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OBJECTIVE: To compare the potential efficacy and safety of dual therapy and quadruple therapy with vonoprazan (VPZ) as well as the standard quadruple therapy of proton pump inhibitor (PPI) for the eradication of Helicobacter pylori (Hp) infection in Hainan province. METHODS: A single-centre, non-blinded, non-inferiority randomized controlled trial was conducted at the outpatient department of gastroenterology at the Second Affiliated Hospital of Hainan Medical University from June 2022 to February 2023. 135 patients aged 18-75 years with Hp infection were enrolled and randomized into three different groups (group V1: VPZ 20 mg twice a day and amoxicillin 1.0 g three times a day for 14 days V2: vonoprazan 20 mg, amoxicillin capsules 1.0 g, furazolidone 0.1 g and bismuth potassiulm citrate 240 mg, twice daily for 14 days;; group V3: ilaprazole 5 mg, Amoxicillin 1.0 g, Furazolidone 100 mg, bismuth potassiulm citrate 240 mg, twice a day for 14 days). Four weeks after the end of treatment, Hp eradication was confirmed by rechecking 13C-urea breath test (UBT). RESULTS: The eradication efficacy of V1 and V3 was non-inferior to that of V2, which is consistent with the results obtained from the Kruskal-Wallis H test. The eradication rate by intentional analysis was 84.4% (38/45, 95%CI 73.4%-95.5%, P>0.05) for all the three groups. If analyzed by per-protocol, the eradication rates were 88.4% (38/43, 95%CI 78.4%-98.4%), 92.7% (38/41, 95%CI 84.4%-101.0%),88.4% (38/43ï¼95%CI 78.4%-98.4%) in groups V1, V2 and V3, respectively, which did not show a significant difference (P > 0.05). The incidence of adverse effects was significantly lower in VPZ dual therapy compared to the other two treatment regimens (P < 0.05). VPZ dual therapy or quadruple therapy was also relatively less costly than standard quadruple therapy. CONCLUSION: VPZ dual therapy and quadruple therapy shows promise of not being worse than the standard quadruple therapy by a clinically relevant margin. More studies might be needed to definitively determine if the new therapy is equally effective or even superior.
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Infecções por Helicobacter , Helicobacter pylori , Pirróis , Sulfonamidas , Humanos , Infecções por Helicobacter/tratamento farmacológico , Bismuto/uso terapêutico , Furazolidona/uso terapêutico , Amoxicilina/uso terapêutico , CitratosRESUMO
PURPOSE: There is controversy concerning the relationship between Helicobacter pylori (H. pylori) infection and osteoporosis. This study is to examine the causal relationship between H. pylori infection and osteoporosis and to analyze the potential mechanism underlying the relationship. METHODS: The clinical data of H. pylori infection and bone mineral density from patients or physical examiner with good general condition in our hospital between September 2019 and September 2020 were retrospectively collected. The relationship between H. pylori infection and osteoporosis was compared and analyzed, using logistic regression to examine the potential mechanism underlying the association. To investigate the causal effects of H. pylori infection and osteoporosis, we conducted a two-sample bidirectional Mendelian randomization (MR) analysis. RESULTS: A total of 470 patients were positive for H. pylori, with a detection rate of 52.22%. It was found that age, SBP, FPG, DBP, ALB, LDL-C, hs-CRP, and OC were positively correlated with osteoporosis, while negative correlations were observed with BMI, LYM, ALB, TP, TG, HDL-C, SCr, UA, and VitD. After stratified analysis of sex and age, it was found that there was a significant correlation between H. pylori infection and osteoporosis. The levels of SBP, ALP, FPG, LDL-C, hs-CRP, and OC in both H. pylori-positive group and osteoporosis group were higher than those in the H. pylori-negative group while the levels of BMI, ALB, TP, HDL-C, SCr, UA, and VitD in the positive group were significantly lower than those in the negative group. Logistic regression analyses with gender and age showed that ALB, FPG, HDL-C, and VitD were common risk factors for osteoporosis and H. pylori infection. In the MR analysis, the IVW results found a positive effect of H. pylori infection on osteoporosis (OR = 1.0017, 95% CI: 1.0002-1.0033, P = 0.0217). Regarding the reverse direction analysis, there was insufficient evidence to prove the causal effects of osteoporosis on H. pylori infection. CONCLUSION: Our study provides evidence for causal effects of H. pylori infection on osteoporosis. H. pylori may affect osteoporosis through serum albumin, high-density lipoprotein, fasting blood glucose and vitamin D.
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Helicobacter pylori , Osteoporose , Humanos , Estudos Retrospectivos , Proteína C-Reativa , LDL-Colesterol , Análise da Randomização Mendeliana , Estudo de Associação Genômica AmplaRESUMO
Traditionally forehead bony lesion is approached directly through the forehead skin or invasive coronal incision resulting prominent scar. An endoscopic approach through mini hairline incisions may provide a unique way to achieve the best esthetic results, but often time the authors encounter potential soft tissue injury from the high-speed burr. The authors present a case with multiple frontal bone osteoma lesions which were successfully removed through 2 small hairline incisions with the help of an otorhinolaryngological system and an innovative mini-trocar. Significant improvement in forehead shape with minimal scars was observed at an 18-month follow-up. This innovative and easily manipulating technique may help surgeons achieve better outcomes when treating frontal bone osteoma endoscopically.
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Autoimmunity is reported involving in reproductive failures, and antinuclear antibody (ANA) positivity has been regarded as a typical feature of autoimmunity. Published studies on the association of ANA with reproductive failures including infertility are controversial. The aim of this meta-analysis was to analyse whether the presence of ANA positivity increases the risk of infertility in women. We searched the PubMed and Embase databases for relevant literature without any restrictions prior to April 28, 2021. All analyses were performed using the RevMan 5.3 software. Twelve studies with 2734 participants, including 1482 patients with infertility, met the inclusion and exclusion criteria. The total positivity rate of ANA was 23.8% (353/1482) in all infertile patients and 8.5% (107/1252) in the control group. Infertile females had a significantly higher ANA positivity rate than the control group (odds ratio [OR] = 2.90, 95% confidence interval [CI]: 1.72-4.87, I2 = 65%, P < .0001). Several subgroup analyses were performed to reduce the heterogeneity. ANA positivity was associated with female infertility in studies either performed by indirect immunofluorescence (OR = 2.26, 95% CI:1.67-3.06, P < .00001) or by ELISA (OR = 10.76, 95% CI:1.82-63.64, P < .00001). ANA was significantly associated with increased risk of women infertility either after the definite exclusion of individuals with autoimmune diseases (AID) or without exclusion [(OR = 1.99, 95% CI:1.29-3.06, P = .002), (OR = 2.76, 95% CI:1.56-4.88, P = .0005), respectively]. This meta-analysis provides a comprehensive overview of the prevalence of antinuclear antibodies (ANA) in infertile women and suggests that ANA positivity increases the risk of infertility.
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Doenças Autoimunes , Infertilidade Feminina , Feminino , Humanos , Anticorpos Antinucleares , Autoimunidade , Ensaio de Imunoadsorção EnzimáticaRESUMO
BACKGROUND: Guidewire slippage into the peritoneal cavity during clinical operations is extremely rare. Therefore, this paper aims to report a successful case of guidewire removal using transgastric natural orifice transluminal endoscopic surgery (NOTES). The goal is to enhance physicians' understanding of the management plan for this unique scenario and provide a valuable reference for clinical practice. CASE SUMMARY: A 64-year-old man presented with abdominal distension and was diagnosed with cirrhosis combined with massive ascites. To proceed with treatment, the patient underwent ultrasound-guided peritoneal puncture and underwent catheterization and drainage. Unfortunately, a 0.035-inch guidewire slipped into the abdominal cavity during the procedure. Following a comprehensive evaluation and consultation by a multidisciplinary team, the guidewire was successfully removed using NOTES. CONCLUSION: This case highlights the potential consideration of transgastric NOTES removal when encountering a foreign body, such as a guidewire, within the abdominal cavity.
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H. pylori infection is gaining increasing attention, but detailed investigations into its impact on gastric microbiota remain limited. We collected gastric mucosa samples from 47 individuals divided into three groups: 1. Group HP: patients with initial positive H. pylori infection (25 cases); 2. Group ck: H. pylori-negative patients (14 cases); 3. Group DiffHP: patients with refractory H. pylori infection (8 cases). The samples were analyzed using 16S rDNA sequencing and functional prediction with PICRUSt. Group HP showed differences in flora distribution and function compared to Group ck, while Group DiffHP overlapped with Group HP. The abundances of Aeromonas piscicola, Shewanella algae, Vibrio plantisponsor, Aeromonas caviae, Serratia marcescens, Vibrio parahaemolyticus, Microbacterium lacticum, and Prevotella nigrescens were significantly reduced in both Group DiffHP and Group HP compared to Group ck. Vibrio shilonii was reduced only in Group DiffHP compared to Group ck, while Clostridium perfringens and Paracoccus marinus were increased only in Group DiffHP. LEfSe analysis revealed that Clostridium perfringens and Paracoccus marinus were enriched, whereas Vibrio shilonii was reduced in Group DiffHP compared to Group ck at the species level. In individuals with refractory H. pylori infection, the gastric microbiota exhibited enrichment in various human diseases, organic systems, and metabolic pathways (amino acid metabolism, carbohydrate metabolism, transcription, replication and repair, cell cycle pathways, and apoptosis). Patients with multiple failed H. pylori eradication exhibited significant changes in the gastric microbiota. An increase in Clostridium perfringens and Paracoccus marinus and a decrease in Vibrio shilonii appears to be characteristic of refractory H. pylori infection.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Helicobacter pylori/fisiologia , Masculino , Pessoa de Meia-Idade , Feminino , Mucosa Gástrica/microbiologia , Adulto , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , IdosoRESUMO
BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported. AIM: To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT. METHODS: We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure. RESULTS: Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT. CONCLUSION: WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.
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Antifibrinolíticos , Doença de Crohn , Microbiota , Humanos , Aminoácidos , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Escherichia coli , Metagenoma , Estudos ProspectivosRESUMO
BACKGROUND: To investigate the clinical and immune characteristics of patients with primary Sjögren's syndrome (pSS) who were negative for anti-Sjögren's-syndrome-related antigen A antibodies (anti-SSA) and anti-Sjögren's-syndrome-related antigen B antibodies (anti-SSB) in Chinese population. METHODS: A retrospective study were performed and 232 patients with pSS were analyzed. Patients positive for anti-SSA or/and anti-SSB were termed as seropositive pSS, and these negative for both anti-SSA and anti-SSB (non-antinuclear antibodies) as seronegative pSS. Clinical manifestations and laboratory findings were compared between the two groups. RESULTS: Among the 232 patients with pSS, 192 (82.8%) were seropositive pSS and 40 (17.2%) were seronegative pSS. Compared to seropositive pSS, seronegative pSS were older and with higher percentage of low disease activity (ESSDAI < 5), xerostomia and xerophthalmia, with higher platelet count and level of creatine kinase. This subgroup was with lower levels of gamma globulin, immunoglobulin G, immunoglobulin A and autoantibodies including rheumatoid factor and antinuclear antibody in serum, and less immunoglobulin G deposition in labial gland. CONCLUSION: Seronegative pSS was a distinct subtype of pSS different from seropositive pSS. Clinical manifestations in seronegative pSS subgroup were restricted to exocrine gland and less B lymphocyte activation, while seropositive pSS were prone to present with systemic involvement and high disease activity. Specific underlying pathogenesis mechanisms and therapeutic strategies in this subgroup needed to be further studied.
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OBJECTIVE: To explore the prevalence of type I and type II Helicobacter pylori infection and investigate risk factors in a population from Hainan Province in China. METHODS: Data came from a large, cross-sectional study conducted from August 2022 to April 2023 involving five cities of Hainan. Subjects with confirmed 14C-urea breath test (UBT) and positive serological assay were included. All subjects had a gastroscopy. According to presence or absence of CagA/VacA proteins, subjects were classified as either type I (present) or type II strains (absent). Gastroscopic findings and several socio-demographic factors were examined for correlation with antibody serotyping. RESULTS: In total, 410 subjects were investigated for H. pylori strain types. The overall prevalence of the highly virulent, type I H. pylori strain was 79% (324/410) and type II strain was 21% (86/410). There was a strong association between type I strain and peptic ulcer disease. Of several sociodemographic factors investigated, only smoking and data over baseline (DOB) values showed significant differences between type 1 and type II strains. Logistic regression analysis showed a lower risk of type I H. pylori infection in smokers compared with non-smokers, and a higher risk of H. pylori type I infection in subjects with medium and high data over baseline (DOB) values compared with subjects who had low DOB values. CONCLUSION: Highly virulent, type I H. pylori infections predominate in Hainan and the co-positivity of CagA and VacA antibodies are related to type I H. pylori infection. We found that Type I H. pylori was closely associated with peptic ulcer disease and the DOB values were generally high.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Masculino , Feminino , China/epidemiologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/diagnóstico , Pessoa de Meia-Idade , Fatores de Risco , Estudos Transversais , Adulto , Proteínas de Bactérias , Prevalência , Antígenos de Bactérias/imunologia , Úlcera Péptica/microbiologia , Úlcera Péptica/epidemiologia , Idoso , Testes Respiratórios , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologiaRESUMO
Fibroblast-like synoviocytes (FLSs) play a central role in RA pathogenesis and are the main cellular component in the inflamed synovium of patients with rheumatoid arthritis (RA). FLSs are emerging as promising new therapeutic targets in RA. However, fibroblasts perform many essential functions that are required for sustaining tissue homeostasis. Direct targeting of general fibroblast markers on FLSs is challenging because fibroblasts in other tissues might be altered and side effects such as reduced wound healing or fibrosis can occur. To date, no FLS-specific targeted therapies have been applied in the clinical management of RA. With the help of high-throughput technologies such as scRNA-seq in recent years, several specific pathogenic FLS subsets in RA have been identified. Understanding the characteristics of these pathogenic FLS clusters and the mechanisms that drive their differentiation can provide new insights into the development of novel FLS-targeting strategies for RA. Here, we discuss the pathogenic FLS subsets in RA that have been elucidated in recent years and potential strategies for targeting pathogenic FLSs.
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Artrite Reumatoide , Fibroblastos , Sinoviócitos , Artrite Reumatoide/patologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/imunologia , Humanos , Fibroblastos/patologia , Fibroblastos/metabolismo , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Membrana Sinovial/patologia , Membrana Sinovial/metabolismo , Animais , Diferenciação Celular/fisiologiaRESUMO
BACKGROUND: Primary Sjögren syndrome (pSjS) is one of the most prevalent systemic autoimmune diseases and characterized with hyperactivation of B cell and the abundant presence of autoantibodies in sera. The salivary gland epithelial cells (SGECs) release autoantigens to evoke autoimmunity through releasing elevated apoptosis or secreting autoantigen-containing exosomes, thus identifying autoantibodies directly to SGECs might provide insights into disease related biomarkers as well as further elucidating pathogenesis mechanisms. The present study was undertaken to identify autoantibodies to SGECs and to evaluate its clinical values in Chinese pSjS. METHODS: Cell-based indirect immunofluorescence and immunostaining, two-dimensional electrophoresis and liquid chromatograph-tandem mass spectrometry were conducted to identify the autoantibodies to human salivary gland cell line A253 in pSjS sera. Enzyme-linked immunosorbent assay (ELISA) was applied to identify autoantibody titer in pSjS cohort and healthy controls. The prevalence and clinical significance of the identified autoantibodies was further assessed in pSjS population. RESULTS: Anti-calreticulin (CALR) antibody was identified as a new autoantibody directly to SGECs in sera from pSjS patients. Anti-CALR antibody were detected in 37 of 120 pSjS patients (30.83 %) and 1 of 54 healthy controls (1.85 %). It was found in 40.85 % pSjS with anti-SSA positive, 53.85 % with anti-SSB positive, and 14.7 % in sero-negative pSjS. Anti-CALR antibody was associated with clinical manifestations including weight loss(p = 0.045), vasculitis (p = 0.031), and laboratory parameters including erythrocyte sedimentation rate (ESR) (r = 0.056, p = 0.021), Krebs von den Lungen-6 (KL-6) (r = 0.121, p = 0.035), IgG (r = 0.097, p < 0.001), IgG2 (r = 0.142, p = 0.022), IgG3 (r = 0.287, p < 0.001), fibrinogen (r = 0.084, p = 0.016), D-Dimer (r = 0.086, p = 0.012) and fibrinogen degradation production (r = 0.150, p = 0.002). The expression of CALR in salivary glands was related to lymphocytes infiltration into salivary glands in pSjS patients (r = 0.7076, p = 0.0034). CONCLUSION: To our knowledge, this was the first study to investigate the prevalence and clinical significance of anti-CALR antibody in Chinses pSjS patients. The present study identified an autoimmune antibody, anti-CALR antibody, as a good autoimmune biomarker for sero-negative pSjS.
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Microdamage and its related inflammation contribute to the development of radiographic axial spondyloarthritis (r-axSpA). Inflammation and cell death in damaged tissues are associated with cell-free DNA (cfDNA) release. Here we investigated whether circulating cfDNA could be a potential biomarker for evaluating disease activity and treatment response in r-axSpA. Circulating cfDNA was detected in the discovery and validation cohort with 79 and 60 newly diagnosed r-axSpA patients respectively and 42 healthy controls using the Quant-iT PicoGreen dsDNA reagent and kit. As a result, cfDNA levels were significantly higher in r-axSpA patients compared with healthy controls in the discovery and validation cohort. Moreover, cfDNA levels were positively correlated with CRP, ASDAS-CRP and neutrophil counts. Additionally, non-steroid anti-inflammatory drugs (NSAIDs) combined with disease-modifying anti-rheumatic drugs or tumor necrosis factor inhibitors but not NSAIDs alone could reduce cfDNA levels. Moreover, a decrease of cfDNA levels after treatment was associated with an effective therapeutic response. Intriguingly, patients with higher levels of cfDNA at diagnosis responded better to combination therapy rather than NSAIDs. However, patients with lower levels of cfDNA displayed similar responses to combination or mono-NSAID treatment. In conclusion, circulating cfDNA levels showed a significant correlation with disease activity as well as treatment efficacy in patients with r-axSpA. Moreover, cfDNA at diagnosis might predict the response to different therapy. Consequently, cfDNA may serve as a useful biomarker of inflammation in r-axSpA.
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Espondiloartrite Axial , Ácidos Nucleicos Livres , Espondilartrite , Espondilite Anquilosante , Humanos , Espondilartrite/diagnóstico por imagem , Espondilartrite/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Biomarcadores , Inflamação/tratamento farmacológicoRESUMO
To investigate the prevalence, types, and risk factors of functional gastrointestinal diseases (FGIDs) in Hainan Province, China, in order to provide insights for future prevention and treatment strategies. A questionnaire survey was conducted from July 2022 to May 2023, using stratified sampling to sample local residents in five cities (20 townships) in Hainan Province. Out of 2057 local residents surveyed, 659 individuals (32.0%) reported experiencing at least one FGID. The most prevalent FGIDs were functional dyspepsia (FD) (10.7%), functional constipation (FC) (9.3%), irritable bowel syndrome (IBS) (6.8%), functional bloating (2.2%), belching disorder (2.2%), functional diarrhea (FDr) (1.5%), functional heartburn (1.5%), and fecal incontinence (0.98%). The study revealed significant associations between FGIDs and factors such as age, sleep quality, anxiety, smoking, alcohol consumption, and the consumption of pickled food (P < 0.05). Older age, poor sleep quality, anxiety, and the consumption of pickled food were identified as independent risk factors for the prevalence of FGIDs (P < 0.05). In Hainan Province, the overall prevalence of FGIDs was found to be 32.0%, with higher prevalences of FC and FD. Older age, poor sleep quality, anxiety, and the consumption of pickled food were identified as risk factors for FGIDs.
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Dispepsia , Gastroenteropatias , Síndrome do Intestino Irritável , Humanos , Prevalência , Gastroenteropatias/epidemiologia , Gastroenteropatias/complicações , Síndrome do Intestino Irritável/epidemiologia , Dispepsia/epidemiologia , Constipação Intestinal/complicações , Fatores de Risco , China/epidemiologia , Inquéritos e QuestionáriosRESUMO
The revolutionary self-healing function for long-term and safe service processes has inspired researchers to implement them in various fields, including in the application of antimicrobial protective coatings. Despite the great advances that have been made in the field of fabricating self-healing and antimicrobial polymers, their poor transparency and the trade-off between the mechanical and self-healing properties limit the utility of the materials as transparent antimicrobial protective coatings for wearable optical and display devices. Considering the compatibility in the blending process, our group proposed a self-healing, self-cross-linkable poly{(n-butyl acrylate)-co-[N-(hydroxymethyl)acrylamide]} copolymer (AP)-based protective coating combined with two types of commercial cationic antimicrobial agents (i.e., dimethyl octadecyl (3-trimethoxysilylpropyl) ammonium chloride (DTSACL) and chlorhexidine gluconate (CHG)), leading to the fabrication of a multifunctional modified compound film of (AP/b%CHG)-grafted-a%DTSACL. The first highlight of this research is that the reactivity of the hydroxyl group in the N-(hydroxymethyl)acrylamide of the copolymer side chains under thermal conditions facilitates the "grafting to" process with the trimethoxysilane groups of DTSACL to form AP-grafted-DTSACL, yielding favorable thermal stability, improvement in hydrophobicity, and enhancement of mechanical strength. Second, we highlight that the addition of CHG can generate covalent and noncovalent interactions in a complex manner between the two biguanide groups of CHG with the AP and DTSACL via a thermal-triggered cross-linking reaction. The noncovalent interactions synergistically serve as diverse dynamic hydrogen bonds, leading to complete healing upon scratches and even showing over 80% self-healing efficiency on full-cut, while covalent bonding can effectively improve elasticity and mechanical strength. The soft nature of CHG also takes part in improving the self-healing of the copolymer. Moreover, it was discovered that the addition of CHG can enhance antimicrobial effectiveness, as demonstrated by the long-term superior antibacterial activity (100%) against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria and the antifouling function on a glass substrate and/or a silica wafer coated by the modified polymer.
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Polímeros , Polímeros/química , Polímeros/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Elasticidade , Antibacterianos/química , Antibacterianos/farmacologia , Clorexidina/química , Clorexidina/farmacologia , Clorexidina/análogos & derivadosRESUMO
BACKGROUND: Three-dimensional (3D) organoids derived from human pluripotent stem cells (hPSCs) have revolutionized in vitro tissue modeling, offering a unique opportunity to replicate physiological tissue organization and functionality. This study investigates the impact of radiation on skeletal muscle response using an innovative in vitro human 3D skeletal muscle organoids (hSMOs) model derived from hPSCs. METHODS: The hSMOs model was established through a differentiation protocol faithfully recapitulating embryonic myogenesis and maturation via paraxial mesodermal differentiation of hPSCs. Key skeletal muscle characteristics were confirmed using immunofluorescent staining and RT-qPCR. Subsequently, the hSMOs were exposed to a clinically relevant dose of 2 Gy of radiation, and their response was analyzed using immunofluorescent staining and RNA-seq. RESULTS: The hSMO model faithfully recapitulated embryonic myogenesis and maturation, maintaining key skeletal muscle characteristics. Following exposure to 2 Gy of radiation, histopathological analysis revealed deficits in hSMOs expansion, differentiation, and repair response across various cell types at early (30 min) and intermediate (18 h) time points post-radiation. Immunofluorescent staining targeting γH2AX and 53BP1 demonstrated elevated levels of foci per cell, particularly in PAX7+ cells, during early and intermediate time points, with a distinct kinetic pattern showing a decrease at 72 h. RNA-seq data provided comprehensive insights into the DNA damage response within the hSMOs. CONCLUSIONS: Our findings highlight deficits in expansion, differentiation, and repair response in hSMOs following radiation exposure, enhancing our understanding of radiation effects on skeletal muscle and contributing to strategies for mitigating radiation-induced damage in this context.
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BACKGROUND: The incidence of colorectal cancer (CRC) in China is steadily rising, with a high proportion of advanced-stage diagnoses. This highlights the significance of early detection and prevention measures to enhance survival rates. Fecal immunochemical testing (FIT) is a globally recommended CRC screening method; however, limited research has been conducted on its application in Hainan. AIM: To assess the efficacy and adherence of FIT screening among average-risk individuals in Hainan, while also examining the risk factors associated with positive FIT results. METHODS: This population-based cross-sectional study implemented FIT screening for CRC in 2000 asymptomatic participants aged 40-75 years from five cities and 21 community health centers in Hainan Province. The study was conducted from August 2022 to April 2023, employing a stratified sampling method to select participants. Individuals with positive FIT results subsequently underwent colonoscopy. Positive predictive values for confirmed CRC and advanced adenoma were calculated, and the relationship between relevant variables and positive FIT results was analyzed using χ 2 tests and multivariate logistic regression. RESULTS: A total of 1788 participants completed the FIT screening, with a median age of 57 years (interquartile range: 40-75). Among them, 503 (28.1%) were males, and 1285 (71.9%) were females, resulting in an 89.4% compliance rate for FIT screening. The overall positivity rate of FIT was 4.4% [79 out of 1788; 95% confidence interval (CI): 3%-5%]. The specific positivity rates for Haikou, Sanya, Orient City, Qionghai City, and Wuzhishan City were 9.6% (45 of 468; 95%CI: 8%-11%), 1.3% (6 of 445; 95%CI: 0.1%-3.1%), 2.7% (8 of 293; 95%CI: 1.2%-4.3%), 3.3% (9 of 276; 95%CI: 1.0%-6.3%), and 4.2% (11 of 406; 95%CI: 1.2%-7.3%), respectively. Significant associations were found between age, dietary habits, and positive FIT results. Out of the 79 participants with positive FIT results, 55 underwent colonoscopy, demonstrating an 82.2% compliance rate. Among them, 10 had a clean gastrointestinal tract, 43 had polyps or adenomas, and 2 were confirmed to have CRC, yielding a positive predictive value of 3.6% (95%CI: 0.9%-4.2%). Among the 43 participants with polyps or adenomas, 8 were diagnosed with advanced adenomas, resulting in an advanced adenoma rate of 14.5% (95%CI: 10.1%-17.7%). CONCLUSION: In the Hainan region, FIT screening for CRC among asymptomatic individuals at average risk is feasible and well-received.