Search

Objectives Nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3-associated autoinflammatory disease (NLRP3 -AID) is a rare autosomal dominant systemic autoinflammatory disease. We aimed to summarize the phenotypic and genotypic features of Chinese adult NLRP3 -AID patients with hearing loss. Methods A retrospective cohort study of twenty-one adult patients with NLRP3 -AID was conducted in Peking Union Medical College Hospital between July 2015 and March 2023. All patients underwent whole exome sequencing and otorhinolaryngologic assessments. Clinical features and therapeutic data were collected and analysed. Results We found that 13/21 (61.90%) of patients had hearing loss with high-frequency impairment in the majority, and most patients presented with vestibular dysfunction as a new finding. The NLRP3 -AID patients with early-onset, cold or stress triggered episodes, red eyes, fatigue, hypopsia and mutations located in the NACHT domain of the NLRP3 protein were more likely to suffer from hearing loss, especially sensorineural hearing loss, perhaps as a result of pathogenic variants of high penetrance. By a series of audiological evaluations, TNF-α inhibitors were confirmed to improve or reverse hearing loss. Conclusions We reported the first cohort of Chinese adult NLRP3 -AID patients with hearing loss and characterized vestibular dysfunction, highlighted the necessity for attention to high-frequency hearing and provided potential alternative treatment. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factors (VEGF), Vascular endothelial growth factor receptors (VEGFR) and their downstream signaling pathways are promising targets in anti-angiogenic therapy. They constitute a crucial system to regulate physiological and pathological angiogenesis. In the last 20 years, many antiangiogenic drugs have been developed based on VEGF/VEGFR system to treat diverse cancers and retinopathies, and new drugs with improved properties continue to emerge at a fast rate. They consist of different molecular structures and characteristics, which enable them to inhibit the interaction of VEGF/VEGFR, to inhibit the activity of VEGFR tyrosine kinase (TK), or to inhibit VEGFR downstream signaling. In this paper, we reviewed the development of marketed anti-angiogenic drugs involved in the VEGF/VEGFR axis, as well as some important drug candidates in clinical trials. We discuss their mode of action, their clinical benefits, and the current challenges that will need to be addressed by the next-generation of anti-angiogenic drugs. We focus on the molecular structures and characteristics of each drug, including those approved only in China. [ABSTRACT FROM AUTHOR]

To explore the feasibility, safety and cost effectiveness of the use of peripherally inserted central catheter (PICC) in children with hemophilia A and inhibitors who underwent ITI treatment. This retrospective cohort study evaluated the effect of PICC placement and ITI on bleeding rates, costs, and parents' satisfaction before and within 6 months after PICC placement in children with hemophilia A and inhibitors. A total of 20 children with hemophilia A and high-titer inhibitors were included, with a success rate for PICC placement of 100%, at a cost of ¥6730.50. Parents' satisfaction with PICC was 100%, and the total length of catheter indwelling was 6055 days. In terms of curative effect, the success rate of ITI treatment was 75%, and the annualized bleeding rate was decreased from 10.90 ± 12.16 times before placement to 2.10 ± 3.32 times (p < 0.05). The transportation expense for children and their parents to the clinic decreased from ¥20,920 ± 32,274.57 before catheter placement to ¥2915 ± 2195.99 (p < 0.05). Time of children missed school and their parents missed work decreased from 10.85 ± 22.36 days to 1.90 ± 3.58 (p < 0.05) days and 40.33 ± 46.11 days to 3.83 ± 7.11 days (p < 0.05), respectively. The use of PICC for ITI treatment in children with hemophilia A and accompanying inhibitors in developing countries (e.g. China) can ensure the effect of ITI, reducing expense and improving the quality of life without obvious side effects. [ABSTRACT FROM AUTHOR]

Shorter interval-time from inhibitor detection to starting immune tolerance induction (ITI) might predict better ITI outcomes for severe Hemophilia A (SHA) patients with high-risk-inhibitors. However, the prediction-impact of interval-time for these patients on low-dose ITI strategy remained unclear. To explore the relationship between interval-time and low-dose ITI outcomes in Chinese SHA children with high-risk-inhibitors. This was a single-center, retrospective study on SHA children with high-risk-inhibitors (each with immediate pre-ITI inhibitor titer>10 Bethesda Units/mL) undergoing low-dose ITI strategy for ≥24 months. ITI outcomes and their predictive factors were evaluated at the 24th month treatment for each patient. The predictive ability of interval-time on ITI success was determined using receiver operating characteristic (ROC) curve. Among 47 patients investigated, 34 (72.3 %) achieved success. Independent predictor for ITI-outcome on multivariate analysis included the interval-time (p = 0.007) and peak inhibitor-titer (p = 0.011). Shorter interval-time predicted ITI success [cut-off value = 22.3 months, area under ROC-curve (AUC) = 0.701] and early-ITI success within 12 month (cut-off value = 9.4 months AUC = 0.704). Linear regression analysis suggested each month interval-time delay delayed success by 0.1552 month. Unlike the interval-time, peak inhibitor-titer had no success-predictive value in high-peak inhibitor-titer patients on ITI with immunosuppressants. Interval-time represented a strong predictive value for outcomes in our low-dose ITI strategy for SHA patients with high-risk-inhibitors. Shorter interval-time was associated with higher success rate and earlier success achievement. The respective interval-time cut-off values were 22.3 months for ITI success and 9.4 months for early-success. • The interval-time is the time from inhibitor detection to starting ITI. • Interval-time for predicting low-dose ITI outcomes remained unclear, for high-risk-inhibitors patients. • Interval-time had a strong predictive value for outcomes in our low-dose ITI strategy. • Interval-time cut-off values were 22.3 for success and 9.4 months for early-success. [ABSTRACT FROM AUTHOR]

Background: Postpartum care is an expanding concept in China, and it is gaining vast attention in Chinese society. However, due to some Chinese traditions and rituals during the postpartum period, the utilization of modern postpartum care should be improved on both individual and community levels from different aspects. This integrative review outlined the inhibitors and facilitators of postpartum care utilization in China. Methods: Writing an integrative review, a literature search was conducted in Chinese and English databases including Wan Fang, China National Knowledge infrastructure, Medline, Web of Science, and Embase till 31 October 2021 to capture citations covering 'postpartum care', 'utilization' and 'China'. Titles and abstracts were screened independently by three reviewers. Included studies were critically appraised using tools and checklists independently for both qualitative and quantitative studies by two different reviewers who also performed thematic synthesis. Results: Of the 4359 citations screened, 41 studies (450,788 patients) were selected. Categorization of the factors influencing postpartum care utilization revealed five components: sociocultural (25 studies); educational (24 studies); organizational (12 studies); economic (19 studies); and physical (6 studies). Factors influencing postpartum care utilization both on individual and community levels were identified. They included facilitated factors such as higher mother's and partner's education level, higher socioeconomic status, lower parity, better insurance coverage, urban geographical location, Han ethnicity, and better transportation. Inhibitory factors such as under-managed policy regulation, migrants without domicile, and lower quality of care were also reported. Conclusion: This review has identified the inhibitors and facilitators of postpartum care utilization in China. Five major aspects including sociocultural, educational, organizational, economic, and physical components have been analysed. Results can be used to improve the utilization of modern postpartum care on both individual and community levels in Chinese society. [ABSTRACT FROM AUTHOR]

Factor (F) VIII inhibitors develop in around 30% of previously untreated patients (PUPs) with severe haemophilia, to a lesser extend in moderate and mild haemophilia A and in up to 10% in severe haemophilia B. Diagnostic challenges and questions remain including access to high quality testing, the role for functional inhibitor testing and binding antibody testing, and the adaptations needed in the presence of non‐factor replacement therapy. Despite significant gains in knowledge there are still many unanswered questions underlying the immunologic mechanisms of inhibitor development and tolerance. Therapeutic options include eradication of inhibitors using immune tolerance induction therapy (ITI), prophylaxis with bypassing agents (i.e., recombinant activated factor VII /rFVIIa or activated prothrombin complex concentrate/aPCC) or non‐factor replacement therapies (e.g., emicizumab) and treatment of bleeds or coverage of surgeries/invasive procedure. Recently a haemophilia centre capacity building program was launched in China to further develop the infrastructure and support needed to improve the diagnosis of haemophilia, detection of inhibitors, and continue to improve the care of patients with haemophilia and inhibitors. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor developing from the esophageal squamous epithelium, and is the most common histological subtype of esophageal cancer (EC). EC ranks 10th in morbidity and sixth in mortality worldwide. The morbidity and mortality rates in China are both higher than the world average. Current treatments of ESCC are surgical treatment, radiotherapy, and chemotherapy. Neoadjuvant chemoradiotherapy plus surgical resection is recommended for advanced patients. However, it does not work in the significant promotion of overall survival (OS) after such therapy. Research on targeted therapy in ESCC mainly focus on EGFR and PD-1, but neither of the targeted drugs can significantly improve the 3-year and 5-year survival rates of disease. Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is an important survival pathway in tumor cells, associated with its aggressive growth and malignant progression. Specifically, proliferation, apoptosis, autophagy, and so on. Related genetic alterations of this pathway have been investigated in ESCC, such as PI3K , AKT and mTOR-rpS6K. Therefore, the PI3K/AKT/mTOR pathway seems to have the capability to serve as research hotspot in the future. Currently, various inhibitors are being tested in cells, animals, and clinical trials, which targeting at different parts of this pathway. In this work, we reviewed the research progress on the PI3K/AKT/mTOR pathway how to influence biological behaviors in ESCC, and discussed the interaction between signals downstream of this pathway, especially eukaryotic translation initiation factors (eIFs) and the development and progression of ESCC, to provide reference for the identification of new therapeutic targets in ESCC. [ABSTRACT FROM AUTHOR]

Introduction: The formation of neutralizing antibodies (FVIII inhibitors) in haemophilia A patients is an immune response to the deficient factor. This process is multifactorial and includes environmental and genetic factors. Some genetic markers that play a decisive role in the immune response have been identified as risk factors for inhibitor development. Objective: Our aim was to investigate the association between polymorphisms in several genes involved in the regulation of the immune response and inhibitor development in patients with haemophilia A in North China. Methods: We analysed eight SNPs (MAPK9 rs4147385, CSF1R rs17725712, CD44 rs927335, STAT4 rs7574865, IKZF1 rs4917014, ETS1 rs6590330, BANK1 rs17266594 and rs10516487) by Snapshot SNP genotyping assays in 100 haemophilia A patients, including 29 with inhibitors and 71 without inhibitors. Results: Our results demonstrated that the rs17725712 A allele and the AA homozygous genotype of CSF1R were more frequent in patients with inhibitors. The rs4147385 G allele in MAPK9 was also more frequent in the inhibitor cohort. Conclusion: We confirmed an association of CSF1R rs17725712 and MAPK9 rs4147385 with inhibitor development in haemophilia A patients in North China. [ABSTRACT FROM AUTHOR]

Sapium sebiferumseeds from Huangshan, Wuhan, and Guiyang in China were studied to identify differences in their 1,000-seed mass and in concentrations of inhibitors of germination in the seed coat or endosperm extracted using methanol or acetone. Seed mass varied significantly in relation to origin, with the highest mass observed in seeds from Wuhan, followed by seeds from Huangshan and Guiyang. Extracts of seed coats or endosperm caused a marked inhibition of the germination index of cabbage seeds, but less inhibition of germination percentages. Endosperm extracts had a stronger inhibitory effect on cabbage seed germination than seed coat extracts. Inhibitor concentrations in whole seeds also varied with seed origin. Seeds from Wuhan exhibited a significantly higher level of inhibition than those from Guiyang or Huangshan, but no significant differences were observed between seeds from Guiyang and Huangshan. The efficacy of methanol or acetone extraction was also evaluated. For whole seeds from Huangshan and Guiyang, methanol was more effective than acetone, while acetone performed better than methanol for seeds from Wuhan. [ABSTRACT FROM PUBLISHER]

This study investigated the influence of copper oxide nanoparticles (CuONPs) and Cu 2+ on the uptake, translocation and subcellular distribution of organophosphate esters (OPEs) in rice seedlings using hydroponic experiments. The OPE concentrations in roots and shoots under the OPEs+CuONPs treatment were significantly lower than those with the OPEs+Cu 2+ (low level) or OPEs-only treatments, indicating that CuONPs can hinder the uptake of OPEs by root via competitive adsorption under short-term exposure. The plasma membrane permeability and antioxidant enzyme activity implied that CuONPs had a negligible impact on rice seedlings and could even reduce the toxicity of OPEs to rice root. A significant negative correlation between translocation factor and octanol-water partition coefficient was observed for the three treatments, implying an important role of hydrophobicity on the acropetal translocation of OPEs. Relatively hydrophobic OPEs were mainly adsorbed on cell wall, while hydrophilic OPEs were concentrated in cell sap. The subcellular distributions of OPEs in the OPEs+Cu 2+ (high level) or OPEs+CuONPs treatments slightly differed from the OPEs-only treatment, indicating that the coexistence of Cu 2+ or CuONPs with OPEs can influence the subcellular distribution of OPEs by affecting their adsorption or partitioning processes. Inhibition experiment suggested that root uptake of OPEs is a non-energy-consuming facilitated diffusion mediated by aquaporin channel, which can be slightly changed by the co-exposure of CuONPs. This study improved the understanding of uptake and translocation of OPEs by rice under the co-exposure to CuONPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Copyright of Journal of China Tourism Research is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose – In order to solve the corrosion problems in the South China Sea, the purpose of this paper was to study the main influences of corrosion including temperature, H2S content and corrosion inhibitor content in CO2/H2S oil field-produced water. Design/methodology/approach – The corrosion products formed on the steel surface were observed and analyzed using scanning electron microscope (SEM) and X-ray diffraction (XRD). Findings – The results indicate that temperature significantly influences the corrosion rate, which is a maximum at 70°C. The corrosion rate decreases as H2S content increases which is less than 10 mg/L, but then it increases rapidly. The FeCO3/FexSy protective film and a corrosion inhibition also were considered. Research limitations/implications – A mixture containing an imidazoline derivate and an organic amine can enhance the corrosion resistance of the corrosion product film. Practical implications – A mixture containing an imidazoline derivate and an organic amine can enhance the corrosion product film corrosion resistance. Social implications – Imidazoline is one kind of environmentally safe agent which can be used in the ocean. Originality/value – The corrosion can be controlled to a satisfactory extent in the presence of a mixture containing an imidazoline derivate and an organic amine. [ABSTRACT FROM AUTHOR]

Littering by visitors has led to severe challenges for rubbish collection in urban parks. One way to solve this problem is to encourage visitors to put rubbish in the bin. The purpose of this study is to explore the mechanism that drives people's use of bins in urban parks. The theoretical model of stimulus-organism-response is used to test the influence of stimuli (personal and social norms) on people's psychology (facilitators and inhibitors), thereby producing responses (the use of bins). In this study, we used a purposeful sampling method. Overall, 400 questionnaires were distributed, and 356 valid questionnaires were collected from visitors to the Shanghai City Park in China. The data were analysed using structural equations. The results show that personal and social norms have a significant impact on visitors' internal psychological state (facilitators and inhibitors). More specifically, personal and social norms are positively correlated with facilitators and negatively correlated with inhibitors. They have a significant positive impact on people's use of bins. We also found that facilitators and inhibitors partially mediate the relationship between norms and behaviours. The study suggests park managers should introduce various measures to influence people's personal norms and cultivate people's awareness of their obligation, responsibility, and commitment to the environment, and managers should also show visitors the consequences of not properly disposing of their rubbish as well as place more rubbish bins in key areas.

Alzheimer's disease (AD) is a common neurodegenerative disease that often occurs in the elderly population. At present, most drugs for AD on the market are single-target drugs, which have achieved certain success in the treatment of AD. However, the efficacy and safety of single-target drugs have not achieved the expected results because AD is a multifactorial disease. Multi-targeted drugs act on multiple factors of the disease network to improve efficacy and reduce adverse reactions. Therefore, the search for effective dual-target or even multi-target drugs has become a new research trend. Many of results found that the dual-target inhibitors of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and acetylcholinesterase (AChE) found from traditional Chinese medicine have a good inhibitory effect on AD with fewer side effects. This article reviews sixty-six compounds extracted from Chinese medicinal herbs, which have inhibitory activity on BACE1 and AChE. This provides a theoretical basis for the further development of these compounds as dual-target inhibitors for the treatment of AD., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Abstract: Detailed polychlorinated biphenyls (PCBs) congener patterns were determined in the flue gas from a medical waste incinerator (MWI) using high-resolution gas chromatograph coupled to high-resolution mass spectrometer (HRGC/HRMS). The total PCBs concentration of all homologues (mono- to deca-chlorinated homologues) in the flue gas ranged from 138.01 to 855.35ng/Nm3 and the WHO-TEQ value varied from 0.046 to 0.549ng/Nm3 under the different operating conditions. PCB-77 concentration was the highest among dioxin-like PCBs and PCB-126 contributed mostly to the WHO-TEQ. The ratios of dioxin-like PCBs in the total PCB concentrations in the flue gas varied between 11.7% and 26.0% (the average value is 18.7%). Three inhibitors, sulfur, urea, and ammonium sulfate were tested to investigate the capacity for preventing PCBs formation. The decomposition efficiency for total PCBs and PCBs TEQ ranged from 38% to 84% and 69% to 92% respectively. It was shown that urea mixed with ammonium sulfate and more activated carbon was proved to be the most effective inhibitor for PCBs formation. The removal efficiencies (REs) of the total PCBs concentration and PCBs TEQ by the bag filter under two conditions were 69% and 85%, and 86% and 94% respectively. [Copyright &y& Elsevier]

Originated in China, coronavirus disease 2019 (COVID-19)- the highly contagious and fatal respiratory disease caused by SARS-CoV-2 has already infected more than 29 million people worldwide with a mortality rate of 3.15% (according to World Health Organization's (WHO's) report, September 2020) and the number is exponentially increasing with no remedy whatsoever discovered till date. But it is not the first time this infectious viral disease has appeared, in 2002 SARS-CoV infected more than 8000 individuals of which 9.6% patients died and in 2012 approximately 35% of MERS-CoV infected patients have died. Literature reports indicate that a chymotripsin-like cystein protease (3CLpro) is responsible for the replication of the virus inside the host cell. Therefore, design and synthesis of 3CLpro inhibitor molecules play a great impact in drug development against this COVID-19 pandemic. In this review, we are discussing the anti-SARS effect of some small molecule 3CLpro inhibitors with their various binding modes of interactions to the target protein. Image 1 • Comparative study of SARS-CoV and SARS-CoV-2. • Overview of various protease inhibitors. • Importance of 3CLpro enzyme for virus replication. • 3CLpro as important target for drug discovery. [ABSTRACT FROM AUTHOR]

Over the past two decades, there have been two major outbreaks where the crossover of animal Betacoronaviruses to humans has resulted in severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In December 2019, a global public health concern started with the emergence of a new strain of coronavirus (SARS-CoV-2 or 2019 novel coronavirus, 2019-nCoV) which has rapidly spread all over the world from its origin in Wuhan, China. SARS-CoV-2 belongs to the Betacoronavirus genus, which includes human SARS-CoV, MERS and two other human coronaviruses (HCoVs), HCoV-OC43 and HCoV-HKU1. The fatality rate of SARS-CoV-2 is lower than the two previous coronavirus epidemics, but it is faster spreading and the large number of infected people with severe viral pneumonia and respiratory illness, showed SARS-CoV-2 to be highly contagious. Based on the current published evidence, herein we summarize the origin, genetics, epidemiology, clinical manifestations, preventions, diagnosis and up to date treatments of SARS-CoV-2 infections in comparison with those caused by SARS-CoV and MERS-CoV. Moreover, the possible impact of weather conditions on the transmission of SARS-CoV-2 is also discussed. Therefore, the aim of the present review is to reconsider the two previous pandemics and provide a reference for future studies as well as therapeutic approaches.

Hemophilia A (HA) is an X-linked bleeding disorder caused by heterogeneous mutations in the factor VIII gene ( F8). Our aim is to identify the causative mutations in a large HA cohort from China. We studied 216 unrelated HA families. Molecular analyses of F8 were performed using a combination of molecular techniques, including polymerase chain reaction, direct sequencing, and multiplex ligation-dependent probe amplification. The deleterious consequences of the unreported missense mutations were evaluated using various bioinformatics approaches. Causative mutations in F8 were identified in 209 families, intron 22 inversion (Inv22) was identified in 89 severe families, and intron 1 inversion (Inv1) was positive in 5 severe families; 95 mutations were detected among 115 noninversion families, of which 42 were novel, including 29 null variations and 13 missense mutations for which causality was demonstrated via bioinformatics. Among the 53 previously reported mutations, more nonsense (5 of 9) and missense (10 of 26) mutation sites were found to occur at Arginine (Arg) sites and multiple small deletions/insertions (5 of 10) located within the poly-A runs of the B domain. The majority of these sequence variants frequently recurred in the database. The odds ratios for the likelihood of developing inhibitors significantly increased in the presence of nonsense mutation. Our F8 defect spectrum was heterogeneous. Small deletions/insertions in the poly-A runs of the B domain and nonsense and missense mutations at Arg sites were identified as mutation hot spots. Nonsense mutation increased the risk of developing inhibitors.

Aims: We analyzed the clinical features of 417 patients with hemophilia from 11 Hemophilia Treatment Centers in Shanxi Province (SP) in China., Methods: We used data collected in the national registry of hemophilia A and hemophilia B in SP from January 2010 to December 2013., Results: Ratio of hemophilia A:hemophilia B patients was 5:1, of which 48% (200/417) were severe, 31% (129/417) moderate and 21% (88/417) mild. Episodes of joint bleeding occurred in 73% (305/417) of patients. Only 4% (15/417) of patients received tertiary prophylaxis. Three percent of patients (2/72) were hepatitis B virus-Ab positive, and 7% (5/72) of patients were hepatitis C virus-Ab positive. The incidence of inhibitors was 6% (11/182)., Conclusion: The ability to manage hemophilia in SP remains suboptimal. However, due to limited data, the evaluation and extrapolation of large hemophilia populations in SP are restricted, therefore, further studies with a large cohort are needed.