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Abstract Purpose To study the influence of sex, age and thyroid function indices on dual-energy computed tomography (DECT)-derived quantitative parameters of thyroid in patients with or without Hashimoto’s thyroiditis (HT). Material and methods A total of 198 consecutive patients who underwent DECT scan of neck due to unilateral thyroid lesions were retrospectively enrolled. Iodine concentration (IC), total iodine content (TIC) and volume of normal thyroid lobe were calculated. Influences of sex, age and thyroid function indices on DECT-derived parameters in overall study population, subgroup patients with, and those without HT were assessed using Mann–Whitney U test, Student’s T-test, and Spearman correlation analyses, respectively, as appropriate. Results HT group showed significantly lower IC and TIC, while higher volume than No-HT group (all p 35 years) age group in all three groups (all p > 0.05). TPOAb and TgAb correlated positively with IC and TIC, and negatively with volume in overall study population (all p

Neutrophils are more innate immune cells found in coronavirus disease in 2019(COVID-19). The accounting of neutrophils and the level of plasma neutrophil extracellular traps(NETs) were positively correlated with the severity of COVID-19. This article reviews the relevant studies of neutrophils, formation and degradation of NETs involved in the pathological process of COVID-19, providing the reference for further studies of pathogenesis and intervention.

Objective: The objective of the study was to observe and analyze the characteristics of negative emotions and quality of life (QoL) in patients with nonsmall cell lung cancer (NSCLC) from 1 to 3 months after surgery, and summarize their population characteristics after surgery. Materials and Methods: The consolidation rehabilitation period was defined as 1 to 3 months after surgery. The main observation indicators were the general Hospital Anxiety and Depression Scale, the European Organization for the Research and Treatment of Cancer Core QoL Questionnaire (EORTC QLQ-C30), and EORTC QLQ-Lung Cancer-13. The secondary observation indicators were peripheral blood cytokines and immune function indicators. Statistical methods such as one-way analysis of variance and logistic regression were used to analyze the characteristics of this part of the population. Results: Among patients who underwent lung surgery, the overall incidence of anxiety during consolidation recovery was 13.66%, and that of depression was 10.38%. The scores of fatigue, pain, dyspnea, insomnia, and loss of appetite were significantly higher than those of other symptoms (P = 0.000). The presence of anxiety was associated with the site of surgery (P < 0.05) and the presence of depression was associated with emotional functioning and dyspnea (P < 0.05). Conclusions: The occurrence of negative emotions in the postoperative NSCLC population is related to gender, and the degree of emotions is negatively correlated with QoL and positively correlated with the degree of symptoms. The main relevant syndromes are the pulmonary and meridian categories.

Many countries have reported increasing rates of penicillin-susceptible methicillin-sensitive Staphylococcus aureus (MSSA-PENS). To date, there is relatively little known about the current situation and molecular characteristics of MSSA-PENS in China. In this study, we carried out a laboratory-based multi-region retrospective study to investigate the genomic epidemiology and characterisation of MSSA-PENS isolated from invasive bloodstream infections (BSIs) across 17 provinces. The prevalence of MSSA-PENS isolates increased significantly over the 6-year period, with the proportion increasing from 3.51% in 2014–8.80% in 2019, an average relative increase of 22.14% per year (95% confidence interval 9.67%-34.61%, P for trend

Elizabethkingia anophelis is an emerging species and has increasingly been reported to cause life-threatening infections and even outbreaks in humans. Nevertheless, there is little data regarding the E. anophelis geographical distribution, phylogenetic structure, and transmission across the globe, especially in Asia. We utilize whole-genome sequencing (WGS) data to define a global population framework, phylogenetic structure, geographical distribution, and transmission evaluation of E. anophelis pathogens. The geographical distribution diagram revealed the emerging pathogenic bacteria already distributed in various countries worldwide, especially in the USA and China. Strikingly, phylogenetic analysis showed a part of our China original E. anophelis shared the same ancestor with the USA outbreak strain, which implies the possibility of localized outbreaks and global spread. These closer related strains also contained ICEEaI, which might insert into a disrupted DNA repair mutY gene and made the strain more liable to mutation and outbreak infection. BEAST analysis showed that the most recent common ancestor for ICEEaI E. anophelis was dated twelve years ago, and China might be the most likely recent source of this bacteria. Our study sheds light on the potential possibility of E. anophelis causing the large-scale outbreak and rapid global dissemination. Continued genomic surveillance of the dynamics of E. anophelis populations will generate further knowledge for optimizing future prevent global outbreak infections.

Introduction: Bufei Huayu Decoction (BFHY) is a clinical prescription with reported efficacy in enhancing the therapeutic outcomes of chemotherapeutic agents for non-small cell lung cancer (NSCLC). However, the underlying metabolic mechanism of BFHY's action remains unexplored. Objective: The objective of this study is to investigate the global metabolic effects of cisplatin and cisplatin plus BFHY on NSCLC. Methods: Three groups (NSCLC, cisplatin, and cisplatin + BFHY) underwent a serum metabolomics procedure based on UHPLC-QE-MS. Then, a pathway analysis was carried out using MetaboAnalyst 3.0 to elucidate the therapeutic action routes of cisplatin and cisplatin plus BFHY in NSCLC. Results: In the subcutaneous NSCLC model, both cisplatin and cisplatin + BFHY reduced the tumor volume and caused cell death. In comparison to cisplatin alone, cisplatin + BFHY showed a stronger tumor-suppressing impact. Furthermore, the same 16 metabolic signaling pathways were shared by the cisplatin and cisplatin + BFHY treatments. These typical metabolites are mainly involved in amino acid metabolism, lipid mobilization, nucleic acid metabolism and carbohydrate metabolites. Conclusions: Potential biomarkers and metabolic networks of cisplatin and cisplatin + BFHY's anti-tumor actions are revealed in our investigation.

Bloodstream infections by bacteria, especially multidrug-resistant bacteria, remain a worldwide public health concern. We evaluated the antibacterial activity of ceftobiprole and comparable drugs against different bloodstream isolates and different sequence types of methicillin-resistant Staphylococcus aureus (MRSA) in China. We found that MRSA, methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-susceptible coagulase-negative Staphylococcus (MSCNS) displayed ceftobiprole sensitivity rates of >95%, which are similar to the rates for linezolid, daptomycin, and vancomycin. Of the tested MRCNS strains, 90.4% were sensitive to ceftobiprole. The sensitivities of ST59, ST398, and ST22 MRSA to ceftobiprole were higher than that of ST239. Ceftobiprole’s MIC50/90 value against Enterococcus faecalis was 0.25/2 mg/L, whereas Enterococcus faecium was completely resistant to this drug. Ceftobiprole exhibited no activity against ESBL-positive Enterobacterales, with resistance rates between 78.6% and 100%. For ESBL-negative Enterobacterales, excluding Klebsiella oxytoca, the sensitivity to ceftobiprole was comparable to that of ceftazidime, ceftriaxone, and cefepime. The MIC50/90 value of ceftobiprole against Pseudomonas aeruginosa was 2/16 mg/L, and for Acinetobacter baumannii, it was 32/>32 mg/L. Thus, ceftobiprole shows excellent antimicrobial activity against ESBL-negative Enterobacterales and Pseudomonas aeruginosa (comparable to that of ceftazidime, ceftriaxone, and cefepime); however, it is not effective against ESBL-positive Enterobacterales and Acinetobacter baumannii. These results provide important information to clinicians.

A total diet study is often used to evaluate a population’s baseline dietary exposure to chemical hazards from across the diet. In 2021–2023, Singapore carried out a TDS, and this article presents an overview of the study design and methodological selections in Singapore’s TDS, as well as its relevance to ensuring food safety. A food consumption survey was conducted on Singapore citizens and permanent residents, where food consumption patterns of the Singapore population were identified. The selection of chemical hazards and foods for inclusion in Singapore’s TDS, as well as principal considerations on sampling, food preparation, and analytical testing are discussed. Commonly consumed foods by the Singapore population in food categories such as grain and grain-based products, meat and meat products, fish and seafood, vegetables, fruits, milk and dairy products were included in this study, and mean concentrations of chemicals tested in each food category were reported, with food categories possessing higher levels identified. Future work will include dietary exposure assessments for the population and analysis of the contributions by food and cooking method.

Abstract Objective To fully understand the overall system and implementation of antimicrobial stewardship (AMS) at different levels in China, an evaluation according to the integrated AMS evaluation tool developed by World Health Organization (WHO) was conducted. Methods A comprehensive search on the AMS relevant government policies, regulations, scientific research results, public and social activities was conducted, and the implementation of AMS strategies in national, subnational and hospital level were evaluated by the standards of the WHO. Results The results shew that the system construction, technical infrastructure and actions of AMS in China at the national level is relatively satisfied, but the AMS system needs to be further strengthened at the subnational and the medical institutional level, especially the integration of multidisciplinary teams and relevant departments; the implementation of professional intervention strategies, national education and publicity, professional education and training are relatively weak. AMS implementation is mainly promoted at the national level, and AMS in primary medical institutions is almost missing. It is necessary to carry out AMS at the provincial level and medical institutions as soon as possible. The focus is to establish a professional AMS team, prepare AMS guideline, implement AMS strategy, raise public awareness and ensure the long‐term and sustainable development of AMS in the country. Conclusion The Chinese government has established a system for AMS, and implemented a multisectoral coordinative mechanism. However, at the subnational and district levels, an AMS system and practice should be set up soon to promote the rational use of antibiotics.

ABSTRACT: Objectives: Patients with inflammatory bowel disease (IBD) are susceptible to Clostridioides difficile infection (CDI), resulting in poor outcomes and recurrence; therefore, the molecular characterization of C. difficile in IBD patients in China needs further investigation. Methods: C. difficile strains were isolated and identified from faecal samples of adult and paediatric IBD patients. Toxigenic strains were typed using multilocus sequence typing and whole genomic sequencing (WGS) to construct the phylogenetic tree. Susceptibility to 10 antimicrobials was evaluated using the Etest. Results: Among the 838 IBD patients, 82 toxigenic C. difficile were identified, which comprised 46 from adults and 36 children. A total of 90.2% (74/82) of the isolates were positive for both toxin A and toxin B genes (A+B+), whereas the remaining 9.8% were negative for toxin A gene but positive for toxin B gene (A–B+). These toxigenic strains were susceptible to metronidazole and vancomycin, but highly resistant to clindamycin, erythromycin, and fluoroquinolones. All moxifloxacin-resistant isolates had mutations resulting in an amino acid substitution in gryA (T82I). The dominant types were ST-35 (20.7%), ST-2 (17.1%), ST-54 (13.4%), and ST-3 (13.4%) in all patients. Conclusion: The incidence and molecular epidemiology of C. difficile infection in adult IBD patients resembled CDI in the general inpatient population. A higher antibiotic resistance rate was identified among the C. difficile isolates obtained from paediatric IBD patients than from adult patients, and a few STs accounted for most multidrug-resistant strains. However, the molecular genetic features of the same ST type between these two groups remains highly correlated.

Background Systemic lupus erythematosus (SLE) is defined as a multisystem autoimmune disease involving various organs, of which exact molecular mechanisms remain elusive. Here, we aimed to investigate a novel circular RNA (circRNA), circRACGAP1, abnormally expressed in SLE and explored its underlying regulatory network. Methods The expression patterns of circRACGAP1 were determined in patients diagnosed with SLE by using a qRT-PCR assay. Spearman correlation analysis was employed to evaluate the correlation between circRACGAP1 and clinicopathological variables in patients with SLE. Flow cytometry and TUNEL assays were subjected to assess the cell apoptosis. Nuclear-cytoplasmic fractionation and luciferase reporter assay was used to verify the circRACGAP1/miR-22-3p/PTEN axis. Western blot analysis was performed to measure the PTEN/AKT signalling-related proteins and apoptotic-related biomarkers. Results Down-regulated circRACGAP1 was observed and correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, anti-double-stranded (ds) DNA, and complement C3 level in patients with SLE. Overexpression of circRACGAP1 significantly alleviated cell apoptosis in Jurkat cells within UVB exposure. Mechanistic investigation revealed that circRACGAP1 could serve as a sponge of miR-22-3p to regulate PTEN/AKT signalling. Conclusions Collectively, circRACGAP1 regulated the AKT signalling pathway via binding to miR-22-3p in the progression of SLE, suggesting therapeutic targets for SLE treatment.

Objective To investigate female iliac vein variations by using the computed tomography angiography (CTA) three-dimensional (3 D) reconstruction technique. Methods We retrospectively studied 1623 patients undergoing abdominal and pelvic CTA scanning for gynecological diseases from December 2009 to December 2018. Accurate digital 3 D models of the iliac vein were constructed using Mimics 19.0 software and used to study the morphology and variations. Variations in the common iliac vein (CIV), external iliac vein (EIV) and internal iliac vein (IIV) were classified as type I, abnormal number of veins; type II, abnormal communicating branches; or type III, other variations. Results The overall variation rates of the iliac vein and CIV were 51.57% (837/1623) and 20.33% (330/1623), respectively. The main type of CIV variation was type II. The main type I CIV variation was the absence of the CIV (98.15%), which mostly occurred on the right side (64.81%, 35/54). Type II CIV variation was the most common, with abnormal communicating branches between the left CIV and right IIV (81.78%, 211/258). The overall variation rates of the EIV and IIV were 36.66% (595/1623) and 49.60% (805/1623), respectively, mainly on the right side. The main type of variation was type I. Among them, the division of the IIV into two branches plus convergence with the ipsilateral EIV was the most common (22.98%, 373/1623). Conclusion In this study, approximately half of the patients had iliac vein variations. The preoperative identification of iliac vein variation may reduce vascular injury in pelvic surgery.

Coupling paired-end whole-genome sequencing with droplet digital PCR enabled precise identification of a transgene insertion in the genetically modified rice event G281 on chromosome 3 and the potential for exploring the native gene integration.

With deep eutectic solvent (DES) as the modifier of silica, the dispersity of silica in styrene butadiene rubber (SBR) was improved by in-situ reaction under the synergistic effect of DES and bis(3-triethoxysilyl-propyl)-tetrasulfide (TESPT). The effects of different types of DES on curing characte-ristics, processing properties, physico-mechanical properties, and micromorphology of SBR/silica composites were researched. The results showed that choline chloride/urea in combination with TESPT could significantly improve the dispersity of silica in SBR matrix and weaken the Payne effect, so the mechanical properties and compression fatigue property of SBR/silica vulcanizates increased. Meanwhile, choline chloride/oxalic acid in combination with TESPT showed outstanding performance in impro-ving the interface adhesion between silica and SBR resulting in excellent wear resistance of SBR/silica composites. However, when the amount of DES was overdosed, the modification effect became worse.

Abstract Background Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19. Methods The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 108 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging. Results Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 109/L vs. 1.78 × 109/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients. Conclusions Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 109 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population. Trial Registration: MEXCOVID, NCT04276987.

Carbapenemase-producing Enterobacteriaceae (CPE) isolates are recognized as one of the most severe threats to public health. However, the population structure and genetic characteristics of CPE isolates among bloodstream infections (BSIs) are largely unknown. To address this knowledge gap, in this study, we included patients with clinically significant BSIs due to Enterobacterales isolates, recruited from 26 sentinel hospitals in China (2014–2015). CPE isolates were microbiologically and genomically characterized, including their susceptibility profiles, molecular typing, phylogenetic features, and genetic context analysis of carbapenemase-encoding genes. Of the 2569 BSI Enterobacterales isolates enrolled, 42 (1.6%) were carbapenemase-positive. Moreover, among the 2242 investigated isolates, 1111 (49.6%) extended-spectrum β-lactamase (ESBL)-producing isolates were identified in Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Proteus mirabilis (P. mirabilis), and Klebsiella oxytoca. Whole genome sequencing analysis showed the clonal spread of K. pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae sequence type (ST) 11 and New Delhi metallo-β-lactamase (NDM)-5-producing E. coli ST167 in our collection. Plasmid analysis revealed that carbapenemase-encoding genes were located on multiple plasmids. A high prevalence of biofilm-encoding type 3 fimbriae clusters and yesiniabactin-associated genes was observed in K. pneumoniae isolates. This work demonstrates the high prevalence of ESBLs and the wide dissemination of CPE among BSI isolates in China, which represent real clinical threats. Moreover, our findings first illustrate a more comprehensive genome scenario of CPE isolates among BSIs. The clonal spread of KPC-2-producing K. pneumoniae ST11 and NDM-5-producing E. coli ST167 needs to be closely monitored.

This study investigated the prevalence and occurrence of 3-monochloropropanediol esters (3-MCPDEs) and glycidyl esters (GEs) in domestically and commercially prepared food in Singapore and assessed the total dietary exposure for the Singaporean population. Minimal impact on the formation of 3-MCPDEs and GEs was observed from the domestic cooking methods commonly practiced in Singapore such as deep frying and stir frying. The estimated total dietary exposure to 3-MCPDEs for the Singaporean population (aged 15 to 92) was 0.982 µg/kg bw/day for general consumers and 2.212 µg/kg bw/day for high consumers (95th percentile), which accounted for 49.1% and 110.6% of the tolerable dietary intake (TDI) at 2 µg/kg bw/day by the European Food Safety Authority (EFSA). The calculated margins of exposure (MOE) for GEs based on the dietary exposure for general consumers at 0.882 µg/kg bw/day and 2.209 µg/kg bw/day for high consumers were below 10,000, indicating a potential health concern. Our study showed that the occurrence of 3-MCPDEs and GEs varied among vegetable oils, and domestic cooking methods did not significantly impact the levels of 3-MCPDEs and GEs in prepared food. The critical factor influencing the prevalence and occurrence of 3-MCPDEs and GEs was the choice of oil used for cooking, which absorbed into the cooked food. It is essential to encourage the food industry to continue its innovation on mitigation measures to control and reduce 3-MCPDEs and GEs in vegetable oil production. Consumers are advised to make informed choices on food consumption and cooking oil for food preparation to reduce their exposure to 3-MCPDEs and GEs.

Abstract Background Immunosuppressive properties grant mesenchymal stromal cells (MSCs) promising potential for treating autoimmune diseases. As autologous MSCs suffer from limited availability, the readily available allogeneic MSCs isolated from menstrual blood (MB-MSCs) donated by young, healthy individuals offer great potential. Here, we evaluate the therapeutic potential of MB-MSCs as ready-to-use allo-MSCs in multiple sclerosis, an autoimmune disease developed by the activation of myelin sheath-reactive Th1 and Th17 cells, by application in its animal model experimental autoimmune encephalomyelitis (EAE). Methods We assessed the therapeutic effect of MB-MSCs transplanted via either intravenous (i.v.) or intraperitoneal (i.p.) route in EAE in comparison with umbilical cord-derived MSCs (UC-MSCs). We used histology to assess myelin sheath integrity and infiltrated immune cells in CNS and flow cytometry to evaluate EAE-associated inflammatory T cells and antigen-presenting cells in lymphoid organs. Results We observed disease-ameliorating effects of MB-MSCs when transplanted at various stages of EAE (day − 1, 6, 10, and 19), via either i.v. or i.p. route, with a potency comparable to UC-MSCs. We observed reduced Th1 and Th17 cell responses in mice that had received MB-MSCs via either i.v. or i.p. injection. The repressed Th1 and Th17 cell responses were associated with a reduced frequency of plasmacytoid dendritic cells (pDCs) and a suppressed co-stimulatory capacity of pDCs, cDCs, and B cells. Conclusions Our data demonstrate that the readily available MB-MSCs significantly reduced the disease severity of EAE upon transplantation. Thus, they have the potential to be developed as ready-to-use allo-MSCs in MS-related inflammation. Graphical abstract

With the development of the national earthquake intensity quick report and early warning project, more and more “earthquake early warning (EEW)” has come into public view. There are more and more questions about “what is EEW” at home and abroad along with a variety of interpretations of EEW techniques. This paper discusses the progress of earthquake early warning in China, the essence and limitation of EEW. The essence of EEW is that the earthquake observation has entered a new stage of intensive observation, and EEW is the alert for application of earthquake quick report from minutes to seconds. Due to the limitations of early warning blind area and inaccurate estimation of earthquake intensity in the practical application of EEW, the understanding of earthquake scientists on the application efficiency of EEW technology has been deepened and changed. They gradually realized the importance of strengthening the alert function of EEW. At the same time, EEW is a complex social engineering. Scientists need to guide the public to understand the limitations of EEW in order to play the role of disaster reduction effectively.

Abstract Background Archaea form a third domain of life that is distinct from Bacteria and Eukarya. So far, many scholars have elucidated considerable details about the typical promoter architectures of the three domains of life. However, a functional promoter from the archaeon Halobacterium salinarum has never been studied in Escherichia coli. Results This paper found that the promoter of Halobacterium salinarum showed a promoter function in Escherichia coli. This Escherichia coli promoter structure contains − 10 box, -10 box extension and − 29 elements, however, no -35 box. The − 29 element is exercised by the TATA box in archaea. And we isolated the RM10 fragment that possessed the fusion characteristics of bacteria and archaea, which was overlapped with functionality of TATA box and − 29 elements. Conclusions The − 29 element reflects the evolutionary relationship between the archaeal promoter and the bacterial promoter. The result possibly indicated that there may be a certain internal connection between archaea and bacteria. We hypothesized that it provided a new viewpoint of the evolutionary relationship of archaea and other organisms.

ABSTRACT Carbapenem-resistant Enterobacteriaceae, especially carbapenemase-producing Klebsiella pneumoniae, is an urgent problem in health care facilities worldwide. K. pneumoniae isolates classified as sequence type 11 (ST11) are largely responsible for the spread of carbapenem-resistant K. pneumoniae (CRKP) in China. Our previous phylogenetic reconstruction suggested that CRKP ST11 capsular locus 64 (KL64) was derived from an ST11-KL47 ancestor through recombination. However, the molecular origin of KL64 remains largely unknown, and our understanding of the recombination is incomplete. Here, we screened a global sample of 22,600 K. pneumoniae genomes and searched for KL64-harboring STs, which were found to be ST1764, ST3685, ST1764-1LV, ST30, ST505, ST147, and ST11, wherein ST1764, ST3685, ST1764-1LV, and ST30 belonged to a clonal complex, CC1764. We compared the genetic structures of representative strains from ST11-KL47, ST11-KL64, CC1764-KL64, ST505-KL64, and ST147-KL64 and further performed phylogenetic analysis and single-nucleotide polymorphism analysis among 248 isolates from all these STs. The results suggested a recombination event has occurred in a homologous ~154-kb region covering KL and the lipopolysaccharide biosynthesis locus (OL) between a recipient ST11-KL47-OL101 and a donor CC1764 (except ST30), giving rise to ST11-KL64-O2v1 strains (recombination I). Furthermore, we also found an infrequent ST11-KL64-O2v1 subclone which was not produced by recombination I but was hybridized from ST11-KL47-OL101 and ST147-KL64-O2v1 strains through recombination of a homologous ~485-kb region covering KL and OL (recombination II). Our findings provide important insights into the role of recombination in the evolution of clinical strains and the diversity of capsule and lipopolysaccharide of widely distributed KPC-associated ST11 K. pneumoniae in China. IMPORTANCE Chromosomal recombination events are considered to contribute to the genetic diversification and ultimate success of many bacterial pathogens. A previous study unravelled the molecular evolution history of ST258 strains, which have been largely responsible for the spread of KPC in the United States. Here, we used comparative genomic analyses to discover two recombination events in ST11 CRKP strains, which is a predominant KPC-associated CRKP clone in China. Two new ST11-CRKP subclones with altered capsule and lipopolysaccharide, which are two primary determinants of antigenicity and antigenic diversity among K. pneumoniae, were produced through these two recombination events, respectively. Horizontal transfer of the KL and OL appears to be a crucial element driving the molecular evolution of K. pneumoniae strains. These findings not only extend our understanding of the molecular evolutionary history of ST11 but also are an important step toward the development of preventive, diagnostic, and therapeutic strategies for CRKP.

Aims: The inertial measurement unit (IMU), as a sensor-based assessment tool, could provide objective and quantitative data for evaluating a patient with adhesive capsulitis (AC). The IMUs have advantages in simplification of implementation, cost, and computation complexity. We aimed to propose an IMU-based approach to extract statistical features for the assessment of AC in daily activity. Methods: Nine healthy subjects and nine AC patients participate in this experiment. The accelerometers are placed on the wrist and arm to measure the movement performance. Each subject is asked to perform three basic shoulder motions, including flexion, extension, and abduction. Eight types of features are extracted from the norm of accelerometer signals, including mean, standard deviation (SD), variation, maximum, minimum, range, kurtosis, and skewness. These features are explored to distinguish the differences in the movement performance between healthy subjects and AC patients. Statistical Analysis Used: Student's t-test and effect size (Cohen's d) are calculated to assess the reliability of the proposed evaluation approach. Results: The results show that the feature of SD extracted from the wrist can achieve significant differences and large effect sizes between healthy subjects and AC patients. Conclusion: We demonstrate the feasibility of the proposed IMU-based functional evaluation for the AC assessment using statistical features.

Before the availability of COVID-19 vaccines, surveys showed that vaccine hesitancy may influence the acceptance of COVID-19 vaccination. In this cross-sectional study, we aimed to investigate COVID-19 vaccination coverage among healthcare workers (HCWs) in obstetrics and gynecology, during the first three-month period of the vaccination campaign after COVID-19 vaccines were approved. A total of 662 eligible HCWs, consisting of 250 HCWs (group one) who participated in a Jiangsu provincial symposium and 412 HCWs (group two) in the department of obstetrics and gynecology, Nanjing Drum Tower Hospital, were invited to answer a 23-question questionnaire. In total, 618 (93.4%) HCWs completed the questionnaire. The vaccine acceptance in group one was higher than that in group two (87.2% [197/226] vs 74.2% [291/392], χ2 = 14.436, P

Purpose: To explore the diagnosis and treatment of traumatic external carotid branch pseudoaneurysms. Methods: Eleven cases of traumatic external carotid artery branch pseudoaneurysms were admitted in our hospital. Digital subtraction angiography was performed in all patients. It revealed that the pseudoaneurysms originated from the internal maxillary artery in 5 cases, superficial temporal artery in 5 cases and occipital artery in 1 case. Five cases of internal maxillary artery pseudoaneurysms and 2 cases of superficial temporal artery pseudoaneurysms were treated by embolization; the other 3 cases were surgically resected. Results: Complete cessation of nasal bleeding was achieved in all the 5 pseudoaneurysms of internal maxillary artery after the endovascular therapies. Scalp bleeding stopped and scalp defect healed up in 2 patients with superficial temporal artery pseudoaneurysms treated by interventional therapy. All patients were followed up for 0.5–2.0 years without recurrence of nosebleed and scalp lump. Conclusion: For patients with repeated severe epistaxis after craniocerebral injury, digital subtraction angiography should be performed as soon as possible to confirm traumatic pseudoaneurysm. Endovascular therapy is an effective method for traumatic internal maxillary artery pseudoaneurysms. For patients with scalp injuries and pulsatile lumps, further examinations including digital subtraction angiography should be performed to confirm the diagnosis. Surgical treatment or endovascular therapy for scalp traumatic pseudoaneurysm is effective.

BackgroundPatients with bloodstream infection of Klebsiella pneumoniae (BSI-KP) have a high risk of death and septic shock. This study aims to identify the risk factors for mortality and severity in patients of BSI-KP.MethodsData of BSI-KP patients were extracted from the MIMIC IV (Medical Information Mart for Intensive Care IV) database, and patients infected with only K. pneumoniae in blood were included in this study. The risk factors of 28-day mortality and septic shock in BSI-KP patients were analyzed, respectively.ResultsA total of 279 patients enrolled and the all-cause 28-day mortality rate was 11.8%. The use of statins (OR 0.220, 95% CI 0.060-0.801, p = 0.022) and quinolones (OR 0.356, 95% CI 0.143-0.887, p = 0.027) were both independent protective factors for death within 28 days, while the use of vasoactive drugs (OR 7.377, 95% CI 1.775-30.651, p = 0.006) was a risk factor. Besides, pulmonary disease (OR 2.348, 95% CI 1.126-4.897, p = 0.023), bleeding and coagulation disorders (OR 3.626, 95% CI 1.783-7.372, p < 0.001), respiratory failure (OR 2.823, 95% CI 0.178-6.767, p = 0.020) and kidney dysfunction (OR 2.450, 95% CI 1.189-5.047, p = 0.015) were independent risk factors for patients suffered from septic shock while hypertension was a protective one. The receiver operating characteristic (ROC) curves could well predict the risk of death within 28-day (area under ROC = 0.855, 95% CI = 0.796–0.914, p < 0.001) and septic shock (AUROC = 0.815, 95% CI = 0.755–0.874, p < 0.001) in patients with BSI-KP.ConclusionThe use of statins could decrease the risk of 28-day mortality in patients of BSI-KP. The risk factor-based prediction model provided evidence for drug treatment in BSI-KP patients. Paying more attention to the strategy of drug treatment will be an optimal way to improve patient’s outcome in clinical practice.

Coastal areas are highly vulnerable to flood risks, which are exacerbated by the changing climate. This paper provides a comprehensive review of the literature on coastal flood risk assessment and resilience evaluation and proposes a smart-resilient city framework based on pre-disaster, mid-disaster, and post-disaster evaluations. First, this paper systematically reviews the origin of the resilience concept and the development of flood resilience. Next, it introduces the social-acceptable risk criteria and the flood resilience level for different flood phases. Then, a coastal flood resilience management system for smart cities is proposed, covering 3 phases of flood disasters (before, during, and after). Risk assessment is essential in pre-disaster scenarios because it provides a comprehensive understanding of the potential hazards and vulnerabilities of an area or system. Big data monitoring during disasters is an essential component of effective emergency management and response that can allow for more informed decisions and thus quicker, more effective responses to disasters, ultimately saving lives and minimizing damage. Data-informed loss assessments are crucial in providing a rapid, accurate understanding of post-disaster impact. This understanding, in turn, is instrumental in expediting recovery and reconstruction efforts by aiding decision-making processes and resource allocation. Finally, the impacts of climate change on the 3 phases of flood disasters are summarized. The development of more resilient coastal communities that are better equipped to withstand the impacts of climate change and adapt to changing environmental conditions is crucial. To address coastal compound floods, researchers should focus on understanding trigging factor interactions, assessing economic and social risks, improving monitoring and emergency response systems, and promoting interdisciplinary research with data openness. These strategies will enable comprehensive and holistic management of coastal flood risks in the context of climate change.

Aim. We sought to profile gut microbiota’s role in combination of Bu Fei Hua Yu (BFHY) with cisplatin treatment. Methods. Non-small cell lung cancer (NSCLC) mice model were constructed followed by treatment with cisplatin alone or combined with BFHY. Mice weight and tumor volume were measured during the experiment. And mice cecum were detected by hematoxylin and eosin, cecum contents were collected for Enzyme Linked ImmuneSorbent Assay, and stool were profiled for metagenomic sequencing. Results. Combination of BFHY with cisplatin treatment decreased the tumor growth and relieved the damage of cecum. Expressions of interleukin-6 (IL-6), interleukin-1β (IL-1β), monocyte chemotactic protein 1 (MCP), and interferon-γ (IFN-γ) were decreased compared with cisplatin treatment alone. Linear discriminant analysis effect size analysis showed that g_Parabacteroides was downregulated and g_Escherichia and g_Blautia were upregulated after cisplatin treatment. After combination with BFHY, g_Bacteroides and g_Helicobacter were decreased. g_Klebsiella, g_Unclssified_Proteobacteria, and g_Unclssified_Clostridiates were increased. Moreover, heatmap results showed that Bacteroides abundance was increased significantly after cisplatin treatment; BFHY combination treatment reversed this state. Function analysis revealed that multiple functions were slightly decreased in cisplatin treatment alone and increased significantly after combination with BFHY. Conclusion. Our study provided evidence of an efficacy of combination of BFHY with cisplatin on treatment of NSCLC and revealed that gut microbiota plays a role in it. The above results provide new ideas on NSCLC treatment.

BackgroundPatients with type 2 diabetes mellitus (T2DM) are at increased risk for COVID-19 related morbidity and mortality. Antibody response to COVID-19 vaccine in T2DM patients is not very clear. The present work aims to evaluate the antibody response to the inactivated SARS-CoV-2 vaccine in this population.MethodsTwo groups of subjects with no history of SARS-CoV-2 infection were included: 63 T2DM patients and 56 non-T2DM controls. Each participant received two doses of inactivated COVID-19 vaccine. IgG antibodies against the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2 (anti-N/S IgG) and receptor binding domain (RBD) proteins (anti-RBD IgG) were quantitatively evaluated by the electrochemiluminescence immunoassays, respectively.ResultsIt was observed that the positive rates and titers of anti-N/S IgG and anti-RBD IgG in T2DM patients were significantly lower than those in controls, respectively (anti-N/S: 85.7 vs. 98.2%, P = 0.034; 25.48 vs. 33.58 AU/ml P = 0.011; anti-RBD: 85.7 vs. 96.4%, P = 0.044; 15.45 vs. 22.25 AU/ml, P = 0.019). Compared to non-T2DM subjects, T2DM patients with uncontrolled glycemia showed lower positive antibody rates and titers (anti-N/S IgG: 75% and 13.30 AU/ml; anti-RBD IgG: 75% and 11.91 AU/ml, respectively, all P < 0.05), while T2DM patients with controlled glycemia had similar positive antibody rates and titers (anti-N/S IgG: 94.3% and 33.65 AU/ml; and anti-RBD IgG: 94.3% and 19.82 AU/ml, respectively, all P > 0.05).ConclusionIn the analysis performed, the data indicate that T2DM patients with uncontrolled glycemia showed a lower level of IgG antibodies compared to non-diabetic controls and individuals with controlled glycemia when immunized with the inactivated COVID-19 vaccine.

Hot-spot creation during flash sintering is considered a key limitation for its industrialization. Establishing a method to predict this phenomenon can address this limitation. Here, a three-phase Gd2O3-m-ZrO2-8YSZ composite was designed to introduce a percolative current, and the induced hot-spot issue was systematically investigated. We show that the percolative current can be induced when the 8YSZ fraction reaches a certain value, but it will be suppressed as Gd2Zr2O7 generated at flash onset. On these bases, the effect of percolative current on sintering behavior was investigated by performing isothermal flash experiments. We demonstrated that hot spots tend to form in the presence of percolative current, and their size increases with increasing voltage. This was further distinguished with respect to onset power density, from which an abnormal rise was observed in the hot-spot samples. This finding was explained in terms of thermal runaway and could be considered an indicator of local heating.

The isolation of chondrocytes from human articular cartilage for single-cell RNA sequencing requires extensive and prolonged tissue digestion at 37 C. Modulations of the transcriptional activity likely take place during this period such that the transcriptomes of isolated human chondrocytes no longer match their original status in vivo. Here, we optimized the human chondrocyte isolation procedure to maximally preserve the in vivo transcriptome. Cartilage tissues were transferred into a hypoxia chamber (4% O2) immediately after being removed from OA patients and minced finely. Collagenase II at concentrations of 0.02%, 0.1%, 0.25%, 0.5%, 1%, and 2% was applied for 0.5, 1, 2, 4, and 18 h to digest the minced tissue. Actinomycin D (ActD) was added to test its capacity in stabilizing the transcriptome. Cell yield, viability, cell size, and transcriptome were determined using counter chamber, flow cytometry, and RNA sequencing (RNA-seq). Collagenase II at 2% concentration released small chondrocytes from cartilage matrix during the first digestion hour and started to release large cells thereafter, reaching a complete release at 4 h. During 4-h digestions, collagenase II at 2% and 1% but not at lower concentrations yielded maximal release also of the large chondrocyte population. RNA-seq analysis revealed that a 4-h digestion period with 1% or 2% collagenase II plus Actinomycin D optimally preserved the transcriptome. Thus, this study provides an isolation protocol for single chondrocytes from human articular cartilage optimized for transcriptome preservation and RNA-seq analysis.

In the framework of a non-relativistic quark model, the mass spectra of the ground and excited states of doubly heavy Ξ and Ω baryons are calculated. We estimate the mass difference between the Ω and corresponding Ξ baryons as MΩ−MΞ≃178 MeV for all the states containing cc,bc, or bb quarks. A simple form of the universal Isgur-Wise function, as the transition form factor between the doubly heavy baryons, is introduced. Working in the close-to-zero recoil limit, we investigate the b→c semileptonic decay widths and branching fractions of the doubly heavy baryons. The obtained results are compared with other theoretical predictions.

Background: Whether gonadotropin-releasing hormone agonist (GnRH-a) pituitary suppression improves clinical outcomes in non-endometriosis patients undergoing frozen embryo transfer remains controversial. The objective of this study is to investigate whether GnRHa combined with hormone replacement treatment (HRT) compared to HRT alone can improve the clinical outcomes of frozen-thawed embryo transfer in patients without endometriosis. Methods: This is a retrospective cohort study. This study involved 2178 frozen-thawed embryo transfer (FET) cycles of non-endometriosis patients between January 2018 and December 2019, of these cycles, 1535 were GnRHa-HRT combined cycles and 643 were HRT alone cycles. The primary outcomes were the clinical pregnancy and live birth rates. SPSS software (version 23.0, IBM Corp., Chicago, IL, USA) was used for data analysis. Results: Single-factor analysis showed that the live birth and implantation rates -were higher in the GnRHa-HRT group than those in the HRT group (p < 0.05). The mid-to-late-term miscarriage rate in the GnRHa-HRT group was lower than that in the HRT group (p < 0.05). The rates of human chorionic gonadotropin (HCG) positivity, clinical pregnancy, early abortion, multiple pregnancy, and preterm delivery between the two groups were comparable. Multivariate logistic regression analysis showed that rate of the live birth in the GnRHa-HRT group was higher than in the HRT group (p = 0.009), and there was no significant difference in the clinical pregnancy rate between the two groups (p = 0.103). Conclusions: This large-scale retrospective study revealed that non-endometriosis women in FET cycles may benefit from the GnRHa downregulation due to increasing the live birth rate.

This study investigated the influence of ‘snackification’ in Singaporean diets, leading to increased dietary acrylamide exposure. Acrylamide concentrations in commonly consumed foods within and outside the main meals were measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). High acrylamide concentrations were detected in vegetables cooked at high temperatures (ranging from 0.5 to 478.4 µg/kg) and potato-based crackers and chips (ranging from 81.8 to 2095.8 µg/kg). The estimated total dietary exposure for the Singapore population was 0.165 µg/kg bw/day for general consumers and 0.392 µg/kg bw/day for high consumers (95th percentile). The acrylamide exposure from outside main meals was nearly equivalent to that from within the main meals. The calculated margins of exposure (MOE) were below 10,000, indicating potential human health concern. These findings highlight the need for industry practices and consumer advisories to reduce acrylamide exposure from foods consumed both within and outside main meals.

Abstract Background Various stimuli, including Clonorchis sinensis infection, can cause liver fibrosis. Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) with massive production of extracellular matrix (ECM). Our previous study showed that the TGF-β1-induced Smad signaling pathway played a critical role in the activation of HSCs during liver fibrosis induced by worm infection; however, the mechanisms that modulate the TGF-β/Smad signaling pathway are still poorly understood. Accumulating evidence demonstrates that miRNAs act as an important regulator of activation of HSCs during liver fibrosis. Methods The target of miR-497 was determined by bioinformatics analysis combined with a dual-luciferase activity assay. LX-2 cells were transfected with miR-497 inhibitor and then stimulated with TGF-β1 or excretory/secretory products of C. sinensis (CsESPs), and activation of LX-2 was assessed using qPCR or western blot. In vivo, the mice treated with CCl4 were intravenously injected with a single dose of adeno-associated virus serotype 8 (AAV8) that overexpressed anti-miR-497 sequences or their scramble control for 6 weeks. Liver fibrosis and damage were assessed by hematoxylin and eosin (H&E) staining, Masson staining, and qPCR; the activation of the TGF-β/Smad signaling pathway was detected by qPCR or western blot. Results In the present study, the expression of miR-497 was increased in HSCs activated by TGF-β1 or ESPs of C. sinensis. We identified that Smad7 was the target of miR-497 using combined bioinformatics analysis with luciferase activity assays. Transfection of anti-miR-497 into HSCs upregulated the expression of Smad7, leading to a decrease in the level of p-Smad2/3 and subsequent suppression of the activation of HSCs induced by TGF-β1 or CsESPs. Furthermore, miR-497 inhibitor delivered by highly-hepatotropic (rAAV8) inhibited TGF-β/smads signaling pathway by targeting at Smad7 to ameliorate CCL4-induced liver fibrosis. Conclusions The present study demonstrates that miR-497 promotes liver fibrogenesis by targeting Smad7 to promote TGF-β/Smad signaling pathway transduction both in vivo and in vitro, which provides a promising therapeutic strategy using anti-miR-497 against liver fibrosis. Graphical Abstract

It is extremely dangerous to treat the posterior third of the superior sagittal sinus (PTSSS) surgically, since it is usually not completely ligated. In this report, the authors described the case of a 27-year-old man with a ruptured and defective PTSSS caused by an open depressed skull fracture, which was treated by ligation of the PTSSS and the patient achieved a positive recovery. The patient's occiput was hit by a height-limiting rod and was in a mild coma. A CT scan showed an open depressed skull fracture overlying the PTSSS and a diffuse brain swelling. He underwent emergency surgery. When the skull fragments were removed, a 4 cm segment of the superior sagittal sinus (SSS) and the adjacent dura mater were removed together with bone fragments. Haemorrhage occurred and blood pressure dropped. We completed the operation by ligating the severed ends of the fractured sagittal sinus. One month after the operation, apart from visual field defects, he recovered well. In our opinion, in primary hospitals, when patients with severely injured PTSSS cannot sustain a long-time and complicated operation, e.g., the bypass using venous graft, and face life-threatening conditions, ligation of the PTSSS is another option, which may unexpectedly achieve good results.

ObjectivesThe addition of novel β-lactamase inhibitors to carbapenems restores the activity against multidrug-resistant Gram-negative bacteria. The aim of this study was to summarize the evidence on the efficacy and safety of novel carbapenem–β-lactamase inhibitor combinations.MethodsWe conducted a meta-analysis of clinical trials comparing novel carbapenem–β-lactamase inhibitor combinations with comparators to assess the clinical and microbiological responses, mortality, and adverse events (AEs).ResultsA total of 1,984 patients were included. The pooled risk ratios (RRs) of clinical cure, microbiological eradication, all-cause mortality, and 28-day mortality were 1.11 (95% CI: 0.98–1.26), 0.98 (95% CI: 0.82–1.16), 0.90 (95% CI: 0.49–0.94), and 0.68 (95% CI: 0.49–0.94) between the novel carbapenem–β-lactamase inhibitor combinations and control groups. Sensitivity analysis revealed that the phase II trial of imipenem–cilastatin/relebactam (ICR) against complicated urinary tract infections could be the most important factor of heterogeneity for the microbiological response. The therapeutic effect of novel carbapenem–β-lactamase inhibitor combinations was better in meropenem–vaborbactam (MEV), phase III trials, and number of patients less than 200. The RRs of AEs from any cause and serious adverse events (SAEs) for patients receiving novel carbapenem–β-lactamase inhibitor combinations were 0.98 (95% CI: 0.93–1.04) and 1.01 (95% CI: 0.75–1.36), respectively.ConclusionsICR and MEV were superior to comparators for clinical cure and survival rate in the treatment of complicated infections, and both were as tolerable as the comparators.

The terrestrial cryosphere functions to provide critical freshwater and serve societies and ecosystems, driving nature's contributions to people (NCP). This becomes increasingly important for the oasis areas in Northwest China. The cryospheric meltwater is in demand to support the economy and reduce poverty, accompanied by growing requirements to protect the environment. We intend to investigate the contributions of cryospheric meltwater by analyzing the spatial functions and services pertinent to provisioning meltwater in China. Based on the currently available datasets during the 2000s of glaciers, snow cover, and permafrost, spatial clustering was utilized to analyze the contributions at the third-level basin scale. Further assessment is carried out for the exposure of primary, secondary, and tertiary industrial sectors to cryospheric meltwater, which reflects the spatiality of potential services that cryospheric meltwater may provide. In results, we spatially cluster the contribution of cryospheric meltwater into six function zones and twenty-seven sub-zones, in association with the degree of their reliance on glaciers, snow cover, and permafrost. Considering the sector's exposure, we further spatially cluster the contribution areas into eleven service zones concerning the potential service of cryospheric meltwater. Generally, the cryosphere contributes approximately 8.3% of the total water resource in China, with function zones mainly distributed in northeastern China, Qinghai−Tibet Plateau (QTP), and other arid regions of Northwest China with various significance. The overall contribution ratios of the glacier, snow cover, and permafrost to cryospheric meltwater are about 35.6%, 56.5%, and 7.9%, respectively. By looking into the service zones, the cryospheric meltwater mainly contributes to the primary industry in Northwest China and QTP, even though it has less significant effects on all other industrial sectors, while the services to the ecosystem are mainly located in QTP and high mountain regions. The results offer an overarching view on the contributions of cryospheric meltwater in China.