Parental willingness to accept and pay human papillomavirus vaccine for boys aged 9-14 in a metropolis area of China: Evidence for developing a vaccination strategy.

BACKGROUND: Increasing countries are expanding the human papillomavirus (HPV) vaccination to men, which has not yet been licensed in China. This study investigated the parental willingness to accept (WTA) and pay (WTP) HPV vaccine for their sons aged 9-14. METHODS: In Shanghai, a metropolis area of China, parents with boys aged 9-14 were recruited to complete an online questionnaire using a convenience sampling strategy. Parental WTA were determined for parents themselves and for their sons. Parental preference of HPV vaccine was measured using discrete choice experiment in two assumed government subsidy scenarios that referred to HPV vaccination subsidy mechanisms for girls in China. Additionally, parental WTP was estimated using contingent valuation method. RESULTS: A total of 2493 parents with boys aged 9-14 were included in the study. Majority of mothers (88.99 % and 90.99 %) and fathers (79.57 % and 85.04 %) showed WTA HPV vaccine for themselves and sons, respectively. Parental gender, age, monthly household income, knowledge, and awareness were positively associated with parental WTA for their sons (each P < 0.05). Remarkably, more mothers showed specific preference of HPV vaccine for themselves (53.67 %) and sons (47.78 %), while more fathers showed no preference for themselves (46.76 %) and sons (53.81 %). In the two assumed government subsidy scenarios, parents mostly preferred domestic HPV vaccines for themselves and sons (each P < 0.05). Additionally, mothers had significantly higher WTP for sons (mean value, 2122.75 CNY) than fathers did (1695.40 CNY) (P < 0.001). However, parental WTP was similar between for themselves and for sons, regardless of mothers and fathers (each P > 0.05). CONCLUSION: Parents have high WTA and WTP HPV vaccine for boys aged 9-14 in Shanghai, which may provide evidence for preparing HPV vaccination strategy. Acceptance of HPV vaccines and roll-out in boys could be enhanced through the availability of government subsidy mechanism and domestic HPV vaccines.

Parental vaccine hesitancy and acceptance of a COVID-19 vaccine: An internet-based survey in the US and five Asian countries.

COVID-19 vaccination rates for children globally are relatively low. This study aimed to investigate parental vaccine hesitancy and parents' acceptance of a COVID-19 for their children for their children in the United States, China, Taiwan, India, Indonesia, and Malaysia.We analyzed data from an opt-in, internet-based cross-sectional study (n = 23,940). Parents were asked about their acceptance of a COVID-19 vaccine for their children, and if they would accept the vaccine with different risk and effectiveness profiles for themselves. Poisson regression was used to generate prevalence ratios (PR) of the relationship between vaccine acceptance for a child and vaccine profile, by country and waves and overall. Between August 2020 and June 2021, COVID-19 vaccine acceptance for children decreased in the United States (89% to 72%) and Taiwan (79% to 71%), increased in India (91% to 96%) and Malaysia (81% to 91%), and was stable in Indonesia (86%) and China (at 87%-90%). Vaccine risk and effectiveness profiles did not consistently affect parent's acceptance of a COVID-19 vaccine for their children. Instead, being not hesitant was a large driver of vaccine acceptance (PR: 1.24, 95% CI: 1.14, 1.36). Adolescent COVID-19 vaccination have already been established in many high and middle-income countries, but our study suggests that there is a movement of vaccine hesitancy which could impede the success of future pediatric and adolescent COVID-19 vaccination programs.

Genomic characterization of Rocahepevirus ratti hepatitis E virus genotype C1 in Yunnan province of China.

The Rocahepevirus ratti hepatitis E virus genotype C1 (HEV-C1) has been documented to infect humans. However, the understanding of HEV-C1 remains constrained. This study aims to determine the prevalence and genomic characteristics of HEV-C1 in small animals in Yunnan province of southwestern China. A total of 444 liver tissues were collected from animals covering the orders Rodentia, Soricomorpha, Scandentia and Erinaceomorpha in three regions in Yunnan. Then Paslahepevirus balayani and Rocahepevirus were examined using RT-qPCR. The detection rate of Rocahepevirus was 12.95 % (36/278) in animals of order Rodentia, with 14.77 % (35/237) in Rattus tanezumi and 33.33 % (1/3) in Niviventer fulvescens. No Paslahepevirus balayani was detected. Additionally, two full-length Rocahepevirus sequences (MSE-17 and LHK-54) and thirty-three partial ORF1 sequences were amplified and determined to be HEV-C1. MSE-17 and LHK-54 shared moderate nucleotide identity (78.9 %-80.3 %) with HEV-C1 isolated in rats and humans. The HEV-C1 isolated from Niviventer fulvescens demonstrated a 100 % nucleotide identity with that from Rattus tanezumi. The rat HEV-C1 sequences isolated in our study and other Asian HEV-C1 sequences were phylogenetically distant from those isolated in North America and Europe. Furthermore, the two full-length sequences isolated in our study had less amino acid substitutions in the motifs of RNA-dependent RNA polymerase domain (F204L and L238F), compared with other Asian sequences. In summary, HEV-C1 commonly spreads in rats in Yunnan province of China. Our findings suggest a spatially associated phylogeny, and potential cross-species transmission of HEV-C1.

Molecular epidemiology and phylogeny of the emerging zoonotic virus Rocahepevirus: A global genetic analysis.

Human infections with Rocahepevirus ratti genotype C1 (HEV-C1) in Hong Kong of China, Canada, Spain, and France have drawn worldwide concern towards Rocahepevirus. This study conducted a global genetic analysis of Rocahepevirus, aiming to furnish comprehensive molecular insights and promote further research. We retrieved 817 Rocahepevirus sequences from the GenBank database through October 31, 2023, categorizing them according to research, sample collection area and date, genotype, host, and sequence length. Subsequently, we conducted descriptive epidemiological, phylogenetic evolutionary, and protein polymorphism (in length and identity) analyses on these sequences. Rocahepevirus genomes were identified across twenty-eight countries, predominantly in Asia (71.73%, 586/817) and Europe (26.44%, 216/817). The HEV-C1 dominates Rocahepevirus (77.2%, 631/817), while newly discovered Rocahepevirus genotypes (C3/C4/C5 and other unclassified genotypes) were primarily identified in Europe (25/120) and China (91/120). Muridae animals (72.5%, 592/817) serve as the primary hosts for Rocahepevirus, with other hosts encompassing species from the families Soricidae, Hominidae, Mustelidae, and Cricetidae. Additionally, Rocahepevirus genomes (C1 genotype) were identified in sewage samples recently. The phylogenetic evolution of Rocahepevirus exhibits considerable variation. Specifically, HEV-C1 can be classified into at least six genetic groups (G1 to G6), with human HEV-C1 distributed across multiple evolutionary clades. The overall ORF1 and ORF2 amino acid sequence lengths were significantly different (P < 0.001) across Rocahepevirus genotypes. HEV-C1/C2/C3 and HEV-C4/C5 displayed substantial differences in amino acid sequence identity (58.4%-59.6%). The identification of Rocahepevirus genomes has expanded across numerous countries, particularly in European and Asian countries, coinciding with an expanding host range and emergence of new genotypes. The evolutionary path of Rocahepevirus is intricate, where the HEV-C1 dominates globally and internally forms multiple evolutionary groups (G1 to G6), exhibiting diverse genetic variation within human HEV-C1. Significant differences exist in the protein polymorphism (in length and identity) across Rocahepevirus genotypes. Given Rocahepevirus's shift from an animal virus to a zoonotic pathogen, worldwide cooperation in monitoring Rocahepevirus genomes is vital.

Rational design of a cross-type HPV vaccine through immunodominance shift guided by a cross-neutralizing antibody.

In vaccine development, broadly or cross-type neutralizing antibodies (bnAbs or cnAbs) are frequently targeted to enhance protection. Utilizing immunodominant antibodies could help fine-tune vaccine immunogenicity and augment the precision of immunization strategies. However, the methodologies to capitalize on the attributes of bnAbs in vaccine design have not been clearly elucidated. In this study, we discovered a cross-type neutralizing monoclonal antibody, 13H5, against human papillomavirus 6 (HPV6) and HPV11. This nAb exhibited a marked preference for HPV6, demonstrating superior binding activity to virus-like particles (VLPs) and significantly higher prevalence in anti-HPV6 human serum as compared to HPV11 antiserum (90% vs. 31%). Through co-crystal structural analysis of the HPV6 L1 pentamer:13H5 complex, we delineated the epitope as spanning four segments of amino acids (Phe42-Ala47, Gly172-Asp173, Glu255-Val275, and Val337-Tyr351) on the L1 surface loops. Further interaction analysis and site-directed mutagenesis revealed that the Ser341 residue in the HPV6 HI loop plays a critical role in the interaction between 13H5 and L1. Substituting Ser341 with alanine, which is the residue type present in HPV11 L1, almost completely abolished binding activity to 13H5. By swapping amino acids in the HPV11 HI loop with corresponding residues in HPV6 L1 (Ser341, Thr338, and Thr339), we engineered chimeric HPV11-6HI VLPs. Remarkably, the chimeric HPV11-6HI VLPs shifted the high immunodominance of 13H5 from HPV6 to the engineered VLPs and yielded comparable neutralization titers for both HPV6 and HPV11 in mice and non-human primates. This approach paves the way for the design of broadly protective vaccines from antibodies within the main immunization reservoir.

Comparison of different intervention methods to reduce the incidence of venous thromboembolism: study protocol for a cluster-randomized, crossover trial.

BACKGROUND: Venous thromboembolism (VTE) remains a priority challenge among orthopedic trauma patients. It is crucial to further improve the prophylaxis against VTE in routine orthopedic treatment. This study aims to compare the efficacy of two low molecular weight heparin (LMWH) regimens and additional intermittent pneumatic compression in preventing VTE among orthopedic trauma patients. METHODS AND ANALYSIS: This is a cluster-randomized crossover clinical study conducted in four hospitals in Shanghai from December 2019 to December 2023. The unit of randomization is orthopedic wards, and each ward will define a cluster. All clusters will implement four diverse intervention measures and one control measure in a given random sequence. Perioperative orthopedic trauma patients aged ≥ 18 years with stable vital signs, Caprini score > 2, and no contraindication of anticoagulation or intermittent pneumatic compression (IPC) devices will be eligible. The sample size will be determined to be 2590, considering cluster effect, period effect, and interactions. We will generally use the intention-to-treat (ITT) at the subject level for each outcome. For the primary outcome of the study, the incidence of VTE will be presented as risk ratio and 95% CIs. Generalized estimating equation (GEE) will be deployed to compare differences and adjust cluster effect, period effect, and interaction among interventions and periods if applicable. DISCUSSION: VTE is a complication that cannot be underestimated after major orthopedic surgery. Early identification, early assessment, and early prevention can significantly reduce the incidence of VTE. Most guidelines recommend both medical and physical prevention, and we hope to demonstrate how they would affect the incidence among perioperative orthopedic patients. We want to explore if there is a difference between the two types of LWMH with or without an IPC device to provide more evidence for future guidelines and prevent more patients from the threat of VTE. ETHICS AND DISSEMINATION: The study received approval from the IRB of the coordinating center and all participating hospitals. Findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: ChiCTR1900027659. Registered on 17 November 2019.

Impact of Varicella Immunization and Public Health and Social Measures on Varicella Incidence: Insights from Surveillance Data in Shanghai, 2013-2022.

To evaluate the impact of a two-dose VarV program on varicella incidence among the whole population, considering the influence of public health and social measures (PHSMs), we extracted surveillance data on varicella cases during 2013-2022 in Minhang, Shanghai. Then, we estimated the incidence trend of varicella through interrupted time-series analyses and quantified the impact of the immunization program and PHSMs using Serfling regression. We also explored the associations between PHSMs and varicella cases. The implementation of the two-dose VarV strategy was followed by a significant decrease in varicella incidence (-1.84% per month). After one year of the program, varicella incidence was estimated at a 45.25% reduction, which was higher in children (59.12% and 54.09%) than in adults (19.49%). The decrease attributed to PHSMs was 31.26% during 2020-2022, and school closing was identified as the most relevant PHSM (b = -8.03 cases, r = -0.67 with a 1-week lag). These findings indicate that the two-dose immunization program has more effectively reduced the varicella incidence compared with the one-dose vaccine, and interventions like school closings are also encouraged to serve as supplementary measures to prevent varicella epidemics.

Epidemiological and clinical characteristics of psittacosis among cases with complicated or atypical pulmonary infection using metagenomic next-generation sequencing: a multi-center observational study in China.

BACKGROUND: Chlamydia psittaci (C. psittaci) causes parrot fever in humans. Development of metagenomic next-generation sequencing (mNGS) enables the identification of C. psittaci. METHODS: This study aimed to determine the epidemiological and clinical characteristics of parrot fever cases in China. A multi-center observational study was conducted in 44 tertiary and secondary hospitals across 14 provinces and municipalities between April 2019 and October 2021. RESULTS: A total of 4545 patients with complicated or atypical pulmonary infection were included in the study, among which the prevalence of C. psittaci was determined to be 2.1% using mNGS. The prevalence of C. psittaci was further determined across demographic groups and types of specimens. It was significantly higher in patients with senior age (2.6% in those > 50 years), winter-spring (3.6%; particularly in December, January, and February), and southwestern (3.4%) and central and southern China (2.7%) (each P < 0.001). Moreover, the prevalence was the highest in bronchoalveolar lavage fluid (BALF) (2.9%), compared with sputum (1.1%) and peripheral blood specimens (0.9%). Additionally, co-infection of principal microorganisms was compared. Certain microorganisms were more likely to co-infect in parrot fever cases, such as Candida albicans in BALF (26.7%) and peripheral blood (6.3%), compared with non-parrot fever cases (19.7% and 1.3%); however, they did not significantly differ (each P > 0.05). CONCLUSION: Parrot fever remains low in patients with complicated or atypical pulmonary infection. It is likely to occur in winter-spring and southwestern region in China. BALF may be the optimal specimen in the application of mNGS. Co-infection of multiple microorganisms should be further considered.

Infectious disease control: from health security strengthening to health systems improvement at global level.

Since the twenty first century, the outbreaks of global infectious diseases have caused several public health emergencies of international concern, imposing an enormous impact on population health, the economy, and social development. The COVID-19 pandemic has once again exposed deficiencies in existing global health systems, emergency management, and disease surveillance, and highlighted the importance of developing effective evaluation tools. This article outlines current challenges emerging from infectious disease control from the perspective of global health, elucidated through influenza, malaria, tuberculosis, and neglected tropical diseases. The discordance among government actors and absent data sharing platforms or tools has led to unfulfilled targets in health system resilience and a capacity gap in infectious disease response. The current situation calls for urgent action to tackle these threats of global infectious diseases with joined forces through more in-depth international cooperation and breaking governance barriers from the purview of global health. Overall, a systematic redesign should be considered to enhance the resilience of health systems, which warrants a great need to sustain capacity-building efforts in emergency preparedness and response and raises an emerging concern of data integration in the concept of One Health that aims to address shared health threats at the human-animal-environment interface.

Coverage and impact of influenza vaccination among children in Minhang District, China, 2013-2020.

Background: Young children have a great disease burden and are particularly vulnerable to influenza. This study aimed to assess the direct effect of influenza vaccination among children and to evaluate the indirect benefit of immunizing children. Methods: The influenza vaccination records for all children born during 2013-2019 in Minhang District and surveillance data for reported influenza cases were obtained from the Minhang CDC. 17,905 children were recorded in the vaccination system and included in this study. Descriptive epidemiology methods were used for data analysis, including an ecological approach to estimate the number of influenza cases averted by vaccination and linear regression to estimate the reduction in influenza cases in the general population per thousand additional childhood vaccination doses. Results: During the study period, the annual vaccination coverage rate ranged from 10.40% in 2013-2014 to 27.62% in 2015-2016. The estimated number of influenza cases averted by vaccination ranged from a low of 0.28 (range: 0.23-0.34) during 2013-2014 (PF: 6.15%, range: 5.11-7.38%) to a high of 15.34 (range: 12.38-18.51) during 2017-2018 (PF: 16.54%, range: 13.79-19.30%). When increasing vaccination coverage rate by 10% in each town/street, a ratio of 7.27-10.69% cases could be further averted on the basis of observed cases. In four selected periods, the number of influenza cases in the general population was most significantly correlated with the cumulative childhood vaccination doses in the prior 2-5 months, and the reduction in influenza cases ranged from 0.73 to 3.18 cases per thousand additional childhood vaccination doses. Conclusion: Influenza vaccination among children is estimated to have direct effects in terms of averted cases and might provide an underlying indirect benefit to the general population. Vaccination coverage in high-coverage areas should be further expanded to avert more influenza cases.

HPV Vaccination Behavior, Vaccine Preference, and Health Beliefs in Chinese Female Health Care Workers: A Nationwide Cross-Sectional Study.

Human papillomavirus (HPV) vaccination has been proven to be the most effective method to prevent cervical cancer. This study aimed to determine the HPV vaccination behavior and preference in Chinese female health care workers. A nationwide cross-sectional study was performed to recruit 15,967 respondents aged 18-45 years from 31 provinces in China's mainland in 2021. Of them, 30.0% have been vaccinated or have made an appointment. Regardless of actual vaccination status, respondents mostly preferred the 9-valent HPV vaccine (58.6%), followed by 4-valent (15.6%) and 2-valent vaccines (3.1%); additionally, 17.9% did not have a preference. Moreover, health beliefs on HPV and HPV vaccination were measured using a health belief model (HBM) analysis. Six HBM constructs differed significantly by HPV vaccination status. Higher levels of perceived susceptibility (beta = 0.074), perceived benefit (beta = 0.072), self-efficacy (beta = 0.304), and cues to action (beta = 0.039) scales were significantly associated with increasing HPV vaccine uptake. In contrast, perceived severity (beta = -0.019) and perceived barriers (beta = -0.089) were negative factors. In conclusion, HPV vaccine uptake is high in Chinese female health care workers. HBM constructs may be effective in facilitating the improvement and delivery of targeted intervention programs to increase HPV vaccine uptake.

Metagenomic surveillance and comparative genomic analysis of Chlamydia psittaci in patients with pneumonia.

Chlamydia psittaci, a strictly intracellular bacterium, is an underestimated etiologic agent leading to infections in a broad range of animals and mild illness or pneumonia in humans. In this study, the metagenomes of bronchoalveolar lavage fluids from the patients with pneumonia were sequenced and highly abundant C. psittaci was found. The target-enriched metagenomic reads were recruited to reconstruct draft genomes with more than 99% completeness. Two C. psittaci strains from novel sequence types were detected and these were closely related to the animal-borne isolates derived from the lineages of ST43 and ST28, indicating the zoonotic transmissions of C. psittaci would benefit its prevalence worldwide. Comparative genomic analysis combined with public isolate genomes revealed that the pan-genome of C. psittaci possessed a more stable gene repertoire than those of other extracellular bacteria, with ~90% of the genes per genome being conserved core genes. Furthermore, the evidence for significantly positive selection was identified in 20 virulence-associated gene products, particularly bacterial membrane-embedded proteins and type three secretion machines, which may play important roles in the pathogen-host interactions. This survey uncovered novel strains of C. psittaci causing pneumonia and the evolutionary analysis characterized prominent gene candidates involved in bacterial adaptation to immune pressures. The metagenomic approach is of significance to the surveillance of difficult-to-culture intracellular pathogens and the research into molecular epidemiology and evolutionary biology of C. psittaci.

The role of group 3 innate lymphoid cell in intestinal disease.

Group 3 innate lymphoid cells (ILC3s), a novel subpopulation of lymphocytes enriched in the intestinal mucosa, are currently considered as key sentinels in maintaining intestinal immune homeostasis. ILC3s can secrete a series of cytokines such as IL-22 to eliminate intestinal luminal antigens, promote epithelial tissue repair and mucosal barrier integrity, and regulate intestinal immunity by integrating multiple signals from the environment and the host. However, ILC3 dysfunction may be associated with the development and progression of various diseases in the gut. Therefore, in this review, we will discuss the role of ILC3 in intestinal diseases such as enteric infectious diseases, intestinal inflammation, and tumors, with a focus on recent research advances and discoveries to explore potential therapeutic targets.

Water-Stable Hybrid Lead-Free Perovskite for Negative Temperature Coefficient Thermistors.

Negative temperature coefficient (NTC) thermistors feature higher sensitivities and faster response speeds and thereby have particular applications in many fields. However, current NTC thermistors are mostly based on inorganic ceramic materials, which show obvious drawbacks in material synthesis, property modulation, and flexible film fabrication. Herein, we report, for the first time, the promising application of an inorganic-organic hybrid NTC thermistor. A new lead-free hybrid iodo bismuthate [1,1',1″-(benzene-1,3,5-triyl)tris(3-methyl-1H-imidazol-3-ium)]Bi2I9 [denoted as (Me3TMP)Bi2I9] was synthesized by a "double-free" strategy. (Me3TMP)Bi2I9 features a lead-free binuclear bismuth iodine anion charge compensated by a "classic hydrogen-bond-free" cation. (Me3TMP)Bi2I9 exhibits remarkable stability in water and UV light irradiation and shows the largest temperature sensitivity coefficient among all reported NTC materials. Theoretical calculation and detailed structural analysis disclose that the seriously distorted (BiI6) octahedra are responsible for the intriguing NTC effect for (Me3TMP)Bi2I9.

New insights on IL­36 in intestinal inflammation and colorectal cancer (Review).

Interleukin (IL)-36 is a member of the IL-1 superfamily, which includes three receptor agonists and one antagonist and exhibits a familial feature of inflammatory regulation. Distributed among various tissues, such as the skin, lung, gut and joints, the mechanism of IL-36 has been most completely investigated in the skin and has been used in clinical treatment of generalized pustular psoriasis. Meanwhile, the role of IL-36 in the intestine has also been under scrutiny and has been shown to be involved in the regulation of various intestinal diseases. Inflammatory bowel disease and colorectal cancer are the most predominant inflammatory and neoplastic diseases of the intestine, and multiple studies have identified a complex role for IL-36 in both of them. Indeed, inhibiting IL-36 signaling is currently regarded as a promising therapeutic approach. Therefore, the present review briefly describes the composition and expression of IL-36 and focuses on the role of IL-36 in intestinal inflammation and colorectal cancer. The targeted therapies that are currently being developed for the IL-36 receptor are also discussed.

Deep vein thrombosis and validation of the Caprini risk assessment model in Chinese orthopaedic trauma patients: a multi-center retrospective cohort study enrolling 34,893 patients.

BACKGROUND: The risk of venous thromboembolism among orthopaedic trauma patients is high, but prevalence of deep vein thrombosis (DVT) remains unknown. In addition, the Caprini risk assessment model (RAM) score in orthopaedic trauma patients is undetermined in previous research. This study is aimed to determine the incidence of DVT and then validate the Caprini RAM in orthopaedic trauma patients. METHODS: This is a retrospective cohort study enrolling orthopaedic trauma inpatients from seven tertiary and secondary hospitals during a 3-year period (from April 1, 2018 through April 30, 2021). Caprini RAM scores were assessed by experienced nurses on admission. The patients with suspected DVT were verified through duplex ultrasonography by qualified radiologists, and then prospectively followed once a year after discharge. RESULTS: In total, 34,893 patients were enrolled in our study. The Caprini RAM identified 45.7% of patients at low risk (Caprini score 0-2), 25.9% at medium risk (3-4), and 28.3% at high risk (5-6), highest risk (7-8), and superhigh risk (> 8). Patients with Caprini score > 5 were likely to be older, female, and with longer length of hospital stay. Moreover, 8695 patients had received ultrasonography to detect DVT. The prevalence of DVT was determined to be 19.0% [95% confidence interval (CI) 18.2-19.9%], which significantly increased with Caprini score. The area under curve of the Caprini RAM for DVT was 0.77 (95% CI 0.76-0.78) with a threshold of 4.5. Furthermore, 6108 patients who had received ultrasonography completed the follow-up. DVT patients had a hazard ratio of 1.75 (95% CI 1.11-2.76; P = 0.005) in the mortality, compared to non-DVT ones. Caprini scores were significantly associated with increase in the mortality [odds ratio (OR) 1.14; 95% CI 1.07-1.21; P < 0.001]; DVT remained an independent effect (OR 1.5; 95% CI 1.02-2.26; P = 0.042). CONCLUSIONS: The Caprini RAM may be valid in Chinese orthopaedic trauma patients. Prevalence of DVT and higher Caprini score were significantly associated with increased all-cause mortality among orthopaedic trauma patients after discharge. Further study is warranted to explore the causes of higher mortality in patients with DVT.

Sequential Two-Photon Delayed Fluorescence Anisotropy for Macromolecular Size Determination.

Time-resolved fluorescence anisotropy (FA) uses the fluorophore depolarization rate to report on rotational diffusion, conformation changes, and intermolecular interactions in solution. Although FA is a rapid, sensitive, and nondestructive tool for biomolecular interaction studies, the short (∼ns) fluorescence lifetime of typical dyes largely prevents the application of FA on larger macromolecular species and complexes. By using triplet shelving and recovery of optical excitation, we introduce optically activated delayed fluorescence anisotropy (OADFA) measurements using sequential two-photon excitation, effectively stretching fluorescence anisotropy measurement times from the nanosecond scale to hundreds of microseconds. We demonstrate this scheme for measuring slow depolarization processes of large macromolecular complexes, derive a quantitative rate model, and perform Monte Carlo simulations to describe the depolarization process of OADFA at the molecular level. This setup has great potential to enable future biomacromolecular and colloidal studies.

A case of pulmonary embolism with bad warfarin anticoagulant effects caused by E. coli infection.

Warfarin is an anticoagulant commonly used as an oral drug in preventing and treating thromboembolic diseases. The international normalized ratio (INR) is a clinical monitoring anticoagulation intensity index that adjusts the dose based on important references. In particular, INR value must be strictly monitored when warfarin is used for anticoagulation therapy in infected patients. Herein, we report a 54-year-old female patient diagnosed with pulmonary embolism and venous thrombosis of the lower limbs. After the warfarin administration, the INR was always substandard. The patient did not take other warfarin-interacting drugs or foods during the hospital stay. Metagenome next-generation sequencing suggested a bloodstream infection caused by Escherichia coli, which was further confirmed by blood culture. After meropenem administration for anti-infective treatment, the INR value rose rapidly to a standard level. Considering the lack of relevant reports, this case is the first report of potential interaction between E. coli and warfarin. Further, in patients with thromboembolic diseases complicated by infection, antibiotics should be chosen reasonably with close monitoring of the INR to avoid the interaction of warfarin and antibiotics and to ensure the effectiveness and safety of warfarin treatment.