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BACKGROUND: APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). METHODS: Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. RESULTS: Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). CONCLUSIONS: This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.
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Biomarcadores , Ditiotreitol , Cirrose Hepática , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Feminino , Adulto , Idoso , Oxirredução , Curva ROC , Estudos de Coortes , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/sangue , Estudo de Prova de ConceitoRESUMO
Purpose: To explore the effect of DSG2 on the growth of cervical cancer cells and its possible regulatory mechanism. Methods: The expression levels and survival prognosis of DSG2 and ADAM17 in cervical squamous cell carcinoma tissues and adjacent normal tissues were analyzed by bioinformatics. CCK-8 assay, colony formation assay and Transwell assay were used to detect the effects of DSG2 on the proliferative activity, colony formation ability and migration ability of SiHa and Hela cells. The effect of DSG 2 on the level of ADAM17 transcription and translation was detected by qPCR and Western blot experiments. The interaction between DSG2 and c-MYC was detected by immunocoprecipitation. c-MYC inhibitors were used in HeLa cells overexpressing DSG2 to analyze the effects of DSG2 and c-MYC on proliferation, colony formation and migration of Hela cells, as well as the regulation of ADAM17 expression. Results: DSG2 was highly expressed in cervical squamous cell carcinoma compared with normal tissues (P<0.05), and high DSG2 expression suggested poor overall survival (P<0.05). After DSG2 knockdown, the proliferative activity, colony formation and migration ability of SiHa and Hela cells were significantly decreased (P<0.05). Compared with adjacent normal tissues, ADAM17 was highly expressed in cervical squamous cell carcinoma (P<0.05), and high ADAM17 expression suggested poor overall survival in cervical cancer patients (P<0.05). The results of immunocoprecipitation showed the interaction between DSG2 and c-MYC. Compared with DSG2 overexpression group, DSG2 overexpression combined with c-MYC inhibition group significantly decreased cell proliferation, migration and ADAM17 expression (P < 0.05). Conclusion: DSG2 is highly expressed in cervical cancer, and inhibition of DSG2 expression can reduce the proliferation and migration ability of cervical cancer cells, which may be related to the regulation of ADAM17 expression through c-MYC interaction.
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BACKGROUND AND AIMS: The efficacy of achieving HBsAg clearance through pegylated interferon (PEG-IFNα) therapy in patients with chronic hepatitis B (CHB) remains uncertain, especially regarding the probability of achieving functional cure among patients with varying baseline HBsAg levels. We aimed to investigate the predictive value of HBsAg quantification for HBsAg seroclearance in CHB patients undergoing PEG-IFNα treatment. METHODS: A systematic search was conducted in PubMed, Embase, and the Cochrane Library up to January 11, 2022. Subgroup analyses were performed for HBeAg-positive and HBeAg-negative patients, PEG-IFNα monotherapy and PEG-IFNα combination therapy, treatment-naive and treatment-experienced patients, and patients with or without liver cirrhosis. RESULTS: This predictive model incorporated 102 studies. The overall HBsAg clearance rates at the end of treatment (EOT) and the end of follow-up (EOF) were 10.6% (95% CI 7.8-13.7%) and 11.1% (95% CI 8.4-14.1%), respectively. Baseline HBsAg quantification was the most significant factor. According to the model, it is projected that when baseline HBsAg levels are 100, 500, 1500, and 10,000 IU/ml, the HBsAg clearance rates at EOF could reach 53.9% (95% CI 40.4-66.8%), 32.1% (95% CI 24.8-38.7%), 14.2% (95% CI 9.8-18.8%), and 7.9% (95% CI 4.2-11.8%), respectively. Additionally, treatment-experienced patients with HBeAg-negative status, and without liver cirrhosis exhibited higher HBsAg clearance rates after PEG-IFNα treatment. CONCLUSION: A successful predictive model has been established to predict the achievement of functional cure in CHB patients receiving PEG-IFNα therapy.
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Antivirais , Antígenos de Superfície da Hepatite B , Hepatite B Crônica , Interferon-alfa , Polietilenoglicóis , Humanos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/sangue , Interferon-alfa/uso terapêutico , Interferon-alfa/administração & dosagem , Antígenos de Superfície da Hepatite B/sangue , Antivirais/uso terapêutico , Polietilenoglicóis/uso terapêutico , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Valor Preditivo dos TestesRESUMO
STUDY OBJECTIVE: Propofol is a commonly utilized anesthetic for painless colonoscopy, but its usage is occasionally limited due to its potential side effects, including cardiopulmonary suppression and injection pain. To address this limitation, the novel compound ciprofol has been proposed as a possible alternative for propofol. This study sought to determine whether there are any differences in the safety and efficacy of propofol and ciprofol for painless colonoscopy. DESIGN: Randomized clinical trial. SETTING: Single-centre, class A tertiary hospital, November 2021 to November 2022. PATIENTS: Adult, American Society of Anesthesiologists Physical Status I to II and body mass index of 18 to 30 kg m-2 patients scheduled to undergo colonoscopy. INTERVENTIONS: Consecutive patients were randomly allocated in a 1:1 ratio to receive sedation for colonoscopy with ciprofol (group C) or propofol (group P). MEASUREMENTS: The primary outcome was the success rate of colonoscopy. The secondary outcomes were onset time of sedation, operation time, recovery time and discharge time, patients and endoscopists satisfaction, side effects (e.g. injection pain, myoclonus, drowsiness, dizziness, procedure recall, nausea and vomiting) and incidence rate of cardiopulmonary adverse events. MAIN RESULTS: No significant difference was found in the success rate of colonoscopy between the two groups (ciprofol 96.3% vs. propofol 97.6%; mean difference - 1.2%, 95% CI: -6.5% to 4.0%, P = 0.650). However, group C showed prolonged sedation (63.4 vs. 54.8 s, P < 0.001) and fully alert times (9 vs 8 min, P = 0.013), as well as reduced incidences of injection pain (0 vs. 40.2%, P < 0.001), respiratory depression (2.4% vs. 13.4%, P = 0.021) and hypotension (65.9% vs. 80.5%, P = 0.034). Patients satisfaction was also higher in Group C (10 vs 9, P < 0.001). CONCLUSIONS: Ciprofol can be used independently for colonoscopy. When comparing the sedation efficacy of ciprofol and propofol, a 0.4 mg kg-1 dose of ciprofol proved to be equal to a 2.0 mg kg-1 dose of propofol, with fewer side effects and greater patient satisfaction during the procedure.
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Colonoscopia , Propofol , Humanos , Propofol/administração & dosagem , Propofol/efeitos adversos , Colonoscopia/efeitos adversos , Colonoscopia/métodos , Método Duplo-Cego , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Satisfação do Paciente , Idoso , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/efeitos adversos , Período de Recuperação da Anestesia , Sedação Consciente/métodos , Sedação Consciente/efeitos adversos , Resultado do Tratamento , Duração da Cirurgia , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversosRESUMO
Background: Oxidative stress has been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). To develop novel antioxidant drugs, it is necessary to explore the key regulatory molecules involved in oxidative stress in PCOS. Plasma YKL-40 levels are elevated in patients with PCOS; however, its role remains unclear. Methods: The follicular fluids of 20 women with PCOS and 12 control subjects with normal ovarian function were collected, and YKL-40 in follicular fluids was measured by enzyme-linked immunosorbent assay. A letrozole-induced PCOS rat model was established and the expression level of YKL-40 in the ovaries was detected by immunohistochemistry. KGN cells were treated with H2O2 to generate an ovarian granulosa cell (OGC) model of oxidative stress. The siRNA was transfected into the cells for knockdown. The effect of YKL-40 knockdown on H2O2-treated KGN cells was evaluated by measuring proliferation, apoptosis, activities of T-SOD, GSH-Px, and CAT, levels of MDA, IL-1ß, IL-6, IL-8, and TNF-α, and the PI3K/AKT/NF-κB signaling pathway. Results: YKL-40 levels were elevated in the follicular fluids of women with PCOS compared with control subjects with normal ovarian function. The expression level of YKL-40 in the ovaries of rats with PCOS is obviously higher than that in the ovaries of the control group rats. H2O2 treatment enhanced YKL-40 mRNA expression and protein secretion. YKL-40 knockdown enhanced cell proliferation and antioxidant capacity while decreasing apoptosis and inflammatory factor levels in KGN cells following H2O2 treatment. The knockdown activated the PI3K/AKT signaling pathway and suppressed NF-κB nuclear translocation from the cytoplasm. Conclusion: YKL-40 levels were elevated in the follicular fluids of women with PCOS and the ovaries of rats with PCOS. YKL-40 expression can be induced by oxidative stress, and YKL-40 knockdown can decrease oxidative stress damage in OGCs.
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Proteína 1 Semelhante à Quitinase-3 , Líquido Folicular , Células da Granulosa , Estresse Oxidativo , Síndrome do Ovário Policístico , Transdução de Sinais , Adulto , Animais , Feminino , Humanos , Ratos , Apoptose , Proliferação de Células , Proteína 1 Semelhante à Quitinase-3/metabolismo , Proteína 1 Semelhante à Quitinase-3/genética , Modelos Animais de Doenças , Líquido Folicular/metabolismo , Técnicas de Silenciamento de Genes , Células da Granulosa/metabolismo , Peróxido de Hidrogênio/metabolismo , NF-kappa B/metabolismo , Ovário/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/genética , Ratos Sprague-DawleyRESUMO
BACKGROUND: Models for predicting hepatitis B e antigen (HBeAg) seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after nucleos(t)ide analog treatment are rare. AIM: To establish a simple scoring model based on a response-guided therapy (RGT) strategy for predicting HBeAg seroconversion and hepatitis B surface antigen (HBsAg) clearance. METHODS: In this study, 75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa (PEG-IFNα) treatment and a 24-wk follow-up. Logistic regression analysis was used to assess parameters at baseline, week 12, and week 24 to predict HBeAg seroconversion at 24 wk post-treatment. The two best predictors at each time point were used to establish a prediction model for PEG-IFNα therapy efficacy. Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0. RESULTS: The two most meaningful predictors were HBsAg ≤ 1000 IU/mL and HBeAg ≤ 3 S/CO at baseline, HBsAg ≤ 600 IU/mL and HBeAg ≤ 3 S/CO at week 12, and HBsAg ≤ 300 IU/mL and HBeAg ≤ 2 S/CO at week 24. With a total score of 0 vs 2 at baseline, week 12, and week 24, the response rates were 23.8%, 15.2%, and 11.1% vs 81.8%, 80.0%, and 82.4%, respectively, and the HBsAg clearance rates were 2.4%, 3.0%, and 0.0%, vs 54.5%, 40.0%, and 41.2%, respectively. CONCLUSION: We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNα therapy.
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Improving the thermal storage stability of nanosuspension concentrate (SC) prepared from low-melting-point pesticide is a recognized problem. In this work, using pyraclostrobin as the raw material, 25 wt% of pyraclostrobin nano-SC was prepared through a water-based grinding method, and the optimal grinding conditions were obtained as follows: a grinding time of 23 h, D-3911 as dispersant and a dispersant dosage of 12 wt%. The pyraclostrobin nano-SC D90 size prepared based on this best formula was 216 nm. Adding glycerin could improve the stability of nano-SC at room temperature, but its thermal storage stability was still poor. For this problem, sodium lignosulfonate and cetyltrimethylammonium bromide (NaLS/CTAB) colloidal spheres were prepared through electrostatic and hydrophobic self-assembly and characterized. The delamination and precipitation of nano-SC can be significantly improved by adding an appropriate amount of colloidal spheres, and the nano-SC D90 size decreased from 2726 to 1023 nm after 7 days of thermal storage. Farmland experiments indicated the control efficiency of pyraclostrobin nano-SC against flowering cabbage downy mildew disease was about 30% higher than that of SC. Especially after adding the wetting agent, the effect of nano-SC could be comparable to that of commercial Kairun (currently the best pyraclostrobin formulation in the world).
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Harnessing the potential of tumor-associated macrophages (TAMs) to engulf tumor cells offers promising avenues for cancer therapy. Targeting phagocytosis checkpoints, particularly the CD47-signal regulatory protein α (SIRPα) axis, is crucial for modulating TAM activity. However, single checkpoint inhibition has shown a limited efficacy. In this study, we demonstrate that ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-mediated magnetic hyperthermia effectively suppresses the expression of CD47 protein on Hepa1-6 tumor cells and SIRPα receptor on macrophages, which disrupts CD47-SIRPα interaction. FVIO-mediated magnetic hyperthermia also induces immunogenic cell death and polarizes TAMs toward M1 phenotype. These changes collectively bolster the phagocytic ability of macrophages to eliminate tumor cells. Furthermore, FVIO-mediated magnetic hyperthermia concurrently escalates cytotoxic T lymphocyte levels and diminishes regulatory T cell levels. Our findings reveal that magnetic hyperthermia offers a novel approach for dual down-regulation of CD47 and SIRPα, reshaping the tumor microenvironment to stimulate immune responses, culminating in significant antitumor activity.
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Hipertermia Induzida , Neoplasias , Humanos , Antígeno CD47 , Regulação para Baixo , Imunoterapia , Fagocitose , Fenômenos Magnéticos , Neoplasias/patologia , Microambiente TumoralRESUMO
With the recent emergence of percutaneous balloon compression (PBC) as a promising treatment for trigeminal neuralgia (TN), there is a growing need for research on its safety and efficacy. This study was designed to evaluate the safety and efficacy of PBC in the treatment of TN patients during the perioperative period. This study involved a total of 400 TN patients who were selected and treated with PBC at our institution. The clinical data and short-term outcomes were analyzed based on sex, initial PBC treatment for TN, and subsequent PBC treatment for recurrent TN after previous PBC or microvascular decompression (MVD) or radiofrequency thermocoagulation (RFT). No statistically significant difference was found when comparing postoperative pain relief between male and female patients with TN. Nevertheless, female patients were found to be more vulnerable than male patients to abnormal facial sensations (P = 0.001), diplopia (P = 0.015), postoperative headache (P = 0.012), and hyposmia (P = 0.029). Additionally, it was observed that there was no substantial difference in the postoperative pain relief rate between the first-time PBC group and PBC for recurrent TN patients postoperatively following procedures such as PBC, MVD, and RFT. In conclusion, this study has shown that PBC treatment is effective in managing TN in both males and females, regardless of whether the treatment was administered as a primary intervention or following prior surgical procedures such as PBC, MVD, or RFT. Nonetheless, it is noted that the risk of postoperative complications appears to be higher in female patients compared to male patients.
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Neuralgia do Trigêmeo , Humanos , Masculino , Feminino , Resultado do Tratamento , Estudos Retrospectivos , Neuralgia do Trigêmeo/cirurgia , Neuralgia do Trigêmeo/etiologia , Estudos Prospectivos , Dor Pós-OperatóriaRESUMO
The comorbidity of chronic pain and mental dysfunctions such as anxiety disorders has long been recognized, but the underlying mechanisms remained poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated that the thalamic paraventricular nucleus (PVT) played a critical role in chronic pain-induced anxiety-like behavioral abnormalities. Fiber photometry and electrophysiology demonstrated that chronic pain increased the activities in PVT glutamatergic neurons. Chemogenetic manipulation revealed that suppression of PVT glutamatergic neurons relieved pain-like behavior and anxiety-like behaviors. Conversely, selective activation of PVT glutamatergic neurons showed algesic and anxiogenic effects. Furthermore, the elevated excitability of PVT glutamatergic neurons resulted in increased excitatory inputs to the basolateral complex (BLA) neurons. Optogenetic manipulation of the PVT-BLA pathway bilaterally modulates both the pain-like behavior and anxiety-like phenotypes. These findings shed light on how the PVT-BLA pathway contributed to the processing of pain-like behavior and maladaptive anxiety, and targeting this pathway might be a straightforward therapeutic strategy to both alleviate nociceptive hypersensitivity and rescue anxiety behaviors in chronic pain conditions.
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Complexo Nuclear Basolateral da Amígdala , Dor Crônica , Neuralgia , Humanos , Ansiedade , Tálamo , Transtornos de Ansiedade , Doença CrônicaRESUMO
OBJECTIVE: To investigate the prevalence of negative emotions in trigeminal neuralgia (TN) patients, to identify risk factors associated with anxiety and depression, and further to explore the impact of percutaneous balloon compression (PBC) on anxiety and depression in TN patients during the perioperative period. METHODS: 400 patients with primary TN treated with PBC at our institution from November 2021 to April 2023 were included. We analyzed visual analogue scale (VAS) and the Hospital Anxiety and Depression Scale (HADS) scores. The patients' clinical data and short-term clinical outcomes were gathered and subjected to statistical analysis. RESULTS: This study included a total of 400 patients diagnosed with primary TN. Patients who had high pain intensity (OR 1.20, 95 % CI 1.02-1.41; p = 0.025) or a history of multiple previous TN procedures (OR 1.49, 95 % CI 1.03-2.16; p = 0.036), were more prone to anxiety. Patients who were female (OR 1.59, 95 % CI 1.03-2.44; p = 0.036), had high pain intensity (OR 1.28, 95 % CI 1.08-1.52; p = 0.004) or had a history of multiple previous TN procedures (OR 1.48, 95 % CI 1.11-1.98; p = 0.008), were more likely to have depression. Significant improvements in anxiety and depressive symptoms were observed in patients who experienced pain relief after PBC (p < 0.001). CONCLUSIONS: Female gender, high pain intensity, and a history of multiple prior TN procedures are associated risk factors for anxiety and depression in TN patients. PBC can provide patients with a high pain relief rate and significantly improve their anxiety and depression symptoms during the perioperative period.
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Neuralgia do Trigêmeo , Humanos , Feminino , Masculino , Neuralgia do Trigêmeo/cirurgia , Neuralgia do Trigêmeo/diagnóstico , Resultado do Tratamento , Estudos Prospectivos , Estudos Retrospectivos , Dor/complicações , Ansiedade/etiologiaRESUMO
BACKGROUND: Most Chinese patients chose to die at home, therefore there is a reliance on the family caregivers to be involved in their palliative care. The needs and coping strategies of family caregivers in home-based palliative care are rooted in culture. Little is known about the needs and coping strategies of family caregivers taking care of dying patients at home. METHODS: A field study using semi-structured interview, participant observation, documents and records collection was employed. The study was conducted in two palliative care outpatient departments in tertiary hospitals and four communities in Beijing, China from March 2021 to July 2022. Using purposive sampling, twenty-five family caregivers were recruited. All collected data were analyzed using content analysis approach. RESULTS: Five themes emerged, including three care needs and two coping strategies. Family caregivers need to learn care skills and acquire care resources, including (i) decision-making about home-based palliative care, (ii) improving patient's quality of life, and (iii) signs of final hours and funeral procedures. In facing the care burden, family caregivers coped by (iv) balancing the roles of caregivers and individuals: giving priority to patient care while maintaining their own normal life. In facing the death of a loved one, family caregivers responded by (v) making room for coming death by facing death indirectly and "rescuing" patients for consolation while preparing for the coming death. CONCLUSION: Family caregivers strive to balance the roles of being caregivers and being themselves. As caregivers, they actively prepare patients for good death with no regrets. As individuals, they preserve themselves from being hurt to maintain normal life. The needs of family caregivers focus on caregiver role and are manifested in care skills and resources. TRIAL REGISTRATION: Not registered.
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Cuidadores , Serviços de Assistência Domiciliar , Humanos , Qualidade de Vida , Cuidados Paliativos/métodosRESUMO
Supercapacitors (SCs) have been the subject of considerable interest because of their distinct advantages. The performance of SCs is directly affected by the electrode materials. Metal oxides derived from Prussian blue analogues (PBAs) are often used as electrode materials for SCs. Herein, we developed a multi-step strategy to fabricate ternary hollow metal oxide (CuO/NiO/Co3O4) heterostructures. The core-shell structured PBA (NiHCC@CuHCC) with Ni-based PBA (NiHCC) as the core and Cu-based PBA (CuHCC) as the shell was prepared by a crystal seed method. The ternary metal oxide (CuO/NiO/Co3O4) with a hollow structure was obtained by calcinating NiHCC@CuHCC. The prepared CuO/NiO/Co3O4 demonstrates an excellent specific capacitance of 262.5 F g-1 at 1 A g-1, which is 27.4% and 16.2% higher than those of CuO/Co3O4 and NiO/Co3O4, respectively. In addition, the material showed outstanding cycling stability with a capacitance retention of 107.9% after 3000 cycles. The two-electrode system constructed with CuO/NiO/Co3O4 and nitrogen-doped graphene hydrogel (NDGH) demonstrates a stable and high energy density of 27.1 W h kg-1 at a power density of 1037.5 W kg-1. The capacitance retention rate was 100.7% after 4000 cycles. The reason for the excellent electrochemical properties could be the synergistic effect of the introduced heterojunction of CuO/NiO, the hollow structure, and various metal oxides. This strategy can greatly inspire the construction of SC electrodes.
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BACKGROUND & AIMS: This study aimed to establish multivariate prediction models according to a response-guided therapy (RGT) based strategy at baseline and week 12 and 24 of follow-up to predict the functional cure for HBeAg-negative patients with chronic hepatitis B (CHB) treated with pegylated interferonα (PEG-IFNα). METHODS: A total of 242 HBeAg-negative patients with CHB were treated with PEG-IFNα for 52 weeks and followed up for 24 weeks. Responses at the end of follow-up (EOF) were defined as hepatitis B surface antigen (HBsAg) loss, and patients were defined as either responders or non-responders. RESULTS: The three most meaningful predictors were an age ≤ 40 years, alanine aminotransferase (ALT) levels ≤ 40 U/L, and HBsAg levels ≤ 100 IU/mL at baseline; ALT levels ≥ 80 U/L, anti-HBc levels ≤ 8.42 S/CO, and HBsAg levels ≤ 50 IU/mL at week 12; and ALT levels ≥ 40 U/L, anti-HBc levels ≤ 8.46 S/CO, and HBsAg levels ≤ 0.2 IU/mL at week 24. The response rates of patients with a score of 0-1 and 4-5 at baseline, week 12, and 24 were 13.5%, 7.8%, and 11.7%; and 63.6%, 68.1%, and 98.1%, respectively. At week 12, the cumulative scores were 0-2, 3-4, 5-7, and 8-10 (response rates 5.0%, 18.9%, 41.3%, and 71.4%, respectively). At week 24, the cumulative scores were 0-3, 4-6, 7-10, and 11-15 (response rates: 1.3%, 12.3%, 37.0%, and 92.5%, respectively). At baseline, patients with scores of 0-1 were slightly recommended; at week 12, patients with 0-1 or 0-2 cumulative scores were recommended to stop treatment. At week 24, patients with a score of 0-1 or a cumulative score of 0-6 were recommended to stop treatment. CONCLUSION: We established a multi-parameter prediction model for the functional cure of HBeAg-negative patients with CHB treated with PEG-IFNα.
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Antígenos E da Hepatite B , Hepatite B Crônica , Humanos , Adulto , Antígenos de Superfície da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Alanina Transaminase , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêuticoRESUMO
Purpose This meta-analysis was conducted to systematically retrieve relevant randomized controlled trials (RCTs) and evaluate the effects of intrauterine infusion of autologous platelet-rich plasma (PRP) in women with thin endometrium, implantation or pregnancy failure undergoing treatment with assisted reproductive technology (ART). Methods We conducted a systematic review and meta-analysis of the retrieved RCTs. Studies on the intrauterine infusion of PRP in women undergoing treatment with ART that were published in PubMed, the Cochrane library, Web of Science, and Embase from inception until June 2022 were included. The data were extracted and analyzed independently using the fixed-effects or random-effects model according to heterogeneity. Results Seven RCTs involving 861 patients (435 in the intervention group and 426 in the control group) were included. The rates of clinical pregnancy (risk ratio [RR]: 2.51; 95% confidence interval [CI]: 2.0-3.13; P < 0.00001), chemical pregnancy (RR: 1.96; 95% CI: 1.58-2.45; P < 0.00001), live births (RR: 7.03; 95% CI: 3.91-12.6; P < 0.00001), and implantation (RR: 3.27; 95% CI: 1.42-7.52; P = 0.005) were significantly higher in the women who received PRP infusion than in the control group. No significant differences were noted in the miscarriage rate (RR: 0.98; 95% CI: 0.39-2.42; P = 0.96) between the two groups. Conclusion In summary, intrauterine infusion of PRP may be an effective therapy for women with thin endometrium and recurrent implantation failure (RIF) undergoing treatment with ART. More population-based RCTs are warranted to verify the efficacy of our evidence.
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Presently, most studies on modified lignin focused on the adsorption to heavy metal cations, but rarely to Ca2+ in hard water. Therefore, this work prepared a new gel-type lignin-based cationic adsorption resin (E-LSAF) through the crosslinking and curing of alkali lignin grafted by sodium sulfite sulfonated acetone to remove Ca2+ in water. Under the determined optimum synthesis conditions, E-LSAF with a highest sulfonic group content of 1.99 mmol/g was obtained. Structural and physicochemical measuring results showed E-LSAF was a gel-type resin, owning strong hydrophilicity, high mechanical strength, excellent thermal stability and acid-alkaline resistance. Adsorption results indicated the adsorption of E-LSAF to Ca2+ was well-fitted by Langmuir model, and the maximum adsorption capacity reached 45.8 mg/g. Pseudo-second-order model can describe this adsorption process well, suggesting it a chemisorption process. Dynamic column adsorption results showed E-LSAF could transform hard water into soft or even very soft water. The regeneration efficiency still maintained 80 % after 5 cycles. The adsorption mechanism was attributed to electrostatic attraction, ion exchange and complexation. This work provided a high-performance lignin-based cationic adsorption material with high adsorption capacity to Ca2+ and excellent acid-alkaline resistance, which filled the research gap of using modified sulfonated lignin to remove Ca2+ from water.
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Lignina , Poluentes Químicos da Água , Lignina/química , Poluentes Químicos da Água/química , Adsorção , Concentração de Íons de Hidrogênio , Água/química , Alcanossulfonatos , Cátions , CinéticaRESUMO
Purpose: To explore the death experiences of nursing students in their personal lives. Methods: This study employed a qualitative descriptive design using the semi-structured interview approach. A purposive sampling method was used to recruit 24 nursing students from September 2020 to July 2022. Data were analyzed using Colaizzi's analysis method. Lincoln and Guba's criteria was used to evaluate the trustworthiness of the data. Results: Four main themes emerged from the interviews: (a) reactions to encounters with death; (b) adjustment strategies; (c) personal growth induced by the death experiences; and (d) professional reflections for preparing nurse role. Conclusions: Although the death of a loved one makes nursing students suffer from grief and emotional distress, we show that the experience promotes the personal growth and professional competencies of nursing students and thereby, developing their overall aptitude towards the profession. Death experiences of nursing students have shown to allow them to reflect on both life and death, to consider the demands of the nursing profession, and to provide foundation for nursing students to be more empathetic and compassionate when facing death in the future. Exploring death experiences of nursing students is vital in better providing better quality education and personal support for nursing students.
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Antibody is the key biomolecule that governing the sensitivity and specificity of an immunoassay for chemical compound, also named hapten molecule. Obviously, predication of hapten effectiveness before chemical synthesis is beneficial to boost success, save cost and improve controllability. Here, we proposed and evaluated an epitopephore based rational hapten design (ERHD) to assist antibody production to chemical compound, combining theoretical evidence and then experimental validation by using dinitrocarbanilide (DNC) as a model analyte. Briefly, epitopephores of DNC were firstly generated by HipHop algorithm after features mapping. A homemade drug database also containing reported fragment haptens (HFR) and new designed full hapten (HFU) were constructed, and then was virtually screened by using generated epitopephore followed by structural analysis and visual inspection. The DNC haptens based on the selected hits were further identified by Density Functional Theory before total synthesis. To prove and clarify the usability of the ERHD, two retrieved HFU haptens, one non-retrieved HFU hapten and three non-retrieved HFR haptens were all selected to produce monoclonal antibodies (mAbs) for comparison purpose. A maximal 6000-fold increased affinity of mAb from retrieved HFU than HFR was observed, while, non-retrieved HFU failed to produce antibody to DNC. More importantly, mAbs from HFU haptens provided highly specificity to DNC, while, mAbs from HFR haptens could recognize 15 others analogues. We then constructed antibody structure and investigated molecular recognition of the mAbs to DNC, well supporting the rationality of the ERHD. Lastly, an icELISA was developed for DNC with an IC50 value as low as 0.19 ng mL-1 with high specificity, which has never achieved before.
Assuntos
Anticorpos Monoclonais , Haptenos , Haptenos/análise , Imunoensaio , Sensibilidade e Especificidade , Ensaio de Imunoadsorção EnzimáticaRESUMO
The molecular simulation software was firstly applied to analyze the adsorption of sulfomethylated lignin (SAL) on dye surfaces. Then, SALs with different sulfonic group contents were prepared and characterized by FTIR, NMR, EA and GPC measurements using alkali lignin (AL) as raw materials and sodium sulfite as sulfonating agents. Next, SAL1.53 was determined to the optimum dispersant by TSI, particle size and thermal storage stability measurements, which had the smallest particle size of 173 nm and highest stability, comparable to the commercial Reax 85A lignin dispersant and basically satisfying the requirement of nano disperse dyes used in the digital printing technology. QCM, AFM and zeta potential results indicated that as the sulfonic group content of SAL increased, the adsorption mass, rigidity of the adsorbed layer, adsorption force and absolute zeta potential value all showed a gradually increasing tendency due to an enhanced hydrophilicity, and thus a decreased intermolecular agglomeration and an increased molecular chain stretching degree. A maximum was observed for SAL1.53. This research not only provided a novel approach to the preparation of high-performance lignin dispersants for nano disperse dyes, but also would broaden the high value-added industrial applications of biomass lignin into the digital printing and dyeing field.