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BACKGROUND: The treatment strategy for patients with severe tooth wear associated with Class II Division 2 malocclusion remains a major challenge for dental practitioners. OBJECTIVES: To systematically review and summarize the literature on treatment strategies, restoration procedures and clinical outcomes for Class II Division 2 malocclusion patients with severe tooth wear. METHODS: A literature review was conducted using Pubmed, Embase, the Cochrane Library, and Web of Science to identify eligible articles. Publications until October 16th, 2023 were searched independently and cross-checked by two researchers. RESULTS: Of 1513 articles screened, 10 reports detailed treatment processes, including six males and four females aged 34-68 years old. Four articles recorded pre-treatment freeway space (FWS) values ranging from 5 to 9 mm. All ten cases had significant occlusal vertical dimension (OVD) loss and the increase in OVD after treatment ranged from 1 to 7 mm. Pre-prosthetic orthodontic treatment was performed in two cases, in one of which only the maxillary region was orthodontically treated. The most common restorations provided were full coverage restorations. In most cases, temporary restorations were applied before the permanent restorations for eight weeks to six months. Four different sequences of final restoration were proposed. Follow-up ranged from four months to six years and included seven patients, one of them showed symptoms of temporomandibular disorder (TMD). CONCLUSIONS: A multidisciplinary team (MDT) approach to treatment is recommended. Consideration of pre-prosthetic orthodontic treatment is essential. Commonly used cephalometric measurements for anterior teeth include the interincisal angle and collum angle. The increases in OVD ranging from 1 to 7 mm can be effectively accommodated. Temporary restorations are recommended to accommodate the OVD, and the transition periods of 8 weeks to 6 months help the patients adapted well. Four different sequences for final rehabilitation have demonstrated positive clinical outcomes. Full crown restorations have emerged as the preferred choice for the ultimate restoration of these patients.
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Novel coumarin-piperazine-2(5H)-furanone hybrids 5a-l were efficiently synthesized by introducing a furanone scaffold into coumarin using piperazine as a linker. The cytotoxicity of all hybrids 5a-l were evaluated by MTT assay on human lung cancer A549 cells and normal human lung fibroblast WI-38 cells with cytarabine (CAR) as a positive control. Hybrid 5l (IC50 = 11.28 µM) was the most toxic to A549 cells, 18-fold more toxic than the reference CAR (IC50 = 202.57 µM). Moreover, hybrid 5l (IC50 = 411.93 µM) was less toxic to WI-38 cells, with a much higher selectivity (5l, SI ≈ 37, WI-38/A549) than CAR (SI ≈ 2). Structure-activity relationship analysis showed that both the cytotoxicity against A549 cells and selectivity (WI-38/A549) were greatly improved when the bornyl group was incorporated in the hybrids (5c, 5f, 5i and 5l). Further, hybrid 5l was more toxic and selective against four types of human lung cancer cells (A549, Calu-1, PC-9 and H460; IC50 = 5.72-45.46 µM; SI ≈ 9-72) than three other types of human cancer cells (SK-BR-3, 786-O and SK-OV-3, IC50 = 39.07-130.82 µM; SI ≈ 0-2), showing remarkable specificity. In particular, hybrid 5l (IC50 = 5.72 µM) showed the highest cytotoxicity against H460 cells with the highest selectivity of up to 72 (WI-38/H460). Flow cytometric analysis showed that hybrid 5l induced apoptosis in H460 cells in a concentration-dependent manner. Molecular docking studies revealed a high binding affinity of hybrid 5l with CDK2 protein. Hybrid 5l is expected to be a leading candidate for anti-lung cancer agents.
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Cumarínicos , Simulação de Acoplamento Molecular , Humanos , Cumarínicos/farmacologia , Cumarínicos/química , Estrutura Molecular , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Neoplasias Pulmonares/tratamento farmacológico , Furanos/farmacologia , Furanos/química , Furanos/síntese química , Células A549 , Piperazinas/farmacologia , Piperazinas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese químicaRESUMO
Objective: To study whether children with peptic ulcer would have abnormalities in cellular and humoral immune functions, and whether Helicobacter pylori (Hp) infection would affect the immune function of children with peptic ulcer. Methods: This is a retrospective study. The subjects of study were 72 children with diagnosed and cured peptic ulcer (ulcer group), and 50 healthy children with physical examination (control group) at Baoding Hospital, Beijing Children's Hospital Affiliated to Capital Medical University from June 2020 to December 2022. Further detection was conducted on T lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+ ratio) and immunoglobulin levels. Results: Of the 72 children with peptic ulcer, 53(73.6%) were positive for Hp (Hp-positive group) and 19 (26.4%) were negative (Hp-negative group). The levels of CD3+, CD4+, and CD4+/CD8+ ratio in the control group were significantly higher than those in the ulcer group, with statistically significant difference (P<0.05); while the level of IgG in the control group was lower than that in the ulcer group, with statistically significant difference (P<0.05). Meanwhile, there were statistically significant differences in that the levels of CD3+, CD4+ and CD8+ were increased in Hp-positive group than those in Hp-negative group before treatment (P<0.05); while CD4+/CD8+ ratio was lower in the former group than that in the latter group, with statistically significant difference (P<0.05). Conclusion: Hp infection can induce the elevation of T lymphocyte subsets. The development of peptic ulcer has an intimate association with the disorder of cellular and humoral immune functions.
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OBJECTIVES: The aims of this clinical study were to investigate success rate, vital pulp survival rate, tooth survival rate and patient-reported masticatory ability by evaluating the pain symptoms and signs of the cracked teeth as well as Index of Eating Difficulty (IED) and Oral Health Impact Profile-14 (OHIP-14) questionnaire after cracked teeth were restored with occlusal veneers. MATERIALS AND METHODS: 27 cracked teeth of 24 patients with cold and/or biting pains without spontaneous/nocturnal pains were recruited in this study. The cracked teeth were restored with occlusal veneers fabricated by lithium disilicate ceramic. Cold test and biting test were used to evaluate pain signs. IED and OHIP-14 questionnaire were used to evaluate masticatory ability. FDI criteria was used to evaluate restorations. The paired Wilcoxon test was used to analyze significant differences of detection rate of pain signs, OHIP scores and IED grade before and after restorations. Kaplan-Meier survival curve was used to describe the success rate, vital pulp survival rate, and tooth survival rate. RESULTS: 27 cracked teeth were restored with occlusal veneers with average of 22.4-month follow-up. Two cracked teeth had pulpitis and pain signs of the other cracked teeth completely disappeared. OHIP total scores were significantly reduced after treatment. Scores of 'pain', 'occlusal discomfort', 'uncomfortable to eat', 'diet unsatisfactory' and 'interrupted meals' reduced significantly after treatment. After treatment, IED grades of 25 vital teeth were significantly lower than those before treatment. FDI scores of 25 restorations except for 2 teeth with pulpitis were no greater than 2. The 12 months accumulated pulp survival rate of the cracked teeth was 92.6%. The 12 months accumulated tooth survival rate was 100%. The success rate at the latest recall was 92.6%. CONCLUSION: Occlusal veneer restorations with success rate of 92.6% and the same pulp survival rate might be an effective restoration for treating the cracked teeth. CLINICAL RELEVANCE: The occlusal veneer restorations might be an option for treating the cracked teeth when cracks only involve enamel and dentin, not dental pulp.
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Síndrome de Dente Quebrado , Facetas Dentárias , Humanos , Feminino , Masculino , Adulto , Seguimentos , Síndrome de Dente Quebrado/terapia , Resultado do Tratamento , Inquéritos e Questionários , Pessoa de Meia-Idade , Medição da Dor , Porcelana Dentária , Restauração Dentária Permanente/métodos , Mastigação/fisiologiaRESUMO
The development of novel therapeutic approaches to facilitate endometrial repair and regeneration while preventing adhesion recurrence is a crucial research objective aimed at enhancing clinical outcomes for women with intrauterine adhesions (IUA). In this study, we introduced an injectable Alg-GMA/PTSB zwitterionic hydrogel, characterized by excellent biocompatibility, anti-protein adsorption properties, and biodegradability. In a rat model, the hydrogel significantly promoted the regeneration and angiogenesis of damaged endometrial tissue, leading to improved recovery of epithelial cells, glands, proliferation, and vascularization. Furthermore, it exhibited the ability to suppress cellular apoptosis and collagen deposition, thereby mitigating fibrosis. Additionally, the hydrogel restored the expression of estrogen/progesterone receptors and endometrial receptivity markers, contributing to enhanced embryo implantation and fertility. These findings underscore the potential of the hydrogel as a promising therapeutic strategy for addressing endometrial injury, reducing fibrosis, restoring fertility, and ultimately improving outcomes for women with IUA.
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Alginatos , Endométrio , Fertilidade , Hidrogéis , Feminino , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Alginatos/química , Alginatos/farmacologia , Ratos , Fertilidade/efeitos dos fármacos , Aderências Teciduais/prevenção & controle , Aderências Teciduais/tratamento farmacológico , Ratos Sprague-Dawley , Injeções , Regeneração/efeitos dos fármacos , HumanosRESUMO
RESEARCH QUESTION: Is intra-abdominal fat obesity associated with infertility? DESIGN: This study analysed data from the 2013-2018 National Health and Nutrition Examination Survey, with a total of 3013 women enrolled. The participants were divided into two groups: infertility and non-infertility. Differences between the two groups were analysed using a weighted Student's t-test or Mann-Whitney U-test for continuous variables, or a weighted chi-squared test for categorical data. Visceral adipose tissue area (VATA) was assessed by dual-energy X-ray absorptiometry. The independent association between infertility and log VATA was assessed by weighted multivariate logistic regression models. Subgroup analyses were performed to assess the strength of the results. Interaction tests were used to examine whether covariates interacted with log VATA to influence infertility. RESULTS: Log VATA was significantly higher in the infertility group compared with the non-infertility group (P < 0.001). After adjustment for potential confounders, the results of multivariate logistic regression analysis revealed that an increase in log VATA was associated with increased prevalence of female infertility (ORâ¯=â¯2.453, 95% CI 1.278-4.792). Subgroup analyses showed this association in individuals aged <35 years (Pâ¯=â¯0.002), Mexican-Americans (Pâ¯=â¯0.033), non-hypertensive individuals (Pâ¯=â¯0.013) and non-diabetic individuals (Pâ¯=â¯0.003). CONCLUSIONS: An enlarged VATA is associated with increased risk of infertility. The direct effect of VATA on female infertility needs to be clarified further to provide a basis for future prevention and treatment of female infertility.
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INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in China. The combination of immune checkpoint inhibitors (ICIs) and antiangiogenic drugs, such as bevacizumab and tyrosine kinase inhibitors, has been recommended as first-line treatment for advanced HCC. However, two-thirds of patients did not benefit from this form of immunotherapy. Currently, data on the subsequent regimen for patients previously treated with ICIs are lacking. Studies have shown that the combination of radiotherapy (RT) and ICIs is a potentially effective second-line therapy for HCC. This study aims to assess the efficacy and safety of combined therapy with stereotactic body RT (SBRT), sintilimab and IBI305 (a biosimilar of bevacizumab) in patients with HCC following the progression of first-line ICI therapy. METHODS AND ANALYSIS: This study is an open-label, single-arm, single-centre, phase 2 trial of 21 patients with advanced HCC in whom previous ICI therapy has failed. Participants will receive approximately 30-40 Gy/5-8F SBRT, followed by 200 mg sintilimab and 15 mg/kg IBI305 intravenously every 3 weeks. Treatment will continue until the development of unacceptable toxicity or disease progression. We will use Simon's two-stage design, with the objective response rate (ORR) as the primary endpoint. Secondary endpoints include ORR of lesions without RT, disease control rate, progression-free survival, overall survival and safety. ETHICS AND DISSEMINATION: The study was authorised by the Medical Ethics Committee. Dissemination of results will occur via a peer-reviewed publication and other relevant media. TRIAL REGISTRATION NUMBER: ChiCTR2200056068.
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Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Hepatocelular/terapia , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias Hepáticas/terapia , Radiocirurgia/métodos , Radiocirurgia/efeitos adversosRESUMO
Clostridioides difficile (C. difficile), as the major pathogen of diarrhea in healthcare settings, has become increasingly prevalent within community populations, resulting in significant morbidity and mortality. However, the therapeutic options for Clostridioides difficile infection (CDI) remain limited, and as of now, no authorized vaccine is available to combat this disease. Therefore, the development of a novel vaccine against C. difficile is of paramount importance. In our study, the complete proteome sequences of 118 strains of C. difficile were downloaded and analyzed. We found four antigenic proteins that were highly conserved and can be used for epitope identification. We designed two vaccines, WLcd1 and WLcd2, that contain the ideal T-cell and B-cell epitopes, adjuvants, and the pan HLA DR-binding epitope (PADRE) sequences. The biophysical and chemical assessments of these vaccine candidates indicated that they were suitable for immunogenic applications. Molecular docking analyses revealed that WLcd1 bonded with higher affinity to Toll-like receptors (TLRs) than WLcd2. Furthermore, molecular dynamics (MD) simulations, performed using Gmx_MMPBSA v1.56, confirmed the binding stability of WLcd1 with TLR2 and TLR4. The preliminary findings suggested that this multi-epitope vaccine could be a promising candidate for protection against CDI; however, experimental studies are necessary to confirm these predictions.
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Novel metal-organic framework MIL-101(Cr)-NH2 functionalised hydrophilic polydopamine-modified Fe3O4 magnetic nanoparticles (Fe3O4@PDA@MIL-101(Cr)-NH2) were synthesised and used as magnetic solid-phase extraction (MSPE) adsorbents for extracting tetracyclines (TCs) from milk samples. The integrated Fe3O4@PDA@MIL-101(Cr)-NH2 exhibited convenient magnetic separation and exceptional multi-target binding capabilities. Furthermore, the PDA coating significantly enhanced the hydrophilicity and extraction efficiency of the material, thereby facilitating the extraction of trace TCs. Various factors affecting MSPE, such as adsorbent dosage, extraction time, pH value, and desorption conditions, were optimised. The developed MSPE method coupled with high-performance liquid chromatography demonstrated good linearity (R2 ≥ 0.9989), acceptable accuracy (82.2%-106.1%), good repeatability (intra-day precision of 0.8%-4.7% and inter-day precision of 1.1%-4.5%), low limits of detection (2.18-6.25 µg L-1), and low limits of quantification (6.54-18.75 µg L-1) in TCs detection. The approach was successfully used for the quantification of trace TCs in real milk samples.
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Nanopartículas de Magnetita , Estruturas Metalorgânicas , Leite , Extração em Fase Sólida , Tetraciclinas , Leite/química , Extração em Fase Sólida/métodos , Extração em Fase Sólida/instrumentação , Estruturas Metalorgânicas/química , Tetraciclinas/isolamento & purificação , Tetraciclinas/química , Tetraciclinas/análise , Animais , Nanopartículas de Magnetita/química , Interações Hidrofóbicas e Hidrofílicas , Cromatografia Líquida de Alta Pressão , Adsorção , Contaminação de Alimentos/análiseRESUMO
ß-Hydroxy-α-amino acids (ß-HAAs) have extensive applications in the pharmaceutical, chemical synthesis, and food industries. The development of synthetic methodologies aimed at producing optically pure ß-HAAs has been driven by practical applications. Among the various synthetic methods, biocatalytic asymmetric synthesis is considered a sustainable approach due to its capacity to generate two stereogenic centers from simple prochiral precursors in a single step. Therefore, extensive efforts have been made in recent years to search for effective enzymes which enable such biotransformation. This review provides an overview on the discovery and engineering of C-C bond formation enzymes for the biocatalytic synthesis of ß-HAAs. We highlight examples where the use of threonine aldolases, threonine transaldolases, serine hydroxymethyltransferases, α-methylserine aldolases, α-methylserine hydroxymethyltransferases, and engineered alanine racemases facilitated the synthesis of ß-HAAs. Additionally, we discuss the potential future advancements and persistent obstacles in the enzymatic synthesis of ß-HAAs.
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Introduction: Bromus japonicus is one of the most notorious agricultural weeds in China. The long-term use of ALS-inhibiting herbicides has led to rapid evolution of herbicide resistance in B. japonicus. B. japonicus population (BJ-R) surviving mesosulfuron-methyl treatment was collected from wheatland. Here, we aimed to confirm the resistance mechanisms in this putative resistant population. Methods: The dose-reponse tests were used to test the resistance level of the B. japonicus to ALS-inhibiting herbicides. Pretreatment with P450 and GST inhibitors and GST activity assays were used to determine whether P450 or GST was involved in the resistance of the BJ-R population. Sanger sequencing was used to analyse the ALS mutation of the BJ-R population. RT-qPCR was used to confirm the the expression levels of the ALS gene in mesosulfuron-methyl -resistant (BJ-R) and-susceptible (BJ-S) B. japonicus. An in vitro ALS activity assay was used to determine the ALS activity of the BJ-R and BJ-S populations. Homology modelling and docking were used to determine the binding energy of the BJ-R and BJ-S populations with ALS-inhibiting herbicides. Results: B. japonicus population (BJ-R) was confirmed to be 454- and 2.7-fold resistant to the SU herbicides mesosulfuron-methyl and nicosulfuron, and 7.3-, 2.3-, 1.1- and 10.8-fold resistant to the IMI herbicide imazamox, the TP herbicide penoxsulam, the PTB herbicide pyribenzoxim and the SCT herbicide flucarbazone-sodium, respectively, compared with its susceptible counterpart (BJ-S). Neither a P450 inhibitor nor a GST inhibitor could reverse the level of resistance to mesosulfuron-methyl in BJ-R. In addition, no significant differences in GST activity were found between the BJ-R and BJ-S. ALS gene sequencing revealed a Pro-197-Thr mutation in BJ-R, and the gene expression had no significant differences between the BJ-R and BJ-S. The ALS activity of BJ-R was 106-fold more tolerant to mesosulfuron-methyl than that of BJ-S. Molecular docking showed that the binding energy of the ALS active site and mesosulfuron-methyl was changed from -6.67 to -4.57 kcal mol-1 due to the mutation at position 197. Discussion: These results suggested that the Pro-197-Thr mutation was the main reason for the high resistance level of BJ-R to mesosulfuron-methyl. Unlike previous reports of the cross-resistance pattern conferred by this mutation, we firstly documented that the Pro-197-Thr mutation confers broad cross-resistance spectrums to ALS-inhibiting herbicides in B. japonicus.
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OBJECTIVE: Diabetic cardiomyopathy (DCM) is the most common cardiovascular complication of type 2 diabetes mellitus (T2DM). Patients affected with DCM face a notably higher risk of progressing to congestive heart failure compared to other populations. Myocardial hypertrophy, a clearly confirmed pathological change in DCM, plays an important role in the development of DCM, with abnormal Ca2+ homeostasis serving as the key signal to induce myocardial hypertrophy. Therefore, investigating the mechanism of Ca2+ transport is of great significance for the prevention and treatment of myocardial hypertrophy in T2DM. METHODS: The rats included in the experiment were divided into wild type (WT) group and T2DM group. The T2DM rat model was established by feeding the rats with high-fat and high-sugar diets for three months combined with low dose of streptozotocin (100mg/kg). Afterwards, primary rat cardiomyocytes were isolated and cultured, and cardiomyocyte hypertrophy was induced through high-glucose treatment. Subsequently, mechanistic investigations were carried out through transfection with si-STIM1 and oe-STIM1. Western blot (WB) was used to detect the expression of the STIM1, Orai1 and p-CaMKII. qRT-PCR was used to detect mRNA levels of myocardial hypertrophy marker proteins. Cell surface area was detected using TRITC-Phalloidin staining, and intracellular Ca2+ concentration in cardiomyocytes was measured using Fluo-4 fluorescence staining. RESULTS: Through animal experiments, an upregulation of Orai1 and STIM1 was revealed in the rat model of myocardial hypertrophy induced by T2DM. Meanwhile, through cell experiments, it was found that in high glucose (HG)-induced hypertrophic cardiomyocytes, the expression of STIM1, Orai1, and p-CaMKII was upregulated, along with increased levels of store-operated Ca2+ entry (SOCE) and abnormal Ca2+ homeostasis. However, when STIM1 was downregulated in HG-induced cardiomyocytes, SOCE levels decreased and p-CaMKII was downregulated, resulting in an improvement in myocardial hypertrophy. To further elucidate the mechanism of action involving SOCE and CaMKII in T2DM-induced myocardial hypertrophy, high-glucose cardiomyocytes were respectively treated with BTP2 (SOCE blocker) and KN-93 (CaMKII inhibitor), and the results showed that STIM1 can mediate SOCE, thereby affecting the phosphorylation level of CaMKII and improving cardiomyocyte hypertrophy. CONCLUSION: STIM1/Orai1-mediated SOCE regulates p-CaMKII levels, thereby inducing myocardial hypertrophy in T2DM.
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Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Cálcio , Cardiomegalia , Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Glucose , Proteína ORAI1 , Molécula 1 de Interação Estromal , Animais , Ratos , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiomegalia/etiologia , Cardiomegalia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Glucose/metabolismo , Glucose/farmacologia , Proteína ORAI1/genética , Proteína ORAI1/metabolismo , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo , Regulação para Cima , Cardiomiopatias Diabéticas/complicações , Ratos Sprague-Dawley , MasculinoRESUMO
Novel rhein-piperazine-furanone hybrids, 5, were designed and synthesized efficiently from rhein. Cytotoxicity of all hybrids 5a-j against A549 human lung cancer cells was superior to the parent rhein and the reference cytarabine (CAR). Hybrid 5e (IC50 = 5.74 µM), the most potent compound, was 46- and 35-fold more toxic against A549 cells than rhein (IC50 = 265.59 µM) and CAR (IC50 = 202.57 µM), respectively. Moreover, hybrid 5e (IC50 = 69.28 µM) was less toxic to normal WI-38 human lung fibroblast cells with good selectivity (WI-38/A549, SI ≈ 12), being much higher than rhein (SI ≈ 1) and CAR (SI ≈ 2). Structure-activity relationship (SAR) analysis showed that cytotoxicity and selectivity against A549 lung cancer cells were greatly enhanced when methoxy-containing furanone was introduced to the hybrids (5e and 5h). Further, hybrid 5e showed better cytotoxicity against four types of human lung cancer cells (H460, A549, PC-9, and Calu-1; IC50 = 4.35-15.39 µM) than six other types of human cancer cells (SK-BR-3, SK-OV-3, 786-O, Huh-7, HCT116, and HeLa; IC50 = 13.77-60.45 µM), showing specificity. In particular, hybrid 5e showed the highest cytotoxicity (IC50 = 4.35 µM) and the highest selectivity (WI-38/H460, SI ≈ 16) against H460 human lung cancer cells. Flow cytometric analysis showed that hybrid 5e induced apoptosis in a concentration-dependent manner in H460 cells. The results show that the cytotoxicity and selectivity of rhein can be greatly enhanced by hybridization with furanone. Hybrid 5e is expected to be a leading candidate for anti-lung cancer drugs.
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Background: Despite the widespread adoption of COVID-19 vaccination, a comprehensive understanding of potential vaccine-induced adverse effects, particularly in the context of pregnancy, remains a critical area of investigation. Elevated concerns surround the maternal and neonatal outcomes subsequent to prenatal maternal COVID-19 vaccination. While existing studies have provided insights into the safety profile of COVID-19 mRNA vaccines, the extrapolation of these conclusions to inactivated COVID-19 vaccines poses uncertainties. Notably, limited data are available regarding the maternal and neonatal effects associated with inactivated COVID-19 vaccines. Objective: To evaluate the prenatal maternal inactivated COVID-19 vaccination and the impact on maternal and neonatal outcomes. Methods: This was a retrospective cohort study of women who delivered between January and June 2022 at a single university-affiliated hospital. Those who have completed at least one dose of inactivated vaccine before or during pregnancy were included in "vaccinated group," and those who were not vaccinated were included in "unvaccinated group," the maternal, pregnancy and neonatal outcomes were evaluated. Propensity score matching (PSM) was performed to balance the baseline parameters of the two groups. Results: A total of 1926 women were enrolled in this study, 827 (42.94%) women were prenatally vaccinated, and 1099 (57.06%) unvaccinated. The gestational week of delivery were slightly lower in the vaccinated group, 38.61 ± 1.89 weeks in the vaccinated group and 38.93 ± 1.49 weeks in the unvaccinated group. There was a higher rate of overall preterm delivery in the vaccinated group (aOR 1.61, 95% CI 1.07-2.42; p = 0.02), however, the probability of delivery before 34 weeks and before 32 weeks (early preterm delivery) were similar (p > 0.05). A total of 2009 infants were born, 851 in the vaccinated group and 1158 in the unvaccinated group. There were similar neonatal outcomes in the two groups. Conclusion: Although we found a slightly lower gestational week of delivery and a possible increased rate of late preterm birth in the vaccination group, there was no difference in mean neonatal weight, incidence of low birth weight infants and other neonatal adverse complications. Meanwhile, there was no difference in pregnancy and maternal outcomes between the two groups.
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Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA-miRNA-lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW's regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA's progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA.
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Artrite Reumatoide , Hedyotis , MicroRNAs , RNA Longo não Codificante , Farmacologia em Rede , RNA Longo não Codificante/genética , Metaloproteinase 9 da Matriz/genética , Simulação de Acoplamento Molecular , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Biologia Computacional , MicroRNAs/genéticaRESUMO
Host cell proteins (HCPs) are impurities that can adversely affect therapeutic proteins, even in small quantities. To evaluate the potential risks associated with drug products, methods have been developed to identify low-abundance HCPs. A crucial approach for developing a sensitive HCP detection method involves enriching HCPs while simultaneously removing monoclonal antibodies (mAbs) before analysis, utilizing liquid chromatography-mass spectrometry (LC-MS). This protocol offers detailed instructions for enriching host cell proteins using commercially available proteome enrichment beads. These beads contain a diverse library of hexapeptide ligands with specific affinities for different proteins. The protocol also incorporates limited digestion and subsequent peptide detection using nano LC-MS/MS. By employing these techniques, HCPs with low abundance can be enriched over 7000-fold, resulting in an impressive detection limit as low as 0.002 ppm. Significantly, this protocol enables the detection of 850 HCPs with a high level of confidence using a NIST mAb. Moreover, it is designed to be user-friendly and includes a video demonstration to assist with its implementation. By following these steps, researchers can effectively enrich and detect HCPs, enhancing the sensitivity and accuracy of risk assessment for drug products.
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Peptídeos , Espectrometria de Massas em Tandem , Animais , Cricetinae , Cromatografia Líquida/métodos , Peptídeos/análise , Anticorpos Monoclonais/metabolismo , Digestão , Cricetulus , Células CHORESUMO
Purpose: This study aimed to translate and cross-culturally adapt the cardiac rehabilitation barriers scale to the Chinese, and examine its reliability and validity among the older population. Methods: An approach comprising translation, cultural adaptation, reliability, and validity examination in the Chinese version was conducted in two hospitals in Jilin, China. The t-tests were used to compare the sex differences between each item. Participants included Chinese individuals >60 who were eligible for the cardiac rehabilitation program. Results: In total, 325 participants completed the questionnaire with an average age of 61.23 ± 9.68 years. The item-total correlations were 0.432 to 0.678. Factor analysis of CRBS-C (Kaiser Meyer Olkin = 0.867, Bartlett's test p = 0.000) revealed four factors: logistical factors, comorbidities/functional status, perceived need/healthcare factors, and work/time conflict. The confirmatory factor analysis (CFA) indicated a good model fit (χ2/df = 1.84, RMSEA = 0.051, CFI = 0.953, TLI = 0.945, SRMR=0.046). Cronbach's alpha was 0.88 for the scale, ranging from 0.801 to 0.88 for each item, which indicates the internal reliability was acceptable. Conclusion: The Chinese version of the CRRS has acceptable reliability and validity in the Chinese elderly population.
RESUMO
The exploration of tumor target genes holds paramount importance for the prevention and treatment of cervical cancer. In this study, we outline the steps involved in the identification of a tumor target gene FAM83A in cervical cancer. First, the Cancer Genome Atlas dataset was employed to validate the expression and prognostic significance of FAM83A in women. A small interfering RNA (siRNA) was used for knockdown of the FAM83A gene in HeLa and C33a cells. Next, 5-ethynyl-2'-deoxyuridine (EdU) staining was conducted to determine the effects on the proliferation capabilities of the tumor cells. Wound healing and porous membrane insert assays were performed to evaluate tumor cell migration and invasion abilities. Western blotting was used to quantify apoptosis-related protein levels. JC-1 staining was employed to evaluate mitochondrial function alterations. Furthermore, cisplatin (diaminedichloroplatinum, DDP) intervention was used to assess the therapeutic potential of the target gene. Flow cytometry and colony formation assays were conducted to further validate the anticancer characteristics of the gene. As a result, FAM83A knockdown was shown to inhibit the proliferation, migration, and invasion of cervical cancer cells and sensitize these cells to cisplatin. These comprehensive methodologies collectively validate FAM83A as a tumor-associated target gene, holding promise as a potential therapeutic target in the prevention and treatment of cervical cancer.
Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Cisplatino/farmacologia , Transformação Celular Neoplásica , Genes Neoplásicos , Apoptose , Proteínas de NeoplasiasRESUMO
The low-carbon transition is a systemic economic and social change that will inevitably have an impact on many areas of the urban system. Has China's ongoing low-carbon transition impacted urban resilience (UR) systems while achieving urban energy saving and carbon emission reduction goals? This paper uses the implementation of the carbon emissions trading pilot policy (CETPP) as a "quasi-natural experiment." It evaluates the impact of the policy on UR using a difference-in-differences model based on the data of prefecture-level cities from 2008 to 2020. The study shows that pilot carbon trading policies favor UR, and the market mechanism of carbon emissions has a heterogeneous cause influence on UR. The impact of pilot carbon trading policies on UR varies according to the respective moderating effects of institutional factors, green technology innovation, industrial structure rationalization, and output effects.
Assuntos
Carbono , Resiliência Psicológica , Cidades , Carbono/análise , Indústrias , China , Desenvolvimento EconômicoRESUMO
Despite substantial efforts to detect host cell proteins (HCPs) in antibody drugs, information regarding HCPs in gene therapy products remains limited and has not been widely integrated into the host cell engineering or purification processes. Most methods that have successfully detected HCPs in antibody drugs are not applicable to gene therapy products, except for the ProteoMiner enrichment method. Here, we demonstrate that ProteoMiner beads effectively enrich HCPs in adeno-associated virus (AAV) products and simultaneously remove the detergent Pluronic F-68 without a loss of low-abundance HCPs. Following optimization of this technique, there was up to a 34-fold increase in the enrichment of HCPs compared to direct digestion. Moreover, the detection limit was significantly lowered with the ability to detect HCPs at levels as low as 0.1 ng/mL after ProteoMiner treatment. This approach holds promise in AAV HCP analysis and may be adaptable to other gene therapy products. The findings from this study provide valuable insights into HCPs in AAV products and may facilitate process development and host cell line optimization. The high sensitivity of this approach also facilitates detection of critical low-abundance HCPs, thereby contributing to risk assessment of their impact on the safety and quality of the AAV-based gene therapy products.