of polymer acceptors with medium-bandgap has impeded the rapid development of indoor all-PSCs. Herein, a highly efficient medium-bandgap polymer acceptor (PYFO-V) is reported through the synergistic effects of side chain engineering and linkage modulation and applied for indoor all-PSCs operation. As a result, the PM6:PYFO-V-based indoor all-PSC yields the highest efficiency of 27.1% under LED light condition, marking the highest value for reported binary indoor all-PSCs to date. More importantly, the blade-coated devices using non-halogenated solvent (o-xylene) maintain an efficiency of over 23%, demonstrating the potential for industry-scale fabrication. This work not only highlights the importance of fine-tuning intramolecular charge transfer effect and intrachain coplanarity in developing high-performance medium-bandgap polymer acceptors but also provides a highly efficient strategy for indoor all-PSC application.

A Difluoro-Methoxylated Ending-Group Asymmetric Small Molecule Acceptor Lead Efficient Binary Organic Photovoltaic Blend.

Developing a new end group for synthesizing asymmetric small molecule acceptors (SMAs) is crucial for achieving high-performance organic photovoltaics (OPVs). Herein, an asymmetric small molecule acceptor, BTP-BO-4FO, featuring a new difluoro-methoxylated end-group is reported. Compared to its symmetric counterpart L8-BO, BTP-BO-4FO exhibits an upshifted energy level, larger dipole moment, and more sequential crystallinity. By adopting two representative and widely available solvent additives (1-chloronaphthalene (CN) and 1,8-diiodooctane (DIO)), the device based on PM6:BTP-BO-4FO (CN) photovoltaic blend demonstrates a power conversion efficiency (PCE) of 18.62% with an excellent open-circuit voltage (VOC) of 0.933 V, which surpasses the optimal result of L8-BO. The PCE of 18.62% realizes the best efficiencies for binary OPVs based on SMAs with asymmetric end groups. A series of investigations reveal that optimized PM6:BTP-BO-4FO film demonstrates similar molecular packing motif and fibrillar phase distribution as PM6:L8-BO (DIO) does, resulting in comparable recombination dynamics, thus, similar fill factor. Besides, it is found PM6:BTP-BO-4FO possesses more efficient charge generation, which yields better VOC-JSC balance. This study provides a new ending group that enables a cutting-edge efficiency in asymmetric SMA-based OPVs, enriching the material library and shed light on further design ideas.

TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

Letermovir prophylaxis reduced cytomegalovirus reactivation and resistance post umbilical cord blood transplantation.

To explore the impact of letermovir (LET) prophylaxis on cytomegalovirus (CMV) reactivation and resistance in both adult and paediatric umbilical cord blood transplantation (UCBT) patients, we retrospectively compared 43 UCBT patients who received LET as CMV prophylaxis with a historical cohort of 207 UCBT patients without LET usage. LET was administered from Day +1 to Day +100. The 180-day cumulative incidence of CMV reactivation (47.3% vs. 74.4%, p < 0.001) and the proportion of refractory CMV reactivation (15.0% vs. 42.9%, p = 0.016) were significantly lower than those in the control group. However, more frequent late CMV infection (31.0% vs. 4.3%, p = 0.002) and the 180-day cumulative incidence of Epstein-Barr virus (EBV) reactivation (9.3% vs. 3.4%, p = 0.087) were observed in UCBT patients with LET prophylaxis. Meanwhile, older age (>15 years old) and the occurrence of pre-engraftment syndrome were identified as the significant risk factors for CMV reactivation, and in patients at high risk, the incidence of CMV reactivation in the LET group was lower than that in the control group (46.7% vs. 86.5%, p < 0.001), while this decline was less pronounced among patients at low risk (47.8% vs. 62.1%, p = 0.120).

Assessment and clinical utility of metagenomic next-generation sequencing for suspected lower respiratory tract infections.

OBJECTIVES: This study aims to compare the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) to traditional diagnostic methods in patients with lower respiratory tract infections (LRTIs), elucidate the etiological spectrum of these infections, and explore the impact of mNGS on guiding antimicrobial therapy. METHODS: We retrospectively analyzed data from 128 patients admitted to the Respiratory Department of Anqing 116 Hospital between July 2022 and July 2023. All patients had undergone both mNGS and conventional microbiological techniques (CMT) for LRTI diagnosis. We assessed the diagnostic performance of these methods and examined the influence of mNGS on antimicrobial decision-making. RESULTS: Overall, mNGS demonstrated superior sensitivity (96.8%) and accuracy (96.8%) compared to CMT. For Mycobacterium tuberculosis detection, the accuracy and sensitivity of mNGS was 88.8% and 77.6%, which was lower than the 94.7% sensitivity of the T-spot test and the 79.6% sensitivity of CMT. In fungal pathogen detection, mNGS showed excellent sensitivity (90.5%), specificity (86.7%), and accuracy (88.0%). Bacteria were the predominant pathogens detected (75.34%), with Mycobacterium tuberculosis (41.74%), Streptococcus pneumoniae (21.74%), and Haemophilus influenzae (16.52%) being most prevalent. Bacterial infections were most common (62.10%), followed by fungal and mixed infections (17.74%). Of the 118 patients whose treatment regimens were adjusted based on mNGS results, 102 (86.5%) improved, 7 (5.9%) did not respond favorably, and follow-up was lost for 9 patients (7.6%). CONCLUSIONS: mNGS offers rapid and precise pathogen detection for patients with suspected LRTIs and shows considerable promise in diagnosing Mycobacterium tuberculosis and fungal infections. By broadening the pathogen spectrum and identifying polymicrobial infections, mNGS can significantly inform and refine antibiotic therapy.

Pivotal Evaluation of Novel Dedicated Venous Stent for Iliofemoral Venous Obstruction: A Prospective Cohort Study.

PURPOSE: The purpose was to evaluate the clinical outcomes of a dedicated venous stent with the tripartite composite segments for the treatment of iliofemoral venous obstruction (IVO) in a mixed cohort of nonthrombotic iliac vein lesion (NIVL) and post-thrombotic syndrome (PTS) over a period of 12 months. METHODS: The Grency Trial is a prospective, multicenter, single-arm, open-label, pivotal study, which was conducted at 18 large tertiary hospitals in China from August 2019 to October 2020. A total of 133 hospitalized patients were screened and 110 patients with clinical, etiology, anatomical, and pathophysiology clinical class (CEAP) clinical grade C>3 and iliac vein stenosis >50% or occlusion, including 72 patients with NIVL and 38 patients with PTS, were implanted with Grency venous stents. Primary endpoint was stent patency at 12 months follow-up, and secondary outcomes were technical success; improvement in venous clinical severity score (VCSS) at 3, 6, and 12 month follow-up; and rates of clinical adverse events. RESULTS: Among 110 patients who were implanted with Grency venous stents, 107 patients completed the 12 month follow-up. All 129 stents were successfully implanted in 110 limbs. Twelve-month primary patency rate was 94.39% [95% confidence interval [CI]=88.19%-97.91%] overall, and 100% [94.94%-100%] and 83.33% [67.19%-93.63%] in the NIVL and PTS subgroups, respectively. Venous clinical severity score after iliac vein stenting improved significantly up to 12 months follow-up. There were 3 early major adverse events (1 intracerebral hemorrhage and 2 stent thrombosis events related to anticoagulation therapy), and 7 late major adverse events (1 cardiovascular death, 1 intracranial hemorrhage with uncontrolled hypertension, and 5 in-stent restenosis cases without stent fractures or migration). CONCLUSIONS: The Grency venous stent system appeared excellent preliminary safe and effective for IVO treatment. Further large-scale studies with longer-term follow-up are needed to evaluate long-term patency and durability of stent. CLINICAL IMPACT: The design of venous stents for iliofemoral venous obstruction (IVO) must address engineering challenges distinct from those encountered in arterial stenting. The Grency venous stent, a nitinol self-expanding stent specifically tailored for IVO, features a composite structure designed to meet the stent requirements of various iliac vein segments. The Grency Trial is a prospective, multicenter, single-arm, open-label pivotal study aimed at evaluating the efficacy and safety of the Grency stent system. Following a 12-month follow-up period, the Grency venous stent system has demonstrated both safety and efficacy in treating iliofemoral venous outflow obstruction.